Cucurbitacins are a group of steroid like triterpenes found in the members of Cucurbitaceae like Momordica Bryonia, Cucumis, Cucurbita, Luffa, Echinocystis, Lagenaria and Citrullusand a few members of Brassicaceae (seeds of Iberis and Lepidium sativum), Scrophulariaceae, Begoniaceae, Primulaceae, Liliaceae, Tropaeolaceae and Rosaceae. The diversity of cucurbitacins lies in variety of its side chain derivatives that contribute to their disparate pharmacological actions. They may be concentrated in fruits and roots of mature plants.
Structure
All cucurbitacins contain a basic 19-(10→9β)–abeo--10α–lanost–5--ene ring skeleton characterised by a double bond at 5, a methyl group at C-9 (rather than C-10) and numerous keto--, hydroxyl--, and acetoxy--groups. Most of the Cucurbitacins are tetracyclic, but some representatives have an extra ring due to formal cyclization between C--16 and C--24 as in cucurbitacins S and T. Certain Cucurbitacins have been discovered in the form of glycosides at C2 and some of them lack C--11 carbonyl function. Chemically, Cucurbitacins are ranked according to presence of various functional groups on rings A and C, diversity in side chain and stereochemical considerations. The structural composition of following Cucurbitacins are known and have been designated by the letters: A, B, C, D, E, F, G, H, I, J, K, L, O, P, Q, R and S. Momordica contain a special group of Cucurbitacins called momordicosides differing in possessing an aldehyde at C19 The sugar linkage is generally present at C-2 (2-O-β-glycosides) in Cucurbitacin glycosides.
Curative properties
Cucurbitacins have been proved to possess curative action against many types of cancer, inflammation, artherosclerosis and diabetes.
Anticancer properies
Cucurbitacins exert anticancer effects on many types of cancers like leukemia, breast cancer, lung cancer etc through a variety of mechanisms, including inhibiting cancer cell proliferation, promoting cell cycle arrest and apoptosis, inhibiting the invasion and metastasis, and destroying the protein skeleton The most significant mechanisms with regard to the apoptotic effects of cucurbitacins are their ability to modify mitochondrial trans-membrane potential and transcriptional activities via nuclear factors or genes and their capability to activate or inhibit pro- or anti-apoptotic proteins. In general, cucurbitacins are considered to be selective inhibitors of the JAK/STAT pathways; however, other mechanisms may be implicated in their apoptotic effects, including the MAPK pathway (known to be important for cancer cell proliferation and survival), PARP cleavage, expression of active caspase-3, decreased pSTAT3 and JAK3 levels, as well as decreases in various downstream STAT3 targets such as Mcl-1, Bcl-2, Bcl-xL, and cyclin D3, all of which are implicated in apoptosis and the cell cycle control.
Anti-inflammatory activities.
Cucurcitacin analogues viz. Cucurbitacin R and DHCB have been reported to possess anti-inflammatory potential and their action is reported to be mediated by inhibition of tumor necrosis factors (TNF)-α and other mediators of inflammation such as nitric-oxide synthase-2 and cyclo-oxygenase-2.
Anti plaque activities.
There have been reports on Cucurbitacin B and E in glycosidic form to exhibit inhibitory effect on lipid oxidation products like- malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE. These reports bolster the therapeutic role of Cucurbitacins in artherosclerosis, which involves modification of lipoproteins by involvement of- MDA and 4-HNE.
Anti-diabetic properties
There have been a plethora of reports on the role of Cucurbitacins for their cytotoxic, hepatoprotective, cardiovascular, and antidiabetic effects. Cucurbitane triterpenoids present in momordica fruits are noted for antidiabetic and anticancer activities, this may provide leads as a class of therapeutics for diabetes and obesity. The 5’-adenosine monophosphate-activated protein kinase (AMPK) pathway is suggested as a probable mechanism for the stimulation of GLUT4 translocation by triterpenoids from M. charantia. It is particularly interesting in relation to diabetes and obesity because activation of AMPK increases fatty acid oxidation, inhibits lipid synthesis, and can improve insulin action. An analogue of 23,24-dihydrocucurbitacin F from Hintonia latiflora has been reported to possess significant hypoglycemic and antihyperglycemic effects. The probable mechanism underlying-- antihyperglycemic effect could be stimulation of insulin release and regulation of hepatic glycogen metabolism.
Other activities
Othe beneficial properties of Cucurbitacins include Spider mite resistance, antioxidant, increasing the rat capillary permeability and to demonstrate antifertility effects in female mice, act as allomones in many plant species and anti-feedants for few insects, birds and as kairomones
Toxicity
Cucurbitacins are highly toxic compounds and instances of severe poisoning and death in sheep and cattle that consumed bitter fruits of Cucumis and Cucurbita are well documented. The range of toxicity of Cucurbitacins based on few in-vivo toxicity reports, has been found to be between 2 -12.5 mg/kg.
Main Reference
Ujjwal Kaushik, Vidhu Aeri, and Showkat R. Mir (2015) Cucurbitacins – An insight into medicinal leads from nature, Pharmacogn Rev. 2015 Jan-Jun; 9(17): 12–18.
doi: 10.4103/0973-7847.156314
Mammen Daniel
