molecules
Review
The Phytochemistry and Pharmacology of Tulbaghia, Allium,
Crinum and Cyrtanthus: ‘Talented’ Taxa from the
Amaryllidaceae
Cynthia Amaning Danquah 1, * , Prince Amankwah Baffour Minkah 1,2 , Theresa A. Agana 3 ,
Phanankosi Moyo 4 , Michael Ofori 1,5 , Peace Doe 6 , Sibusiso Rali 4 , Isaiah Osei Duah Junior 7 ,
Kofi Bonsu Amankwah 8 , Samuel Owusu Somuah 9 , Isaac Newton Nugbemado 1 , Vinesh J. Maharaj 4 ,
Sanjib Bhakta 10 and Simon Gibbons 11
1
2
3
4
5
6
Citation: Danquah, C.A.; Minkah,
P.A.B.; Agana, T.A.; Moyo, P.; Ofori,
M.; Doe, P.; Rali, S.; Osei Duah Junior,
7
8
I.; Amankwah, K.B.; Somuah, S.O.;
et al. The Phytochemistry and
9
Pharmacology of Tulbaghia, Allium,
Crinum and Cyrtanthus: ‘Talented’
10
Taxa from the Amaryllidaceae.
Molecules 2022, 27, 4475. https://
11
doi.org/10.3390/molecules27144475
*
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences,
Kwame Nkrumah University of Science and Technology, PMB, Kumasi, Ghana; p.minkah@kccr.de (P.A.B.M.);
michof2825@gmail.com (M.O.); nugbemadokorbla@gmail.com (I.N.N.)
Global Health and Infectious Disease Research Group, Kumasi Centre for Collaborative Research in Tropical
Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology,
PMB, Kumasi, Ghana
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences,
Kwame Nkrumah University of Science and Technology, PMB, Kumasi, Ghana; tessyagana4christ@gmail.com
Department of Chemistry, University of Pretoria, Pretoria 0028, South Africa; u13386842@tuks.co.za (P.M.);
u21749745@tuks.co.za (S.R.); vinesh.maharaj@up.ac.za (V.J.M.)
Department of Pharmaceutical Sciences, Dr. Hilla Limann Technical University, Wa P.O. Box 553, Ghana
Department of Pharmaceutical Sciences, School of Pharmacy, Central University, Accra, Ghana;
pdoe@central.edu.gh
Department of Optometry and Visual Science, College of Science, Kwame Nkrumah University of Science and
Technology, PMB, Kumasi, Ghana; oseiduahisaiah@gmail.com
Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana;
kamankwah@stu.ucc.edu.gh
Department of Pharmacy Practice, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana;
sosomuah@uhas.edu.gh
Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck,
University of London, Malet Street, London WC1E 7HX, UK; s.bhakta@bbk.ac.uk
The Centre for Natural Products Discovery (CNPD), Liverpool John Moores University,
Liverpool L3 3AF, UK; s.gibbons@ljmu.ac.uk
Correspondence: cadanquah.pharm@knust.edu.gh; Tel.: +233-265458216
Academic Editors:
Agnieszka Ludwiczuk and
Yoshinori Asakawa
Received: 16 May 2022
Accepted: 28 June 2022
Published: 13 July 2022
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Copyright: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
Abstract: Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity
to develop new drugs. The genera Allium, Tulbaghia, Cyrtanthus and Crinum biosynthesize novel
alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae
biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and
immunomodulatory effects. Traditionally, natural products from Amaryllidaceae are utilized to
treat non-communicable and infectious human diseases. Galanthamine, a drug from this family, is
clinically relevant in treating the neurocognitive disorder, Alzheimer’s disease, which underscores
the importance of the Amaryllidaceae alkaloids. Although Amaryllidaceae provide a plethora of
biologically active compounds, there is tardiness in their development into clinically pliable medicines.
Other genera, including Cyrtanthus and Tulbaghia, have received little attention as potential sources
of promising drug candidates. Given the reciprocal relationship of the increasing burden of human
diseases and limited availability of medicinal therapies, more rapid drug discovery and development
are desirable. To expedite clinically relevant drug development, we present here evidence on bioactive
compounds from the genera Allium, Tulgbaghia, Cyrtanthus and Crinum and describe their traditional
and pharmacological applications.
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Molecules 2022, 27, 4475. https://doi.org/10.3390/molecules27144475
https://www.mdpi.com/journal/molecules
Molecules 2022, 27, 4475
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Keywords: Amaryllidaceae; alkaloids; Allium; Crinum; Tulbaghia; Cyrtanthus; phytochemicals; natural
products; pharmacological activity; drug discovery
1. Introduction
Amaryllidaceae belongs to the order Asparagales and consists of bulbous flowering
plants separated into three infrageneric ranks: Agapanthoideae, Allioideae and Amaryllidoideae, as delineated by the Angiosperm Phylogeny Group [1]. The term “Amaryllidaceae”
is frequently used in either phytochemical or pharmacological literature to refer to plants or
alkaloids originating from the subfamily Amaryllidoideae [2,3]. Monocotyledonous plants
constitute seventy-nine genera (including Allium, Crinum, Cyrtanthus, and Tulbaghia) with
over 1000 species [4]. Aside from their broad pantropical distribution, Amaryllidaceae are
located in Africa, the Mediterranean Coast and South America, and have high adaptation
and speciation [5]. The genus Allium is distributed in temperate, arid, semi-arid and subtropical areas such as the Mediterranean region, central Asia, Africa and parts of Europe.
As herbaceous geophyte perennials, Allium comprises a plethora of species with pungent
linear leaves that may or may not arise from a bulb or rhizome [6,7]. The Tulbaghia genus,
popularly called “sweet garlic”, “wild garlic”, or “pink agapanthus”, is crown shaped with
outgrowth or appendages of the perianth and predominantly colonizes the Eastern cape
belt of South Africa, and is adapted for growth in areas such as Europe and America [8,9].
The genus Crinum encompasses 104 species and appear as showy flowers on leafless stems,
which thrive in the tropics and warm temperate parts, specifically Asia, Africa, America,
and Australia [10]. Cyrtanthus is popularly known as “fire lily” due to its unique rapidly
flowering response to natural bush fires. Most species are found in South Africa and play
an important role in South African traditional medicine [11].
Amaryllidaceous plants are known for their ornamental, nutritional, and medicinal
value. Given their attractive flowering plant-like features, Crinum species are prized for
their umbel lily-like blossoms in China and Japan [3]. Concurrently, Amaryllidaceae are
known for their longstanding exploitation in medicinal therapy owing to their inherent
biosynthesis of chemically diverse bioactive compounds with peculiar biological properties. The use of proximate and mineral composition analysis enabled the identification
of phytoconstituents [10,12], while in vitro, in vivo, and in silico model systems have permitted the unravelling of intrinsic pharmacological activities of the natural products and
other alkaloids isolated from this source [13–15]. Of note, bioactive compounds from
Amaryllidaceae possesses a wide range of bioactivities ranging from antioxidant [16,17],
anti-inflammatory [16,18], antimicrobial [17], antifungal [19], antiviral [20,21], antiplasmodial [22–24], anticarcinogenic [18,25,26], antispasmodic [1,27], antiplatelet [28], antiasthmatic [29], antithrombotic [30,31], antitumor [25], antihyperlipidemic [25], antihyperglycemic [25,32,33], antiarthritic [25], antimutagenic [16], immunomodulatory [16] and
several others [34].
Given the aforementioned biological activities, Allium, Tulbaghia, Cyrtanthus and
Crinum are utilized in traditional medicinal therapy for varying diseases and conditions [35–41]. For example, Allium is used as concoctions, decoctions, extracts, and herbal
preparations to treat angina, amoebic dysentery, arthritis, cardiovascular diseases, cholera,
catarrh, dysmenorrhea, fever, headaches, hepatitis, stomach disorders, throat infections,
and prostatic hypertrophy [30,31,35–38]. The genus Tulbaghia has unique pharmacotherapeutic properties and is utilized to manage ailments such as earache, pyrexia, tuberculosis,
and rheumatism [9,42]. Crinum species are used to treat haemorrhoids, malaria, osteoarthritis, varicosities, wounds, urinary tract infections, and gynaecological remedies [40,41].
Cyrtanthus are also employed in the management of ailments associated with pregnancy, as
well as cystitis, age-related dementia, leprosy, scrofula, headaches, chronic coughs, among
others [43,44]. In modern clinical practice, galanthamine from Amaryllidaceae is a primary choice of drug in managing symptomatic neurological disorders such as Alzheimer’s
Molecules 2022, 27, 4475
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disease due to its selective inhibitory action on the acetylcholine biosynthetic enzyme,
acetylcholinesterase [45]. The pancratistatin phenanthridone class of alkaloids are also
promising chemotherapeutic drug candidates with unique cell line-specific antiproliferative
properties, conferring a selective advantage for clinical development [46].
Although Amaryllidaceae represents a source of valuable bioactive compounds, developing promising drug candidates into clinically relevant therapeutics has been slow.
Similarly, other genera in this family, including Cyrtanthus, Crinum and Tulbaghia, are
untapped reservoirs and could serve as an alternative window for novel drug targets
and warrant further investigation. This review consolidates evidence on the bioactive
compounds from Allium, Tulbaghia, Crinum and Cyrtanthus and ascertains their traditional
and pharmacological applications. Specifically, bibliographic searches were conducted
on multiple standard databases (such as, Scopus, Web of Science, MEDLINE, Sci verse,
Embase, Google scholar among others) using MESH and non-MESH terms to retrieve and
synthesize relevant publications over the 3-month search period. This review highlights
panoply of promising biomolecules from the taxa Amaryllidaceae and their prominent
medicinal values. The evidence from this study could hasten drug discovery among the
pharmaceutical industries. An update on the natural products from these lesser explored
genera could also augment the lean pipeline of novel therapeutics.
2. The Genus Tulbaghia
2.1. Botanical Description
Tulbaghia is made up of monocotyledonous species with herbaceous perennial bulbs
covered by brown scales and are mostly found in Africa [8]. South African species possess
bulb-like corms or rhizomes which are swollen, irregularly shaped and wrapped in dry,
fibrous leaves [8]. Members of this genus usually possess a raised crown-like structure or
ring at the center of their flower tube [8]. Their seeds are black, flat and elongated with the
mature ones having embryos [8]. Examples of species of this genus are Tulbaghia violacea
(T. violacea), Tulbaghia acutiloba Harv. (T. acutiloba), Tulbaghia capensis L. (T. capensis) and
Tulbaghia cepacea L.f (T. cepacea) [8].
2.2. Geographical Distribution and Traditional Uses of Tulbaghia Species
With approximately 66 species (https://www.kew.org/science accessed on 22 February 2022) [47], Tulbaghia is the second-most species-rich genus within Amaryllidaceae.
Tulbaghia is a monocotyledonous genus comprised morphologically of herbaceous perennial bulbous species, which produce a variety of volatile sulfur compounds, hence resulting
in a distinct pungent garlic odor released by bruised plants [8,48]. The genus was named
by Carl Linnaeus after Ryk Tulbagh (1699–1771), a former governor of the Cape of Good
Hope in South Africa, where most of the native species are to be found, particularly in the
Eastern Cape Province [49]. In addition to South Africa, the genus is widely distributed
across southern African countries including Botswana, Lesotho, Swaziland, and Zimbabwe,
where the plant is revered in folk medicine being used for the treatment of a plethora of
infectious and non-infectious diseases [9] as highlighted in Table 1.
Table 1. Geographical distribution and traditional uses of Tulbaghia species.
Plant
Species
Geographical Distribution
T. violacea
Indigenous to the Eastern Cape, KwaZulu-Natal,
Gauteng, Free State and Mpumalanga Provinces of
South Africa.
T. alliacea
Native to South Africa and grows mostly in the
Eastern Cape and southern KwaZulu-Natal
Provinces of South Africa.
Traditional Uses
The leaves and bulbs are used in the management of fever
and colds, tuberculosis, asthma, and stomach problems.
The leaves are eaten as vegetables and for the management
of oesophageal cancer. It is also used as a snake repellent.
Its bruised rhizome is used locally in bathwater to relieve
fever, rheumatism, and paralysis, and in small doses as a
laxative. T. alliacea is used for the management of stomach
problems, asthma, and pulmonary tuberculosis. Its
rhizome infusion is administered as an enema.
References
[8,50]
[8,51]
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Table 1. Cont.
Plant
Species
Geographical Distribution
Traditional Uses
References
T. simmleri
Native to the South African Drakensberg
mountains growing as isolated plants on
rocky ledges.
Bulbs and leaves are used as a remedy for gastrointestinal
ailments, enemas, high blood pressure, heart problems,
chest complaints, high cholesterol, constipation,
rheumatism, asthma, fever, pulmonary tuberculosis,
earache, human immunodeficiency virus (HIV), paralysis,
and cardiovascular diseases.
[50,52]
T. acutiloba leaves are used as a culinary herb and snake
repellent. It is used to treat barrenness, flu, bad breath, and
as an aphrodisiac. It is also cultivated to keep snakes away
from the homestead.
[8]
It is used as a culinary herb and snake repellent.
[53]
It is used for ornamental purposes.
[8]
Its rhizome is scraped clean and boiled in stews or roasted
as a vegetable. Its leaves and stems are used as a culinary
herb and protective charm.
[53]
It is traditionally used as a love charm.
[53]
T. acutiloba
T. natalensis
T. cernua
T. leucantha
T. ludwigiana
Found in the rainfall regions of southern Africa,
occurring in the Eastern Cape, KwaZulu-Natal,
Limpopo, Free State, Gauteng, North West, and
Mpumalanga Provinces of South Africa, as well as
in Lesotho, Swaziland and Botswana.
Although native to South Africa, but is now
grown worldwide.
Commonly found in the Eastern Cape, Free State,
Gauteng, KwaZulu-Natal, Limpopo, Mpumalanga,
North West and Western Cape Provinces of
South Africa.
Widely distributed in southern Africa including
Botswana, Lesotho, South Africa, Swaziland,
Zambia, and Zimbabwe.
Commonly found in the Eastern Cape,
KwaZulu-Natal, Northern Provinces of South
Africa and in Swaziland.
2.3. Phytochemistry of Tulbaghia
Tulbaghia produces many different classes of compounds with diverse chemical structures dominated by sulfur-containing natural products (Figure 1; Table S1).
Figure 1. Chemical space of compounds identified from T. violacea. Blue circles are sulfur-containing
compounds while red circles are compounds devoid of sulfur in their chemical structures. PCA
analysis carried out using DataWarrior [54].
Most compounds reported have a small molecular weight (<500) and are of a broad
lipophilicity (Figure 2).
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Figure 2. Analysis of cLogP and molecular weight space occupied by compounds identified in
T. violacea. Blue circles are sulfur-containing compounds while red circles are compounds devoid of
sulfur in their chemical structures. Plot generated using DataWarrior [54].
Tulbaghia violacea has been the most widely investigated for its phytochemistry and
pharmacological properties. To date, close to 100 compounds have been tentatively identified, largely using gas chromatography techniques, from different parts of this species
(Supplementary File S1) [55]. Most prominent are the sulfur compounds with reported
broad-spectrum pharmacological activity. The thiosulfinate marasmicin (1) is the most
prolific antimicrobial compound reported thus far from this genus [56]. This compound is
formed from its precursor compound marasmin (2), by the enzyme c-lyase. Marasmicin
is responsible for the characteristic garlic odor generated by damaged plants [48]. Other
notable compounds produced by this species include phenols, tannins and flavonoids [55],
which are also responsible for several observed biological activities. Phytochemical characterization has been carried out, albeit minimally for other Tulbaghia species particularly
T. alliacea and T. acutiloba. Unlike other genera in Amaryllidaceae, Tulbaghia is so far devoid
of any alkaloids [57,58]. Despite the extensive in vitro pharmacological screening of extracts
of Tulbaghia, it is possible that less effort has been made to isolate and identify their active
principles. Hence, the phytochemistry of the genus Tulbaghia largely remains understudied.
The chemicals structurers of noteworthy compounds isolated from T. violacea have been
represented in Figure 3.
2.4. Pharmacological Studies of Tulbaghia Species
Because of its perceived medicinal value, Tulbaghia has received marked interest within
the scientific community which has meticulously subjected it to various in vitro and in vivo
studies experimentally evaluating its pharmacological activities. The volume of published
studies generated from these investigations mirror the distribution of the genus with most
articles on Tulbaghia having emerged from South Africa (Table 2), a country highly rich in
this genus both in terms of species diversity and abundance.
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Figure 3. Chemical structures of compounds identified in T. violacea. (1) Marasmicin (1), (2)
β →
marasmin (2), allicin (3)—possesses antibacterial and antifungal activity, D-fructofuranosyl-β(2→6)α
β
→ α
α
methyl-α-D-glucopyranoside (4), β-D-fructofuranosyl-(2→6)-α-D-glucopyranoside (5), methyl-αD -glucopyranoside (6), bis(methylthiomethyl) disulfide (7)—found to constitute 48% of volatiles
in aerial parts of T. violacea [55], methyl-2-thioethyl thiomethyl trisulfide (8)—found to constitute
16% of volatile compounds in aerial parts of T. violacea [55], methyl (methylthio)methyl disulfide
(9)—found to constitute 10 % of volatile compounds in aerial parts of T. violacea [55], naphthalene
(10)—interestingly observed to significantly increase in concentration in plants infected by the fungus
Beauveria bassiana in comparison to untreated controls [59], nonanal (11)—also observed to significantly decrease in concentration in plants infected by the fungi Beauveria bassiana in comparison to
untreated controls [59] and finally kaempferol (12)—which possesses multiple biological activities
including antioxidant, anticancer and anti-inflammatory properties [60–62].
Table 2. Published documents on the genus Tulbaghia per country.
Country
No. of Documents *
South Africa
United Kingdom
United States
Czech Republic
Italy
India
99
15
12
8
7
6
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Table 2. Cont.
Country
No. of Documents *
Germany
Australia
China
Belgium
5
3
3
2
* Data retrieved following query of the Scopus database (https://www.scopus.com/, accessed on 22 February
2022) using the keyword “Tulbaghia”. The search was carried out on 22 February 2022.
The greatest numbers of pharmacological screens have been on interrogating the antimicrobial properties of this genus. This is closely followed by cardiovascular, antioxidants
and cancer investigations as shown in Table 3. T. violacea prominently features, being the
most studied species, with T. alliacea and T. aticulata having received minimal attention.
Table 3. Number of published studies per specific disease or pharmacological area.
Disease
No. of Published Studies #
Antimicrobial
Cancer
Antioxidant
Diabetes
Cardiovascular
Antithrombogenic
Miscellaneous
26
11
13
2
12
2
17
# Studies considered are those published from 1997 to 2022. A number of these, published before 2013, have been
succinctly discussed by Aremu and Van Staden [8].
2.4.1. Antimicrobial and Antiparasitic Activity
As antimicrobial resistance continues to be a global health threat, the need to find therapeutic alternatives has never been more urgent [63]. This has encouraged scientists to search
for novel alternatives with natural products having drawn marked interest as a potential
oasis of new antimicrobial agents [64–66]. Tulbaghia has received significant relevance in
this regard, with multiple studies providing ample evidence substantiating its use as an
antimicrobial agent. Extracts of T. violacea have potency against many microbial species
including those designated as priority by the World Health Organization. These include
Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus) and Klebsiella pneumoniae (K. pneumoniae) with MIC values ranging between 20 and 300 µg/mL [67]. This activity
was confirmed in another study where the disc diffusion method was used [68]. In addition
to bacteriostatic activity, extracts of T. violacea have shown noteworthy potency against
yeasts including Candida albicans (C. albicans) and Candida parapsilosis (C. parapsilosis) with
MIC and MMC values ranging between 20 and 40 µg/mL [68]. Beyond human pathogens,
extracts of T. violacea have activity against microorganisms of agricultural significance, for
example against the fungus Aspergillus flavus (A. flavus), which is responsible for significant
agricultural produce loss at a global scale due to production of aflatoxins [69]. Extracts of T.
violacea compromised cell wall synthesis by significantly reducing β-glucan and chitin synthesis in A. flavus corresponding to a dose-dependent inhibition of the enzymes β-glucan
and chitin synthase, respectively [70]. Further studies suggested an alternative mode of
action (MoA) via reduction of ergosterol production in fungi [71]. Interestingly, related to
value in agriculture, a patent has been filed on the use of extracts of T. violacea as a plant
protecting remedy as a substitute for chemical agents [72]. Some thought-provoking studies
have shown that growth conditions including light intensities, watering frequency and pH,
substantially impact both growth and biological potency of T. violacea extracts against Fusarium oxysporum (F. oxysporum) [73,74]. Likewise, storage conditions of dried plant material
also affect the antimicrobial potency of extracts [56]. In addition to antimicrobial activity,
T. violacea has shown good antiparasitic activity against the parasitic worm Meloidogyne
incognita (M. incognita) on tomato roots and in soil [75]. Antiparasitic activity has also
Molecules 2022, 27, 4475
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been observed against Trypanosoma brucei (T. brucei) (IC50 = 2.83 µg/mL) and Leishmania
tarentolae (L. tarentolae) (IC50 = 6.29 µg/mL) [67]. Table 4 highlights the antimicrobial activity
of Tulbaghia species.
Table 4. Antimicrobial activity of Tulbaghia species.
Plant Species
Extraction Solvent
Plant Part Used
T. violacea
Dichloromethane
Bulbs
T. violacea
Hexane and ethanol
Flowers and
callus cultures
T. violacea
Water
Bulbs
T. violacea
Acetone
Bulbs
T. violacea
Water
Roots, bulbs, leaves
and flowers
T. violacea
Dichloromethane
Bulbs
Biological Activity
MIC ranging from 20 to 300 µg/mL against Bacillus
subtilis, methicillin-resistant S. aureus, S. epidermidis, E. coli,
K. pneumoniae, P. aeruginosa, C. albicans and C. parapsilosis.
Moderate to strong broad-antimicrobial (E. coli, P.
aeruginosa, S. aureus, Aspergillus niger and C. albicans)
activity observed by zone of inhibition in the agar well
disc diffusion method.
Significant reduction in A. flavus β-glucan and chitin
synthesis corresponding to a dose-dependent inhibition
of the enzymes β-glucan and chitin synthase,
respectively.This results in inhibition of ergosterol
production in the fungus.
Varied light intensities, pH and watering frequencies
substantially impacted both growth and potency of plant
extracts against the fungi F. oxysporum.
Significantly compromised population densities of the
nematode M. incognita race 2 on tomato roots
and in the soil.
Antiparasitic activity against T. brucei (IC50 = 2.83 µg/mL)
and L. tarentolae (IC50 = 6.29 µg/mL).
References
[67]
[68]
[70,71]
[73,74]
[75]
[67]
2.4.2. Anticancer Activity
Owing to the need for novel anticancer agents [76] and motivated by the success of
cancer drug discovery projects from natural products [77], Mthembu and Motadi in (2014),
evaluated the in vitro anticancer properties of crude methanol extracts of T. violacea using
an MTT assay [78]. Extracts displayed time- and concentration-dependent antiproliferative
properties against cervical cancer cell lines with an IC50 of 150 µg/mL. The MoA was
deciphered to be induction of apoptosis by a p53-independent pathway [78]. However, in
contrast to this finding, continued work showed a proportional increase in the activity of
caspase 3/7, and the expression of p53 genes strongly suggests apoptosis was triggered
by a p53-dependent pathway [79]. This latter finding has been partly substantiated by
data emerging from a study examining the antineoplastic properties of T. violacea against
ovarian tumor cells. These extracts were shown to partially induce both apoptosis and
necrosis with the most pronounced activity due to induction of autophagy [80].
Triple-negative breast cancer remains one of the most challenging cancers, being highly
aggressive [81]. T. violacea extracts have demonstrated good cytotoxic activity against MDAMB-231, with an IC50 of 300 µg/mL [82]. Additionally, extracts inhibited migration of the
cancer cell lines (metastasis), an important physiological process in the progression of this
cancer [83]. In addition to the gynecological cancers, antineoplastic properties of T. violacea
were further observed against pancreatic cancer with 63% inhibition of cell proliferation at
a concentration of 250 µg/mL [68]. Against a non-sex-specific cancer, T. violacea showed
noticeable activity against oral cancer with an IC50 of 0.2 and 1 mg/mL for acetone and
water-soluble extracts, respectively. Extracts activated caspase activity in a dose-dependent
manner leading to induction of apoptosis in the human oral cancer cell line [84]. Using
a bioassay guided approach, the active anticancer compounds in T. violacea have been
identified to be glucopyranosides D-fructofuranosyl-β (2→6)-methyl-α-D-glucopyranoside
and β-D-fructofuranosyl-(2→6)-α-D-glucopyranoside. Both compounds act by mediating
induction of apoptosis in Chinese hamster cells by targeting the mitochondrial (intrinsic)
pathway [85,86]. A summary of the anticancer activity of Tulbaghia species is shown in
Table 5.
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Table 5. Anticancer activity of Tulbaghia.
Plant Species
Extraction Solvent
Plant Part Used
T. violacea
Methanol
Leaves and roots
T. violacea
Methanol, butanol,
and hexane
Leaves
T. violacea
Methanol:water:formic
acid (80:20:0.1, v/v/v)
Flowers
T. violacea
Water and methanol
Leaves
T. violacea
Hexane and ethanol
Flowers and callus
cultures
T. violacea
Acetone and water
Leaves
T. violacea
Methanol:water (1:1)
Whole plants
T. violacea
Water
Whole plants
Biological Activity
Marked time- and dose-dependent cytotoxic effect on
cancer cell lines. Induced apoptosis using
p53-independent pathway.
Methanol extract was prolific against multiple cell lines.
Hela and ME-180 cell lines treated with methanol and
hexane extracts showed an increase in caspase 3/7 activity.
Both methanol and hexane extracts induced a 10-fold
increase in expression of p53 gene in Hela cells.
Demonstrated activity against ovarian tumor cells.
Water-soluble extract emerged as the most cytotoxic
(IC50 = 314 µg/mL), compared to the methanol extract
(IC50 = 780 µg/mL), against the MDA-MB-231
triple-negative breast cancer cell line. Water-soluble extract
prevented cell migration completely for 13 h at 300 µg/mL.
Extracts showed marked cytotoxicity (60–74% growth
inhibition at 250 µg/mL) against three different cell lines
(Hep G2, PC-3 and MCF-7).
Anticancer activity against oral cancer with an IC50 (acetone
extract) of 0.2 mg/mL; IC50 (water extract) of 1 mg/mL.
Two pro-apoptotic glucopyranosides D-fructofuranosyl-β
(2→6)-methyl-α-D-glucopyranoside and
β-D-fructofuranosyl-(2→6)-α-D-glucopyranoside isolated
and identified as active anticancer agents in the plant.
MoA of the three compounds, namely
methyl-α-D-glucopyranoside, D-fructofuranosyl-β
(2→6)-methyl-α-D-glucopyranoside and
β-D-fructofuranosyl-(2→6)-α-D-glucopyranoside isolated
from the water extract, deciphered to be through induction
of apoptosis by targeting the
mitochondrial (intrinsic) pathway
References
[78]
[79]
[80]
[82]
[68]
[84]
[85]
[86]
2.4.3. Antioxidant Activity
The imbalance of reactive oxygen species (ROS) and antioxidants in the body can lead
to oxidative stress [87]. This physiological condition can result in cellular and tissue damage [88]. Oxidative stress is associated with pathologies including cancer, cardiovascular
disease, diabetes, and neurodegenerative diseases amongst others [88,89]. To avert the
development of oxidative stress, attenuation of ROS has been identified as a viable target,
with natural products seen as a potential source capable of neutralizing it [88]. Tulbaghia
has generated some interest on this front particularly as it is rich in compounds with
proven antioxidant activity including phenols, tannins and flavonoids. Multiple studies
have demonstrated that extracts of Tulbaghia have marked antioxidant activity as assessed
using different assays in vitro including Trolox equivalent antioxidant capacity (TEAC;
also commonly referred to as the ABTS assay), ferric-reducing antioxidant power (FRAP)
and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) (Table 6) [58,80,90,91]. Furthermore,
using an in vivo model of Caenorhabditis elegans, T. violacea extracts attenuated oxidative
stress produced by a free radical generator, (2,2′ -azobis-2-amidinopropane dihydrochloride;
AAPH), in the roundworm [80]. Data from these studies strongly suggested continued investigation of other species in the search for more potent antioxidant agents from Tulbaghia.
The antioxidant activity of Tulbaghia species is highlighted in Table 6.
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Table 6. Antioxidant activity of Tulbaghia species.
Plant Species
Extraction Solvent
Plant Part Used
T. violacea
Water
Leaves
T. violacea
Methanol/water/formic
acid (80:20:0.1, v/v/v)
T. acutiloba
Hydro-methanolic
extracts
T. violacea
Hexane and ethanol
T. violacea
T. acutiloba
T. alliacea
T. cernua
T. leucantha
T. ludwigiana
T. natalensis
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Flowers
Roots, rhizomes,
leaves and flowers
Flowers and callus
cultures
Leaves
Leaves
Leaves
Leaves
Leaves
Leaves
Leaves
Biological Activity
Dose-dependent antioxidant activity measured using the
DPPH (Log IC50 = 0.49 mg/mL) and ABTS
(Log IC50 = 0.24 mg/mL) assays
Marked antioxidant activity was observed using 3 different
types of assays, namely DPPH, FRAP and TREC
Dose-dependent antioxidant activity observed with the
rhizome extract emerging as the most active plant part
(IC50 DPPH = 0.202 mg/mL and peak scavenging
activity of 95)
Dose-dependent antioxidant activity with IC50 ranging from
1.933 to 7.350 mg/mL in the DPPH assay
IC50 DPPH = 0.08 mg/mL; IC50 ABTS = 0.03 mg/mL
IC50 DPPH = 0.16 mg/mL; IC50 ABTS = 0.07 mg/mL
IC50 DPPH = 0.06 mg/mL; IC50 ABTS = 0.06 mg/mL
IC50 DPPH = 0.21 mg/mL; IC50 ABTS = 2.34 mg/mL
IC50 DPPH = 0.39 mg/mL; IC50 ABTS = 0.03 mg/mL
IC50 DPPH = 0.26 mg/mL; IC50 ABTS = 0.09 mg/mL
IC50 DPPH = 2.70 mg/mL; IC50 ABTS = 0.04 mg/mL
References
[92]
[80]
[91]
[68]
[84]
[84]
[84]
[84]
[84]
[84]
[84]
2.4.4. Antidiabetic, Anticardiovascular and Antithrombogenic Activity
The incidence of diabetes and cardiovascular diseases continues to grow substantially across the globe, with both conditions combined accounting for the highest global
morbidity and mortality [93,94]. Both of these chronic conditions are closely linked with
cardiovascular disease being responsible for high morbidity and mortality in diabetic
patients [95]. Tulbaghia has been documented in ethnopharmacological studies for the
treatment of these ailments with emerging scientific data strongly validating its use. In
streptozotocin diabetes-induced rat models, T. violacea attenuated diabetes-associated physiological conditions resulting in improved body weights, reduced fasting blood glucose
levels, enhanced glucose tolerance and significantly elevated plasma insulin and liver
glycogen content [96]. These data were corroborated in another study in which T. violacea
noticeably reduced blood glucose and serum lipid (triglyceride (TG), total cholesterol
(TC), and very low-density lipoprotein (VLDL)) levels while raising plasma insulin in a
streptozotocin-induced diabetic rat model [97]. In an assessment for negating cardiovascular associated conditions, T. violacea in in vivo models markedly reduced systolic blood
pressure (BP), diastolic BP, mean arterial pressure (MAP) and the heart rate in both ageinduced and spontaneous hypertensive rats [98]. Furthermore, dosing rats with extracts
of T. violacea led to improved kidney function [99]. This is an essential pharmacological
property as kidney function is impaired in hypertension leading to high morbidity and
mortality in people suffering from cardiovascular diseases [100].
One of the multiple factors strongly associated with cardiovascular disease is atherothrombotic vascular disease (AVD). Platelet aggregation plays a role in development of AVD and
subsequent cardiovascular events [90,101]. Against this background, platelet aggregation
has been identified as a key process to target to prevent AVD. Encouragingly, T. violacea
demonstrated marked potency being able to significantly inhibit platelet adhesion 15 min
post-exposure (Table 7) [90,92].
Table 7. Antidiabetic, anticardiovascular and antithrombogenic activity of Tulbaghia species.
Plant Species
Extraction Solvent
Plant Part Used
T. violacea
Methanol
Rhizome
T. violacea
Methanol
Rhizome
Biological Activity
References
Diabetes
Attenuated diabetes associated physiological complications in
streptozotocin-induced diabetic rats.
Noticeably reduced blood glucose and serum lipid (TG, TC,
and VLDL) levels while raising plasma insulin in a
streptozotocin-induced diabetic rat model.
[96]
[97]
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Table 7. Cont.
Plant Species
Extraction Solvent
Plant Part Used
T. violacea
Methanol
Leaves
T. violacea
Methanol
Rhizome
T. acutiloba
Hydro-methanolic
extracts
Roots, rhizomes,
leaves and flowers
T. violacea
Water
Leaves
T. violacea
Water
Leaves
Biological Activity
References
Cardiovascular
Markedly reduced systolic BP, diastolic BP, mean arterial
pressure and the heart rate in both age-induced and
spontaneous hypertensive rats.
50 mg/kg significantly improved kidney function in vivo.
All extracts inhibited the Angiotensin-1-Converting Enzyme
in vitro (> 50 % inhibition at a concentration range of
125–1000 µg/mL). Extracts of leaves demonstrated activity
comparable to that of the control drug ramipril.
[98]
[99]
[91]
Antithrombogenic
Noticeable inhibition of platelet adhesion by a novel scaffold
consisting of polycaprolactone incorporated with 10 % (w/w)
plant extracts.
Marked inhibition of platelet adhesion (70% inhibition at
0.1 mg/mL within 15 min post-exposure).
[90]
[92]
2.4.5. Miscellaneous Pharmacological Activity
In addition to diabetes and cardiovascular diseases, T. violacea has shown activity
against another chronic condition, Alzheimer’s disease. In an in vivo Alzheimer’s disease
transgenic C. elegans strain model, T. violacea significantly reduced 1-42 β-amyloid peptide
formation (Table 8) [80]. T. violacea exhibited in vivo anticonvulsant activity by attenuating
tonic convulsions induced by either pentylenetetrazole, bicuculline, picrotoxin, strychnine
or NMDLA [102] and validating its traditional use for the treatment of epilepsy. T. violacea
displayed marked tick repellence properties of fungus-exposed plants at low treatment
concentrations (5% w/v and 10% w/v) [59], further enhancing its credentials as a potential
agricultural product. Somewhat concerning is that, extracts of T. violacea also induced
genotoxic effects albeit at high test concentrations (250, 500 and 1000 µg/mL) in the Allium
cepa assay [103]. Furthermore, broad murine macrophage antiproliferative and cytotoxicity
activity, influenced by extract test concentrations, type of solvent and plant part used, have
been observed (Table 8) [104]. There is consequently a need for rigorous assessment of
safety of extracts of this and other species of the genus Tulbaghia.
Table 8. Miscellaneous biological properties of extracts of Tulbaghia species.
Plant Species
Extraction Solvent
T. violacea
Methanol/water/formic
acid (80:20:0.1, v/v/v)
Plant Part Used
Flowers
T. violacea
Methanol
Leaves
T. violacea
Acetone
Mixture of leaves
and bulbs
T. violacea
Water
Leaves, stems,
and roots
T. violacea
Water and ethanol
Leaves, stems,
and roots
Biological Activity
Reduced 1-42 β-amyloid peptide formation and arrested
oxidative stress in vivo.
Demonstrated in vivo anticonvulsant activity by
attenuating tonic convulsions induced by either
pentylenetetrazole, bicuculline, picrotoxin, strychnine
or NMDLA.
Marked tick repellence properties of fungus-exposed plants
at low treatment concentrations (5 % w/v and 10 % w/v).
Induced conspicuous genotoxicity effects at high test
concentrations (250, 500 and 1000 µg/mL) in the
A. cepa assay.
Broad murine macrophage antiproliferative and cytotoxicity
activity influenced by both extract test concentrations, type
of solvent and plant part used.
References
[80]
[102]
[59]
[103]
[104]
3. The Genus Allium
3.1. Botanical Description
Species of the genus Allium are mostly found in warm–temperate and temperate zones
of northern hemisphere as well as the boreal zone [105]. They are petaloid perennial herbs
with parallel narrow leaves [33] and possess true bulbs, which are sometimes found on
rhizomes [106]. Allium species are also characterized by onion or garlic odor and flavor
similar to Tulbaghia [106]. Well known species include Allium cepa (A. cepa), Allium sativum
Molecules 2022, 27, 4475
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(A. sativum), Allium ascalonicum (A. ascalonicum,), Allium porrum (A. porrum), and Allium
schoenoprasum (A. schoenoprasum) (chive) [33]
Allium has over 500 species making it the largest genus of Amaryllidaceae [6,7]. There
are plethora of species, notably A. cepa and A. sativum [107–109]. Other examples grown for
their medicinal and nutraceutical value are Allium ducissae (A. ducissae), Allium strictum (A.
strictum), Allium umbilicatum (A. umbilicatum), Allium victorialis (A. victorialis), A. ascalonicum,
Allium chinense (A. chinense), Allium tuberosum (A. tuberosum), Allium griffithianum (A. griffithianum), Allium oreoprasum (A. oreoprasum), and Allium oschaninii (A. oschaninii). Species
tolerate varying climatic conditions, hence are geographically distributed across several
continents, including Asia, Africa, the Americas, and Europe [107,110]. Fernandes et al.
identified A. cepa that colonizes four different geographical regions of the Madeira island, an
archipelago near the North Atlantic ocean with a hot and/or warm-summer Mediterranean
climate conditions [107]. As the world’s second-most relevant and cultivated horticulture
vegetable crop, the onion (A. cepa), is distributed in over 175 countries and covers approximately six million hectares of the total land size of the world. Approximately two-thirds
(66%) of global onion production emanates from the Asia, with China and India being the
world’s largest producers [111]. The maximal diversification of A. cepa is found in Iran and
Afghanistan’s Mediterranean basin. A. cepa thrives in areas with boreal, temperate, and
tropical climates [108]. Similarly, A. sativum (garlic) bears close resemblance to onions and
originates from Central Asia but has spread to include regions in Europe, America, and
Africa [112]. The global garlic production estimates show that out of the 28.5 million tonnes
(MT) of A. sativum cultivated, the majority (91.6%; 26.1 MT) were from Asia, followed by
Europe (3.0%; 0.86 MT), America (2.9%; 0.83 MT), and with the least from Africa (2.7%;
0.73 MT) [112]. Bartolucci et al. identified A. ducissae, a new breed of Allium that grows
in the mountainous regions of the Central Apennines in the Abruzzo and Lazio counties
of Italy [113]. Furthermore, A. strictum, a Eurasian species, is distributed across China,
Europe, Russia, Kazakhstan, Kyrgyzstan, and Mongolia [114,115]. A. umbilicatum, also
called gladiolus or leek is usually localized in semi-arid regions and can tolerate sub-zero
freezing winters [116]. It occurs as a weed in oases and span across Afghanistan, Iran,
Pakistan, Turkmenistan, Tajikistan, and central and Eastern Asian regions [116]. As a representative circumboreal plant, A. victorialis has a wide altitudinal climatic tolerance [117].
It is predominantly located in lowland deciduous forest and subalpine birch forest, but
seldom found in the subalpine meadows [117]. This species is scattered distribution on
the island stretches of Japan, Russia, and Northern China [117,118]. Although practically
grown throughout the world, A. ascalonicum, also called shallot, is native to the Middle
East, and the name is derived from the Syrian city Ascalon. These shallots are distributed
on the main islands of Indonesia, in Bangladesh, Japan, Korea, Malaysia, Taiwan, and
Thailand [119]. A. chinense (locally referred to as Chinese/Japan onion or scallion, Kiangski
scallion, oriental onion, Rakkyo) is an uncommon Allium species found mainly in the tropical and sub-tropical regions of China, Japan, Vietnam, and eastern areas of India [111,120].
A. tuberosum is an indigenous species native to southeastern Asia and regarded as a lateseasonal bloomer. During the initial growth phases, A. tuberosum is evergreen in hot
climates but succumbs to cold climatic conditions. However, the Chinese chive becomes
tolerant to all seasonal variations [121,122]. A. griffithianum and A. oreoprasum are geographically skewed towards the mountainous regions of Pakistan, Afghanistan, Kyrgyzstan,
Uzbekistan, and Tajikistan [123], whereas A. oschaninii are located in the Darvaz mountains
of Central Tajikistan [124].
3.2. Traditional Uses of Genus Allium
Increasing scientific evidence asserts the traditional uses of plants in folklore
medicine [124–126]. Researchers over the years have investigated various parts of local medicinal plants to identify phytoconstituents with potential bioactivity, and further develop them into new drug therapies [127,128]. Allium species contain the common phytocompounds (anthocyanins, flavonoids, organosulfur, sterols, saponins, phe-
Molecules 2022, 27, 4475
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nolic acids, amino acids, vitamins and minerals) [129–132] with innumerable biological
properties [130–133]. Owing to these biological advantages, Allium species are locally
used in managing various diseases affecting human organs and organ systems such as
inflammation, microbial pathologies and oxidative stress injuries [130–133]. In particular, A.
cepa is used to treat alopecia, hearing impairment, menstrual disorders, erectile dysfunction
and ocular and metabolic diseases [133–135]. Similarly, A. sativum is employed in the
management of hematological disorders, carcinomas, muscle weakness and compromised
airways [135–139]. Other varieties of Allium species also serve as appetizers, nerve soothers,
and relieving agents against digestive, respiratory, and urinary system discomfort as seen
in Table 9.
Table 9. Traditional medicinal uses of Allium species.
Plant Species
Mode of Preparation
A. cepa
Raw, juice of bulb or rhizome, paste,
decoctions, cataplasm, maceration,
infusion
A. sativum
Extracts of leaves or bulb
A. umbilicatum
Raw or cooked bulb, leaves, flowers
A. victoralis
Fresh, pickled, boiled and salted flowers,
leaves and roots
A. ascalonicum/A. cepa
var aggregatum
Bulb and leaves
A. chinense
Flower, leaves, roots, seedpods
A. tuberosum
Raw or cooked leaves, roots, oils
from seed
A. griffithianum
Leaves and bulb
A. oreoprasum
Leaves and bulb
Traditional Medicinal Uses
Alopecia, antilithic (stone disease), anti-obesity, blood
purifying, bronchitis, constipation, cardiovascular
disease, cough, diabetes, eye diseases, erectile
dysfunction, fever, hearing loss, headaches,
hemorrhoids, epilepsy, oligomenorrhea, jaundice,
lower gastrointestinal bleeding, prostate cancer,
rheumatism, rubefacient, sinusitis, stomach pains,
snake bites, skin diseases, teeth disorders, reduce
flatulence, wound healing
Antiseptic, anthelmintic, antithrombotic, antilipidemic,
aphrodisiac, anti-greying of hair, bronchitis,
carminative, cough, colic, cancers (gastric, prostate,
colorectal adenomatous polyps, squamous cell
carcinoma), diabetes, diaphoretic, dysentery, eczema,
facial paralysis, fever, flatulence, galactagogue, high
blood pressure, intestinal worms, liver disorders,
rheumatism, scabies, tetanus, stomach
pains, tuberculosis
Non-specific reduction in blood cholesterol levels,
tonify digestive and circulatory systems
Appetizer, amenorrhea, pediatric otitis, bronchitis,
diarrhea, dropsy, expectorant, hypofunction of
stomach, inflammatory eye diseases, meteorism,
gastroenteritis, heart
diseases (atherosclerosis), rheumatism
Allergies, appetizer, cold, cancers, fever, obesity,
rheumatoid arthritis, soothes nerves, diabetes,
post-menopausal syndrome
Angina pectoris, astringent, bronchitis, carminative,
chest pains, diarrhea, expectorant, pleurisy, tenesmus
in cases of dysentery, reducing cholesterol, tonic to the
digestive and circulatory systems
Asthma, abdominal pain, carminative, cuts and
wounds, diabetes, diarrhea, kidney and bladder
weakness, nocturnal emission, urinary incontinence,
spermatorrhea, stomachic
Carminative, colic indigestion, dyspepsia,
diabetes control
Cough and cold, diabetes control, diarrhea, dysentery,
fever, gastritis, oedema, headache, jaundice,
stomachache, rheumatism, numbness of limbs
Reference
[133–135]
[135–139]
[116]
[140]
[141–145]
[146]
[147]
[124]
3.3. Phytochemistry of Allium
Owing to the numerous traditional uses of these species, it is not surprising that the
genus contains several phytoconstituents which may be responsible for their observed
activity. Table 10 outlines various phytochemicals isolated, their geographic location and
their biological activity.
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Table 10. Bioactive compounds isolated from Allium species.
Plant Species
Plant Part
Country
A. ursinum L.
Leaves,
underground parts,
fresh flowers
Poland
Bulgaria
A. mongolicum
Aerial parts
China
A. cepa.
A. cepa L.
Pigmented scales of
red onion,
bulbs,
red onion skin waste
Naples
Isolated Compounds
1,2-di-O-α-linolenoyl-3-O-β-D-galactopyranosyl-snglycerol; β-sitosterol3-O-β-D-glucopyranoside;
kaempferol 3-O-β-glucopyranoside and kaempferol
3-O-β-neohesperidoside.
(-S-)-spirost-5-en-3β-ol tetrasaccharide,
(25R)-spirost-5,25(27)-dien-3 β-ol tetrasaccharide,
3-hydroxypregna-5,16-dien-20-one glycoside.
Thymidine, adenosine, astragalin
(kaempferol-3-O-β-D-glucopyranoside, kaempferol-3-Oβ-D-glucopyranosyl-7-O-β-D-glucopyranoside,
kaempferol-3-O-β-D-neohesperoside, and
kaempferol-3-O-β-D-neohesperoside-7-O-β-D
glucopyranoside.
Mongoflavonoids A1 , A2 , A3 , A4 , B1 , B2 and
monogophenosides A1 , A2 , A3 , B.
Quercetin.
3-O-(3′′ -O-β-glucopyranosyl-6′′ -O-malonyl-βglucopyranoside)-4-O-β-glucopyranoside, cyanidin
3,4′ -di-O-β-glucopyranoside,
cyanidin-4′ -O-β-glucoside, peonidin
3-O-(6′′ -O-malonyl-β-glucopyranoside).
5-hydroxy-3-methyl-4-propylsulfanyl-5H-furan-2-one,
(hydroxymethyl) furfural, acetovanillone, methyl
4-hydroxyl cinnamate and ferulic acid methyl ester.
3-O-β-glucopyranoside and
3-O-(6′′ -O-malonyl-β-glucopyranoside) of
5-carboxypyranocyanidin.
Ceposide A, ceposide B and ceposide C.
Spiraeoside (4′ -O-glucoside of quercetin).
Onionin A1 , onionin A2 , onionin A3 , onionin B1 and B2 .
Onionin A1 (3,4-dimethyl-5-(1E-propenyl)tetrahydrothiophen-2-sulfoxide-S-oxide).
Cyanidin 3-glucoside (Cy 3-Glc), 3-malonylglucoside
(Cy3-MaGlc), cyanidin 3-laminaribioside (Cy 3-Lam)
and 3-malonyllaminaribioside (Cy 3-MaLam).
Bioactivity
References
Anti-ADP-aggregation activity in human
blood platelets.
Inhibition of human platelet aggregation.
Cytotoxic activity against murine melanoma
B16 and sarcoma XC.
[148–151]
Increase in the height of mouse small intestine.
[152]
Anti-inflammatory and immunomodulatory
effect.
Induction of quinone reductase.
Antifungal activity.
Radical scavenging, anti-inflammatory,
inhibition of the expression of B-cell
lymphoma 2.
Suppression of tumor progression in mouse
ovarian cancer (Onionin A1 ).
Suppression of tumor-cell proliferation
through the inhibition of polarization of M2
activated macrophages.
[153–161]
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Table 10. Cont.
Plant Species
Plant Part
A. sativum.
A. sativum L. var.
voghiera.
A. sativum L.
Root, protobulb, leaf
sheath and blade,
bulbs,
tuber
A. schoenoprasum
Whole plant,
pale-purple flowers
A. minutiflorum
Regel
Bulbs
A. neapolitanum
Extracts
Country
Isolated Compounds
Bioactivity
References
Italy
Nerolidol, α-pinene, terpinolene.
Voghieroside A1/A2, voghieroside B1/B2, voghieroside
C1/C2, voghieroside D1/D2 and voghieroside E1/E2.
Adenosine and guanosine.
Antifungal activity against Sclerotium
cepivorum.
Antimicrobial activity.
Strong inhibitory effect on human platelet
aggregation generated by 2 µM ADP in both
primary and secondary waves (adenosine).
[162–164]
Cytotoxicity against HCT 116 and HT-29
human colon cancer lines.
[165,166]
Antifungal activity.
[167]
Antiplatelet aggregation activity.
[168]
(20S, 25S)-spirost-5-en-3β, 12β,21-triol 3-O-α-Lrhamnopyranosyl-(1→2)-β-D-glucopyranoside, (20S,
25S)-spirost-5-en-3β, 11α,21-triol 3-O-α-Lrhamnopyranosyl-(1→2)-β-D-glucopyranoside,
laxogenin 3-O-α-L-rhamnopyranosyl–(1→2)-[β-Dglucopyranosyl-(1→4)]-[β-D-glucopyranoside,
(25R)-5α-spirostan-3β, 11α-diol 3-O-β-Dglucopyranosyl-(1→4)]-β-D-galactopyranoside.
(cyanidin 3-O-β-glucosideAII) (kaempferol 3-O-(2-O-βglucosylFIII-β-glucosideFII)-7-O-β-glucosiduronic
acid FIV) malonate AIII (AII-6→AIII-1, FIV-2→AIII-3),
1, (cyanidin 3-O-(3-O-acetyl-β-glucosideAII)
(kaempferol 3-O-(2-O-β-glucosylFIII-β-glucosideFII)7-O-β-glucosiduronic acid FIV) malonate AIII
(AII-6→AIII-1, FIV-2→AIII-3), 2, and
7-O-(methyl-O-β-glucosiduronateFIV).
Minutoside A, minutoside B, Minutoside C, alliogenin,
neoagigenin
3-O-{[2-O-α-1-rhamnopyrnosyl-4-O-β-Dglucopyranosyl]-β-D-glucopyranoside}, isorhamnetin;
3-O-{[2-O-α-1-rhamnopyrnosyl-6-O-β-Dglucopyranosyl]-β-D-glucopyranoside}, isorhamnetin;
3-O-{[2-O-α-1-rhamnopyranosyl-4-O-β-Dglucopyranosyl]-β-D-glucopyranoside}-7-O-β-Dglucopyranoside and isorhamnetin;
3-O-{[2-O-α-1-rhamnopyranosyl-6-O-β-Dgentiobiosyl]-β-D-glucopyranoside}.
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Table 10. Cont.
Plant Species
Plant Part
A. tripedale
Bulbs,
leaves
A. porrum L.
Bulbs
A. chinense.
A. chinense G. Don
Bulbs
Country
Iran
Isolated Compounds
6,7-dimethoxy-N-trans-caffeoyltyramine;
N-trans-feruloyltyramine.
(+)-S-(1-butenyl)-L-cysteine sulfoxide (homoisoalliin),
S-(1-butenyl)-L-cysteine (desoxyhomoisoalliin).
Kaempferol
3-O-[2-O-(trans-3-methoxy-4-hydroxycinnamoyl)-β-Dgalactopyranosyl]-(1→4)-O-β-D-glucopyranoside;
Kaempferol
3-O-[2-O-(trans-3-methoxy-4-hydroxycinnamoyl)-β-Dglucopyranosyl]-(1→6)-O-β-D-glucopyranoside.
(25R)-5 α-spirostan-3 β, 6 β-diol 3-O-[O-β-D-glucopyranosyl(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-Dglucopyranosyl-(1→4)-β-D-galactopyranoside}; (25R)-5
α-spirostan-3 β, 6 β-diol
3-O-{O-β-D-glucopyranosyl-(1→3)-O-β-D-glucopyranosyl(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-Dgalactopyranosyl-(1→4)-β-D-galactopyranoside}
Chinenoside II and chinenoside III.
(25 R,S)-5 α-Spirostan-3β-ol tetrasaccharide, (25R)-3
β-hydroxy-5 α-spirostan-6-one di- and tri-saccharides.
Xiebai-saponin I (laxogenin 3-O-β-xylopyranosyl
(1→4)-[α-arabinopyranosyl (1→6)-β-glucopyranoside),
laxogenin 3-O-α-arabinopyranosyl
(1→6)-β-glucopyranoside, laxogenin, isoliquiritigenin,
isoliquiritigenin-4-O-glucoside, and β-sitosterol glucoside.
Bioactivity
References
NR.
[167,168]
Antiplatelet aggregation activity.
Antifungal activity.
[169–171]
Inhibition of cAMP phosphodiesterase.
Antitumor-promoting activity (laxogenin).
[172–175]
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Table 10. Cont.
Plant Species
A. macrostemon.
A. macrostemon
Bunge
Plant Part
Bulbs,
leaves
Country
Isolated Compounds
Bioactivity
References
Japan
Macrostemonoside G (26-O-β-D-glucopyranosyl-22-hydroxy5-β-furost-25(27)-ene-3 β,12 β,26 triol
3-O-β-D-glucopyranosyl(1–>2)-β-D-galactopyranoside) and I
(26-O-β-D-glucopyranosyl-22-hydroxy-5
β-furost-25(27)-ene-12-one-3 β,26-diol
3-O-β-D-glucopyranosyl(1→2)-β-D-galactopyranoside).
tigogenin-3-O-β-D-glucopyranosyl(1–>2)
[β-D-glucopyranosyl(1→3)1]-β-D-glucopyranosyl(1→4)-βD -galactopyranoside (1) and
tigogenin-3-O-β-D-glucopyranosyl(1→2)[β-Dglucopyranosyl (1→3)(6-O-acetyl-β-D-glucopyranosyl)]
(1→4)-β-D-galactopyranoside (2).
Macrostemonoside E-(25R)-26-O-β-D-glucopyranosyl-5
α-furost-20(22)-ene-3 β,26-diol-3-O-β-D-glucopyranosyl
(1→2) [β-D-glucopyranosyl (1→3)]-β-D-glucopyranosyl
(1→4)-β-D-galactopyranoside; Macrostemonoside
F(II)-(25R)-26-O-β-D-glucopyranosyl-5 β-furost-20(22)-ene-3
β,26-diol-3-O-β-D-glucopyranosyl (1→2)-β-D-galactoside.
Allimacronoid A (1-O-(E)-feruloyl-β-D-glucopyranosyl
(1-2)-[β-D-glucopyranosyl (1-6)]-β-D-glucopyranose),
Allimacronoid B (1-O-(E)-feruloyl-{β-D-glucopyranosyl
(1-4)-[β-D-glucopyranosyl (1-2)]}-[β-D-glucopyranosyl
(1-6)]-β-D-glucopyranose) and Allimacronoid
Cn1-O-(E)-feruloyl-{β-D-glucopyranosyl
(1-6)-[β-D-glucopyranosyl (1-2)]}-[β-D-glucopyranosyl
(1-6)]-β-D-glucopyranose.
In vitro inhibition of ADP-induced human
platelet aggregation (macrostemonoside G).
Inhibitory activity against rabbit platelet
aggregation induced by ADP (1).
[176–179]
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Table 10. Cont.
Plant Species
Plant Part
A. schubertii
Bulbs
A. tuberosum
Seeds
Country
Shanghai
Isolated Compounds
(25R and S)-5 α-spirostan-2 α,3 β,6 β-triol
3-O-β-D-glucopyranosyl-(1→2)-O-[4-O-benzoyl-β-Dxylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-Dgalactopyranoside, (25R and S)-5 α-spirostan-2α,3β,6 β-triol
3-O-β-D-glucopyranosyl-(1→2)-O-[3-O-benzoyl-β-Dxylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-Dgalactopyranoside, (25R and S)-5 α-spirostan-2α,3β,6 β-triol
3-O-β-D-glucopyranosyl-(1→2)-O-[4-O-(3S)-3-hydroxy-3methylglutaroyl-β-D-xylopyranosyl-(1→3)]-O-β-Dglucopyranosyl-(1→4)-β-D-galactopyranoside and
26-O-β-D-glucopyranosyl-(25R and S)-5
α-furostan-2α,3β,6β,22 zeta,26-pentol 3-O-β-Dglucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-βD -glucopyranosyl-(1→4)-β- D -galactopyranoside.
(2α, 3β, 5α, 25S)-2,3,27-trihydroxyspirostane
3-O-α-L-rhamnopyranoyl-(1→2)-O-[α-L-rhamnopyranosyl(1→4)]-β-D-glucopyranoside.
Tuberoside J-(25R)-5 α-spirostan-2α,3
β,27-triol
3-O-α-L-rhamnopyranosyl-(1–>2)-β-D-glucopyranoside;
Tuberoside K-(25R)-5α-spirostan-2α,3β 27-triol
3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl(1→4)]-β-D-glucopyranoside; and Tuberoside
L-27-O-β-D-glucopyranosyl-(25R)-5α-spirostan-2α,3
β,27-triol 3-O-α-D-rhamnopyranosyl-(1–>2)-[α-Lrhamnopyranosyl-(1→4)]-β-D-glucopyranoside.
Tuberoside M-(25S)-5β-spirostane-β,3 β-diol
3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside.
Tuber-ceramide
(N-(2′ ,3′ -dihydroxy-tetracosenoyl)-2-amino-1,3,4-trihydroxy
octadecane), and Cerebroside
(N-(2′ ,3′ -dihydrox-tetra-cosenoyl)-2-amino-1,3,4-trihydroxy
octadecane).
Bioactivity
References
NR.
[180]
Tuberoside M inhibits the proliferation of the
human promyelocytic leukemia cell line
(HL-60)
[181–183]
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Table 10. Cont.
Plant Species
A. albopilosum and
A. ostrowskianum
Plant Part
Country
Bulbs
A. fistulosum.
A. fistulosum L.
Whole plant,
leaves,
seeds
Iran
A. carolinianum DC
Bulb
Mongolia
Isolated Compounds
(25 R and S)-5 α-spirostane-2α, 3 β,6 β-triol
3-O-(O-β-D-glucopyranosyl-(1→2)-O-[3-O-acetyl-β-Dxylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-Dgalactopyranoside),
(25R)-2-O-[(S)-3-hydroxy-3-methylglutaroyl]-5
α-spirostane-2α, 3β, 6β-triol 3-O-(O-β-D-glucopyranosyl(1→2)-O-[β-D-xylopyranosyl-(1—
>3)]-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside),
(22S)-cholest-5-ene-1β, β,16 β,22-tetraol
1-O-α-L-rhamnopyranoside 16-O-(O-α-L-rhamnopyranosyl(1→3)-β-D-glucopyranoside), 1β, 3β,
16β-trihydroxycholest-5-en-22-one
1-O-aα-L-rhamnopyranoside 16-O-(O-α-L-rhamnopyranosyl(1→3)-β-D-glucopyranoside), 1β,3β,16 bβ-trihydroxy-5
α-cholestan-22-one 1-O-α-L-rhamnopyranoside 16-O-(O-α-Lrhamnopyranosyl-(1→3)-β-D-glucopyranoside) and
(22S)-cholest-5-ene-1β,3β, 16β,22-tetraol
16-O-(O-β-D-glucopyranosyl-(1→3)-β-D-glucopyranoside).
Fistulomidate A ((1Z,2E)-Methyl3-(3,4-dimethoxyphenyl)-N(4-hydroxyphenethyl) acrilimidate) and Fistulomidate B
((1Z,2E)-Methyl3-(3,4-dihydroxyphenyl)-N-(4hydroxyphenethyl)acrilimidat).
Onionin A1 , onionin A2 , and onionin A3 .
Glycerol mono-(E)-8,11,12-trihydroxy-9-octadecenoate,
tianshic acid, 4-(2-formyl-5-hydroxymethylpyrrol-1-yl)
butyric acid, p-hydroxybenzoic acid, vanillic acid, and
daucosterol.
Cinnamoylphenethylamine derivative
Bioactivity
References
NR.
[184]
Antibacterial and cytotoxic activity.
Suppression of tumor progression in mouse
ovarian cancer (onionin A1 ).
Inhibition of the growth of Phytophtohora
capsici on V8 media (glycerol
mono-(E)-8,11,12-trihydroxy-9-octadecenoate
and V).
[159,185,186]
Weak cytotoxic activity
[187]
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Table 10. Cont.
Plant Species
Plant Part
A. ampeloprasum
var. porrum (Leek)
Plant parts
A. ascalonicum L.
Country
China
A.siculum
Bulbs
Zwanenburg, The
Netherlands
A.chrysanthum
Barks
Guangzhou,
China
A. L.
melanocrommyum
section
Megaloprason.
Bulbs
Central Asia
Isolated Compounds
Bioactivity
References
A-β- D -glucopyranoside
Anticancer activity against MCF-7 human
breast cancer cell.
[187]
NR.
[188,189]
NR.
[190]
NR.
[191]
NR.
[192]
Ascalonicoside C-(25R)-26-O-β-D-glucopyranosyl-22hydroxy-5α-furost-2-one-3β,5,6β,
26-tetraol-3-O-α-L-rhamnopyranosyl-(1→2)-β-Dglucopyranoside. Ascalonicoside
D -(25R)-26-O-β- D -glucopyranosyl-22-methoxy-5α-furost-2one-3β,5,6β,
26-tetraol-3-O-α-L-rhamnopyranosyl-(1→2)-β-Dglucopyranoside.
(25R)-26-O-β-D-glucopyranosyl-22-hydroxy-5-ene-furostan3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→4)-α-Lrhamnopyranosyl-(1→4)-[
α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside. 25R)26-O-β-D-glucopyranosyl-22-hydroxy-5-ene-furostan-3β,
26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-Larabinofuranosyl-(1→4)]-β-D-glucopyranoside.
(Z)-Butanethial S-oxide, (R(S),R(C),E)-S-(1-butenyl)cysteine
S-oxide (homoisoalliin).
Chrysanthumones A (6′′ ,6′′ -dimethyl-4′′ ,5′′ -dihydropyrano
[2′′ ,3′′ : 8,7]-6”′ ,6′′′ -dimethyl-prenyl-4′′′ ,5′′′ -dihydropyrano
[2′′′ ,3′′′ :2′ ,3′ ]apigenin) and B
((E)-5,7-dihydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-1enyl)-4H-chromen-4-one).
L-(+)-S-(2-pyridyl)-cysteine sulfoxide.
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Table 10. Cont.
Plant Species
Plant Part
Country
Isolated Compounds
Bioactivity
References
United States of
America
Ampeloside Bs1 (apigenin 3-O-β-glucopyranosyl (1 →
3)-β-glucopyranosyl (1 → 4)-β-galactopyranoside),
ampelosides Bf1 ((25R)-26-O-β-glucopyranosyl-22-hydroxy5α-furostane-2α,3β,6β,26-tetraol-3-O-β-glucopyranosyl(1
→ 3)-β-glucopyranosyl-(1 → 4)-β-galactopyranoside) and
Bf2 ((25R)-26-O-β-glucopyranosyl-22-hydroxy-5α-furostane2α,3β,6β,26-tetraol-3-O-β-glucopyranosyl(1 →
4)-β-galactopyranoside).
Weak antifungal activity by ampeloside Bs1 .
[193]
Adenosine, guanosine, and tryptophan, β-sitosterol
β-D-glucoside.
Strong inhibitory effect on human platelet
aggregation generated by 2 µM ADP in both
primary and secondary waves (adenosine).
[162]
Cytotoxic activity.
[194]
NR.
[195]
A. ampeloprasum L.
Bulbs
A. bakeri Reg.
Tuber
A.victorialis var.
platyphyllum
Aerial parts, bulbs
A. nutans L.
Underground
plant parts
A.giganteum
Bulbs
Japan
A. hookeri
Thwaites
Rhizomes
China
NR: not reported.
Korea
Gitogenin 3-O-lycotetroside, astragalin and kaempferol 3,
4′ -di-O-β-D-glucoside.
Deltoside, nolinofuroside D, 25R ∆(5)-spirostan
3β-ol-3-O-α-L-rhamnopyranosyl(1–>2)-[β-Dglucopyranosyl(1→4)]-O-β-D-galactopyranoside and 25R
∆(5)-spirostan 1 β, 3β-diol 1-O-β-D-galactopyranoside.
3-O-acetyl-(24S,25S)-5α-spirostane-2α,3β,5α,6β,24-pentol
2-O-β-D-glucopyranoside.
Di-2-propenyl trisulfide, diallyl disulfide, and dipropyl
trisulfide.
Inhibition of cAMP phosphodiesterase
activity.
Antimicrobial activity against Aspergillus
fumigatus and C. albicans.
[196]
[197]
α
α β α β
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The chemical structures of compounds from the genus Allium are shown in Figure 4.
Figure 4. Chemical structures of compounds isolated from the genus Allium. Quercetin (13), vanillic
acid (14) and adenosine (15).
3.4. Pharmacological Effects of Allium
There are several species within Allium whose biological activities have been well
established [198]. This section focuses on the pharmacological activities associated with
these species.
3.4.1. Antimicrobial Activities
Garlic has shown antimicrobial effects against Gram-positive, Gram-negative and acid
fast stain organisms [199–201]. Allicin from garlic showed effectiveness toward methicillinresistant S. aureus (MRSA) [200]. Extracts from garlic also showed broad-spectrum fungicidal effect against several fungi including Candida, Trichophyton, Cryptococcus, Aspergillus,
Trichosporon and Rhodotorula species. Garlic extract was recently found to inhibit Meyerozyma
guilliermondii and Rhodotorula mucilaginosa germination and growth [202]. A study by Fufa
reported the antifungal activity of various A. sativum extracts, namely aqueous, ethanol,
methanol, and petroleum ether against human pathogenic fungi such are Trichophyton
verrucosum, T. mentagrophytes, T. rubrum, Botrytis cinereal (B. cinerea), Candida species, Epidermophyton floccosum, A. niger, A. flavus, Rhizopus stolonifera, Microsporum gypseum, M.
audouinii, Alternaria alternate, Neofabraea alba, and Penicillium expansum [203]. Essential oil
from garlic showed antifungal activity against a number of fungi such as (C. albicans, C.
tropicalis and Blastoschizomyces capitatus). Saponins extracted from A. sativum had antifungal
activity against B. cinerea and Trichoderma harzianum [204]. Allium species from Ghana were
reported by Danquah et al. to possess anti-infective and resistance modulatory effects
on selected microbial strains [205]. Allium hirtifolium was found to exhibit antimicrobial
activities against E. faecalis [206].
Previous studies have shown that garlic extract inhibit the growth of Blastocystis
species in vivo and this effect was attributed to the several phytochemicals contained in
garlic extracts. Examples of these phytochemicals are thiosulfinates and allicin which have
been investigated to possess antibacterial and antiprotozoal effects [204,207]. Garlic extracts
have been evaluated for antiviral effects against influenza B, human rhinovirus type 2,
human cytomegalovirus (HCMV), parainfluenza virus type 3, Herpes simplex type 1 and -2,
vaccinia virus, and vesicular stomatitis virus [208]. Danquah et al. again reported the
antitubercular effects of analogues of disulfides from A. stipitatum as well as their antibiofilm and anti-efflux effects [209].
3.4.2. Antioxidant Properties
It has been reported that frequent garlic intake promotes internal antioxidant activities
and reduces oxidative adverse effects either by increasing the endogenous antioxidant synthesis or reducing the production of oxidizing agents such as oxygen-free radical species
(ORS) [210]. It has also been demonstrated that garlic possesses protective properties
against gentamycin as well as acetaminophen-induced hepatotoxicity by improving antioxidant status, and regulating oxidative stress [200]. Garlic extract was found to elevate the
activities of selected antioxidant enzymes (e.g., superoxide dismutase (SOD)) and decrease
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glutathione peroxidase (GSH-Px) in rats’ hepatic tissues [13,118,211]. Saponins extracted
from garlic were reported to scavenge intracellular ROS and protect mouse-derived C2 C12
myoblasts towards growth inhibition and H2 O2 -induced DNA damage [13,212]. A. ursinum
aqueous extract also demonstrated antioxidant effect which lasted approximately 16 h [213].
A. hirtifolium was reported to possess antioxidant capacity by neutralizing the free radical
species in a system [214].
3.4.3. Anti-Inflammatory Properties
It has been reported widely that garlic extracts and its related phytochemicals possess
anti-inflammatory activity. A study by Ahmad et al. revealed that garlic extracts significantly impaired liver inflammation and damage caused by Eimeria papillata infections [215].
The mechanism underlying the anti-inflammatory effects of garlic was attributed to the
inhibition of emigration of neutrophilic granulocytes into epithelia as described by Hobauer
et al. [216] and Gu et al. [217]. The chloroform extract of aged black garlic acts by reducing NF-κB activation in human umbilical vein endothelial cells caused by tumor necrosis
factor-α (TNF-α) and the methanolic extract also reported to prevent the cyclooxygenase-2
(COX-2) and prostaglandin E2 (PGE2 ) production by NF-κB inactivation [218]. A report by
Jin et al. confirmed that thiacremonone (a sulfur compound isolated from garlic) prevents
neuroinflammation and amyloidogenesis by blocking the NF-κB activity, and therefore
makes it an ideal remedy to manage neurodegenerative disorders (e.g., Alzheimer’s disease)
related to inflammation [219].
Krejčová et al. reported that pyrithione and related sulfur-containing pyridine Noxides from Persian shallot possessed anti-inflammatory and neurological activity [220].
The extracts of A. stipitatum were reported to exhibit antibacterial effect in vivo against
methicillin-resistant S. aureus [221]. Anti-inflammatory effect of A. hookeri on carrageenaninduced air pouch mouse model was also established by Kim et al. [222].
3.4.4. Anticancer Activity
Comparison of the anticancer effect of raw garlic extracts against other extracts
from different plants found garlic to be the most effective and highly specific anticancer
agent [223]. The anticancer mechanisms of garlic extracts were reported to be mediated via
inhibition of cell growth and proliferation, regulation of carcinogen metabolism, stimulation of apoptosis, prevention of angiogenesis, invasion, and migration; and thus affording
the anticancer agent with minimal negative effects [13]. Chabria et al. reported that allicin
isolated from garlic suppresses colorectal cancer metastasis through enhancing immune
function and preventing the formation of tumor vessels as well as surviving gene expression to enhance the cancer cell’s apoptosis [224]. Fleischauer and Arab [225] reported
that continuous garlic intake could decrease different kinds of cancer propagation such
as cancer of the lung, colon, stomach, breast, and prostate. Piscitelli et al. reported that
garlic reduced the plasma concentrations of saquinavir by approximately 50% in healthy
participants after a 3-week garlic supplement intake. In addition to this, many researchers
evaluated the antitumor and cytotoxic actions of garlic and its related constituents in vitro
and in vivo [226].
3.4.5. Other Pharmacological Effects of Allium Species
Investigations on extracts of A. sativum (garlic) revealed anticholinesterase effects,
which could be further developed and utilized in the management of Alzheimer’s disease [227–229]. Garlic is known to possess hypolipidemic effects by reducing the total
glycosaminoglycans concentration in heart and aorta [230]. Garlic is also known to reduce
the level of cholesterol either by acid stimulation and excretion of neutral steroids or by
reducing the cholesterogenic and lipogenic effects of fatty acid synthase, 3-hydroxy-3methyl-glutaryl-CoA reductase, malic acid, and glucose-6 phosphate dehydrogenase in
hepatocytes [231]. Garlic tablets formulated by Ashraf et al. and administered at a dose of
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600 mg/day for 12 weeks in diabetic patients with dyslipidemia resulted in high HDL, low
LDL and TC levels [232].
Allicin, a constituent in garlic, was found to reduce diabetes mellitus in rats, which
was similar to that demonstrated by glibenclamide and insulin [233]. Garlic extracts reduce
body weight, adipose tissue mass and improved plasma lipid profiles in mice with high-fat
diet-induced obesity [234]. The mechanism of these activities is downregulation of multiple
gene expression such as adipogenesis along with upregulation of the mitochondrial inner
membrane proteins expression [234]. Garlic extract is widely known to significantly control
blood pressure by reducing both systolic and diastolic pressures [235]. Moreover, several
reports have confirmed the antihypertensive effects of garlic [236]. Extracts of A. stipitatum
were also assessed and established to possess significant wound healing properties [237].
4. The Genus Crinum
4.1. Geographical Distribution of Crinum
Crinum, which also belongs to the Amaryllidaceae family, comprises approximately
160 beautiful lilies that grow naturally in coastal areas of the tropics and subtropics. They
are widely distributed in Africa, Asia, Australia and America [238–241]
4.2. Traditional Uses of Crinum
Plants of the genus Crinum have been used to treat various diseases across the
world [242]. In China and Vietnam, Crinum plants in traditional medicine are believed to
possess antiviral and immune-stimulatory properties. A hot aqueous extract of Crinum
latifolium (C. latifolium) is used as an antitumor agent. Crinum asiaticum (C. asiaticum) is used
in Malaysia to treat rheumatism and to relieve local pain [239]. Crinum amabile Donn. (C.
amabile) is used in Vietnam to induce emesis, as well as for rheumatism and earache [241].
The bulbs of C. asiaticum L. are used as a tonic, laxative and expectorant in Indian
traditional medicine, as well as for treating urinary tract diseases [241]. The seeds are used
as purgatives, diuretics, and tonics, while the raw roots are used as an emetic. The leaves
are also very useful in the management of skin problems, inflammation and cough [241]. C.
latifolium L. is also used to treat rheumatism, abscesses, earaches, and as a tonic. Crinum
pratense (C. pratense) and Crinum longifolium (C. longifolium) are also used as bitter tonics,
laxatives and in the management of chest illnesses [243].
Crinum zeylanicum (C. zeylanicum) L. is used in Sri Lanka to treat abscesses and fevers;
the bulbs are also used as rubefacient in rheumatism and against snake bites; and the juice
from the leaves used to treat earaches [244].
The roots of Crinum species have been used in African traditional medicine to cure
urinary infections, coughs and colds, renal and hepatic disorders, ulcers, sexually transmitted infections, and backache, as well as enhance breastfeeding in both animal and human
mothers [241]. Crinum kirkii Bak. (C. kirkii), a widespread East African grassland plant, is
used to heal wounds in Kenya. In Tanzania, the fruit and inner part of the bulbs are used as
purgatives, and the outer scales employed as rat poison [245,246]. Extracts of Crinum delagoense (C. delagoense) Verdoorn is utilized in Zulu and Xhosa traditional medicine in South
Africa to treat urinary tract infections and body oedema [247–249]. Rheumatism, aching
joints, septic sores, varicose veins, and kidney and bladder infections have all been treated
using the South African Crinum bulbispermum (C. bulbispermum) [250]. In Cameroon, Crinum
pupurascens (C. pupurascens) Herb is used to treat sexual asthenia and spleen disorders.
Crinum species (C. defixum Keraudren et Gawl., C. firmifolium Baker, C. modestum Baker) are
as well used in Madagascar to treat abscesses, anthrax, and otitis. It is also employed as an
emetic, diaphoretic, and emollient. Externally, Crinum firmifolium (C. firmifolium) is used to
treat a variety of parasite skin afflictions [40,243].
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4.3. Phytochemistry of Crinum
Several phytochemical and pharmacological studies have been conducted on the
genus Crinum. The compounds isolated from various species of Crinum as well as their
biological activities have been outlined in Table 11.
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Table 11. Bioactive compounds isolated from Crinum species.
Plant Species
Plant Part
Country
C. x amabile
C. x amabile Donn ex
Ker Gawl
Bulbs
Stems, roots
Ecuador
Brazil
Thailand
C. defixum Ker-Gawl
Bulbs
India
C. moorei
Bulblets
C. biflorum
Bulbs
C. asiaticum
C. asiaticum var.
sinicum
C. asiaticum L.
C. asiaticum var.
japonicum.
C. asiaticum L. var.
sinicum.
Seeds,
rhizome, fruits
Bulbs, stems,
leaves
Senegal
Beijing, China,
Hainan
Province,
Japan,
Island of Jeju
in
Korea
Isolated Compounds
Haemanthamine/crimine-type
alkaloid.
Lycorine-type alkaloid
Galanthamine-type alkaloid.
Augustine N-oxide, buphanisine
N-oxide.
Amabiloid A.
Hydrazide derivative.
(E)-N-[(E)-2-butenoyl]-2-butenoylhydrazide.
Cherylline, crinamidine, crinine, epibuphanisine, lycorine,
powelline, undulatine, 1-epideacetylbowdensine,
3-O-acetylhamayne.
3-[4′ -(8′ -aminoethyl) phenoxy] bulbispermine, mooreine.
5,6,7-trimethoxy-3-(4 hydroxybenzyl) chroman-4-one,
3-hydroxy-5,6,7-trimethoxy-3-(4-hydroxybenzyl) chroman-4-one,
3-hydroxy-5,6,7-trimethoxy-3-(4-methoxybenzyl) chroman-4-one,
5,6,7-trimethoxy-3-(4-methoxybenzyl) chroman-4-one,
(E)-N-(4-hydroxyphenethyl)-3-(4-hydroxyphenyl) acrylamide.
Flavonoids
Isopowellaminone.
(2R,3S)-7-methoxyflavan-3-ol (1:), (2R,3S)-7-hydroxy-flavan-3-ol (2:),
(2R,3S)-2 ′ -hydroxy-7-methoxy-flavan-3-ol (3:).
Norgalanthamine.
Crinamine
CAL-n.
Crijaponine A, crijaponine B, ungeremine, lycorine,
2-O-acetyllycorine, 1,2-O-diacetyllycorine, (-)-crinine,
11-hydroxyvittatine, hamayne,(+)-epibuphanisine, crinamine,
yemenine A, epinorgalanthamine.
Criasiaticidine A, pratorimine, Lycorine,
4′ -hyd’oxy-7-methoxyflavan.
Crinamine, lycorine, norgalanthamine, epinorgalanthamine.
Asiaticumines A, asiaticumines B.
Bioactivity
References
Anticholinesterase
(anti-AChE) and antibutyrylcholinesterase
(anti-BuChE) activity.
[249–251]
Anti-genotoxic activity.
[252]
NR.
[253]
Anticancer, anti-AChE, anti-glucosidase
activity.
[254,255]
Inhibitory activity against LPS-induced
nitric oxide production.
Anticancer activity (against cervical cancer
SiHa cells).
Inhibition of platelet aggregation.
Promotion of hair growth through dermal
papilla proliferation.
Inhibition of the growth of HepG2 tumor
cells.
Anti-AChE activity, cytotoxic activity.
Cytotoxic against Meth-A (mouse sarcoma)
and Lewis lung carcinoma (mouse lung
carcinoma).
Inhibition of the activity of hypoxia
inducible factor-1 (crinamine).
Cytotoxicity.
[256–266]
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Table 11. Cont.
Plant Species
Plant Part
Country
C. kirkii Baker
Bulbs
C. macowanii
Bulbs
C. firmifolium
Leaves
Madagascar
C. latifolium
Bulbs
Leaves
China.
Hanoi,
Vietnam
C. scillifolium
Bulbs
C. zeylanicum (L)
Bulbs, leaves,
flowers, fruits
Cuba
Sri Lanka
C. jagus (J. Thomps)
Dandy
Bulbs, leaves
Senegal
Ghana
C. abyscinicum
Hochst. ExA. Rich
Bulbs
Ethiopia
C. erubescens
Above ground
plant parts
C. yemense
Bulbs
Puntarenas,
Costa Rica
Yemen
Isolated Compounds
Bioactivity
References
Noraugustamine, 4aN-dedihydronoraugustamine,
3-O-acetylsanguinine, 1,2-diacetyllycorine.
Antiparasitic activity against Trypanosoma
brucei (T. brucei) rhodesiense, Trypanosoma
cruzi (T. cruzi).
[267,268]
NR.
[249]
Antiplasmodial activity.
[269]
Cytotoxic against tumor cell lines,
antimicrobial activity, antioxidant activity.
Inhibitory activity against human umbilical
venous endothelial cells.
[270–272]
Mild antiplasmodial activity
[273]
Antiproliferative effect.
[246,274]
Anti-AChE activity,
inhibitors of TcAchE, hAChE and hBChE
[275,276]
6-hydroxycrinamine, lycorine.
Antiproliferative activity against A2780
epithelial ovarian cancer and MV4-11 acute
myeloid leukemia cell lines.
[277]
Cripowellin A, cripowellin B, cripowellin C, cripowellin D,
hippadine.
Antiplasmodial activity.
[278]
6-hydroxy-2H-pyran-3-carbaldehyde.
Yemenines A, B and C, 1, (+)-bulbispermine, (+)-crinamine,
(+)-6-hydroxycrinamine, (-)-lycorine.
Tyrosinase inhibitor.
Inhibit nitric oxide production, induce nitric
oxide synthase.
[277–280]
Macowine, lycorine, cherylline, crinine, krepowine, powelline,
buphanidrine, crinamidine, undulatine, 1-epideacetylbowdensine,
4a-dehydroxycrinamabine.
2-alkylquinolin-4(1H), 2-alkylquinolin-4(1H).
4,8-dimethoxy-cripowellin C. 4,8-dimethoxy-cripowellin D,
9-methoxy-cripowellin B, 4-methoxy-8-hydroxy-cripowellin B,
cripowellin C.
C. latines A, C. latines B and C. latines C.
4-senecioyloxymethyl-3,4-dimethoxycoumarin, 5,6,3
′ -trihydroxy-7,8,4 ′ -trimethoxyflavone.
4-methyloxysenecioyl-6,7-dimethoxycoumarin,
5,6,3′ -trihydroxy-7,8,4′ trimethoxyflavone.
Scillitazettine, scilli-N-desmethylpretazettine.
Crinine, Lycorine, 11-O-acetoxyambelline, ambelline,
6-hydroxybuphanidrine, 6-ethoxybuphanidrine, 3-acetylhamayne,
6-hydroxycrinamine, hamayne, 6-methoxycrinamine.
Gigantelline, gigantellinine, gigancrinine, sanguinine, cherylline,
lycorine, crinine, flexinine, hippadine.
Galanthamine, galanthamine N-oxide, powelline.
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Table 11. Cont.
Plant Species
Plant Part
Country
C. bulbispermum
C. bulbispermum III
Bulbs
Egypt
C. powellii
Bulbs
Switzerland
Colombia
C. glaucum
Bulbs
Nigeria
C. purpurascens
Leaves
Cameroon
NR: not reported.
Isolated Compounds
8-hydroxylycorin-7-one, 2-deoxylycorine, vittatine,
11-hydroxyvittatine, hippamine.
4-hydroxy-2′ ,4′ -dimethoxydihydrochalcone,
4,5-methylenedioxy-4′ -hydroxy-2-aldehyde [1,1′ -biphenyl],
hippacine, 4′ -hydroxy-7-methoxyflavan-3-ol,
′
′
2(S),3 ,4 -dihydroxy-7-methoxy flavan, isolarrien, isoliquiritigenin,
liquiritigenin.
Bulbispermine.
Linoleic acid ethyl ester, alkaloid hippadine, calleryanin,
4′ -hydroxy-7-methoxyflavan.
Lycorine, 1-O-acetyllycorine, ismine.
Hamayne, lycorine, haemanthamane, crinamine.
4,5-ethano-9,10-methlenedioxy-7-phenanthridone,
4,5-ethano-9-hydroxy-10-methoxy-7-phenanthridone,
α-D-glucopyranoside.
Bioactivity
References
NR.
[281–283]
AChE inhibitor (linoleic acid ethyl ester).
Inhibition of topoisomerase 1 activity.
[284,285]
Choline esterase inhibitory activity.
[286]
Antibacterial activity
[287]
α
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Chemical structures of common compounds from Crinum are shown in Figure 5.
Figure 5. Chemical structures of compounds isolated from the genus Crinum. Lycorine (16), crinamine
(17), galantamine (18) and crinine (19).
4.4. Pharmacological Activities of Crinum
4.4.1. Anti-Inflammatory and Analgesic Effects
The anti-inflammatory and the analgesic properties of various Crinum species have
been investigated by several authors. The anti-inflammatory effect of C. asiaticum as well as
its effect on bradykinin-induced contractions on isolated uterus has been reported [288–291].
The ethanolic extract of C. asiaticum demonstrated significant analgesic effect in an aceticacid-induced writhing test [292]. Antipyretic and anti-inflammatory properties of C. jagus
were recently reported by Minkah and Danquah [291]. Leaf extract of C. bulbispermum has
also been established to possess antinociceptive effects [293,294].
4.4.2. Anticancer and Cytotoxicity Effects
The cytotoxic effects of C. asiaticum extract was investigated and was shown to exert
toxic effect on brine shrimps and murine P388 D1 cells [294–298]. Yui et al. demonstrated
that hot water extracts of C. asiaticum exhibited potent inhibition of calprotectin-induced
cytotoxicity in MM46 mouse mammary carcinoma cells. This activity whi1ch was later
attributed to lycorine, an active compound in C. asiaticum [297]. Some alkaloids isolated
from the bulbs of C. asiaticum have been reported to show remarkable inhibition against
tumor cell lines A549, LOVO, HL-60, and 6T-CEM [261].
The extract of C. asiaticum exhibited antiproliferative and chemosensitizing effects
against multi-drug-resistant cancer cells [298,299]. The antiangiogenic activity of the
methanolic leaf extract of C. asiaticum was evaluated and established by Yusoff [300].
The cytotoxic effect of the essential oil extracted from C. asiaticum was as well established
in MCF-7 cells [301]. A recent work done by Yu et al. reported the inhibition of the growth
of HepG 2 cells in a dose-dependent manner by polysaccharide CAL-n, an isolate from C.
asiaticum [262]. Also, the neuroprotection and anti-neuroinflammatory effects in Neuronal
Cell Lines were reported by Lim et al. [279,302]. Alkaloids from C. bulbispermum have also
been reported to possess cytotoxic activities [284]. Evaluation of the cytoprotective potential
of C. bulbispermum, after induction of toxicity using rotenone, in SH-SY5Y neuroblastoma
cells proved that, the plant has such effect as reported [303]. Aboul-Ela et al. [279] tested
the cytotoxic effect of C. bulbispermum bulbs using the brine shrimp bioassay.
4.4.3. Antimicrobial Properties
The in vitro antitubercular effects of C. asiaticum on Mycobacterium tuberculosis (M.
tuberculosis) surrogate, Mycobacterium smegmatis (M. smegmatis), were reported [291,304].
C. asiaticum was shown to possess a broad-spectrum antimicrobial activity against Grampositive, Gram-negative bacteria and fungal pathogens [291,299]. Antifungal activities
of the essential oil and extracts of C. asiaticum against pathogenic fungi have also been
established [305,306]. It is reported that the methanolic root extract of C. asiaticum exerts significant anti-HIV-1 activity [307]. The ethanolic extract of C. asiaticum significantly inhibited
Molecules 2022, 27, 4475
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selected bacteria as evaluated by Naira et al. [308]. Dichloromethane extract of C. asiaticum
was found to be the most effective against selected oral and vaginal Candida species [309].
Minkah and Danquah again demonstrated the antimicrobial activity of extracts of C. jagus
against clinically significant microorganisms in the High-throughput spot culture growth
inhibition (HT-SPOTi) assay [291]. Water/Ethanol extract of C. jagus was observed to be
active on Shigella flexneri-induced diarrhea in rats [310]. The antimicrobial and antioxidant
properties of C. jagus make it suitable as a wound healing agent [311]. The crude methanolic
extract of C. jagus was investigated to have effect on Mycobacterium tuberculosis [312,313].
The crude alkaloid of C. jagus inhibited Dengue virus infection [314]. C. macowanii has also
been shown to possess biological effects such as antifungal, antiviral and antiplasmodial
activities [315].
4.4.4. Antioxidant Properties
There antioxidant effects of C. asiaticum have been studied extensively. The ethanolic extract exhibited protective effects on human erythrocyte [316]. C. asiaticum bulbs
also exerted remarkable free radical scavenging ability [317]. The antioxidant activity
of the ethanolic extract of C. asiaticum leaves in alloxan-induced diabetic rats was well
demonstrated [318]. More recent work on the methanolic extract of C. asiaticum showed
antioxidant effects [319]. Potent DPPH radical scavenging activity was also observed for the
aqueous C. asiaticum leaf extract [304]. Both the leaves and bulbs of C. jagus are important
sources of antioxidant compounds [320]. A methanolic bulb extract of C. bulbispermum
showed mild radical scavenging activity [321]. The leaf extracts of C. bulbispermum also
showed modest antioxidant activity in a thiobarbituric acid reactive substances assay [297].
4.4.5. Other Pharmacological Properties
Kumar reported the wound healing activities of the ethanolic C. asiaticum extract.
The extract was found to possess pro-healing effects when topically applied on animal
models by influencing various stages of healing process [322]. C asiaticum extract and
norgalanthamine potentially influenced hair growth via inhibition of 5α-reductase activity
and TGF-β1-induced canonical pathway [39,314]. There is a report on the inhibitory effects
of three C. asiaticum genotypes against key enzymes implicated in the pathogenesis of
Alzheimer’s disease and diabetes [319].
The anti-obesity effect of the C. asiaticum extract on a high-fat diet-induced obesity in
monogenic mice has been reported [323,324]. An active fraction of C. jagus was shown to
possess anticonvulsant activities in experimental rats [325].
Ethyl acetate and methanol extracts of C. bulbispermum have also been shown to exhibit
acetylcholinesterase inhibitory properties [321]. The alkaloid galanthamine isolated from C.
bulbispermum and other genera of Amaryllidaceae, has been approved for the treatment
of Alzheimer’s disease [326]. Cognitive enhancing effect of a hydroethanolic extract of C.
macowanii against memory impairment induced by aluminum chloride in balb/c mice has
as well been reported [327].
5. The Genus Cyrtanthus
5.1. Botanical Description
Another large genus of the family Amaryllidaceae is Cyrtanthus. Cyrtanthus is derived
from a Greek word for curved flower [6]. Species of this genus have numerous, black,
winged seeds and give off a strong onion smell [6]. They possess a rhizome or bulb, flowers
and a loculicidal capsule fruit [6]. They have leaves that are linear to lorate [6]. Flowers
are funnel shaped with their stamens fixed in the corolla tube [6]. Species that belong to
this genus include Cyrtanthus elatus (C. elatus) (Jacq.) Traub, Cyrtanthus obliquus (C. obliquus)
(L.f.) Aiton, and Cyrtanthus mackenii (C. mackenii) Hook [44].
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5.2. Geographical Distribution
Cyrtanthus is diverse and is a large sub-Saharan Africa genus consisting of approximately 55 species found mostly in South Africa. Cyrtanthus extends from the summer-dry
southwest to the summer rainfall northeast [328]. The genus displays diverse floral morphology. The three major lineages show varying biogeographic affinities.
Clade A comprises taxa located in Southern African Grassland Biome with a few
outliers in the Savanna Biome to the east and north, the Indian Ocean Coastal Belt Biome to
the extreme east and the Fynbos Biome to the south [328]. Hence, it falls in the Afrotemperate Phytogeographical Region [329] that encompasses Afromontane phytochorion in
the north and the Cape Floristic Region in the south [328]. Most existing species in the
Afrotemperate lineage (Cyrtanthus attenuatus (C. attenuatus), Cyrtanthus macowanii (C. macowanii), Cyrtanthus epiphyticus (C. epiphyticus), C. mackenii subsp. cooperi, Cyrtanthus huttonii
(C. huttonii), Cyrtanthus macmasteri (C. macmasteri), Cyrtanthus suaveolens (C. suaveolens),
Cyrtanthus stenanthus (C. stenanthus var. stenanthus) and Cyrtanthus flanaganii (C. flanaganii)
occur currently in the south-eastern African temperate grasslands. Cyrtanthus tuckii var.
transvaalensis (C. tuckii) is the only species found in the grassland of the Highveld in the
northern parts of South Africa. Few species are found outside this grassland area and
includes Cyrtanthus angustifolius (C. angustifolius), Cyrtanthus fergusoniae (C. fergusoniae) and
Cyrtanthus aureolinus (C. aureolinus) in the Cape Region together with C. mackenii subsp.
Mackenii and Cyrtanthus brachyscyphus (C. brachyscyphus) that occupies drainage lines on the
subtropical Indian Ocean Coastal Belt [330]. Southern Africa is the area where Cyrtanthus
breviflorus (C. breviflorus) is found extending northwards in a series of disjunct populations
along mountain corridors to East Africa and Angola.
Clade B is limited to the Fynbos and Succulent Karoo Biomes which constitute the
Greater Cape Region, referred to hereafter as ‘the Cape’ [331]. Cyrtanthus labiatus (C.
labiatus) and Cyrtanthus montanus (C. montanus) from the Baviaansklo of Mountains and
Eastern Cape are found at the interface of the Fynbos and Albany Thicket Biomes. The
Richtersveld species, Cyrtanthus herrei (C. herrei) is found in the semi-arid Succulent Karoo [328]. Most species found in ‘the Cape’ lineage are located on the summer-dry, southeast
coast forelands with half the number in the Fynbos of the nonseasonal rainfall Eastern
Cape. Cyrtanthus carneus (C. carneus, C. elatus, Cyrtanthus guthrieae (C. guthrieae, C. labiatus,
Cyrtanthus leptosiphon (C. leptosiphon), Cyrtanthus leucanthus (C. leucanthus, Cyrtanthus montanus (C. montanus), and Cyrtanthus odorus (C. odorus) are found in specific vegetation types
and soils.
Only two species of this taxon, namely Cyrtanthus collinus (C. collinus) and Cyrtanthus
ventricosus (C. ventricosus) are well known, inhabiting the same soils and aspect in habitats
on the continuous Cape Fold mountain ranges [328]. Cyrtanthus collinus is found on the
coastal and inland mountains of the southern Cape and C. ventricosus extends from the
Cape Peninsula into the Eastern Cape [328].
Most species of Clade C are found in the eastern lowlands and midlands of southern Africa, where they are concentrated in the subtropical biomes, Albany Thicket and
Savanna [330,332]. This lineage constitutes Cyrtanthus flammosus (C. flammosus) and Cyrtanthus spiralis (C. spiralis), which are narrowly widespread to the Albany Thicket Biome.
Confined to the Savanna Biome are Cyrtanthus eucallus (C. eucallus) and Cyrtanthus galpinii
(C. galpinii) in the Lowveld. Other species span the Albany Thicket and Savanna Biomes: the
Eastern Cape Cyrtanthus helictus (C. helictus) and, extending northwards from the Albany
region through South Africa, Zimbabwe, western Mozambique and East Africa into Sudan,
is Cyrtanthus sanguineus (C. sanguineus) [328]. Cyrtanthus obliquus, adapted to nutrient-poor
soils, occupies rocky habitats in east–west tending valleys. A summary of their geographic
distribution is presented in Table 12.
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Table 12. Geographical distribution of the Genus Cyrtanthus.
Lineage
Location
Clade A
Southern Africa Grassland
Southeastern African temperate grasslands
Grassland of the Highveld in the northern parts
Subtropical Indian Ocean Coastal Belt
East Africa and Angola
Clade B
Baviaanskloof Mountains and Eastern Cape (Fynbos
and Albany Thicket Biomes)
Semi-arid Succulent Karoo
Greater Cape Region (“the Cape”)
Coastal and inland mountains of the southern Cape
Cape Peninsula into the Eastern Cape
Clade C
Albany Thicket Biome
Savanna Biome
Northwards from the Albany region through South
Africa, Zimbabwe, Western Mozambique and East
Africa into Sudan
Albany Thicket and Savanna Biomes
Extends beyond the Savanna Biome into the
Sub-Escarpment
and Highveld grasslands
Fynbos Biome
Southern parts of the Nama Karoo
Species
C. attenuatus, C. macowanii,
C. epiphyticus, C. mackenii subsp. cooperi, C. huttonii, C.
macmasteri, C. suaveolens, C. stenanthus var. stenanthus,
C. flanaganii
C. tuckii var. transvaalensis
C. angustifolius, C. fergusoniae
C. aureolinus, C. mackenii subsp. Mackenii, C.
brachyscyphus
C. breviflorus
C. labiatus, C. montanus
C. herrei
C. carneus, C. elatus, C. guthrieae, C. labiatus, C.
leptosiphon, C. leucanthus,
C. montanus, C. odorus
C. collinus
C. ventricosus
C. flammosus, C. spiralis
C. eucallus, C. galpinii
C. sanguineus
C. helictus
C. contractus
C. wellandii
C. smithiae
References
[328]
[328]
[328]
5.3. Traditional Uses
Cyrtanthus obliquus, locally known as umathunga in South Africa, is used traditionally
in the management of chronic coughs, headaches and scrofula [43,44]. C. obliquus root
infusions are also employed in the management of stomach aches [333] while the crushed
roots have been reported to find use in the management of leprosy [334]. Cyrtanthus species
are also employed in the management of ailments associated with pregnancy, as well as
cystitis, age-related dementia and leprosy [43,44]. Bulbs of C. contractus extracted in May
and September is widely used locally in the management of mental illness, infections,
inflammation, and cancer [335]. Infusions from species such as C. breviflorus, C. contractus,
C. mackenii, C. sanguineus, C. stenanthus and C. tuckii are used by the Zulu in South Africa as
protective sprinkling charms against storms and evil spirits [336]. Extracts of C. breviflorus
Harv. are used as an anti-emetic agent and in the management of worm infestations such
as tapeworm and roundworm. Extracts of C. elatus also finds use in the management of
cough, headache and in labour induction [337].
5.4. Phytochemistry of Cyrtanthus
Species of Cyrtanthus have been identified as reservoirs for a host of chemical compounds. In a study performed by Mahlangeni et al., four homoisoflavanones, namely 5,7dihydroxy-6-methoxy-3-(4′ -methoxybenzyl)chroman-4-one, 5,7-dihydroxy-6-methoxy-3(4′ hydroxybenzyl)chroman-4-one and two 5,7-dihydroxy-6-methoxy-3-(4′ -methoxybenzylidene)chroman-4-one, 5,7-dihydroxy-3-(4′ hydroxybenzylidene)-chroman-4-one were isolated from the hexane, methanol and dichloromethane extracts of Cyrtanthus obliquus [338].
The bulbs of C. obliquus extracted with ethanol also revealed the presence of novel alkaloid
obliquine, as well as 1α-hydroxygalanthamine, 3-epimacronine, narcissidine, tazettine and
trisphaeridine [339].
The presence of lycorine, tazettine and 11-hydroxyvittatine in dried bulb ethanol
extract of Cyrtanthus mackenii (Hook f.) has been demonstrated by Masi et al. [340]. Fresh
bulb methanol extracts of C. contractus also contains a phenanthridone alkaloid called
narciclasine [335]. Furthermore, two crinine alkaloids; haemanthamine and haemanthidine
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have been isolated from fresh bulb ethanol extracts of C. elatus. Further studies on the
alcoholic extracts of the fresh bulbs also yielded the alkaloids zephyranthine, galanthamine
and 1,2-O-diacetylzephyranthine [43,44]. Tazettine, maritidine, O-methylmaritidine, and
papyramine are all phytochemicals that have been identified in fresh bulb methanol extracts
of C. falcatus [337].
Chemical structure of compounds isolated from Cyrtanthus have been shown in Figure 6.
Figure 6. Chemical structures of selected compounds from Crytanthus. Zephyranthine (20),
1,2-O-diacetylzephyranthine (21), haemanthamine (22), haemanthadine (23), galanthamine (18),
ꞌ
ꞌ
′
5,7-dihydroxy-6-methoxy-3-(4′ -methoxybenzyl)chroman-4-one (24),
ꞌ 5,7-dihydroxy-6-methoxy-3-(4 methoxybenzylidene)chroman-4-one
(25), 5,7-dihydroxy-6-methoxy-3-(4′ hydroxybenzyl)chromanꞌ
′
4-one (26), 5,7-dihydroxy-3-(4 hydroxybenzylidene)-chroman-4-one (27) and naciprimine (28).
5.5. Pharmacological Activities
5.5.1. Antioxidant Activity
′
5,7-dihydroxy-6-methoxy-3-(4′ -methoxybenzyl)chroman-4-one and 5,7-dihydroxy-6′
methoxy-3-(4′ -hydroxybenzyl)chroman-4-one isolated from the fresh bulbs of C. obliquus
have been shown to possess significant antioxidant activity with an IC50 of 371.54 and
288.40 µg/mL, respectively [338].
5.5.2. Anti-Inflammatory Activity
The methanol extract of the bulbs of C. contractus has been investigated and shown
to possess significant anti-inflammatory activity. The extract exhibited dose-dependent
inhibition of E-selectin, a proinflammatory agent, when tested on endothelial cells. Further
studies of the methanol extract on human umbilical vein endothelial cells revealed a
concentration-dependent reduction in THP-1 adhesion via blockade of the expression
of endothelial adhesion molecule ICAM-1. Narciclasine was identified as the main antiinflammatory compound in the methanol extract of the bulbs of C. contractus [335].
The dichloromethane (DCM) extracts of C. falcatus (roots) and C. mackenii (leaves)
were shown to interfere with the activity of cyclooxygenase 2 (COX-2) by at least 90%.
DCM extract of C. suaveolens also blocked prostaglandin synthesis via antagonizing COX-2
activity by 81.6 %. Moderate inhibition (approximately 70%) of COX-2 activity was also
observed with the methanol extracts of the roots and leaves of C. falcatus [341,342]. Selective
inhibition of COX-2 by these extracts makes them suitable candidates for development for
clinical use.
5.5.3. Inhibition of Acetylcholinesterase
The phenanthridone alkaloid nacriprimine, isolated from the ethanolic bulb extract of
C. contractus has been shown to possess mild acetylcholinesterase inhibition property with
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an IC50 of 78.9 µg/mL compared to the 40-fold more potent standard galanthamine with
an IC50 of 1.9 µg/mL [11].
5.5.4. Antimicrobial Activity
Cyrtanthus species and their isolated compounds have demonstrated noteworthy
antimicrobial activity against a panel of microorganisms. C. suaveolens bulbs/roots and
leaves isolated with DCM demonstrated broad-spectrum antimicrobial activity against
B. subtilis, E. coli, K. pneumoniae, M. luteus and S. aureus with zones of inhibition ranging
between 0.13–0.91 mm. DCM extracts of C. falcatus also inhibited the growth of B. subtilis S.
aureus and E. coli. C. mackenii bulb/root extracts also inhibited the growth M. luteus and S.
aureus [337].
Haemanthamine and haemanthidine isolated from the bulbs of C. elatus have been
investigated for their activity against parasitic protozoans [43]. Haemanthamine showed
activity against trophozoite stage of Entamoeba histolytica (E. histolytica) HK9 with an IC50
of 0.75 µg/mL and mild activity against Plasmodium falciparum (P. falciparum) NF54 with
an IC50 of 0.67 µg/mL. The activity against E. histolytica was compared to ornidazole with
an IC50 0.28 µg/mL whiles the activity against P. falciparum was compared to chloroquine
with an IC50 of 0.004 µg/mL and artemisinin with an IC50 of 0.002 µg/mL [43].
Haemanthidine also showed weak activity against P. falciparum, T. brucei rhodesiense
STIB 900, and T. cruzi Tulahuen C4 with an IC50 of 0.70, 1.1 and 1.38 µg/mL, respectively.
Melarsoprol with an IC50 of 0.002 µg/mL and benznidazole with an IC50 of 0.56 µg/mL
were used as standards for Trypanosoma brucei rhodesiense STIB 900, and Trypanosoma cruzi
Tulahuen C4, respectively [43].
5.5.5. Cytotoxic Activity
Haemanthamine isolated from C. elatus was shown to possess cytotoxic activity which
was mediated via the apoptotic pathway as depicted in rat hepatoma cell (5123tc). The ED50
was determined at 15 µM and this result was of particular interest due to its selectivity;
haemanthamine demonstrated insignificant activity in normal human embryo kidney (293t)
cells [337].
Alkaloids isolated from C. obliquus tested for cytotoxic activity against Chinese Hamster ovarian and human hepatoma (hepG2) cells showed no cytotoxic activity up to a
concentration of 100 µg/mL [339].
Tazettine isolated from C. falcatus and other members of Amaryllidaceae has been
reported to possess cytotoxic activity on colon cell line murine alveolar non-tumoral fibroblast [343,344]. Papyramine, also extracted from C. falcatus showed cytotoxic activity against
murine alveolar non-tumoral fibroblast and human lymphoid neoplasm as well [343,344].
5.5.6. Miscellaneous Pharmacological Activities
Roots of C. falcatus and C. surveolens extracted with DCM exhibited mutagenicity in
Salmonella strain TA98 which was higher than that observed in the leaves of these plants.
Mutagenicity was, however, not observed in the methanol extracts of these plants [337].
The mutagenicity of C. suaveolens has been attributed to the compound captan isolated
from the bulbs/roots using DCM [344].
A summary of the traditional uses, phytochemicals and pharmacological activities of
Cyrtanthus species have been highlighted in Table 13.
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Table 13. A summary of the traditional uses, phytochemicals and pharmacological activities of
Cyrtanthus species.
Plant Species
C. obliquus
Traditional Uses
Compounds
Pharmacological Activities
References
Chronic cough, headache
and scrofula
5,7-dihydroxy-6-methoxy-3-(4′ methoxybenzyl)chroman-4-one,
5,7-dihydroxy-6-methoxy-3-(4′ hydroxybenzyl)chroman-4-one
Antioxidant activity
[338]
[337]
C. contractus
Mental illness, protective charm
against evil spirits
NarciclasineNarciprimine
Anti-inflammatory activity (via
inhibition of E-selectin, blockade of
the expression of endothelial
adhesion molecule
ICAM-1)Acetylcholinesterase
inhibitor
C. breviflorus
Emesis, worm infestations,
protective charm against
evil spirits
haemanthamine, lycorine, crinamine
hydrochloride and tazettine
Antihelminthic
[337,342]
C. elatus
Cough, headache,
labor induction
Antiprotozoan activity, selective
cytotoxic activity
[43,44,337]
C. falcatus
Not known to be used by the
traditional South African people
C. suaveolens
No traditional use has
been reported
Haemanthamine, zephyranthine,
galanthamine and
1,2-O-diacetylzephyranthine
Papyramine, epipapyramine,
maritidine, O-methylmaritidine and
tazettine
Captan
Antibacterial activity against B.
subtilis S. aureus and E. coli,
mutagenicity, cytotoxic activity
Mutagenicity, anti-inflammatory
activity via inhibition of
COX-2, fungicide
[342–344]
[342,344]
6. Conclusions
The discovery of new drugs in response to the growing burden of infectious and
non-communicable diseases is of utmost necessity in this era. The genera Tulbaghia, Allium, Crinum, and Cyrtanthus of the Amaryllidaceae family have been well presented and
shown to be a source of promising medicinal compounds with varying biological properties. Further research is therefore necessary to propel these compounds through clinical
trials for possible usage in therapeutics. Although natural products have been attributed
with high safety profiles, the presence of mutagenic compounds in crude extracts of these
plants underscores the importance of pharmacological studies prior to their use in traditional medicine. These findings are relevant in light of augmenting the lean pipeline of
drug discovery.
Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/molecules27144475/s1, Table S1: Compounds from Tulbaghia.
Reference [345] is cited in the Supplementary Materials.
Author Contributions: Conceptualization and study design, C.A.D. and P.A.B.M.; literature search
and review, C.A.D., P.A.B.M., T.A.A., P.M., M.O., P.D., S.R., I.O.D.J., K.B.A., S.O.S., I.N.N., V.J.M.,
S.B. and S.G.; writing—original draft preparation, C.A.D., P.A.B.M., T.A.A., P.M., M.O., P.D., S.R.,
I.O.D.J., K.B.A., S.O.S., I.N.N., V.J.M., S.B. and S.G.; writing—review and editing, C.A.D., P.A.B.M.,
P.M., I.O.D.J., V.J.M., S.B. and S.G.; formatting and design—P.A.B.M. and P.M.; project administration,
C.A.D. and P.A.B.M.; supervision, C.A.D. All authors have read and agreed to the published version
of the manuscript.
Funding: The authors received no specific grant from the government, private or non-profit organizations.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
Molecules 2022, 27, 4475
36 of 48
Abbreviations
MIC, minimum inhibitory concentration; MBC, minimum bactericidal concentration;
MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide; MoA, mode of action;
ROS, reactive oxygen species; TEAC, Trolox equivalent antioxidant capacity; FRAP, ferricreducing antioxidant power; DPPH, 2,2-diphenyl-1-picryl-hydrazyl-hydrate; AAPH, 2,2′ azobis-2-amidinopropane dihydrochloride; TG, triglyceride; TC, total cholesterol; VLDL,
very low-density lipoprotein; HDL, high-density lipoprotein; BP, blood pressure; AVD,
atherothrombotic vascular disease; DCM, dichloromethane.
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