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Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1146
Pharmacological Review of Caralluma
r.br: A Potential Herbal Genus
Sireesha Malladi1
, Venkata Nadh Ratnakaram2
, K. Suresh Babu3
,
M. Sreenivasulu1
1
Department of Science and Humanities, Vignan’s Foundation for Science, Technology and Research,
Guntur, Andhra Pradesh, India, 2
Department of Chemistry, GITAM University, Bengaluru, Karnataka, India,
3
Department of Chemistry, Mallareddy Engineering College, Hyderabad, Telangana, India
Abstract
In history, medicinal plants were proven as a source of active compounds with therapeutic applications, and at
present, they are an important collection for the discovery of novel drug leads. Caralluma is a genus used as
traditional medicine. The present article thoroughly reviewed about the classification of Caralluma into subgenera,
number of its species, its distribution in different parts of the world, and pharmacological activities exhibited by
different species of Caralluma.
Key words: Biological activities, caralluma, medicinal herb, phytochemicals
Address for correspondence:
Dr. Venkata Nadh Ratnakaram, Department of Chemistry,
GITAM University, Bengaluru Campus, Nagadenahalli,
Doddaballapur Taluk, Bengaluru – 561 203, Karnataka,
India. Phone: +91-9902632733.
E-mail: doctornadh@yahoo.co.in
Received: 08-06-2018
Revised: 07-12-2018
Accepted: 18-12-2018
INTRODUCTION
M
edicinal herbs are a versatile source
for therapeutic applications and play
a vital role in maintaining the proper
health as well as in managing various disease
conditions of both animals and humans all
over the world. India is one of the prominent
places for plant-based medicines in the world.
It is estimated that about 25,000 plant based
medical formulations are effectively used in
folk medicine. They are also known to be very
famous to rural communities of India. India
is a huge depository for the medicinal plants
that were became very popular in traditional
medical treatments.[1]
Several plant species are
used by the various systems of medicines such
as Ayurveda, Siddha, and Unani to treat a range
of diseases.[2]
As allopathic medicines possess
toxic nature and side effects, the use of plant-
based medicine is becoming popular. This lead
to a sudden enhancement in the production of
herbal drugs.[3]
Plant-derived compounds are recently gaining
much interest due to their wide range of
applications.[4]
Medicinal plants become
a prominent resource of folk medicines,
food supplements, modern medicines, new
drug leads, nutraceuticals, pharmaceutical
intermediates, and chemical units for synthetic
drugs.[5]
A number of remarkable outcomes
were found through the usage of natural products to treat
diseases, most particularly polypharmacological applications
and synergistic effects of plant extracts.[6]
Botanists,
ethnopharmacologists, microbiologists, and natural product
chemists are investigating for new phytochemicals which
could be used in the treatment of different infectious
diseases[7]
specifically in the radiance of the emerging drug-
resistant microorganisms, and there is a need to develop more
and more efficient antimicrobial agents. The present article
describes about Caralluma genus and pharmacological
activities of its different species.
ASCLEPIADACEAE
Asclepiadaceae was considered formerly as a plant
family, but now it is constituted as a subfamily with name
Asclepiadoideae under Apocyanaceae family.[8]
The name
“Asclepiadoideae” is originated from the word “Asclepias”
which means milkweeds.[9]
Worldwide, Asclepiadoideae
subfamily includes 348 genera with 2900 plant species. In
REVIEWARTICLE
Malladi, et al.: Medicinal values of Caralluma species
Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1147
India, Asclepiadoideae can be represented, especially, by
43 genera which includes 243 species. Of 43 genera, 5 are
endemic.[10]
CARALLUMA GENUS
Caralluma genus belongs to Asclepiadoideae and is widely
distributed inAsia (countries such asAfghanistan, India, Iran,
Pakistan, and Sri Lanka), Africa, Arabian Peninsula, Canary
Islands, and Southeast Europe.[11,12]
The word “Caralluma”
is originated from the Arabian word “qarh al-luhum” and
it means wound in the flesh or abscess.[13]
Caralluma is
considered as the synonym of Boucerosia, but both are
differing in floral arrangement.[13]
Caralluma plant species are
morphologically erect, creeping as well scrambling succulent
herbs with tetragonal branches.[11]
Certain Indian succulent
plants species containing very elongated flowering were
grouped under one genus, and it was named as Caralluma by
R. Brown.[14]
In 1834, Wight and Arnott[15]
divided the genus
Caralluma into two new genera Hutchinia and Boucerosia.
Boucerosia was characterized by the plant species with
flowers in terminal umbels and widely distributed in Arabian,
Indian, and Mediterranean areas of the world. Hutchinia
was characterized by creeping underground succulent plant
species and a few erect plant species containing flowers as
terminal umbels. All the genera were compiled under genus
Caralluma by Brown in 1892.[16]
More controversy was
created due to the addition of a number of similar succulents
in the same genus. Later, in 1895, Schumann[17]
divided the
genus into three subgenera such as Boucerosia, Lacruma,
and Eucaralluma (Caralluma). In 1990, the Caralluma
genus was again divided by Gilbert into four subgenera such
as Boucerosia, Caralluma, Desmidorchis, and Urmalcala.
Plowes[18]
divided the Caralluma genus into 17 genera,
and of them, only four genera (such as Apteranthus,
Boucerosia, Caralluma, and Caudanthera) are distributed
in India. The species of the genus Caralluma are included
under three subgenera such as Boucerosia, Desmidorchis,
and Urmalcala.[19]
In India, Caralluma exists in the form
of 12 species with seven varieties, in which 11 species are
mostly found in South India.[10]
Many taxonomists tried to
solve the difficulties in classifying different Indian taxa of
Caralluma but unable to clear the ambiguity.
Caralluma is one of the prominent genera and it grows well
in dry regions such as India, Africa, and the Middle East.[20]
In folkloric medicine, as well as in Unani and Ayurvedic
systems of medicine, the plants of Caralluma are being used
for the treatment of diabetic patients and rheumatism.[21]
Tribals consider some of them as food during famines[22]
and
also as a part of traditional medicinal system.[23]
In India and
Pakistan, Caralluma species have been used as emergency
foods for the past few centuries.[24]
A spectrum of biological
activities of Caralluma species can be expected due to the
existence of pregnane glycosides,[25]
stigmasterol, and other
phytochemicals in them.[26]
At present, Caralluma is gaining
much importance from researchers because it possesses an
array of immunostimulating activities due to the presence of
various phytochemicals.[27]
Caralluma acutangula
The results of Al-Faifi et al.[28]
revealed that alcoholic
extracts of C. acutangula exhibited excellent anticancer
activity on hepatocellular carcinoma cell and MCF7 (breast
cancer cell) when compared to standard drugs (Doxorubicin
and 5-Fluorouracil).
Caralluma adscendens
Uddandapu et al.[29]
studied about phytochemical and
antibacterial studies as well as physicochemical parameters
of C. adscendens along with 15 other medicinal plants.
Antimicrobial property of the methanolic extract of
C. adscendens was tested against four pathogenic bacteria
such as Escherichia coli, Proteus vulgaris, Klebsiella
pneumoniae, and Staphylococcus aureus and minimum
inhibitory concentration (MIC) values were also determined.
C. adscendens has shown comparatively good antimicrobial
activity against K. pneumonia and S. aureus. C. adscendens
was found to exhibit antibacterial and antifungal, where the
aqueous and ethanolic extracts of the plant were studied
against five bacterial strains (E. coli, P. vulgaris, Pseudomonas
aeroginosa, S. aureus, and Salmonella typhi).[30]
Polar solvent
extracts (ethanolic and aqueous) were found to be more
effective against E. coli and S. typhi, out of the tested bacteria.
On the other hand, no antifungal activity was observed with
both polar and non-polar extracts against the tested fungi,
namely Candida albicans, Aspergillus niger, and Mucor.
Antioxidant activity or radical scavenging activities of
C. adscendens var. fimbriata extracts were studied against a
variety of synthetic and natural free radicals (trolox equivalent
antioxidant capacity, ferric reducing antioxidant power, total
antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl, OH˙, and
NO).[31]
The total phenolics and flavonoids were correlated
with antioxidant activity. Methanol and water extracts were
proved to contain strong antioxidant capability compared to
other extracts due to the presence of high flavonoids and total
phenol content in them. Based on their studies, these extracts
were suggested as an alternative to synthetic antioxidants in
nutraceuticals and food preparations.Antioxidant activity and
hypolipidemic activity of various extracts of C. adscendens
Roxb were studied by Tatiya et al.[32]
Butanolic extract of
C. adscendens Roxb had effectively decreased the blood
glucose levels in addition to the minimization of low-density
lipoprotein, cholesterol, total cholesterol/high-density
lipoprotein (HDL) and triglycerides and also improved the
HDL in diabetic rats which were used for test.
Hypolipidemic activity of the aqueous extract of
C. adscendens var. fimbriata in hyperlipidemic rats (induced
Malladi, et al.: Medicinal values of Caralluma species
Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1148
by triton as well as methimazole) was studied by using various
animal models.[33]
In vitro anthelmintic activity of different
extracts of C. adscendens var. fimbriata against Pheretima
posthuma (Annelida) and Ascaridia galli (nematode) was
carried out by Noorulhuda et al.,[34]
and their studies proved
the presence of significant activity for the aqueous extract
of C. adscendens var. fimbriata in comparison with other
extracts. Significant antimutagenicity of ethanolic extract
of C. adscendens against the tested strains was reported
by Gowri and Chinnaswamy.[35]
Ames Salmonella histidine
reversion method was used to determine the antimutagenic
activity of C. adscendens (Roxb) in species of Salmonella
typhimurium (TA98, TA100, and TA153). A review on
C. adscendens Roxb phytopharmacology was carried out
by Tambe et al.[36]
Wound healing capacity of three different
extracts (using petroleum ether, ethyl acetate, and methanol)
of C. adscendens (Roxb) was reported in rats by Tambe
et al.[37]
These studies were carried out using excision,
incision as well as dead space wound models. In these
studies, significant wound healing potential was observed
for methanolic extracts of C. adscendens with a high rate of
wound contraction.
Caralluma arabica
C. arabica was investigated for its antioxidant activity in
H2
O2
-induced rat liver containing oxidative stress. The
freeze-dried extracts were subjected to total antioxidant
capacity (TAC) as well as glutathione (GSH) assays under
the presence of H2
O2
 (0.1%). Treatment with H2
O2
causes
in vitro oxidative stress, and it was evident from depletion
of GSH and decrease of TAC levels, but prior treatment with
plant extracts increased H2
O2
-induced GSH depletion as well
as TAC levels. Based on these results, it was concluded that
C. arabica may be used to minimize oxidative stress and its
corresponding problems in the human health.[38]
Antioxidant
activity, anticancer as well as anti-inflammatory potential of
C. arabica (for ethanol, n-hexane, ethyl acetate, n-butanol,
and aqueous extracts) were studied by Khasawneh et al.[39]
In
these studies, ethyl acetate and ethanol extracts have shown
the highest antioxidant activity due to their high phenolic
content. Good anti-inflammatory activity as well as good
cytotoxic activity (against MCF7 breast cancer cell line) was
exhibited by ethyl acetate extract.
Caralluma attenuata
Mounika et al.[40]
studied the anthelmintic and antitubercular
activities of aqueous methanolic extract of C. attenuata
after preliminary phytochemical screening. Considerable
antitubercular activity and anthelmintic potentiality were
observed at 50 μg/mL and 300 μg/mL concentrations,
respectively. Kumar et al.[41]
investigated on antioxidant
effect and antidiabetogenic activities of ethanolic extract
of C. attenuata in streptozotocin-induced diabetic rats.
C. attenuata was suggested as an antidiabetic agent because
its extracts were able to reduce the blood glucose levels.
In addition, an increase in food intake, body weight, and
glucose tolerance limits was also observed. Hypoglycemic
activity of C. attenuata in alloxan-induced white albino
diabetic rats was studied by Kalaivani and Hristy.[42]
Their
results have shown that there is a marked decrease in blood
sugar levels after treating with ethanol extract of C. attenuata
and also it has shown notable changes in the concentrations
of different biomolecules such as hemoglobin, insulin,
glycosylated hemoglobin, protein, hexokinase, urea,
pyruvate kinase, fructose 1,6 biphosphatase, and glucose-6-
phosphatase levels. Based on their studies, it was proposed
that C. attenuata extracts induce hypoglycemic activity in
diabetic rats due to suppression of gluconeogenesis as well as
stimulation of glucose oxidation through pentose phosphate
pathway. Antihyperglycemic activity of chloroform, ethanol,
and butanol extracts of C. attenuata on glucose-supplied
diabetic rats and alloxan-induced diabetic rats was studied
by Venkatesh et al.[43]
Butanol extracts were found to exhibit
significant antihyperglycemic activity.
Caralluma cicatricose
Hepatoprotective activity of methanol extracts of
C. cicatricose was assessed in CCl4
-induced liver-damaged
rabbits. C. cicatricose improved serum protein levels and
exhibited a dose-dependent reduction with respect to blood
glucose level, hepatic enzymes levels, and blood urea
nitrogen. From reports of histopathological studies on the liver
of rabbits, it is evidenced that there is a reduction in injury
induced by CCl4
. Based on their results, it was suggested
that C. cicatricose can be used as a natural hepatoprotective
agent.[44]
Caralluma dalzielii
Ethanolic extract of C. dalzielii was studied for ameliorative
effect in fructose-induced diabetic Wistar rats by taking five
groups of rats. The test was carried out using glibenclamide
as a positive control and distilled water as negative control.
C. dalzielii extracts notably reduced the total cholesterol in
Wistar rats.[45]
Phytochemical constituents and acute toxicity
of the alcohol extract of C. dalzielii were studied.[46]
Anti-
inflammatory and analgesic activities were studied in mice
and rats (chemical and thermal-induced pain models and
carrageenan-inducedacuteinflammation)usingtheseextracts.
Based on the results, it was concluded that these extracts can
be used in the removal of pain and inflammation.[46]
Caralluma edulis
Nutritional assessment and antioxidant activity of C. edulis
were investigated along with other plants by Shad et al.,[47]
and among the tested six plant species, comparatively
C. edulis was found to contain maximum antioxidant activity.
Ethanolic extracts of C. edulis were proved to possess a potent
Malladi, et al.: Medicinal values of Caralluma species
Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1149
antidiabetic activity by the studies in diabetic rats induced
by streptozotocin.[48]
The extract has shown an increased
effect in cellular antioxidant defense mechanism to sustain
oxidative damage.
Caralluma europaea
Seventy-four volatile compounds (58 compounds are non-
aromatic and 16 compounds are aromatic) were isolated from
the essential oils which were extracted from stems and fruits of
C. europaea using hydrodistillation. These compounds were
found to possess antimicrobial potential against pathogenic
microbes.[49]
Headspace gas chromatography method
was used to determine the volatile components present in
flowers of C. europaea. Of the identified 41 compounds,
the major compounds are monoterpenoids (linalool - 18.4%,
α-terpinene - 19.1%, and terpinolene - 23.3%) and carbonylic
compounds (hexanoic acid - 1.7%, heptanal - 2.0%, and
octanoic acid - 2.4%) along with minor compounds such as
indole and dimethyl sulfide.[50]
Caralluma fimbriata
A study on quantitative and qualitative analysis of
phytochemical as well as nutritional analysis of the aqueous
extract of C. fimbriata was carried out by Padwal et al.[51]
C. fimbriata extract was proved to be very useful to prevent
and manage the oxidative stress in kidneys, based on the
evaluation of renoprotective effect of its aqueous alcohol
extracts on Wistar rats.[52]
Ethanolic extracts of C. fimbriata
were found to possess a significant antimutagenicity as these
extractsinhibitedthereversioncreatedbydirectmutagenssuch
as hydroxylamine, ethidium bromide, and sodium azide.[53]
S. typhimurium was used in these studies for determination
of antimutagenicity. Aqueous extracts of C. fimbriata were
found to be active against pathogenic bacteria (Bacillus
subtilis, E. coli, and S. aureus) and concluded that it can
be used to treat diseases such as diarrhea, throat, ear and
intestinal tract infections, skin diseases, and fever.[54]
Priya et al.[55]
proved the in vitro anticancer potential of
the methanolic extract of C. fimbriata against A549 lung
cancer cell line, and dose fixation was suggested to be above
100 μg/mL. A relationship between inhibition on growth of
cancer cell lines and dose/duration was established. A study
on antidiabetic and hepatoprotective effect was carried out
for methanolic extract of C. fimbriata in streptozotocin-
induced diabetic rats. The treated rats were recovered from
diabetic condition, hepatotoxicity, and renal toxicity. Hence,
the methanol extract of C. fimbriata can be effectively used
in the treatment of diabetes and its related complications.[56]
Effect of dry extract of C. fimbriata on appetite and lipid
profile was studied in Wistar rats nurtured with cafeteria/
hypercaloric diet. It was concluded that C. fimbriata can be
used in treating obesity as their dry extracts have effectively
reduced the gain in body weight and also alterations in
lipid profile in rats fed with cafeteria diet.[57]
Methanolic
extract of C. fimbriata was found to inhibit the hyperplastic
obesity.[58]
Antiobesogenic and antiatherosclerotic activities
of the alcoholic extract of C. fimbriata were studied using
diet-induced obesity rat models. An increase in serum
leptin levels was observed, and lipid profile alterations
with respect to weight gain were inhibited. C. fimbriata
was proved to be significant in suppressing appetite as well
as a potent antiobesogenic agent on rats fed with cafeteria
diet.[59]
A review on phytochemistry, traditional uses, and
pharmacological properties of C. fimbriata was carried out
by Devi and Dhamotharan[60]
and Naingade et al.[61]
Of the
three extracts (using solvents petroleum ether, chloroform,
and aqueous methanol) of C. fimbriata, high analgesic
activity was exhibited by aqueous methanol extracts when
tested against albino mice.[62]
Caralluma indica/Boucerosia indica
B. indica extracts were subjected to qualitative phytochemical
testing and antimicrobial screening. Polar solvent (methanol
and aqueous) extracts were found to be more effective
against the tested pathogenic bacteria compared to acetone/
petroleum ether extracts.[63]
Caralluma lasiantha/Boucerosia lasiantha
C. lasiantha (syn. B. lasiantha) belongs to the subfamily
Asclepiadoideae and its local name is Kundeti Kommulu
(in Telugu)/Sirumankeerai (in Tamil).[64]
Recent publications
report about its biological activities such as antibacterial,[65]
hyperglycemic,[66]
cytotoxic,[67,68]
antioxidant,[69]
and
immunostimulating.[70]
Its vital role in the Indian Traditional
Medicine was reviewed by Malladi et al.[71]
Caralluma nilagiriana
Chloroform,methanolic,andaqueousextractsofC. nilagiriana
were found to contain higher antimicrobial potential against
K. pneumoniae compared to other microbes (E. coli, S. aureus,
P. aeroginosa, and S. typhi) and even more than the standard
tetracycline. Similarly, the methanolic extract has shown
greater activity against P. aeroginosa compared to standard.[72]
Caralluma penicillata
In vitro evaluation of antileishmanial, antiplasmodial,
and antitrypanosomal activity of the methanolic extract
of C. penicillata along with other 24 medicinal plants
was carried out by Mothana et al.[73]
From the results, it
was evident that C. penicillata has shown a significant
antiplasmodial activity against Plasmodium falciparum and
moderate antitrypanosomal activity against Trypanosoma
brucei. Ethanolic extract of C. penicillata was evaluated
for anti-inflammatory activity as well as gastritis protection
Malladi, et al.: Medicinal values of Caralluma species
Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1150
Name of the plant Biological activity References
Caralluma adscendens Antibacterial [96]
Antifungal [96]
Hypolipidemic [33]
Antimutagenic [35]
Analagesic [97]
Antioxidant and hypolipidemic [32]
Antibacterial and antifungal [35]
Wound healing potential [37]
Immunostimulating [70]
Anti-inflammatory [98]
Hyperglycemic [99]
Caralluma adscendens var. attenuata Antioxidant [69]
Antiadipogenesis [100]
Antiproliferative properties [67]
Immunostimulating [70]
Caralluma adscendens var. fimbriata Antioxidant capacity [31]
Antiadipogenesis [100]
Antiproliferative properties [67]
Anthelmintic [34]
Caralluma adscendens var. Gracilis Antioxidant, antimicrobial, and cytotoxic [101]
Caralluma arabica Antioxidant [38]
Antioxidant and lipoxygenase inhibitory [39]
Antigastric ulcer and cytoprotective [102]
Antinociceptive and anti-inflammatory [20]
Antihyperglycemic [103]
Caralluma attenuata Anthelminthic and antitubercular [40]
Antidiabetic [104]
Cytotoxic [68]
Antidiabetogenic and antioxidant [41]
Hypoglycemic [42]
Hyperglycemic [105]
Antihyperglycemic [43]
Anti-inflammatory and antinociceptive [21]
Caralluma cicatricose Hepatoprotective [44]
Caralluma dalzielii Ameliorative effect [45]
Analgesic and anti-inflammatory [46]
Antidiabetic [106]
Caralluma diffusa Cytotoxic [68]
Caralluma edulis Antioxidant [47]
Antidiabetic [48]
Antioxidant [107]
Caralluma fimbriata Antimutagenic [53]
Renoprotective [52]
Antimicrobial [54]
Table 1: Pharmacological activities exhibited by different species of Caralluma genus
(Contd...)
Malladi, et al.: Medicinal values of Caralluma species
Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1151
Name of the plant Biological activity References
Atoprotective and antidiabetic [56]
Anticancer [55]
Antiobesity [57]
Antinociceptive [62]
Antiobesogenic and antiatherosclerotic [58]
Effect on food intake, appetite, and anthropometry [108]
Caralluma flava (Desmidorchis flava) Antiproliferation [109]
Antioxidant [110]
Caralluma russelliana Antitrypanosomal [87]
Caralluma stalagmifera Antioxidant [69]
Antiadipogenesis [100]
Antiproliferative properties [67]
Immunostimulating [70]
Anti-inflammatory and antiarthritic [111]
Caralluma stalagmifera var. longipetala Antiadipogenesis [100]
Antioxidant [69]
Antiproliferative properties [67]
Immunostimulating [70]
Caralluma tuberculata Hypoglycemic and hypolipidemic [80]
Neuroprotective [112]
Antihypertensive [82]
Antioxidant [81,113]
Antifungal, antioxidant, cytotoxic, phytotoxic [86]
Phytotoxic and antioxidant [84]
Sedative, muscle relaxant, and antinociceptive [85]
Antifungal, antibacterial, and phytotoxic [114]
Antiproliferative [115]
Antiplasmodial and antitrypanosomal [87]
Anti-inflammatory [116]
Caralluma umbellata Nephroprotective and antioxidant [88]
Antibacterial [89]
Cytotoxic [68]
Antiadipogenesis [100]
Antioxidant [69]
Antiproliferative properties [67]
Nephroprotective [90]
Antioxidant [91]
Hepatoprotective [92]
Anti-inflammatory [93]
Antinociceptive and anti-inflammatory [94]
Anti-inflammatory and antinociceptive [117]
Caralluma lasiantha Antihyperglycemic [66]
Antioxidant [69]
Table 1: (Continued)
(Contd...)
Malladi, et al.: Medicinal values of Caralluma species
Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1152
Name of the plant Biological activity References
Antiadipogenesis [100]
Antiproliferative [67]
Cytotoxic [68]
Immunostimulating [70]
Boucerosia diffusa Antiangiogenic [79]
Boucerosia indica Antimicrobial [63]
Caralluma nilagiriana Antibacterial [72]
Boucerosia truncato-coronata Antioxidant [78]
Antiangiogenic [79]
Caralluma pauciflora Cytotoxic,antimicrobial, and antioxidant [101]
Caralluma penicillata Anti-inflammatory and gastritis protection [74]
Antiplasmodial, antitrypanosomal, and antileishmanial [73]
Caralluma sinaica Anticancer and antifolate activities [76]
Antidiabetic [77]
Caralluma longidens Antimicrobial [95]
Caralluma quadrangula Antimicrobial [75]
Antidiabetic [118]
Caralluma negevensis Anticancer [13]
Caralluma acutangula Anticancer [28]
property against indomethacin in guinea pigs. The extract was
also tested for acute anti-inflammatory activity, and single
dose of extract was equally active as that of indomethacin
but shorter in time duration. Repeated doses of the ethanolic
extract of C. penicillata were reported as less significant
against chronic inflammation than indomethacin with respect
to ulcerogenic effect. At the same time, combination of
extract and indomethacin minimized the gastritis property of
indomethacin depending on ulcer index.[74]
Caralluma quadrangular
ExtractsofC.quadrangularhaveshownantimicrobialactivity
against four strains (P. aeruginosa, E. coli, Micrococcus
luteus, and C. albicans) but not against B. subtilis. Higher
activity was reported with acetone and ethanolic extracts
compared to the extracts using distilled water, ethyl alcohol,
Tris-HCl, and Zamzam water.[75]
Caralluma sinaica
Methanolic extracts of C. sinaica exhibited strong antifolate
and anticancer activities compared to the extracts of other
five plants studied by the authors. In vitro antitumor
activities were carried against human breast, CNS, and lung
cancer cell lines for all the six plants, whereas antifolate
studies were carried out using commercial dihydrofolate
reductase.[76]
Ethanolic extracts of C. sinaica have decreased
the blood glucose levels more significantly compared to
standard (glibenclamide) in streptozotocin-induced diabetic
rabbits.[77]
Boucerosia truncato coronata/Caralluma
truncato-coronata
Comparable antioxidant potential was observed for the
ethanolic extracts of B. truncate coronata plants cultured
both in vivo and in vitro.[78]
Extracts of B. truncate coronata
and Boucerosia diffusa were tested for antiangiogenic
activity using in vivo chick chorioallantoic membrane assay.
Ethanolic and chloroform extracts of B. diffusa have shown
high antiangiogenic activity, whereas methanolic extract
of B. truncato coronata exhibited good antiangiogenic
activity.[79]
Caralluma tuberculata
Hypolipidemic and hypoglycemic effects of C. tuberculata
was studied with respect to the safety of the kidney and liver
of diabetic rats. No harmful effect was observed.[80]
Based
on significant effect on normalization of blood glucose
and good antioxidant potential in streptozotocin-induced
diabetic rats, C. tuberculata was recommended for
diabetic patients to suppress oxidative stress-instigated
complications.[81]
Antihypertensive effect of aqueous
methanolic extract of C. tuberculata was studied in both
normotensive and hypertensive Sprague Dawley rats.
Table 1: (Continued)
Malladi, et al.: Medicinal values of Caralluma species
Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1153
A marked decrease in systolic blood pressure, mean blood
pressure, diastolic blood pressure, and heart rate was
observed at all doses compared to control in normotensive
models. Significant antihypertensive effect was shown in
hypertensive models. A high decrease in blood pressure
was observed in hypertensive models than in normotensive
models. Based on the results, it was concluded that aqueous
methanolic extract of C. tuberculata can be used as an
effective antihypertensive agent.[82]
Bibi et al.[83]
authored a review article on C. tuberculata.
Different extracts (using solvents such as n-hexane, ethyl
acetate, chloroform, and methanol) of C. tuberculata were
studied for phytochemical composition and, antioxidant as
well as phytotoxic potential. Methanolic extract was proved
to exhibit high phytotoxic activity, whereas CHCl3
extract
has exhibited good antioxidant potential.[84]
C. tuberculata
extracts were used to study sedative, muscle relaxant, and
antinociceptive activities. Chloroform and ethyl acetate
fractions have exhibited significant sedative and muscle
relaxationeffectscomparedton-hexanefraction.[85]
Significant
activities (free radicals scavenging, phytotoxic, antifungal,
and cytotoxic) were reported for the methanolic extracts of
C. tuberculata.[86]
Good antiplasmodial and antitrypanosomal
activities were exhibited by petroleum ether fraction of MeOH
extract of C. tuberculata, whereas moderate cytotoxicity was
shown by chloroform fraction of MeOH extract.[87]
Caralluma umbellata
Bharathi et al.[88]
reported significant nephroprotective
and antioxidant activities for the methanolic extracts of
C. umbellata.C.umbellataextractsfromnon-polarendtopolar
end (using different solvents such as hexane, benzene, diethyl
ether, chloroform, acetone, and methanol) were evaluated
for their antibacterial activity. Based on the antibacterial
activity of C. umbellata Haw against E. coli, B. subtilis, and
Bacillus cereus, the scientific basis for its use in the traditional
treatment of stomach disorder was explained.[89]
Total phenol content as well as in vitro antioxidant activity
of aqueous alcoholic extract of C. umbellata was studied
by Kumar and Sandhya[90]
and concluded that the presence
of phenolic content is the main reason for good antioxidant
activity of C. umbellata. In vitro antioxidant activities of
aqueous and methanolic extracts of C. umbellata were
also studied by Kalyani and Anuradha.[91]
Prevention of
lipid peroxidation and good scavenging activity of extracts
were reported. Hepatoprotective effect of C. umbellata on
acetaminophen-induced hepatic damage rats was estimated
and found to contain significant activity.[92]
Good anti-
inflammatory effect was reported for Carumbelloside-II
and III (from C. umbellata) and good anti-inflammatory
activity was also reported for Carumbelloside-II. The
traditional use of C. umbellata in healing of pain and
inflammation was substantiated based on these results.[93,94]
Caralluma longidens
Methanolic extract of C. longidens was evaluated for
antimicrobial activity against clinical pathogens, and MICs
were also determined. Of all the microbes, K. pneumoniae,
S. typhi, S. aureus, C. albicans, and Candida krusei were more
sensitive towards these extracts compared to others such as
Corynebacterium ulcerans, Proteus rettgeri, Pseudomonas
fluorescens, and A. niger.[95]
In continuation to the above pharmacological activity
collection, efforts of various researchers on their study
pertaining to different species of Caralluma are compiled in
Table 1.
PHYTOCHEMICAL AND
PHARMACOLOGICAL ACTIVITIES
Enthusiastic researchers in this field can extend their
investigation in relating the pharmacological activities
exhibited by Caralluma species to their corresponding
phytochemicals such as flavone glycoside, luteoline-4’
-O-
neohesperiodoside,[21]
pregnane glycosides,[101,118]
acylated
pregnane glycosides,[119]
acylated steroidal glycosides,[115]
and pregnane steroid.[120,121]
Advancement of new routes[122-125]
and novel approaches[126-133]
of synthesis are helping the synthesis of molecules of
therapeutic importance. However, researchers are striving
further due to resistance gained by strains toward these drugs.
Plant-based products are gaining momentum in the market
in view of the lack of any side products.[134]
Hence, based on
the screening of phytochemicals, they can be used directly
or new molecules can be produced using them as precursors.
CONCLUSION
Caralluma genus is a potential source for phytochemicals
with medicinal usage. Thorough literature collection shows
that few species are explored for pharmacological activities so
far. However, many other species (such as Caralluma flava,
Caralluma negevensis, Caralluma pauciflora, Caralluma
retrospiciens, Caralluma russeliana, and Caralluma
wissmannii) have to be further explored.
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Effect of ethanol extract of Caralluma dalzielii NE Br.
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2012;3:4980-4.
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109.	Raees MA, Hussain H, Rehman NU, Khan HY,
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Al Abadi H, Al-Burtamani SK. Antioxidant capacity of
some edible and wound healing plants in Oman. Food
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Anti-inflammatory activity of Stapelia nobilis and
Caralluma stalagmifera. Fitoterapia 1996;67:545-52.
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tuberculata on ameliorating cognitive impairment
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screening of Caralluma lasiantha: Isolation of C21
pregnane steroid. Orient J Chem 2017;33:963-67.
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Phytochemical investigation of Caralluma lasiantha:
Isolation of stigmasterol, an active immunomodulatory
agent. Int J Chem Sci 2017;15:399-407.
122.	Sudhir MS, Nadh RV. Antibacterial activity of some
newer 1,2,3 – benzotriazole derivatives synthesized by
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of novel 1,2,3 –benzotriazolederivatives synthesized
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approach toward the synthesis of n-substituted anilines
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126.	Arunkumar T, Nadh RV, Srinivasu N, Murthy GN. Novel
pyrazolyl benzoxazole conjugates: Design, synthesis,
molecular docking studies and in vitro anticancer
activities. Lett Org Chem 2018;1570-1786.
127.	Vishnu VR, Krupanidhi S, Nadh RV. In-vivo evaluation
of rifampicin loaded nanospheres: Biodistribution
and mycobacterium screening studies. Curr Trends
Biotechnol Pharm 2018;12:169-76.
128.	Garbapu S, Nadh RV, Srinivasu N, Durgaprasad Y.
Synthesis and antitumor activity evaluation of
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pyridine piperazine hybrid molecules. Lett Org Chem
2018;15:1070-7.
129.	Arunkumar T, Nadh RV, Srinivasu N, Kishore K. Novel
hybrid molecules of quinazoline chalcone derivatives:
Synthesis and study of in vitro cytotoxic activities. Lett
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130.	Arunkumar T, Nadh RV, Srinivasu N, Kishore K. Novel
hybrid molecules of isoxazole chalcone derivatives:
Synthesis and study of in vitro cytotoxic activities. Lett
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131.	Malladi S, Nadh RV, Babu KS, Babu PS. Synthesis
and antibacterial activity studies of 2, 4-di substituted
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132.	SureshG,NadhRV,SrinivasuN,YennityD.A convenient
new and efficientcommercial synthetic route for dasatinib
(Sprycel®). Synth Commun 2017;47:1610-21.
133.	Suresh G, Nadh RV, Srinivasu N, Kaushal K. Novel
coumarin isoxazoline derivatives: Synthesis and study of
antibacterialactivities.SynthCommun2016;46:1972-80.
134.	Vijetha P, Nadh RV, Naidu KR, Sundari TS. A study on
extraction of plant based bio colours. J Rural Dev Soc
Trends Sci Technol 2017;1:1.
Source of Support: Nil. Conflict of Interest: None declared.

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Pharmacological Review of Caralluma r.br: A Potential Herbal Genus

  • 1. Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1146 Pharmacological Review of Caralluma r.br: A Potential Herbal Genus Sireesha Malladi1 , Venkata Nadh Ratnakaram2 , K. Suresh Babu3 , M. Sreenivasulu1 1 Department of Science and Humanities, Vignan’s Foundation for Science, Technology and Research, Guntur, Andhra Pradesh, India, 2 Department of Chemistry, GITAM University, Bengaluru, Karnataka, India, 3 Department of Chemistry, Mallareddy Engineering College, Hyderabad, Telangana, India Abstract In history, medicinal plants were proven as a source of active compounds with therapeutic applications, and at present, they are an important collection for the discovery of novel drug leads. Caralluma is a genus used as traditional medicine. The present article thoroughly reviewed about the classification of Caralluma into subgenera, number of its species, its distribution in different parts of the world, and pharmacological activities exhibited by different species of Caralluma. Key words: Biological activities, caralluma, medicinal herb, phytochemicals Address for correspondence: Dr. Venkata Nadh Ratnakaram, Department of Chemistry, GITAM University, Bengaluru Campus, Nagadenahalli, Doddaballapur Taluk, Bengaluru – 561 203, Karnataka, India. Phone: +91-9902632733. E-mail: doctornadh@yahoo.co.in Received: 08-06-2018 Revised: 07-12-2018 Accepted: 18-12-2018 INTRODUCTION M edicinal herbs are a versatile source for therapeutic applications and play a vital role in maintaining the proper health as well as in managing various disease conditions of both animals and humans all over the world. India is one of the prominent places for plant-based medicines in the world. It is estimated that about 25,000 plant based medical formulations are effectively used in folk medicine. They are also known to be very famous to rural communities of India. India is a huge depository for the medicinal plants that were became very popular in traditional medical treatments.[1] Several plant species are used by the various systems of medicines such as Ayurveda, Siddha, and Unani to treat a range of diseases.[2] As allopathic medicines possess toxic nature and side effects, the use of plant- based medicine is becoming popular. This lead to a sudden enhancement in the production of herbal drugs.[3] Plant-derived compounds are recently gaining much interest due to their wide range of applications.[4] Medicinal plants become a prominent resource of folk medicines, food supplements, modern medicines, new drug leads, nutraceuticals, pharmaceutical intermediates, and chemical units for synthetic drugs.[5] A number of remarkable outcomes were found through the usage of natural products to treat diseases, most particularly polypharmacological applications and synergistic effects of plant extracts.[6] Botanists, ethnopharmacologists, microbiologists, and natural product chemists are investigating for new phytochemicals which could be used in the treatment of different infectious diseases[7] specifically in the radiance of the emerging drug- resistant microorganisms, and there is a need to develop more and more efficient antimicrobial agents. The present article describes about Caralluma genus and pharmacological activities of its different species. ASCLEPIADACEAE Asclepiadaceae was considered formerly as a plant family, but now it is constituted as a subfamily with name Asclepiadoideae under Apocyanaceae family.[8] The name “Asclepiadoideae” is originated from the word “Asclepias” which means milkweeds.[9] Worldwide, Asclepiadoideae subfamily includes 348 genera with 2900 plant species. In REVIEWARTICLE
  • 2. Malladi, et al.: Medicinal values of Caralluma species Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1147 India, Asclepiadoideae can be represented, especially, by 43 genera which includes 243 species. Of 43 genera, 5 are endemic.[10] CARALLUMA GENUS Caralluma genus belongs to Asclepiadoideae and is widely distributed inAsia (countries such asAfghanistan, India, Iran, Pakistan, and Sri Lanka), Africa, Arabian Peninsula, Canary Islands, and Southeast Europe.[11,12] The word “Caralluma” is originated from the Arabian word “qarh al-luhum” and it means wound in the flesh or abscess.[13] Caralluma is considered as the synonym of Boucerosia, but both are differing in floral arrangement.[13] Caralluma plant species are morphologically erect, creeping as well scrambling succulent herbs with tetragonal branches.[11] Certain Indian succulent plants species containing very elongated flowering were grouped under one genus, and it was named as Caralluma by R. Brown.[14] In 1834, Wight and Arnott[15] divided the genus Caralluma into two new genera Hutchinia and Boucerosia. Boucerosia was characterized by the plant species with flowers in terminal umbels and widely distributed in Arabian, Indian, and Mediterranean areas of the world. Hutchinia was characterized by creeping underground succulent plant species and a few erect plant species containing flowers as terminal umbels. All the genera were compiled under genus Caralluma by Brown in 1892.[16] More controversy was created due to the addition of a number of similar succulents in the same genus. Later, in 1895, Schumann[17] divided the genus into three subgenera such as Boucerosia, Lacruma, and Eucaralluma (Caralluma). In 1990, the Caralluma genus was again divided by Gilbert into four subgenera such as Boucerosia, Caralluma, Desmidorchis, and Urmalcala. Plowes[18] divided the Caralluma genus into 17 genera, and of them, only four genera (such as Apteranthus, Boucerosia, Caralluma, and Caudanthera) are distributed in India. The species of the genus Caralluma are included under three subgenera such as Boucerosia, Desmidorchis, and Urmalcala.[19] In India, Caralluma exists in the form of 12 species with seven varieties, in which 11 species are mostly found in South India.[10] Many taxonomists tried to solve the difficulties in classifying different Indian taxa of Caralluma but unable to clear the ambiguity. Caralluma is one of the prominent genera and it grows well in dry regions such as India, Africa, and the Middle East.[20] In folkloric medicine, as well as in Unani and Ayurvedic systems of medicine, the plants of Caralluma are being used for the treatment of diabetic patients and rheumatism.[21] Tribals consider some of them as food during famines[22] and also as a part of traditional medicinal system.[23] In India and Pakistan, Caralluma species have been used as emergency foods for the past few centuries.[24] A spectrum of biological activities of Caralluma species can be expected due to the existence of pregnane glycosides,[25] stigmasterol, and other phytochemicals in them.[26] At present, Caralluma is gaining much importance from researchers because it possesses an array of immunostimulating activities due to the presence of various phytochemicals.[27] Caralluma acutangula The results of Al-Faifi et al.[28] revealed that alcoholic extracts of C. acutangula exhibited excellent anticancer activity on hepatocellular carcinoma cell and MCF7 (breast cancer cell) when compared to standard drugs (Doxorubicin and 5-Fluorouracil). Caralluma adscendens Uddandapu et al.[29] studied about phytochemical and antibacterial studies as well as physicochemical parameters of C. adscendens along with 15 other medicinal plants. Antimicrobial property of the methanolic extract of C. adscendens was tested against four pathogenic bacteria such as Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae, and Staphylococcus aureus and minimum inhibitory concentration (MIC) values were also determined. C. adscendens has shown comparatively good antimicrobial activity against K. pneumonia and S. aureus. C. adscendens was found to exhibit antibacterial and antifungal, where the aqueous and ethanolic extracts of the plant were studied against five bacterial strains (E. coli, P. vulgaris, Pseudomonas aeroginosa, S. aureus, and Salmonella typhi).[30] Polar solvent extracts (ethanolic and aqueous) were found to be more effective against E. coli and S. typhi, out of the tested bacteria. On the other hand, no antifungal activity was observed with both polar and non-polar extracts against the tested fungi, namely Candida albicans, Aspergillus niger, and Mucor. Antioxidant activity or radical scavenging activities of C. adscendens var. fimbriata extracts were studied against a variety of synthetic and natural free radicals (trolox equivalent antioxidant capacity, ferric reducing antioxidant power, total antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl, OH˙, and NO).[31] The total phenolics and flavonoids were correlated with antioxidant activity. Methanol and water extracts were proved to contain strong antioxidant capability compared to other extracts due to the presence of high flavonoids and total phenol content in them. Based on their studies, these extracts were suggested as an alternative to synthetic antioxidants in nutraceuticals and food preparations.Antioxidant activity and hypolipidemic activity of various extracts of C. adscendens Roxb were studied by Tatiya et al.[32] Butanolic extract of C. adscendens Roxb had effectively decreased the blood glucose levels in addition to the minimization of low-density lipoprotein, cholesterol, total cholesterol/high-density lipoprotein (HDL) and triglycerides and also improved the HDL in diabetic rats which were used for test. Hypolipidemic activity of the aqueous extract of C. adscendens var. fimbriata in hyperlipidemic rats (induced
  • 3. Malladi, et al.: Medicinal values of Caralluma species Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1148 by triton as well as methimazole) was studied by using various animal models.[33] In vitro anthelmintic activity of different extracts of C. adscendens var. fimbriata against Pheretima posthuma (Annelida) and Ascaridia galli (nematode) was carried out by Noorulhuda et al.,[34] and their studies proved the presence of significant activity for the aqueous extract of C. adscendens var. fimbriata in comparison with other extracts. Significant antimutagenicity of ethanolic extract of C. adscendens against the tested strains was reported by Gowri and Chinnaswamy.[35] Ames Salmonella histidine reversion method was used to determine the antimutagenic activity of C. adscendens (Roxb) in species of Salmonella typhimurium (TA98, TA100, and TA153). A review on C. adscendens Roxb phytopharmacology was carried out by Tambe et al.[36] Wound healing capacity of three different extracts (using petroleum ether, ethyl acetate, and methanol) of C. adscendens (Roxb) was reported in rats by Tambe et al.[37] These studies were carried out using excision, incision as well as dead space wound models. In these studies, significant wound healing potential was observed for methanolic extracts of C. adscendens with a high rate of wound contraction. Caralluma arabica C. arabica was investigated for its antioxidant activity in H2 O2 -induced rat liver containing oxidative stress. The freeze-dried extracts were subjected to total antioxidant capacity (TAC) as well as glutathione (GSH) assays under the presence of H2 O2  (0.1%). Treatment with H2 O2 causes in vitro oxidative stress, and it was evident from depletion of GSH and decrease of TAC levels, but prior treatment with plant extracts increased H2 O2 -induced GSH depletion as well as TAC levels. Based on these results, it was concluded that C. arabica may be used to minimize oxidative stress and its corresponding problems in the human health.[38] Antioxidant activity, anticancer as well as anti-inflammatory potential of C. arabica (for ethanol, n-hexane, ethyl acetate, n-butanol, and aqueous extracts) were studied by Khasawneh et al.[39] In these studies, ethyl acetate and ethanol extracts have shown the highest antioxidant activity due to their high phenolic content. Good anti-inflammatory activity as well as good cytotoxic activity (against MCF7 breast cancer cell line) was exhibited by ethyl acetate extract. Caralluma attenuata Mounika et al.[40] studied the anthelmintic and antitubercular activities of aqueous methanolic extract of C. attenuata after preliminary phytochemical screening. Considerable antitubercular activity and anthelmintic potentiality were observed at 50 μg/mL and 300 μg/mL concentrations, respectively. Kumar et al.[41] investigated on antioxidant effect and antidiabetogenic activities of ethanolic extract of C. attenuata in streptozotocin-induced diabetic rats. C. attenuata was suggested as an antidiabetic agent because its extracts were able to reduce the blood glucose levels. In addition, an increase in food intake, body weight, and glucose tolerance limits was also observed. Hypoglycemic activity of C. attenuata in alloxan-induced white albino diabetic rats was studied by Kalaivani and Hristy.[42] Their results have shown that there is a marked decrease in blood sugar levels after treating with ethanol extract of C. attenuata and also it has shown notable changes in the concentrations of different biomolecules such as hemoglobin, insulin, glycosylated hemoglobin, protein, hexokinase, urea, pyruvate kinase, fructose 1,6 biphosphatase, and glucose-6- phosphatase levels. Based on their studies, it was proposed that C. attenuata extracts induce hypoglycemic activity in diabetic rats due to suppression of gluconeogenesis as well as stimulation of glucose oxidation through pentose phosphate pathway. Antihyperglycemic activity of chloroform, ethanol, and butanol extracts of C. attenuata on glucose-supplied diabetic rats and alloxan-induced diabetic rats was studied by Venkatesh et al.[43] Butanol extracts were found to exhibit significant antihyperglycemic activity. Caralluma cicatricose Hepatoprotective activity of methanol extracts of C. cicatricose was assessed in CCl4 -induced liver-damaged rabbits. C. cicatricose improved serum protein levels and exhibited a dose-dependent reduction with respect to blood glucose level, hepatic enzymes levels, and blood urea nitrogen. From reports of histopathological studies on the liver of rabbits, it is evidenced that there is a reduction in injury induced by CCl4 . Based on their results, it was suggested that C. cicatricose can be used as a natural hepatoprotective agent.[44] Caralluma dalzielii Ethanolic extract of C. dalzielii was studied for ameliorative effect in fructose-induced diabetic Wistar rats by taking five groups of rats. The test was carried out using glibenclamide as a positive control and distilled water as negative control. C. dalzielii extracts notably reduced the total cholesterol in Wistar rats.[45] Phytochemical constituents and acute toxicity of the alcohol extract of C. dalzielii were studied.[46] Anti- inflammatory and analgesic activities were studied in mice and rats (chemical and thermal-induced pain models and carrageenan-inducedacuteinflammation)usingtheseextracts. Based on the results, it was concluded that these extracts can be used in the removal of pain and inflammation.[46] Caralluma edulis Nutritional assessment and antioxidant activity of C. edulis were investigated along with other plants by Shad et al.,[47] and among the tested six plant species, comparatively C. edulis was found to contain maximum antioxidant activity. Ethanolic extracts of C. edulis were proved to possess a potent
  • 4. Malladi, et al.: Medicinal values of Caralluma species Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1149 antidiabetic activity by the studies in diabetic rats induced by streptozotocin.[48] The extract has shown an increased effect in cellular antioxidant defense mechanism to sustain oxidative damage. Caralluma europaea Seventy-four volatile compounds (58 compounds are non- aromatic and 16 compounds are aromatic) were isolated from the essential oils which were extracted from stems and fruits of C. europaea using hydrodistillation. These compounds were found to possess antimicrobial potential against pathogenic microbes.[49] Headspace gas chromatography method was used to determine the volatile components present in flowers of C. europaea. Of the identified 41 compounds, the major compounds are monoterpenoids (linalool - 18.4%, α-terpinene - 19.1%, and terpinolene - 23.3%) and carbonylic compounds (hexanoic acid - 1.7%, heptanal - 2.0%, and octanoic acid - 2.4%) along with minor compounds such as indole and dimethyl sulfide.[50] Caralluma fimbriata A study on quantitative and qualitative analysis of phytochemical as well as nutritional analysis of the aqueous extract of C. fimbriata was carried out by Padwal et al.[51] C. fimbriata extract was proved to be very useful to prevent and manage the oxidative stress in kidneys, based on the evaluation of renoprotective effect of its aqueous alcohol extracts on Wistar rats.[52] Ethanolic extracts of C. fimbriata were found to possess a significant antimutagenicity as these extractsinhibitedthereversioncreatedbydirectmutagenssuch as hydroxylamine, ethidium bromide, and sodium azide.[53] S. typhimurium was used in these studies for determination of antimutagenicity. Aqueous extracts of C. fimbriata were found to be active against pathogenic bacteria (Bacillus subtilis, E. coli, and S. aureus) and concluded that it can be used to treat diseases such as diarrhea, throat, ear and intestinal tract infections, skin diseases, and fever.[54] Priya et al.[55] proved the in vitro anticancer potential of the methanolic extract of C. fimbriata against A549 lung cancer cell line, and dose fixation was suggested to be above 100 μg/mL. A relationship between inhibition on growth of cancer cell lines and dose/duration was established. A study on antidiabetic and hepatoprotective effect was carried out for methanolic extract of C. fimbriata in streptozotocin- induced diabetic rats. The treated rats were recovered from diabetic condition, hepatotoxicity, and renal toxicity. Hence, the methanol extract of C. fimbriata can be effectively used in the treatment of diabetes and its related complications.[56] Effect of dry extract of C. fimbriata on appetite and lipid profile was studied in Wistar rats nurtured with cafeteria/ hypercaloric diet. It was concluded that C. fimbriata can be used in treating obesity as their dry extracts have effectively reduced the gain in body weight and also alterations in lipid profile in rats fed with cafeteria diet.[57] Methanolic extract of C. fimbriata was found to inhibit the hyperplastic obesity.[58] Antiobesogenic and antiatherosclerotic activities of the alcoholic extract of C. fimbriata were studied using diet-induced obesity rat models. An increase in serum leptin levels was observed, and lipid profile alterations with respect to weight gain were inhibited. C. fimbriata was proved to be significant in suppressing appetite as well as a potent antiobesogenic agent on rats fed with cafeteria diet.[59] A review on phytochemistry, traditional uses, and pharmacological properties of C. fimbriata was carried out by Devi and Dhamotharan[60] and Naingade et al.[61] Of the three extracts (using solvents petroleum ether, chloroform, and aqueous methanol) of C. fimbriata, high analgesic activity was exhibited by aqueous methanol extracts when tested against albino mice.[62] Caralluma indica/Boucerosia indica B. indica extracts were subjected to qualitative phytochemical testing and antimicrobial screening. Polar solvent (methanol and aqueous) extracts were found to be more effective against the tested pathogenic bacteria compared to acetone/ petroleum ether extracts.[63] Caralluma lasiantha/Boucerosia lasiantha C. lasiantha (syn. B. lasiantha) belongs to the subfamily Asclepiadoideae and its local name is Kundeti Kommulu (in Telugu)/Sirumankeerai (in Tamil).[64] Recent publications report about its biological activities such as antibacterial,[65] hyperglycemic,[66] cytotoxic,[67,68] antioxidant,[69] and immunostimulating.[70] Its vital role in the Indian Traditional Medicine was reviewed by Malladi et al.[71] Caralluma nilagiriana Chloroform,methanolic,andaqueousextractsofC. nilagiriana were found to contain higher antimicrobial potential against K. pneumoniae compared to other microbes (E. coli, S. aureus, P. aeroginosa, and S. typhi) and even more than the standard tetracycline. Similarly, the methanolic extract has shown greater activity against P. aeroginosa compared to standard.[72] Caralluma penicillata In vitro evaluation of antileishmanial, antiplasmodial, and antitrypanosomal activity of the methanolic extract of C. penicillata along with other 24 medicinal plants was carried out by Mothana et al.[73] From the results, it was evident that C. penicillata has shown a significant antiplasmodial activity against Plasmodium falciparum and moderate antitrypanosomal activity against Trypanosoma brucei. Ethanolic extract of C. penicillata was evaluated for anti-inflammatory activity as well as gastritis protection
  • 5. Malladi, et al.: Medicinal values of Caralluma species Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1150 Name of the plant Biological activity References Caralluma adscendens Antibacterial [96] Antifungal [96] Hypolipidemic [33] Antimutagenic [35] Analagesic [97] Antioxidant and hypolipidemic [32] Antibacterial and antifungal [35] Wound healing potential [37] Immunostimulating [70] Anti-inflammatory [98] Hyperglycemic [99] Caralluma adscendens var. attenuata Antioxidant [69] Antiadipogenesis [100] Antiproliferative properties [67] Immunostimulating [70] Caralluma adscendens var. fimbriata Antioxidant capacity [31] Antiadipogenesis [100] Antiproliferative properties [67] Anthelmintic [34] Caralluma adscendens var. Gracilis Antioxidant, antimicrobial, and cytotoxic [101] Caralluma arabica Antioxidant [38] Antioxidant and lipoxygenase inhibitory [39] Antigastric ulcer and cytoprotective [102] Antinociceptive and anti-inflammatory [20] Antihyperglycemic [103] Caralluma attenuata Anthelminthic and antitubercular [40] Antidiabetic [104] Cytotoxic [68] Antidiabetogenic and antioxidant [41] Hypoglycemic [42] Hyperglycemic [105] Antihyperglycemic [43] Anti-inflammatory and antinociceptive [21] Caralluma cicatricose Hepatoprotective [44] Caralluma dalzielii Ameliorative effect [45] Analgesic and anti-inflammatory [46] Antidiabetic [106] Caralluma diffusa Cytotoxic [68] Caralluma edulis Antioxidant [47] Antidiabetic [48] Antioxidant [107] Caralluma fimbriata Antimutagenic [53] Renoprotective [52] Antimicrobial [54] Table 1: Pharmacological activities exhibited by different species of Caralluma genus (Contd...)
  • 6. Malladi, et al.: Medicinal values of Caralluma species Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1151 Name of the plant Biological activity References Atoprotective and antidiabetic [56] Anticancer [55] Antiobesity [57] Antinociceptive [62] Antiobesogenic and antiatherosclerotic [58] Effect on food intake, appetite, and anthropometry [108] Caralluma flava (Desmidorchis flava) Antiproliferation [109] Antioxidant [110] Caralluma russelliana Antitrypanosomal [87] Caralluma stalagmifera Antioxidant [69] Antiadipogenesis [100] Antiproliferative properties [67] Immunostimulating [70] Anti-inflammatory and antiarthritic [111] Caralluma stalagmifera var. longipetala Antiadipogenesis [100] Antioxidant [69] Antiproliferative properties [67] Immunostimulating [70] Caralluma tuberculata Hypoglycemic and hypolipidemic [80] Neuroprotective [112] Antihypertensive [82] Antioxidant [81,113] Antifungal, antioxidant, cytotoxic, phytotoxic [86] Phytotoxic and antioxidant [84] Sedative, muscle relaxant, and antinociceptive [85] Antifungal, antibacterial, and phytotoxic [114] Antiproliferative [115] Antiplasmodial and antitrypanosomal [87] Anti-inflammatory [116] Caralluma umbellata Nephroprotective and antioxidant [88] Antibacterial [89] Cytotoxic [68] Antiadipogenesis [100] Antioxidant [69] Antiproliferative properties [67] Nephroprotective [90] Antioxidant [91] Hepatoprotective [92] Anti-inflammatory [93] Antinociceptive and anti-inflammatory [94] Anti-inflammatory and antinociceptive [117] Caralluma lasiantha Antihyperglycemic [66] Antioxidant [69] Table 1: (Continued) (Contd...)
  • 7. Malladi, et al.: Medicinal values of Caralluma species Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1152 Name of the plant Biological activity References Antiadipogenesis [100] Antiproliferative [67] Cytotoxic [68] Immunostimulating [70] Boucerosia diffusa Antiangiogenic [79] Boucerosia indica Antimicrobial [63] Caralluma nilagiriana Antibacterial [72] Boucerosia truncato-coronata Antioxidant [78] Antiangiogenic [79] Caralluma pauciflora Cytotoxic,antimicrobial, and antioxidant [101] Caralluma penicillata Anti-inflammatory and gastritis protection [74] Antiplasmodial, antitrypanosomal, and antileishmanial [73] Caralluma sinaica Anticancer and antifolate activities [76] Antidiabetic [77] Caralluma longidens Antimicrobial [95] Caralluma quadrangula Antimicrobial [75] Antidiabetic [118] Caralluma negevensis Anticancer [13] Caralluma acutangula Anticancer [28] property against indomethacin in guinea pigs. The extract was also tested for acute anti-inflammatory activity, and single dose of extract was equally active as that of indomethacin but shorter in time duration. Repeated doses of the ethanolic extract of C. penicillata were reported as less significant against chronic inflammation than indomethacin with respect to ulcerogenic effect. At the same time, combination of extract and indomethacin minimized the gastritis property of indomethacin depending on ulcer index.[74] Caralluma quadrangular ExtractsofC.quadrangularhaveshownantimicrobialactivity against four strains (P. aeruginosa, E. coli, Micrococcus luteus, and C. albicans) but not against B. subtilis. Higher activity was reported with acetone and ethanolic extracts compared to the extracts using distilled water, ethyl alcohol, Tris-HCl, and Zamzam water.[75] Caralluma sinaica Methanolic extracts of C. sinaica exhibited strong antifolate and anticancer activities compared to the extracts of other five plants studied by the authors. In vitro antitumor activities were carried against human breast, CNS, and lung cancer cell lines for all the six plants, whereas antifolate studies were carried out using commercial dihydrofolate reductase.[76] Ethanolic extracts of C. sinaica have decreased the blood glucose levels more significantly compared to standard (glibenclamide) in streptozotocin-induced diabetic rabbits.[77] Boucerosia truncato coronata/Caralluma truncato-coronata Comparable antioxidant potential was observed for the ethanolic extracts of B. truncate coronata plants cultured both in vivo and in vitro.[78] Extracts of B. truncate coronata and Boucerosia diffusa were tested for antiangiogenic activity using in vivo chick chorioallantoic membrane assay. Ethanolic and chloroform extracts of B. diffusa have shown high antiangiogenic activity, whereas methanolic extract of B. truncato coronata exhibited good antiangiogenic activity.[79] Caralluma tuberculata Hypolipidemic and hypoglycemic effects of C. tuberculata was studied with respect to the safety of the kidney and liver of diabetic rats. No harmful effect was observed.[80] Based on significant effect on normalization of blood glucose and good antioxidant potential in streptozotocin-induced diabetic rats, C. tuberculata was recommended for diabetic patients to suppress oxidative stress-instigated complications.[81] Antihypertensive effect of aqueous methanolic extract of C. tuberculata was studied in both normotensive and hypertensive Sprague Dawley rats. Table 1: (Continued)
  • 8. Malladi, et al.: Medicinal values of Caralluma species Asian Journal of Pharmaceutics • Oct-Dec 2018 (Suppl) • 12 (4) | S1153 A marked decrease in systolic blood pressure, mean blood pressure, diastolic blood pressure, and heart rate was observed at all doses compared to control in normotensive models. Significant antihypertensive effect was shown in hypertensive models. A high decrease in blood pressure was observed in hypertensive models than in normotensive models. Based on the results, it was concluded that aqueous methanolic extract of C. tuberculata can be used as an effective antihypertensive agent.[82] Bibi et al.[83] authored a review article on C. tuberculata. Different extracts (using solvents such as n-hexane, ethyl acetate, chloroform, and methanol) of C. tuberculata were studied for phytochemical composition and, antioxidant as well as phytotoxic potential. Methanolic extract was proved to exhibit high phytotoxic activity, whereas CHCl3 extract has exhibited good antioxidant potential.[84] C. tuberculata extracts were used to study sedative, muscle relaxant, and antinociceptive activities. Chloroform and ethyl acetate fractions have exhibited significant sedative and muscle relaxationeffectscomparedton-hexanefraction.[85] Significant activities (free radicals scavenging, phytotoxic, antifungal, and cytotoxic) were reported for the methanolic extracts of C. tuberculata.[86] Good antiplasmodial and antitrypanosomal activities were exhibited by petroleum ether fraction of MeOH extract of C. tuberculata, whereas moderate cytotoxicity was shown by chloroform fraction of MeOH extract.[87] Caralluma umbellata Bharathi et al.[88] reported significant nephroprotective and antioxidant activities for the methanolic extracts of C. umbellata.C.umbellataextractsfromnon-polarendtopolar end (using different solvents such as hexane, benzene, diethyl ether, chloroform, acetone, and methanol) were evaluated for their antibacterial activity. Based on the antibacterial activity of C. umbellata Haw against E. coli, B. subtilis, and Bacillus cereus, the scientific basis for its use in the traditional treatment of stomach disorder was explained.[89] Total phenol content as well as in vitro antioxidant activity of aqueous alcoholic extract of C. umbellata was studied by Kumar and Sandhya[90] and concluded that the presence of phenolic content is the main reason for good antioxidant activity of C. umbellata. In vitro antioxidant activities of aqueous and methanolic extracts of C. umbellata were also studied by Kalyani and Anuradha.[91] Prevention of lipid peroxidation and good scavenging activity of extracts were reported. Hepatoprotective effect of C. umbellata on acetaminophen-induced hepatic damage rats was estimated and found to contain significant activity.[92] Good anti- inflammatory effect was reported for Carumbelloside-II and III (from C. umbellata) and good anti-inflammatory activity was also reported for Carumbelloside-II. The traditional use of C. umbellata in healing of pain and inflammation was substantiated based on these results.[93,94] Caralluma longidens Methanolic extract of C. longidens was evaluated for antimicrobial activity against clinical pathogens, and MICs were also determined. Of all the microbes, K. pneumoniae, S. typhi, S. aureus, C. albicans, and Candida krusei were more sensitive towards these extracts compared to others such as Corynebacterium ulcerans, Proteus rettgeri, Pseudomonas fluorescens, and A. niger.[95] In continuation to the above pharmacological activity collection, efforts of various researchers on their study pertaining to different species of Caralluma are compiled in Table 1. PHYTOCHEMICAL AND PHARMACOLOGICAL ACTIVITIES Enthusiastic researchers in this field can extend their investigation in relating the pharmacological activities exhibited by Caralluma species to their corresponding phytochemicals such as flavone glycoside, luteoline-4’ -O- neohesperiodoside,[21] pregnane glycosides,[101,118] acylated pregnane glycosides,[119] acylated steroidal glycosides,[115] and pregnane steroid.[120,121] Advancement of new routes[122-125] and novel approaches[126-133] of synthesis are helping the synthesis of molecules of therapeutic importance. However, researchers are striving further due to resistance gained by strains toward these drugs. Plant-based products are gaining momentum in the market in view of the lack of any side products.[134] Hence, based on the screening of phytochemicals, they can be used directly or new molecules can be produced using them as precursors. CONCLUSION Caralluma genus is a potential source for phytochemicals with medicinal usage. Thorough literature collection shows that few species are explored for pharmacological activities so far. However, many other species (such as Caralluma flava, Caralluma negevensis, Caralluma pauciflora, Caralluma retrospiciens, Caralluma russeliana, and Caralluma wissmannii) have to be further explored. REFERENCES 1. GroverJK,YadavS,VatsV.MedicinalplantsofIndiawith anti-diabetic potential. J Ethnopharm 2002;81:81-100. 2. Negi CS, Nautiyal S, Dasila L, Rao KS, Maikhuri RK. Ethnomedicinal plant uses in a small tribal community in a part of central Himalaya, India. 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