Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG(2) through nuclear factor-kappa B pathway

作者：Verma Amita; Ahmed Bahar; Anwar Firoz; Rahman Mahfoozur; Patel Dinesh Kumar; Kaithwas Gaurav; Rani Ravi; Bhatt Prakash C; Kumar Vikas^*

来源：InflammoPharmacology, 2017, 25(1): 159-175.

DOI：10.1007/s10787-017-0310-y

• Diethylnitrosamine
• Ferric nitrilotriacetate
• Reactive oxygen species
• Inflammation
• Pro-inflammatory cytokines

A new compound derivative of glycoside 19-alpha-hydroxy-ursolic acid glucoside (19-alpha-hydroxyurs-12(13)-ene-28-oic acid-3-O-beta-d-glucopyranoside (HEG) was isolated from whole plant of Wedelia calendulacea (Compositae). The structure was elucidated and established by standard spectroscopy approaches. Diethylnitrosamine (DEN) (200 mg/kg) and ferric nitrilotriacetate (Fe-NTA) (9 mg/kg) were used for induction of renal cell carcinoma (RCC) in the rats. The rats were further divided into different groups and were treated with HEG doses for 22 weeks. Anti-cancer effect in RCC by HEG was dose dependent to restrict the macroscopical changes as compared to DEN + Fe-NTA-control animals. Significant alteration in biochemical parameters and dose-dependent alleviation in Phase I and Phase II antioxidant enzymes were responsible for its chemo-protective nature. HEG in dose-dependent manner was significant to alter the elevated levels of pro-inflammatory cytokines and inflammatory mediators during RCC. The histopathological changes were observed in the HEG pre-treated group, which was proof for its safety concern as far as its toxicity is concerned. The isolated compound HEG can impart momentous chemo-protection against experimental RCC by suppressing the cyclooxygenase (COX-2) and prostaglandin E2 (PGE(2)) expression via nuclear factor-kappa B (NF-kappa B) pathway.

• 出版日期2017-2