A mini review on a Caralluma tuberculata N . E . Br . uncommon and wild succulents but having exciting pharmacological attributes

Caralluma tuberculata belongs to milky weed family Apocynaceae which upholds 424 genera. This natural medicinal plant is widely distributed in South Asia, Africa, Middle East, and Spain etc. Overall phytochemistry of Caralluma tuberculata is endowed with flurry of pharmacologically active constituents like pregnane glycosides and aglycones, flavanoid, saponins and titerpenes etc. Caralluma tuberculata and its various other species of this genus have been explored for their anti-inflammatory action, strong hypoglycemic and weight reduction effect, quite effective for rheumatoid arthritis, paralysis stomach disorders, abdominal pain, migraine, fever wound healing and cardiac problems. Present review focuses on the comprehensive profile of Caralluma tuberculata with respect to its highly valuable phytoconstituent along with their available pharmacological characteristics and therapeutic prospective.


Introduction
Natural product term widely cover the natural bio source products i.e. plant, animal and microbes.It may be in the form of a mix or single pure compound (secondary metabolites) like alkaloids, limonoids, steroid, flavonoid, lignana, terpenoids, organosulfur, tannin, furyl, polylines, chlorophyllins, thiophenes, saponins, sulphides, coumarins, etc. [1].The worth of medicinal plants lies in these metabolites that are non-nutritive for plants but produce certain physiological action in plants and human against different types of infectious disease and metabolic disorders [2].These natural constituents can be classified into two groups on the basis of their role in metabolism.Construction and maintenance of plant body is carried out by primary constituents.There was a thought in history that secondary constituents have no vital role in building or continuance of body of a plant but at present their ecophysiological role has been established.They act as defensive tool and attract pollinators or symbionts towards plant.These are also involved in growth regulation, modulation of genetic expression and transduction of signals.Some secondary components mimic body chemicals like signaling molecules, ligands, hormones, neurotransmitters and may act as activators or inhibitors of target cells.Above cited properties can be used to benefit human body such as cytotoxic secondary components for microbes can act as effective antimicrobial agent in human body.Constituents used as defense by plants against herbivores may affect Central Nervous System of human being and act as muscle relaxant, sedative, antidepressant or anesthetic [3,4].Phytotherapy history is as old as the history of humankind itself [5].People believe that locally originated diseases can be cured by local remedy [6].Natural plant products are considered to be in good health than artificial medicine [7].There are many side effects that are caused by the use of allopathic medicines [8].The medicinal efficacy of antibiotics existing today is decreasing by the appearance of multidrugresistant microbes [9].Unlike synthetic medicines, phytomedicines may produce their positive effects by additive and synergetic action of many chemical components that act on their target sites to produce a physiological change [10].Mostly the formulation schemes were kept secret by traditional healers, herbalist and shaman who pose as major obstacle to check the authenticity of these formulations on scientific basis [11].Despite of ever increasing human knowledge regarding conventional usage of natural products; appropriate modern scientific approaches have only been applied to a very little part of the world's flora.It is matter of grave concern to exploit the potential of those plant species that are in waiting line before they become endangered [12].and each having pollen mass one.Glabrous Follicles with size about 9-11 cm are progressively tapering to the tip.Flowering season is June.It mostly grows widely on rocks after rain but it is also cultivated in some areas.Its stem and roots are not only eaten raw as famine food but also cooked due to its pharmacological potential.The complete taxonomical classification of Caralluma tuberculata is deciphered in Figure 1.

Botanical name
Caralluma tuberculata N.E.Br.The literature survey indicates that the pregnane glycocydes were isolated from various parts of the plant.With polar solvents like ethylacetate, n-butanol, methanol, ethanol and water, the compounds like C21 class of steroidal glycosides with high molecular weight compounds were obtained but on other hand compounds having low molecular weight like cumarin, sterol, steroid, terpenoid were obtained when the same parts were extracted with non-polar solvents like n-hexane, benzene etc. Similarly saponins, such as the derivatives of glycyrrhetinic acid and triterpenoid saponins were also reported to have antiulcer effects in rats.It therefore appears responsible to suggest that flavonoids and saponins in Caralluma tuberculata may be totally or partially responsible for its antigastric ulcer activity [69].Pregnane glycosides, Penicilloside E showed the highest antitrypanosomal activity (IC50 1.01 µg/mL) followed by caratuberside C (IC50 1.85 µg/mL), which exhibited the highest selectivity index (SI 12.04).It was noticed that acylation is required for the antitrypanosomal activity while glycosylation at C-20 has no significant effect on the activity.The methanolic extract of Caralluma tuberculata N. E. Br. as well as its petroleum ether, chloroform and n-butanol extract were also examined for antitrypanosomal and antimalarial potential, additional to their cytotoxic potential against diploid embryonic cell line (MRC5) of human.Six compounds (1-6) were extracted from the chloroform fraction and identified by spectral means and were also tested for their antimalarial, antitrypanosomal and antiprotozoal activity against malaria and trypanosomiasis.As for the anti-malarial activity, only petroleum ether soluble fraction demonstrated moderate inhibitory effect (IC50 7.94 lg/mL), this fraction showed high cytotoxicity on MRC5 (IC50 0.8 l g/mL) [70].As for the antitrypanosomal activity, the methanolic extract was inactive, while the petroleum ether soluble fraction showed potent activity (IC50 0.5 lg/mL) with a selectivity index of 1.6.On the other hand, the CHCl3 soluble fraction was moderately active (IC50 3.5 lg/mL) with a selectivity index of 17.9.Accordingly, the CHCl3 soluble fraction was chosen for isolating the bioactive compounds.Compounds 1-6 were isolated from this fraction and their antimalarial and antitrypanosomal activity were evaluated [28].Other members of this genus like Caralluma fimbriata and Caralluma siniaca were considered to reduce body weight and blood glucose level respectively [49,54].Caralluma fimbriata is listed in The Wealth of India (1992) as medicinal plant used as an appetite suppressant and has also been used to treat diabetes, pain, fever, and inflammation [71].Its pregnane glycosides were thought to inhibit the action citrate layase enzyme and malonyl coenzyme A thus inhibiting the synthesis of fat cells.The blockage of action by this plant extract eventually stimulates the burning process of already stored fat reserves of body and finally reduces circumference of muscles and body lose weight.Caralluma fimbriata extracts have also been found to be appetite suppressant and is well known to Indian tribals and hunters.Indian folklore records its use as a potent appetite suppressant and weight loss promoter Caralluma adscendens is a thick, succulent perennial herb found wild in Africa, the Canary Islands, India, Arabia, Southern Europe, and Afghanistan.In India, it is found in the dry hills of Andhra Pradesh, Warangal and some other district.It is a traditional food consumed in pickle form and is also eaten during famines [35].It is locally known as "Makadshenguli/Shengulmakad".The local people use it in raw form for treatment of diabetes and it is also utilized as a vegetable [74].Caralluma attenuata is eaten raw as a cure for diabetes and the juice of the plant along with black pepper is recommended in the treatment of migraine.It also usually exhibits antinociceptive activity owing to its luteolin-49-O-neohesperidoside components [43].Caralluma dalzielii N. E. Br. is a succulent herb growing wildly on the Sahelian region of West Africa from Senegal to Nigeria where it was used in folk medicine as antispasmodic and analgesic remedy.Plant latex, in Bandiagara area of Mali, is used for wound healing, while the stems are grounded and eaten raw as tonic and for cardiac problems.A previous phytochemical study on this plant reported the isolation of two tomentogenin esters [75].In short, worldwide distribution and pharmacological properties of some significant species of Caralluma genus are represented in summarized form in Table 1 and Figure 4.

Figure 1 .
Figure 1.Taxonomy of Caralluma tuberculata N.E.Br.and whole plant along with flower [24].Caralluma edulis is also famous for its antidiabetic potential [72].Similarly hypoglycemic synergistic effect was noticed when C. edulis and C. attenuate were used in combination along with extract of phlorizin for reducing blood and urine glucose level in conjunction with weight loss [73].Figure 3 briefly explains the possible mechanisms of action of Caralluma on the reduction of blood glucose in the animal body.In Nepal and Sri Lanka, stem of wild Caralluma umbellata are used in stomach disorders and abdominal pains [22].

Figure 2 .
Figure 2. The proposed model of pregnane compound arbitrated apoptosis.Pregnane glycosides of Cralluma tuberculata N. E. Br. are considered in to stimulate the apoptosis process in cancer cell either through caspase dependent (Extrinsic & intrinsic pathways) or caspase indendent pathways (calcium mediated endoplasmic reticulumn stress pathway and stress & xenobiotic receptors activation.

Figure 3 .Figure 4 .
Figure 3. Possible mechanisms of action of Caralluma on the reduction of blood glucose in the animal body

Caralluma are normally leafless [18]. This
perennial herb has 15-45 cm height with a succulent, fleshy leafless, erect and 4 angled stem having grooves on it.Quadrangular stem bear small flowers in several varieties of dark colour [