Search for a novel antioxidant, anti-inflammatory/analgesic or anti-proliferative drug: cucurbitacins hold the ace.

Abstract

Cucurbitacins are triterpenoid steroids reported to have several biological activities and are predominantly isolated from Cucurbitaceae family. They are efficient anti-oxidant and this property lies in their ability to scavenge free-radicals such as hydroxyl radical, superoxide anions and singlet oxygen. This broad spectrum radical-scavenging capacity surpasses what had been reported for other natural antioxidants such as grape-seed extract, wheat, alfalfa and ginkgo biloba extracts. Reports also show that cucurbitacins adequately inhibit lipid peroxidation and oxidation. Two cucurbitacins, 23, 24 dihydrocucurbitacin and cucurbitacin R isolated from the root of Cayaponia tayuya exhibit the anti-inflammatory and analgesic properties typical of cucurbitacins. The mechanism lies in their ability to inhibit the expression of TNF in macrophages and lymphocytes and the expression of such pro-inflammatory mediators such as nitric-oxide synthase-2 and cyclooxygenase-2.Cucurbitacins display strong anti-tumorigenic activity. Abnormal activation of STAT3 is prevalent in breast, pancreatic, ovarian, head and neck, brain, and prostate carcinomas, as well as in melanomas, leukemias, and lymphomas. In those tumors investigated, aberrant STAT3 activation is required for growth and survival. Antiproliferative effect of cucurbitacins is mediated through suppression of phosphotyrosine STAT3 levels which results in the inhibition of STAT3 DNA binding. Studies showed that cucurbitacins induce dramatic changes in the cytoskeleton, inhibit proliferation and induce significant S-phase cell cycle arrest and apoptosis. It is a general knowledge among researchers working with natural medicinal products that any of the cucurbitacins have the attributes or potential to become fully patented as anti-inflammatory or anti-cancer drug. Key words: Antioxidant, anti-inflammatory, analgesic, anti-proliferative, cucurbitacins.