plants
Systematic Review
The Genus Cynometra: A Review of Ethnomedicine, Chemical,
and Biological Data
Shabnam Sabiha 1 , Rita Serrano 1 , Kamrul Hasan 1 , Isabel B. Moreira da Silva 1 , João Rocha 1 ,
Nurul Islam 2 and Olga Silva 1, *
1
2
*
Citation: Sabiha, S.; Serrano, R.;
Hasan, K.; Moreira da Silva, I.B.;
Rocha, J.; Islam, N.; Silva, O. The
Genus Cynometra: A Review of
Ethnomedicine, Chemical, and
Biological Data. Plants 2022, 11, 3504.
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa,
1649-003 Lisbon, Portugal
Department of Zoology, Faculty of Biological Sciences, University of Rajshahi, Rajshahi 6205, Bangladesh
Correspondence: osilva@edu.ulisboa.pt; Tel.: +351-217-946-400
Abstract: Cynometra L. is a Fabaceae genus that is widely distributed throughout the tropics, consisting
of tropical forest trees with ecological and economic importance since they are used as food and
herbal medicines by the populations of their natural habitats. Our goal is to provide a review of the
research data concerning the potential of this botanical genus as a source of herbal medicines and
secondary metabolites that are useful for human health. To that end, scientific databases, including
PubMed, Science Direct, ISI Web of Science, Scopus, and Google Scholar, were searched using
the following terms: Cynometra, medicine, chemical, biological activity, toxicity, and “AND” as
the Boolean connector. Eleven Cynometra species (9.7%) were reported to be used in traditional
medicine to treat different ailments. A total of 185 secondary metabolites of various chemical classes,
mainly flavonoids and terpenoids, were identified in eight Cynometra species (7.1%). Vitexin was
the only flavonoid identified as bioactive in the sequence of bioguided studies on this botanical
genus. Ten species (8.8%) were submitted to in vitro and in vivo biological activity assays. The main
evaluated activities were in vitro antioxidant, antimicrobial, cytotoxic, and in vivo anti-inflammatory
activities, but no human clinical trials or safety data about this genus were found. Cynometra cauliflora
and Cynometra ramiflora were the most studied species. The present work confirms the use of
Cynometra species as a source of medicinal plants. However, more experimental studies must be
conducted to better understand this botanical genus’s usefulness as a source of raw materials for
pharmaceutical use.
https://doi.org/10.3390/
plants11243504
Academic Editor: Ain Raal
Keywords: antimicrobial; anti-inflammatory; Cynometra; cytotoxic; herbal medicines; secondary
metabolites; traditional medicine
Received: 14 November 2022
Accepted: 6 December 2022
Published: 14 December 2022
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4.0/).
1. Introduction
The genus Cynometra L. is a species-rich genera in the most significant tropical family
Fabaceae (Leguminosae) and subfamily Detarioideae, described for the first time in 1741 by
Linnaeus and included in the first edition of Species Plantarum (published in 1753) [1]. This
botanical genus has a wide distribution and high diversity. It is classified using regional
groupings of species (the Neotropics, Tropical Africa, Madagascar, the Comoros Islands,
and the Indo-Pacific groups) [1–3]. According to phylogenetic studies, the Cynometra genus
is polyphyletic [4–8].
According to the data of Plants of the World Online (https://powo.science.kew.org/;
accessed on 5 November 2021) [9], The plant list (http://www.theplantlist.org/; accessed
on 1 June 2021) [10], the World Flora Online (WFO) (http://www.worldfloraonline.org./;
accessed on 1 January 2022) [11], and the Global Biodiversity Information Facility (GBIF)
(https://www.gbif.org/; accessed on 1 January 2022) [12], the genus Cynometra integrates
113 species (Table 1) of shrubs to large trees. It has a broad tropical distribution [9]. They
grow in tropical lowland, rain, and swamp forests, often along rivers and sublittoral zones,
Plants 2022, 11, 3504. https://doi.org/10.3390/plants11243504
https://www.mdpi.com/journal/plants
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and seasonally also in dry forest, woodland, bushland, or thickets, often on white sands.
Some species grow gregariously, forming dominant stands; some are prominent mangrove
species. [9,13].
Concerning the status of Cynometra species and based on the Red List of Threatened
Species of the International Union for the Conservation of Nature (IUCN) [14], 36% of these
species are considered as not evaluated (NE), 29% as least concern (LC), 19% as endangered
(EN), 6% as vulnerable (VU), and 5% as near threatened (NT). Additionally, 3% and 2% are
referred to as data deficient (DD) and critically endangered (CR), respectively (Figure 1).
— evaluated, DD—data
— deficient, LC—least
—
Figure 1. Conservation status of Cynometra species. NE—not
—
—
— endangered.
concern, NT—near—threatened, VU—vulnerable,
EN—endangered,
CR—critically
Cynometra species are generally recognized as used in traditional medicine in the
countries where they exist as part of the spontaneous flora. Traditional practitioners usually
prepare medicine from different plant parts and by different modes of preparation to treat
various ailments. However, it should be noted that only a little information was available
related to the concrete use for the treatment of different pathological signals or symptoms
and their chemical, pharmacological, and toxicological properties. So, to gain and give a
clear idea about a genus, it is very important to collect, arrange, and review all necessary
information concerning medicinal importance of the genus.
In the present work, a revision of the ethnomedical, chemical, pharmacological, and
toxicological data on the genus Cynometra is presented and discussed to better characterize
the potential of this botanical genus as a source of medicinal plants and traditional herbal
medicines, and as a source of natural products that could be useful for the development of
new drugs.
Table 1. Cynometra species.
Cynometra Species
C. abrahamii Du Puy & R. Rabev.
C. craibii Gagnep.
C. hemitomophylla (Donn. Sm.) Rose
C. alexandri C.H. Wright
C. crassifolia Benth.
C. hondurensis Dwyer
C. americana Vogel
C. cubensis A.Rich.
C. hostmanniana Tul.
C. ananta Hutch. & Dalziel
C. cuneata Tul.
C. humboldtiana Stergios
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Table 1. Cont.
Cynometra Species
C. ankaranensis Du Puy & R.Rabev.
C. cynometroides (Merr. &
L.M.Perry) Rados.
C. inaequifolia A.Gray
C. aurita R.Vig.
C. dauphinensis Du Puy & R. Rabev.
C. insularis A.C.Sm.
C. basifoliola (Verdc.) Rados.
C. dongnaiensis Pierre
C. iripa Kostel.
C. bauhiniifolia Benth.
C. letestui (Pellegr.) J. Léonard
C. polyandra Roxb.
C. beddomei Prain
C. longicuspis Ducke
C. portoricensis Krug & Urb.
C. bourdillonii Gamble
C. longifolia Huber
C. psilogyne (Harms) Rados.
C. brachymischa Harms
C. longipedicellata Harms
C. ramiflora L.
C. brachyrrhachis Harms
C. lujae De Wild.
C. retusa Britton & Rose
C. brassii (Merr. & L.M. Perry) Rados.
C. lukei Beentje
C. rosea (K.Schum.) Rados.
C. browneoides (Harms) Rados.
C. lyallii Baker
C. roseiflora W.E.Cooper
C. capuronii Du Puy & R.Rabev.
C. macrocarpa A.S.Tav.
C. sakalava Du Puy & R.Rabev.
C. cauliflora L.
C. madagascariensis Baill.
C. sanagaensis Aubrév.
C. cebuensis F.Seid.
C. malaccensis Meeuwen
C. schefferi (K.Schum.) Rados.
C. cerebriformis Rados.
C. mannii Oliv.
C. schlechteri Harms
C. commersoniana Baill.
C. marginata Benth.
C. schottiana Hochr.
C. congensis De Wild.
C. mariettae (Meeuwen) Rados.
C. sessiliflora Harms
C. copelandii (Elmer) Merr.
C. marleneae A.S.Tav.
C. simplicifolia Harms
C. duckei Dwyer
C. mayottensis Labat & O. Pascal
C. sphaerocarpa Pittier
C. dwyeri Rados.
C. megalocephala (Harms) Rados.
C. steenisii (Meeuwen) Rados.
C. elmeri Merr.
C. megalophylla Harms
C. stenopetala Dwyer
C. engleri Harms
C. michelsonii J.Léonard
C. steyermarkii Rados.
C. falcata A.Gray
C. minor (A.C. Sm.) Rados.
C. suaheliensis (Taub.) Baker f.
C. filifera Harms
C. minutiflora F.Muell.
C. travancorica Bedd.
C. fissicuspis (Pittier) Pittier
C. mirabilis Meeuwen
C. trinitensis Oliv.
C. floretii Labat & O.Pascal
C. novoguineensis Merr. & L.M.Perry
C. tumbesiana Rados.
C. fortuna-tironis (Verdc.) Rados.
C. nyangensis Pellegr.
C. ulugurensis Harms
C. gillmanii J.Léonard
C. oaxacana Brandegee
C. vestita (A.C.Sm.) Rados.
C. glomerulata Gagnep.
C. oddonii De Wild.
C. vitiensis Rados.
C. grandiflora A.Gray
C. palustris J.Léonard
C. vogelii Hook.f.
C. greenwayi Brenan
C. parvifolia Tul.
C. warburgii Harms
C. hankei Harms
C. pedicellata De Wild.
C. webberi Baker f.
C. katikii Verdc.
C. pervilleana Baill.
C. yokotae Kaneh.
C. lenticellata (C.T.White) Rados.
C. phaselocarpa (B.Heyne)
J.F.Macbr./C. spruceana Benth.
C. zeylanica Kosterm.
C. leonensis Hutch. & Dalziel
C. plurijuga (Merr. & L.M.Perry) Rados.
Adapted from: [9–12].
2. Results and Discussions
2.1. Selection of the Information
Details of data collection and choice are given in Figure 2. The initial titles and
abstract search yielded 8309 results. After excluding duplicates, 4980 scientific publications
were reviewed for eligibility. Of those, 4895 scientific publications were excluded for
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the following reasons: repeated results, no relation to medicinal issues, and inclusion of
irrelevant or incomplete information. Finally, a total of 85 scientific publications were
considered eligible to be included in this review. The inclusion criteria were publications
related to Cynometra genus; abstracts or full texts in English; and studies on Cynometra
species concerning medicinal importance. In Figure 3, the number of selected scientific
publications according to the respective publication years is presented.
Figure 2. Data screening based on PRISMA methodology.
2.2. Ethnomedicinal Data
Eleven Cynometra species, i.e., C. brachyrrhachis, C. capuronii, C. cauliflora, C. hankei, C.
iripa, C. manii, C. megalophylla, C. ramiflora, C. spruceana, C. vogelii, and C. webberi, have been
reported for their ethnomedicinal uses (Table 2). The leaf, fruit, seed, stem, bark, resin,
and root of these species are traditionally used for the treatment of digestive disorders,
respiratory problems, skin, and inflammatory diseases. For example, the decoction of the
C. cauliflora leaf is used to treat diabetes and hyperlipidemia [15]; however, in Indonesia,
the fruit of this species is used as food, and the leaf is used as medicine for the treatment of
diarrhea [16].
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Figure 3. Number of selected Cynometra scientific publications by year.
Table 2. Ethnomedicinal uses of the genus Cynometra.
Species
Part Used
Country
Traditional Uses
Method of
Preparation
Refs.
C. brachyrrhachis
root
Tanzania
fungal infections
not available
[17]
C. capuronii
leaf
Madagascar
yellow fever
decoction
[18]
leaf
Indonesia
diarrhea
not available
[16]
leaf
Malaysia
hyperlipidemia and diabetes
decoction
[15,19]
fruit
Malaysia
loss of appetite
seed oil
India
skin diseases
stem bark
Africa
dental pain and rheumatism
leaf, seed, stem
India
wound healing
leaf
India
ulcers
seed oil
India
cholera
[24]
stem
Nigeria
to suppress swelling in the cheeks
[25]
bark
Nigeria
cancer
seed
Nigeria
fibroid treatment
leaf
Benin
stomach infections
[28]
leaf, root
India
purgative, skin diseases
[29]
whole plant
Bangladesh
skin diseases
C. spruceana
resin
Brazil
weakness of the lungs,
tuberculosis, chronic cough
C. vogelii
stem
Nigeria
oral hygiene
C. webberi
root
Tanzania
skin diseases
C. cauliflora
C. hankei
C. iripa
C. manii
C. megalophylla
C. ramiflora
is
[20]
not available
[21]
[22]
decoction
not available
powder
[23]
e
[26]
[27]
[30]
[31]
not available
[32]
[17]
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The leaf was found to be the most used Cynometra plant part for medicinal purposes.
The decoction and powder are mainly used in the preparation of herbal medicine.
According to our results, among the total number of 113 Cynometra species, only 9.7%
have been recorded for their traditional uses (Table 2).
2.3. Chemical Compounds
In Table 3, the main compounds isolated and identified from the studied chemicals
of eight Cynometra species (7.1%) are presented. Flavonoids and terpenoids are the major
chemical classes reported on this botanical genus beside fatty acids, alkaloids, esters, and
other phenol derivatives. C. cauliflora was the most studied plant species.
The presence of tannins, flavonoids, and terpenoids was reported in the aqueous
extracts of stem, bark, and leaf [19], as well as in a methanolic extract of C. cauliflora
leaf [33]. Cardiac glycosides were present in the different parts of the plant, except on the
stem [19]. Ethanol extract of C. ramiflora leaf was revealed to contain alkaloids, phenolic
compounds, and terpenoids (saponins and steroids) [34,35]. The existence of tannins
was found in the ethanol, hexane, and dichloromethane extracts of the stem and root of
C. vogelli [32]. Preliminary phytochemical screening of an ethanolic extract of C. malaccensis
leaf, twig, and stem bark showed the presence of flavonoids, terpenoids, and high content
of tannins. [36]. The presence of alkaloids in the leaf and stem [37] and different type of fatty
acids in leaf and seed [38] have been reported in C. iripa. Basak et al. (1996) also noted the
presence of chlorophyll, carotenoids, proteins, polyphenols, and tannins in the seed of this
species [39]. The existence of phenol derivatives, including gallotannins, leucoanthocyanins
and anthraquinones, and of saponins and steroids were reported from C. capuronii leaf [18].
In the essential oil of C. cauliflora leaf, twig, and fruit twenty-six, seventeen, and fifty
compounds (mainly monoterpenoids and sesquiterpenoids) were identified, respectively.
For the leaf oil, the major constituents were α-terpineol (34.62%), (z)-β-ocimene (20.77%),
and γ-terpinene (12.27%); meanwhile, trans-sabinene hydrate (58.77%), an oxygenated
monoterpenoid, dominated the twig oil. On the other hand, oxygenated sesquiterpenoids
were predominant in the fruit essential oil, accounting for 65.48% of the total essential oil
content [40]. Different flavonoids such as apigenin, xanthotoxin, catechin, cyanidin, and
vitexin [15,41], have also been identified in the leaf of this species (Table 3).
From the C. megalophylla root essential oil, 43 compounds were identified. Monoterpenoids were the major constituents of it, namely, α-phellandrene (32.0%), p-cymene (18.2%),
and γ-terpinene (12.1%) [42].
Gartlan et al. (1980) reported the presence of cyanidin in the mature leaf and seed of C.
hankei [43].
At least 14 fatty acids were found in the oil of C. iripa seed, while 10 fatty acids were
in the leaf oil. Linoleic acid (34.2%) was prominent in seed oil, and palmitic acid (33.5 %)
was prominent in leaf oil [38].
The presence of imidazole alkaloids that are characteristic of this botanical genus
were noticed in C. anata (leaf) [44], C. hankei (stem bark and seed) [45], and C. lujae (not
indicated) [44]. In Figure 4, some examples of imidazole alkaloids are given.
Some chemical studies related to the quantification of representative secondary metabolites classes were also performed. The total phenolic content (TPC) of a young leaf of
C. cauliflora was found to be 1831.47 ± 1.03 mg GAE (gallic acid equivalent)/g, and the total
flavonoid content (TFC) was found to be 33.63 ± 0.25 mg CE (catechin equivalent)/g [19].
However, the ethanol extract of the leaf and fruit of C. cauliflora was reported to have TPC
344.17 ± 10.80 and TPC 122.04 ± 3.17 mg GAE/g plant extract [46,47]. The methanol and
aqueous extracts of C. cauliflora fruit showed a TPC of 1868.94 ± 11.68 (mg GAE/100 g
edible portion) and of 1.30 ± 0.10 (mg GAE/g dry weight), respectively, [48,49], whereas
in another study, the aqueous extract of this species showed TPC 4.6 ± 0.06 mg GAE/g
dry weight. The TMAC (total monomeric anthocyanin content) and vitamin C content of
C. cauliflora fruit aqueous extract were 8.66 ± 1.68 and 21.8 ± 0.33, respectively [50]. In a recent study, Abeysuriya et al. (2020) reported low content of vitamin C (37.9 ± 1.8 mg/100 g
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fresh weight) from seedless fruit extract of C. cauliflora (extraction solvent: 3% (w/v)
meta-phosphoric acid and 8% (v/v) glacial acetic acid) and medium TPC (428.5 ± 1.3 mg
GAE/100 g fresh weight) and TFC (26.1 ± 1.0 mg QE (quercetin equivalent)/100 g fresh
weight) from MeOH (methanol) extract of the same [51].
In a methanol extract of C. ramiflora stem, TPC, TFC, and total tannins content were
found to be 96.2 mg GAE/g, 166.4 mg QE/g, and 80.4 mg GAE/g dry weight, respectively [52].
Table 3. Chemical compounds identified from Cynometra species.
Species
Part Used
Chemical Class
Compounds
Ref.
C. anata
leaf
Alkaloids
anantine, cynometrine and cynodine
[44]
leaf
Flavonoids
xanthotoxin, fraxetin, capensine, naringenin, malvidin, cyanidin,
amorphigenin, nobiletin, isorhamnetin, epigallocatechin, gallate,
apigenin, and oenin
[41]
stem
Flavonoids
apigenin
[53]
twig
Flavonoids
naringenin, eriodictyol, apigenin, acacetin, luteolin, luteolin 3’,5
dimethyl ether, 3’,4’,7-trihydroxyflavone, 4’,7-dihydroxyflavone
and 5,7-dihydroxychromone
[54]
Monoterpenoids
α-thujene, α-pinene, β-pinene, myrcene, δ-3-carene, α-terpinene,
p-cymene, limonene, (z)-β-ocimene, γ-terpinene, terpinolene, linalool,
α-terpineol, neo-dihydrocarveol, cis-carvone oxide,
trans-dihydro-a-terpinyl acetate
Sesquiterpenoids
α-bulnesene, β-chamigrene, α-himachalene, trans-cadin-1,4-diene
Phenols
p-vinyl guaiacol
Hydrocarbons
(3E)-2-methyl-octen-5-yne
Monoterpenoids
(z)-β-ocimene, santolina alcohol, (E)-cis-jasmonol, cis-verbenol, linalool,
geraniol, cis-4-caranone, trans-sabinene hydrate, dihydromyrcenol
Sesquiterpenoids
squamulosone, occidol acetate, α-eudesmol acetate
Fatty acids
octanoic acid, decanoic acid, dodecanoic acid, linoleic acid
Flavonoids
fragranol
Sesquiterpenoids
β-cubebene, β-elemene, α-guaiene, prezizaene, ishwarane,
β-chamigrene, germacrene d, α-muurolene, β-bisabolene, α-bulnesene,
γ-cadinene, (E)-γ-bisabolene, γ-cuprenene, trans-cadina-1,4-diene,
selina-3,7(11)-diene, 9-epi-(E)-caryophyllene, α-chenopodiol,
longiborneol, trans-β-elemenone, α-acorenol, agarospirol, occidenol,
cryptomerione, curcumenol, hinesol, nootkatol, sesquisabinene,
α-muurolol, β-calacorene, γ-eudesmol, elemol, eremoligenol, (2E,6E)farnesol, (E)-nuciferol, (z)-lanceol, 11-αH-himachal-4-en-1-β-ol, globulol,
cubebol, longipinanol, valerianol, allohimachalol, epi-β-bisabolol,
occidol acetate, longiborneol acetate
Monoterpenoids
limonene, cis-thujone, trans-pulegol, cis-β-farnesene
Fatty acids
linoleic acid
Condensed
tannins
procyanidin trimer, procyanidin tetramer, procyanidin hexamer
Flavonoids
catechin, taxifolin pentoside, vitexin, isovitexin, kaempferol hexoside,
quercetin pentoside, quercetin hexoside,
apigenin-6-C-glucoside-8-C-glucoside, kaempferol–coumaroyl hexoside
and isorhamnetin hexoside
leaf
twig
C. cauliflora
fruit
leaf
[40]
[15]
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Table 3. Cont.
Species
C. hankei
Part Used
Chemical Class
Compounds
Ref.
Leaf, seed
Flavonoids
cyanidin
[43]
stem bark,
seed
Alkaloids
N1 -demethyl cynometrine, N1 -demethyl cynodine, cynometrine, and
cynodine
[45]
Fatty acids
leaf—lauric acid, myristic acid, pentadecanoic acid, palmitic acid,
stearic acid, arachidic acid, behenic acid, oleic acid and cis-11-eicosenoic
acid, linolenic acidseed—caproic acid, lauric acid, myristic acid,
palmitic acid, stearic acid, arachidic acid, behenic acid, tricosanoic acid,
lignoceric acid, oleic acid, linoleic acid, linolenic acid, cis-8, 11,
14-eicosatrienoic acid, cis-13, 16-docosadienoic acid
[38]
Triterpenoids
squalene, β-sitosterol, stigmast-4-en-3-one,
cholesta-4,6-diene-3-ol (3-beta)
Tetraterpenoids
β-carotene
Esters
1,2-benzenedicarboxylicacid mono (2-ethylexyl) ester, butyric acid
2-pentadecyl ester, 1,2-benzenedicarboxylic acid butyl 2-ethylhexyl ester
Fatty alcohols
1-eicosanol, falcarinol
Quinones
2,5-di-ter-butyl-1,4-benzoquinone
Phenolic
aldehydes
3,5-di-ter-butyl-4-hydroxybenzaldehyde
Vitamins
vitamin E
Hormones
progesterone
Alkaloids
anantine, cynometrine, isoanantine, isocynometrine, isocynodine
noranantine, hydroxyanantine and cynolujine
Monoterpenoids
α-pinene, α-thujane, sabinene, β-pinene, myrcene, α-phellandrene,
α-terpinene, p-cymene, limonene, β-phellandrene, (E)-β-ocimene,
γ-terpinene, terpinolene, 1,8-cineole, cis-p-menth-2-en-1-ol,
trans-p-menth-2-en-1-ol, borneol, terpinen-4-ol, carvacrol, p -cymen-8-ol,
trans-piperitol, terpinen-4-yl acetate
Sesquiterpenoids
caryophyllene oxide, α-eudesmol, β-eudesmol, hinesol, globulol,
β-selinene, germacrene D, allo-aromadendrene, α-humulene,
α-guaiene, β-caryophyllene
Hydrocarbon
decane, dodecane, undecane, N-tridecane, tetradecane, pentadecane,
hexadecane, heptadecane, octadecane
Triterpenoids
glutinol, glutinone, β-sitosterol
Ester
ethyl 4- ethoxy benzoate
Sesquiterpenoids
β-caryophyllene, α- and β-selinene
Fatty acid
isopropyl palmitate
leaf, seed
oil
C. iripa
seed, seed
coat
C. lujae
C. megallophylla
not
indicated
root oil
C. ramiflora
leaf
C. vogelii
leaf oil
[55]
[44]
[42]
[56]
[57]
2.4. Biological Studies
Results of the in vitro and in vivo biological activity tests made on the Cynometra
genus are summarized in Table S1 (please consult our supplementary data, all references
are orderly according to its occurrence on this table). A total of ten species (8.8%), namely, C.
bauhiniifolia, C. brachyrrhachis, C. cauliflora, C. cloiselii, C. iripa, C. madagascariensis, C. ramiflora,
C. spruceana, C. travancorica, and C. vogelii, were studied. Among them, C. cauliflora and
C. ramiflora were found to be the most important species concerning biological activities.
Methanol and ethanol were mostly used as extraction solvents, and leaf and fruit were the
most important plant parts to show different biological activities.
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Figure 4. Examples of Imidazole alkaloids (a) anantine, (b) cynometrine, and (c) cynodine identified
on Cynometra species.
The leaf and fruit of C. cauliflora were the most biologically tested plant parts of
this species:
A methanol leaf extract showed significant antioxidant [15,60,62,63]; antibacterial
(against Staphylococcus aureus, Escherichia coli, Porphyromonas gingivalis, and methicillinresistant Staphylococcus aureus [33,62,67]); anti-viral (against herpes simplex virus type
1) [71]; anti-diabetic; antidiarrheal (in vivo) [63]; and cytotoxic potentiality against brine
shrimp (Artemia salina) and Vero cells [71,72]. An ethanol leaf extract showed anti-inflammatory
activity by inhibiting the activities of arachidonate-5-lipoxygenase and hyaluronidase [64].
In addition, the same extract exhibited strong antioxidant and high inhibitory alphaglucosidase activities [46], as well as moderate cytotoxic activity (against HeLa cancer
cells) [74]. Moreover, this extract and vitexin, a flavonoid isolated from this medicinal
plant, were observed to be involved in its in vivo anti-obesity and lipid-lowering activities [69], and an aqueous leaf extract showed antioxidant and potent anti-diabetic activity
in vivo [65,73].
A methanol extract of the fruit exhibited cytotoxic activity (against human promyelocytic leukemia HL-60 and normal mouse fibroblast NIH/3T3 cell lines) and low antioxidant
activities [46,59]. A fruit’s hexane, chloroform, ethyl acetate, ethanol, methanol, and aqueous extracts showed antifungal activity against four species of yeasts (Candida albicans,
Candida parapsilosis, Candida krusei, and Cryptococcus neoformans), and two species of filamentous fungi (Aspergillus fumigatus and Trichophyton interdigitale) [66]. In two other studies,
the fruit aqueous extract showed significant antioxidant activity [49,50]. In contrast, the
methanol extract of the same plant part showed a low antioxidant activity [48].
Concerning C. cauliflora, the stem and the essential oils were also studied:
The stem ethyl acetate and methanol extracts showed, strong antioxidant and anticholinesterase activities (>80% inhibition), respectively [53,68].
The essential oils obtained from leaves, twigs, and fruits showed antioxidant activity,
’s
whereas the observed twig oil was more active than the oil from the other plant parts and
showed significant antibacterial and cytotoxic activities (against MCF-7 cells) [40].
C. ramiflora was also one of the main Cynometra species studied, and the leaf was the
most used plant part:
A methanol extract of this medicinal plant showed significant antihyperglycemic
activity [80], low anti-ulcer activity (13.9% inhibition) [35], antioxidant activity [86], and
cytotoxic activity (against brine shrimp) [52].
Plants 2022, 11, 3504
10 of 14
An ethanol extract exhibited cytotoxic activity (against HeLa, T47D, and WiDr cell
lines) [85,87], low antiproliferative activity (against MCF-7 cell), and weak antimicrobial
activity against Escherichia coli and Bacillus subtilis [82,89].
An ethyl acetate fraction of a C. ramiflora seed methanol extract (fractioned) showed
strong antioxidant and anti-lipid peroxidation activities [79], and a methanol extract of
C. ramiflora bark showed low toxicity against mouse fibroblasts [81]. Additionally, the
methanolic and an ethanol extract of C. ramiflora bark showed antibacterial activity (against
Vibrio cholerae, Salmonella typhi, Staphylococcus aureus, Escherichia coli, Shigella dysenteriae,
Shigella sonnei, Shigella boydii, Shigella flexneri, Enterococci, Staphylococcus epidermis, and
Pseudomonas aeruginosa) [83,84]. Moreover, the bark methanol extract exhibited in vivo
antinociceptive activity [83].
2.5. Toxicity
Only one study had been found concerning the toxicity of Cynometra medicinal plants
and preparations. In this study, the authors reported that C. ramiflora leaf ethanolic extracts
at 1000 and 1500 mg/kg BW (body weight) doses cause in vivo inflammation in the rat
kidney [99].
No clinical toxic effects of Cynometra species on humans have been recorded.
3. Materials and Methods
This review was performed following the criteria described in the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 2020 (https://
prisma-statement.org/prismastatement/flowdiagram.aspx; accessed on 1 January 2022)).
3.1. Search Strategy
The scientific data were collected from PubMed, Science Direct, Web of Science, B-on,
and Google Scholar, selecting all the scientific publications published between 1 January
1980 and 30 June 2022, by using keywords Cynometra AND medicine, Cynometra AND
chemical compounds, Cynometra AND biological activity, and Cynometra AND toxicity.
3.2. Data Inclusion and Exclusion Criteria
3.2.1. Inclusion Criteria
•
•
•
Related to Cynometra genus;
Abstract or full text in English;
Studies on Cynometra species concerning medicinal importance.
3.2.2. Exclusion Criteria
•
•
•
Duplicate scientific publications;
Not directly related to medicinal issues;
Containing irrelevant or incomplete information.
4. Conclusions and Future Perspectives
The results of our work revealed that from the total amount of 113 species of the
Cynometra genus, eleven (9.7%) have been reported as used in ethnomedicine, mainly for
skin disease treatment. Eight species (7.1%) of this botanical genus were submitted to
chemical studies and ten species (8.8%) to biological activity. The main activities evaluated
were the antioxidant, antimicrobial, cytotoxic, and anti-inflammatory activities, but safety
data on species of this botanical genus were almost inexistent. It has also observed that not
all the species cited as used in traditional medicine, such as C. capuronii, C. manii, and C.
webberi, were chemically or biologically studied. On the other hand, the leaf, and seed of C.
megallophylla were documented as traditional medicines, but only the root was submitted to
phytochemical studies, and no biological data have been reported concerning this species.
The genus Cynometra was observed to be a botanical resource of secondary metabolites
that can be related to the biological activities and the therapeutical uses described for the
Plants 2022, 11, 3504
11 of 14
medicinal plants integrating it. However, to form a better conclusion about the medicinal
value of each of these medicinal plants, more scientific studies concerning their safety and
mode of action must be conducted, in addition to studies concerning their metabolomic,
botanical, and genetic profiles, which will allow for the establishment of the much-needed
quality control criteria for their better use in medicine.
Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/plants11243504/s1, Table S1: In vitro and in vivo biological
studies reported from the genus Cynometra [15,17,19,33–35,40,46–53,57–98].
Author Contributions: S.S. and K.H.: Information collection, writing. I.B.M.d.S. and J.R., R.S. and
N.I.: Revision of the manuscript. O.S.: Supervision, conceptualization, study design, writing, editing,
and revision the manuscript. All authors agree to be accountable for all aspects of work, ensuring
integrity and accuracy. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by the Foundation for Science and Technology (FCT, Portugal)
through national funds to iMed.ULisboa (UIDP/04138/2020).
Data Availability Statement: Not Applicable.
Conflicts of Interest: The authors confirm that they have no conflict of interest regarding the content
of this article.
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