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      Cucurbitacins – An insight into medicinal leads from nature

      Pharmacognosy Reviews
      Medknow Publications
      cucurbitaceae, cucurbitacin, triterpenoids

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          Abstract

          Cucurbitacins which are structurally diverse triterpenes found in the members of Cucurbitaceae and several other plant families possess immense pharmacological potential. This diverse group of compounds may prove to be important lead molecules for future research. Research focused on these unattended medicinal leads from the nature can prove to be of immense significance in generating scientifically validated data with regard to their efficacy and possible role in various diseases. This review is aimed to provide an insight into the chemical nature and medicinal potential of these compounds exploring their proposed mode of action, probable molecular targets and to have an outlook on future directions of their use as medicinal agents.

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          Most cited references153

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          STAT proteins: novel molecular targets for cancer drug discovery.

          Signal Transducers and Activators of Transcription (STATs) are a family of cytoplasmic proteins with roles as signal messengers and transcription factors that participate in normal cellular responses to cytokines and growth factors. Frequently, however, abnormal activity of certain STAT family members, particularly Stat3 and Stat5, is associated with a wide variety of human malignancies, including hematologic, breast, head and neck, and prostate cancers. Application of molecular biology and pharmacology tools in disease-relevant models has confirmed Stat3 as having a causal role in oncogenesis, and provided validation of Stat3 as a target for cancer drug discovery and therapeutic intervention. Furthermore, a constitutively-active mutant form of Stat3 is sufficient to induce oncogenic transformation of cells, which form tumors in vivo. Constitutive activation of Stat3 signaling is accompanied by upregulation of cyclin D1, c-Myc, and Bcl-x, changes consistent with subversion of normal cellular growth and survival control mechanisms. Block of constitutive Stat3 signaling results in growth inhibition and apoptosis of Stat3-positive tumor cells in vitro and in vivo. The observed dependence of certain tumors on constitutive Stat3 signaling for growth and survival has wide implications for cancer therapy, offering the potential for preferential tumor cell killing. This review evaluates constitutive Stat3 activation as a 'cancer-causing' factor, and proposes a number of molecular strategies for targeting Stat3 signaling for therapeutic intervention.
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            Cytotoxicity and genotoxicity of lipid-oxidation products.

            The autoxidation of unsaturated lipids contained in oils, fats, and food and the endogenous oxidative degradation of membrane lipids by lipid peroxidation result in the formation of a very complex mixture of lipid hydroperoxides, chain-cleavage products, and polymeric material. Experimental animal studies and biochemical investigations lend support to the hypothesis that lipid-oxidation products, ingested with food or produced endogenously, represent a health risk. The oral toxicity of oxidized lipids is unexpectedly low. Chronic uptake of large amounts of such materials increases tumor frequency and incidence of atherosclerosis in animals. 4-Hydroxynonenal, a chain-cleavage product resulting from omega 6 fatty acids, disturbs gap-junction communications in cultured endothelial cells and induces several genotoxic effects in hepatocytes and lymphocytes. Although the concentrations of the aldehyde needed to produce these effects are in the range expected to occur in vivo, their pathological significance is far from clear. Recent findings strongly suggest that in vivo modification of low-density lipoprotein by certain lipid-peroxidation products (eg, 4-hydroxynonenal and malonaldehyde) renders this lipoprotein more atherogenic and causes foam-cell formation. Proteins modified by 4-hydroxynonenal and malonaldehyde were detected by immunological techniques in atherosclerotic lesions.
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              Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway.

              Four cucurbitane glycosides, momordicosides Q, R, S, and T, and stereochemistry-established karaviloside XI, were isolated from the vegetable bitter melon (Momordica charantia). These compounds and their aglycones exhibited a number of biologic effects beneficial to diabetes and obesity. In both L6 myotubes and 3T3-L1 adipocytes, they stimulated GLUT4 translocation to the cell membrane--an essential step for inducible glucose entry into cells. This was associated with increased activity of AMP-activated protein kinase (AMPK), a key pathway mediating glucose uptake and fatty acid oxidation. Furthermore, momordicoside(s) enhanced fatty acid oxidation and glucose disposal during glucose tolerance tests in both insulin-sensitive and insulin-resistant mice. These findings indicate that cucurbitane triterpenoids, the characteristic constituents of M. charantia, may provide leads as a class of therapeutics for diabetes and obesity.
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                Author and article information

                Journal
                26009687
                4441156
                10.4103/0973-7847.156314
                http://creativecommons.org/licenses/by-nc-sa/3.0

                Pharmacology & Pharmaceutical medicine
                cucurbitaceae,cucurbitacin,triterpenoids
                Pharmacology & Pharmaceutical medicine
                cucurbitaceae, cucurbitacin, triterpenoids

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