pharmacological review of caralluma r.br
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DESCRIPTION
Caralluma adscendens belongs to family Ascalpedaceae has beenused to treat obesity traditionally. According to the literature survey Caralluma adscendens is used as a thirstquenching agent.TRANSCRIPT
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Pharmacological Review of Caralluma R.Br.with Special Reference to Appetite Suppression and Anti-Obesity
Harish Chander Dutt,1 Surjeet Singh,2 Bharathi Avula,3 Ikhlas A. Khan,3 and Yashbir S. Bedi4
1Department of Botany, University of Jammu, Jammu, India.2Pharmacology and 4Plant Biotechnology Divisions, Indian Institute of Integrative Medicine, Jammu, India.3National Center for Natural Product Research, The University of Mississippi, Oxford, Mississippi, USA.
ABSTRACT Caralluma fimbriata extract has received Generally Recognized As Safe (GRAS) status for use as a nu-
traceutical to combat the most serious public health concern (i.e., obesity). More than 260 species grouped under the genus
Caralluma (Family Apocynaceae) are distributed in tropical Asia and Mediterranean regions of the globe. Ethnobotanically,
some species have been used as traditional and modern dietary ingredients to suppress appetite. Many species of Caralluma
are commonly used as traditional medicine for the treatment of rheumatism, diabetes, leprosy, paralysis, and inflammation and
have antimalarial, antitrypanosomal, anti-ulcer, antioxidant, antinociceptive, and antiproliferative activities. The genus is
known for compounds like pregnane glycosides, flavonoid glycoside, flavones, magastigmane glycosides, pregnane steroids,
steroidal glycosides, saturated and unsaturated hydrocarbons, aromatic and nonaromatic volatile compounds, and b-sitosterol.An extract of C. fimbriata (Slimaluna, Gencor Nutrients, Anaheim, CA, USA) is used as an anti-obesity agent and appetite
suppressor. It is also seen that the pregnane glycosides isolated and identified from African Hoodia are reported as anti-obesity
and appetite-suppressant compounds. On reviewing the studies undertaken on the chemistry, pharmacology, and therapeutic
potential of Caralluma, it is concluded that the genus is also composed of pregnane glycosides as one of the major con-
stituents. Availability of pregnane glycosides in Caralluma is an indication of the appetite-suppressant property of this genus.
This coupled with the GRAS status of the extract of C. fimbriata has opened the possibility of developing an anti-obesity/
appetite-suppressant product from other species of Caralluma. The main objective of this article is to review the studies
undertaken on the plant in light of further research for anti-obesity drugs and nutraceuticals from species of Caralluma.
KEY WORDS: anti-obesity appetite suppressor Caralluma Indian Hoodia pregnane glycoside
INTRODUCTION
The genus Caralluma R. Brown, belonging to thefamily Apocynaceae, is composed of about 260 species,which are grouped in three different subgenera: Carallumasubgen.Boucerosia (Wight &Arn.)M.G.Gilbert,Carallumasubgen. Desmidorchis (Ehrenb.) M.G.Gilbert, and Car-alluma subgen. Urmalcala M.G.Gilbert.1,2 Caralluma isdistributed in the dry regions of tropical Asia, the southernMediterranean, and northern, central, and eastern Africa.The genus was previously placed in the Asclepiadaceaefamily but now has been merged into the Apocynaceaefamily under the subfamily Asclepiadoideae.2
Morphologically, Caralluma plants are quadrangular,perennial succulents with small caducous leaves (Fig. 1).3
Some species (e.g., Caralluma adscendens or Carallumaattenuata) grow only in the warmer and drier regions andcannot withstand a temperature below 50F; however, they
can be grown in a greenhouse or window garden undercontrolled conditions. Species of Caralluma can be plantedin small open pots with maximum drainage. Seeds, cuttings,or divisions are all suitable for propagation; however, di-vision is the easiest approach for the multiplication of thespecies.4 Macroscopic and microscopic studies and detailednomenclature of the C. adscendens var. fimbriata have alsobeen presented in detail.5
Species of Caralluma are used as food in many partsof the world (e.g., in Indian desert states, fruits andyoung shoots of Caralluma edulis are used as a vegeta-ble by local residents). Thus, the species has becomeindeterminate, vulnerable, and endangered in Bikaner,Jaisalmer, and Jodhpur, respectively.6 It is also notedthat the very harsh desert conditions are not suitablefor the growth of Caralluma species and that theirhabitat is restricted to shaded niches between rockswhere dew is produced after cold nights.7,8 Carallumatuberculata and C. edulis are distributed in the NorthwestHimalayas.3
In vitro propagation of succulent plants including Car-alluma has been successfully achieved for conservation
Manuscript received 30 December 2010. Revision accepted 26 September 2011.
Address correspondence to: Harish Chander Dutt, Department of Botany, University ofJammu, Jammu 180006, India, E-mail: [email protected]
JOURNAL OF MEDICINAL FOODJ Med Food 15 (2) 2012, 108119# Mary Ann Liebert, Inc. and Korean Society of Food Science and NutritionDOI: 10.1089/jmf.2010.1555
108
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purposes.9,10 In addition, a species specific micropropagationprotocol is available for C. edulis and C. adscendens. Thesame protocol can be modified for other species of the ge-nus.11 An effective protocol has also been developed for thein vitro propagation of Caralluma sarkariae Lavranos &R.M.I. Frandsen.12
Obesity has emerged as one of the most serious publichealth concerns in the 21st century.13 In particular, child-hood obesity is a global epidemic and is increasing in bothdeveloped and developing countries.14 Excessive bodyweight is associated with various metabolic diseases and isknown to reduce life expectancy.15 Increasing rates ofobesity may be due to easily accessible and palatable diets;unchecked body weight due to high appetite is known as amajor cause of obesity.16
The major bioactive compounds in Caralluma are thepregnane glycosides.1722 These pregnane glycosides iso-lated from an African plant, Hoodia, are known appe-tite suppressors.23 Appetite-suppressant and weight lossproperties of Caralluma species are mentioned in Indiantraditional records and have encouraged the use of Gena-Slim (Country Life, Hauppage, NY, USA) capsules forbody weight control; the capsules contain the extract of C.fimbriata.23 However, the plant species is generally eatento treat obesity, whereas C. adscendens var. fimbriata isused by ethnic populations of middle India as an appetitesuppressant.23,24 In a double-blind, placebo-controlled,randomized clinical trial, C. fimbriatawas shown to be safebut to have no significant effect on body weight loss.24
However, the mechanism of action for weight reductionand the safety of C. fimbriata extract Slimaluna (GencorNutrients, Anaheim, CA, USA) have also been reviewed.25
In addition, use of the species has been described for otherbody ailments like malaria, inflammation, hyperglycemia,ulcers, cancer, etc. The important phytoactive chemicalpregnane glycoside is an important target for future re-search for anti-obesity and appetite-suppressant drugs andnutraceuticals.
ETHNOBOTANY
Traditionally the aerial parts of Caralluma species areused as a culinary herb and are cooked with meat duringwinter.26 Although the entire plant of Caralluma quad-rangula is edible, in some communities the juice obtainedfrom its stem is added to fresh milk and consumed as ageneral tonic.27 C. attenuata is eaten raw as a cure for dia-betes (anecdotal information from users), and the juice ofthe plant along with black pepper is recommended for thetreatment of migraine.28,29
C. tuberculata growing both wild and cultivated in Pa-kistan is either eaten raw or cooked as a vegetable. Beside itsconsumption as food, it is commonly used in the treatmentof rheumatism, diabetes, leprosy, paralysis, joint pains, fe-ver and as an antipyretic in the northwest Himalayas.3032
Stems of C. adscendens var. attenuata and Caralluma la-siantha are eaten by the Palliyars community of WesternGhats, India.33 Stem tendrils of C. adscendens and C. at-tenuata are used for the preparation of chutney and curry inAndhra Pradesh, India.34 C. adscendens is cultivated in sa-cred groves of the Madurai district of Tamil Nadu and isused for its cooling effect and for curing ulcers.35 C. fim-briata, known as Indian Hoodia, has been used as anappetite suppressant in India since the Vedic times.4 Theextract of C. fimbriata has been released under the tradename GenaSlim for body weight control.23 C. fimbriata isalso used in traditional medicine to treat various conditionssuch as diabetes, pain, fever, and inflammation.4 The plantspecies is generally eaten to treat obesity, whereas C. ad-scendens var. fimbriata is used by ethnic populations ofmiddle India as an appetite suppressant.23,24 Likewise,Caralluma dalzielii is claimed to be medicinally importantin African traditional medicine.36 The juice of Carallumastalagmiferamixed with black pepper is recommended to betaken orally for treating migraine, and a decoction of thefresh stems is used orally for treating diabetes.37,38 C. tu-berculata (syn. Boucerosia aucheriana Decne.) is consid-ered a stomachic, carminative, and tonic and also used tocure diabetes and rheumatism.39
CHEMICAL CONSTITUENTS
Several species of Caralluma have been studied forphytochemical constituents, and many molecules have beenisolated and identified from the genus. In this context, dif-ferent classes of organic compounds of medicinal interesthave been reported from Caralluma. The phytochemistry ofthe genus Caralluma is characterized by many pregnaneglycosides, whereas megastigmane glycosides and fewflavones have also been isolated and identified from C.tuberculata, Caralluma negevensis, and Caralluma arabi-ca.1822 The chloroform extract of the aerial parts ofCaralluma russelliana yielded four acylated pregnane gly-cosides.40 In addition, the presence of pregnane steroids inseveral species has increased the range of chemical con-stituents in Caralluma.4042 Phytochemical analysis of C.adscendens var. fimbriata identified 12 pregnane glycosidesand pregnane steroids, one of which was identical to
FIG. 1. Fruiting plant of C. tuberculata, growing at the IndianInstitute of Integrative Medicine.
PHARMACOLOGICAL REVIEW OF CARALLUMA R.BR. 109
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stalagmoside-V isolated from C. stalagmifera.41,43 In addi-tion to flavonoid glycoside (luteolin neohesperidoside), thewhole plant of C. lasiantha also possesses two bisdesmo-sidic C-21 steroidal glycosides.44 Two novel bisdesmosidicsteroidal glycosides have also been isolated from Carallumaindica.43 Moreover, five more steroidal glycosides havebeen isolated and characterized from C. stalagmifera.43
Pregnane ester aglycones have been isolated by acidic hy-drolysis of a fraction obtained from the alcoholic extract of
the aerial parts of Caralluma retrospiciens.45 Six poly-oxypregnane glycosides have been isolated and character-ized from leaves of C. retrospiciens.46 C. tuberculata ischaracterized by the presence of boucerin, dihydroboucerin,and caratubersides (Fig. 2).4750 Pregnane glycosides likecarumbellosides IVI and pregnane steroids includingbourcergenin, caraumbellogenin, and umbellosides IIVhave been isolated from the whole plant of Caralluma um-bellata.42,5155
FIG. 2. Structure of caratubersides CG, penicillosides AG, and russeliosides BE.
110 DUTT ET AL.
-
The petroleum ether extract of C. fimbriata gave a waxysolid hydrocarbon (i.e., pentatriacontane).56,57 C. attenuatais also known for the presence of hydrocarbons.58,59 3,4-Secotriterpene has also been isolated from Carallumaburchardii.60 Five steroidal glycosides and 27 pregnaneglycosides have been isolated and characterized from thewhole plant of C. dalzielii.61,62 Eighteen fatty acids, fourhydrocarbons (hentriacontane, tritriacontane, triacontane,and nonacosane), and b-sitosterol have been isolated fromthe ethyl acetate fraction of the vegetative parts of C. edu-lis.63 Edible parts of C. edulis (consumed in the Tharparkardistrict in Pakistan) possess a high percentage of water(95.8%), a low percentage of fiber (0.59%), and lowamounts of proteins (0.17%), lipids (0.23%), and carbohy-drates (2.52%). Moreover, the species is rich in Ca, Fe, P,and Zn.64 In addition, headspace analysis has recentlyidentified 74 volatile compounds (16 aromatic and 58 non-aromatic) and several fatty acids from stems and fruits ofCaralluma europaea.65,66 Thus it is clear that the genusCaralluma is a rich source of steroidal glycosides of thepregnane type (Fig. 2).6770
A simple high-performance liquid chromatographyultraviolet detection method has also been developed forthe determination of five marker compounds: boucerin(1), caraumbelloside I (2), caraumbelloside III (3), car-aumbelloside II (4), and caraumbellogenin (5). The methodidentifies the chemical fingerprint analysis of Carallumaspecies (C. fimbriata, C. attentuata, and C. umbellata) anddietary supplements claiming to contain C. fimbriata. Fur-ther application of this method has shown that C. umbellatacontains compounds 25, but C. attentuata and C. fimbriatado not show the presence of compounds 15. Two com-mercial extracts, one plant sample, and dietary supplementslabeled as C. fimbriata showed the presence of all fivecompounds. Further identification of these compoundswas confirmed by a more sensitive liquid chromatographytandem mass spectrometry technique. Caralluma is a genusof plants consisting of more than 260 species, and adulter-ation between species is quite possible, so that developinganalytical methods becomes crucial for product validity andsafety. An in-depth study of the chemical fingerprintingtechnique is in progress for identification of various Car-alluma species.71 Chromium has also been reported fromCaralluma, used as a hypoglycemic drug in Pakistan.72
PHARMACOLOGY
Caralluma species have been used for centuries in semi-arid areas of Pakistan as an emergency food, and thesespecies are also known for their antihyperglycemic activity.In this context, C. edulis has been evaluated for its antidi-abetic properties.7375 The medicinal properties of Car-alluma species have been attributed to their glycosides. C.fimbriata is an edible vegetable in the semi-arid regions ofWestern India and is well known as a famine food, appetitesuppressant, and a thirst quencher when its green folliclesare boiled and salted.73 It is surprising that no significantweight loss was seen in a double-blind, placebo-controlled,
randomized clinical trial on C. fimbriata extract (Slimalu-na); during the clinical trial the subjects were tested forchanges in key indicatorsnamely, weight loss, includinganthropometry, body fat composition, body mass index, netweight, and systemic functions.20 However, based on asafety study, the extract of C. fimbriata, was assignedGenerally Recognized As Safe (GRAS) status on June 30,2006, which has allowed the nutraceutical industry to startdeveloping products with Slimaluna.76,77 The mechanism ofaction for weight reduction and safety of C. fimbriata hasbeen reviewed and found to be similar to mechanisms pro-posed for Garcinia cambogia except for its direct effect onthe hypothalamus.78 The mechanism of action of G. cam-bogia has proven to be safe for those desiring to loseweight.79 In addition, clues to how C. fimbriata works toreduce weight may come from our knowledge of G. cam-bogia. The active component in G. cambogia is hydro-xycitrate, which has been reported to cause weight loss inhumans without stimulating the central nervous system.78
Because it is a competitive inhibitor of ATP-citrate lyase, anextramitochondrial enzyme is involved in the initial steps ofde novo lipogenesis.78 Consequently, hydroxycitrate re-duces the transformation of citrate into acetyl-coenzyme A,a step necessary for the formation of fatty acids in the liver.It is believed that the pregnane glycoside blocks the activityof citrate lyase enzyme, thereby inhibiting fatty acid bio-synthesis. Furthermore, it also blocks formation of malonyl-coenzyme A, thereby encouraging stored fatty acid oxida-tion (Fig. 3). Therefore, this is more effective than othersuch compounds that block the fat biosynthesis at one step
FIG. 3. Schematic diagram showing the effect of pregnane glyco-sides on the formation of fatty acid. CoA, coenzyme A; iP, inorganicphosphate; OAA, oxaloacetic acid.
PHARMACOLOGICAL REVIEW OF CARALLUMA R.BR. 111
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Table1.SummaryofChemicalConstituents,Bioactivity,andEthnobotanicalUsesofCarallumaSpecies
Studynumber
Nameofplantspecies
Majorchem
icalconstituents
Bioactivity
Ethnobotany
1C.adscendensR.Br.
NA
NA
Speciesisusedforitscoolingeffect
andto
cure
ulcersin
theMaduari
districtofTam
ilNadu35
2C.adscendensvar.fimbriata
(Wall.)
Gravely&
Mayur
Pregnaneglycosides,steroid
41
NA
Usedbypeople
ofcentral
India
asappetitesuppressant24
3C.adscendensvar.attenuata
(Wight)
Grav.&
Mayur
NA
NA
Eaten
asavegetable
bythePalliyar
communityofwestern
Ghats;people
ofAndhra
Pradeshuse
thetender
stem
sto
preparechutney
and
curry
33,34
4C.arabicaN.E.Br.
Flavonoids19
Antinociceptive,anti-inflam
matory,
antigastric
ulcer,andcytoprotective
properties
8991
NA
5C.attenuata
Wight
Hydrocarbons58,59
Antihyperglycemic,anti-inflam
matory,
andantinociceptive2
8,74,92
Eaten
raw
asacure
fordiabetes,and
juicewithblack
pepper
isusedto
treatmigraine2
8,29
6C.burchardiiN.E.Br.
3,4-Secotriterpene6
0NA
NA
7C.dalzieliiN.E.Br.
Steroidal
glycosides,pregnane
glycosides
36,61,62
Antiproliferative3
6Thespeciesisclaimed
asamedicinal
herbin
African
traditional
medicine3
6
8C.edulisBenth.ex
Hook.f.
b-Sitosterol,hydrocarbons,
fattyacids6
3
Antioxidant,antidiabetic26,75
NA
9C.europaea
(Guss.)N.E.Br.
Essential
oils65,66
NA
NA
10
C.fimbriata
Wall.
n-Pentatriacontaneandother
hydrocarbons5659
Anti-obesity23,24
Besideuse
asan
appetitesuppressantin
Indiasince
theVedictimes,itisalso
usedto
treatvariousconditionssuch
asdiabetes,pain,fever,and
inflam
mation4
11
C.flava
N.E.Br.
Antioxidant27
NA
12
C.indicaN.E.Br.
Bisdesmosidic
steroidal
glycoside4
3NA
NA
(continued)
112
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Table1.(Continued)
Studynumber
Nameofplantspecies
Majorchem
icalconstituents
Bioactivity
Ethnobotany
13
C.lasianthaN.E.Br.
Luteolinneohesperidoside
bisdesmosidic
C-21steroidal
glycoside4
4
NA
ThespeciesiseatenbythePalliyar
communityas
avegetable33
14
C.negevensisZoharyex
Feinbrun
Megastigmaneglycosides,
flavones
18,21
NA
NA
15
C.penicillata
N.E.Br.
Pregnaneglycosides,penicilloside9
3Antitrypanosomal,antiplasm
odial93,94
NA
16
C.quadrangula
N.E.Br.
NA
Itisusedas
ageneral
tonic27
17
C.retrospiciensN.E.Br.
Polyoxypregnaneglycosides,pregnane
esteraglycones
45,46
NA
NA
18
C.russelliana(Courbonex
Brongn.)
Cufod.
Pregneneglycosides,acylatedpregnane
glycosides
40
Antitrypanosomal,antiplasm
odial93,94
NA
19
C.sinaicaA.Berger
Coumarins,terpenoids,glycosides,
tannins,phenoliccompounds95
Insulinpromoter,hypoglycemic,and
anti-inflam
matory
9698
NA
20
C.stalagmiferaC.E.C.Fisch.
Stalagmoside-V,steroidal
glycosides
43
NA
Thejuiceoftheplantspecieswith
black
pepper
isgiven
orallyto
treat
migraine;
decoctionoffreshstem
isusedorallyto
treatdiabetes
37,85
21
C.tuberculata
N.E.Br.
Flavoneglycosides,bourcerin,
dihydrobourcerin,caratubersides,
pregneneglycosides
22,38,4750,93
Antimalarial,antitrypanosomal,
antiplasm
odial,hypoglycemic,and
gastric
mucosa
protective9
3,94,99101
Thespeciesiseatenraworcooked
asa
vegetable,isusedtherapeutically,
andisapotentantidiabetic,
antipyretic,stomachic,carm
inative,
tonic,andantirheumatic.Itisalso
usedto
cure
leprosy
30,31,39,47,101
22
C.umbellata
Haw
.Carumbellosides,pregnene-type
steroid,bourcergenin,
caraumbellogenin
5154
NA
NA
NA,notavailable.
113
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only. Simultaneously, appetite suppression activity of C.fimbriata is hypothesized as a secondary effect on the ap-petite control center of the brain.78 Hydroxycitrate has beendemonstrated to reduce food intake in animals, suggesting arole in the treatment of obesity, and has been demonstratedto increase the availability of serotonin in isolated rat braincortex, which could affect satiety.8087 More specifically, itis believed that the pregnane glycosides in C. fimbriata in-hibit the hunger sensory mechanisms of the hypothalamus.However, it is unclear how pregnane glycosides and theirrelated molecules suppress appetite, although it is thoughtthat they amplify the signaling of the energy sensing func-tion in the basal hypothalamus.88
Safety reports of C. fimbriata, to be consumed at re-commended doses, are in consonance with the use of cactusin the food chain without any significant adverse side effect,its listing in Wealth of India as a famine food, testimonialsby individuals for its use as a raw vegetable, its established50% lethality dose (> 5 g/kg), and clinical studies revealingno significant adverse effects.1921 Pregnane glycosidesisolated from genus Caralluma (Caralluma penicillata, C.tuberculata, and C. russelliana) showed antitrypanosomaland antiplasmodial activity (Tables 1 and 2).93,94 In additionto this, six compounds isolated from C. tuberculata havebeen tested for antimalarial and antitrypanosomal activities;the antitrypanosomal activities were found to be more ef-fective than the antimalarial activity (Tables 1 and 2).100 Theethanolic extract of C. tuberculata has also been screenedfor its potential to protect gastric mucosa against the injuriescaused by 80% ethanol, 0.2M NaOH, hypertonic saline, andindomethacin.99,102
Because of the strong antioxidant activity in the extractsderived from aerial parts of C. edulis, the extracts fromCaralluma species are the object of increasing interestfor nutraceutical companies.22 C. arabica has also shownanti-inflammatory, antihyperglycemic, antinociceptive,gastric mucosa protective, and antiulcer properties (Tables 1and 3).15,16,24,8991,99 Extracts of C. stalagmifera are reportedto possess anti-inflammatory activity.33 Caralluma flavashowed weaker antioxidant activities in the 2,2-diphenyl-1-picrylhydrazyl assay (Tables 1 and 3).23 Administration ofCaralluma sinaica extract in different doses (50, 100, 150,and 200mg/kg, p.o.) to normal rabbits caused significant(P < .01) decreases in glucose levels. C. sinaica has alsobeen reported to contain chemical constituents like cou-marins, terpenoids, glycosides, flavonoids, tannins, andphenolic compounds. However, the exact chemical con-stituent responsible for the hypoglycemic effect remainsunknown (Tables 1 and 3).98 Several investigators haveshown that phenolic compounds (e.g., tannins, coumarins,and flavonoids), triterpenoids, and most of the othersecondary plant metabolites possess hypoglycemic and anti-inflammatory effects in various experimental animal mod-els.9597 The fresh juice of C. tuberculata has been reportedto possess hypoglycemic activity.101 C. attenuata alsopossesses significant antihyperglycemic activity (Tables 1and 3).74,92 It is also known that the decrease in fasting bloodglucose levels with aqueous and alcoholic extracts is com-
parable to that of a 100mg/kg tolbutamide dose.103 C. at-tenuate contains luteolin-4-O-neohesperidoside with asignificant anti-inflammatory and antinociceptive activity;similarly, C. umbellata has also been evaluated foranti-inflammatory and antinociceptive activity (Tables 1and 3).15,24
Several members of the genus Caralluma have beenfound to be medicinally active in the treatment of rheuma-tism, diabetes, and leprosy and as antiseptics and disinfec-tants.104 In several pharmacological studies on species ofCaralluma, some of the isolated pregnane glycosides ortheir esters showed antitumor activity, and others werepostulated to be precursors of cardenolides.55,105108 Com-bined treatment with C. tuberculata and cyclophosphamideshowed that the species diminished the effect of cyclo-phosphamide on DNA levels; however, RNA levels werefurther suppressed, resulting in increased cytotoxicity.102
Steroidal glycosides and pregnane glycosides isolated fromC. dalzielii were tested for their antiproliferative activity onmurine monocyte/macrophage cell lines ( J774.A1), humanepithelial kidney cell lines (HEK-293), and murine fibro-sarcoma cell lines (WEHI-164) cell lines; moderate to highpotency of cytotoxicity was found in almost all testedcompounds, confirming the significant cytotoxic activity ofpregnane glycosides (Tables 1 and 2).31,43 Antifungal andanthelmintic activities of C. fimbriata Wall. has also beenstudied in detail.109
CONCLUSIONS
The genus Caralluma is composed of about 260 species,the ethnobotanical properties of some of which have beendescribed. Caralluma species have been extensively usedfor the treatment of various ailments. The phytochemicalanalysis revealed that a large number of active compoundshave been isolated from different species of Caralluma. Thepharmacological data summarized in this review reveal thatno work has been conducted on the isolated compounds foranti-obesity and appetite-inhibitory activities. Only onedrug from C. fimbriata has been released under the tradename Genaslim for body weight control, but the clinicaltrials on the product does not support appetite-suppressantactivity in the extract even though GRAS status has beengiven to the extract of C. fimbriata (Slimaluna). Becauseonly the extract of C. fimbriata is believed to be an anti-obesity agent and appetite suppressor and no significantscientific evidence supports such uses, therefore more re-search on the active biomolecules within the extract andother species of this genus is required. Other biologicalactivities suggest possible leads for researchers to discoverherbal or galenic remedies with bona fide effects, but mostof the evidence remains suggestive but not conclusive sofurther phytochemical and pharmacological research isneeded. Additional interventions are needed to address themost serious public health concerns (i.e., obesity and dia-betes) prevailing in developed and developing countries;therefore plants in the genus Caralluma should be furtherevaluated for their safety and efficacy. Several other
114 DUTT ET AL.
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Table2.Compounds/ExtractofCarallumaShowingtheBioactivities(InVitro),Dose,Model,andToxicity
Activity,
extract/pure
compound
IC50
(lg/mL)
Model/modeof
administration
Cytotoxicity
on
MRC5IC
50(lg/mL)
References
Antitrypanosomal
TrypanosomabruceibruceiGUTat
3.1
strain
(invitro)
Petroleum
ether-soluble
fractionofmethanol
extractofC.tuberculata
0.5
62.6
93,94,100
Chloroform
-soluble
fractionofmethanolextract
ofC.tuberculata
3.5
62.6
93,94,100
Petroleum
ethersoluble
fractionofC.tuberculata
0.5
0.8
100
CHCl 3extractofC.tuberculata
3.5
62.6
100
PenicillosideA
7.07
>100
100
PenicillosideB
>12.5
ND
100
PenicillosideC
8.44
>100
100
PenicillosideD
9.51
0.25
100
PenicillosideE
1.01(1.83)a
0.34
100
PenicillosideF
6.04(9.09)a
100
100
RusseliosideB
>12.5
ND
100
RusseliosideC
>12.5
ND
100
RusseliosideD
>12.5
ND
100
RusseliosideE
7.03
>100
100
Melarsoprol(control)
11106
1.4
100
Pentamidine(control)
11104
5.7
100
Suramine(control)
1.58
>100
100
Effornithine(control)
2.27
>100
100
Antiplasm
odial(antimalarial)
Petroleum
ether-soluble
fractionofmethanol
extractofC.tuberculata
>1.56
Chloroquine-resistantPlasm
odium
falciparumstrain
(K1)
andsensitivestrain
(FCR3)(invitro)
62.6
94
Petroleum
ether
extractofC.tuberculata
7.94
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
0.8
100
FractionC-2
6.2
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
5.0
100
FractionC-3
7.0
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
ND
100
FractionC-4
>12.5
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
ND
100
FractionC-5
>12.5
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
ND
100
FractionC-2
3.0
Drug-sensitivestrain
ofP.falciparum(FCR3)(invitro)
5.0
100
FractionC-3
5.0
Drug-sensitivestrain
ofP.falciparum(FCR3)(invitro)
ND
100
FractionC-4
11.0
Drug-sensitivestrain
ofP.falciparum(FCR3)(invitro)
ND
100
FractionC-5
4.8
Drug-sensitivestrain
ofP.falciparum(FCR3)(invitro)
ND
100
CaratubersideC
7.0
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
22.28
100
CaratubersideD
6.2
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
17.75
100
CaratubersideE
>12.5
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
64.11
100
CaratubersideF
10.8
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
19.20
100
CaratubersideG
6.6
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
>100
100
Artem
isinin
(control)
0.005
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
45.1
100
Chloroquine(control)
0.17
Drug-resistantstrain
ofP.falciparum(K1)(invitro)
18.5
100
Antiproliferative
36
Pregnaneglycosides
b0.0500.71lM
J774AI
NA
0.060.95lM
HEK-293
NA
0.0920.2lM
WEHI-164celllines
NA
90%
inhibitory
concentration(lg/m
L).
bTwenty-six
glucosides
havebeenstudiedforantiproliferativeactivityin
threecelllines.Therangeof50%
inhibitory
concentration(IC50)values
aregiven.
NA,notavailable;ND,notdetermined.
115
-
objectives such as genetic engineering for improved syn-thesis of desired metabolites in the species should be also beincluded in future research.
DISCLOSURE STATEMENT
No competing financial interests exist.
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Table3.Compounds/ExtractofCarallumaShowingBioactivities,Dose
Range,Dose,Model,andToxicity
Biologicalactivity
Extract/pure
compounds
Dose
range
Effective
dose
Model
Toxicity/references
Antidiabetic
C.sinacia80%
ethanolic
extract
50200mg/kg
100mg/kg
Malealbinorabbits
Notoxic
effect
upto
200mg/kg98
Butanolextractof
C.attenuata
NA
250mg/kg
Rats
Notoxic
effects74
Aqueousextractof
C.attenuata
NA
100mg/kg
Rats
92
Antinociceptive
10%
ethanolicextract
200400mg/kg
NA
Mice/rats
90
Carabelloside-1
NA
Mice
20
Antigastric
10%
ethanolicextract
200400mg/kg
NA
91
Ethanolicextractof
C.tuberculata
250,500,1000mg/kg
Rats
Notoxic
effects99
Anti-inflam
matory
Luteolin-4-O
-neohisperidoside
NA
NA
NA
28
Anti-obesity(clinical
trial)
C.fimbriata
extract
NA
LD50=5g/kg
Humans
Notoxic
effects23,24
Antioxidant(chem
ical
method;cell-freesystem
)C.flava
(whole
plantextract)
NA
31.51.0;3350.5
DPPHassay;phosphomolybdate
assay
27
C.quadrangula
(shole
plant)
NA
14.51.4;89929.5
DPPHassay;phosphomolybdate
assay
27
DPPH,2,2-diphenyl-1-picrylhydrazyl;LD50,50%
lethalitydose;NA,notavailable.
116 DUTT ET AL.
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