Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG₂ through nuclear factor-κB pathway

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• 作者：Amita Verma ; Bahar Ahmed ; Firoz Anwar ; Mahfoozur Rahman…
• 关键词：Diethylnitrosamine ; Ferric nitrilotriacetate ; Reactive oxygen species ; Inflammation ; Pro ; inflammatory cytokines
• 刊名：Inflammopharmacology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：25
• 期：1
• 页码：159-175
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Immunology; Rheumatology; Gastroenterology; Dermatology; Allergology;
• 出版者：Springer International Publishing
• ISSN：1568-5608
• 卷排序：25

文摘

A new compound derivative of glycoside 19-α-hydroxy-ursolic acid glucoside (19-α-hydroxyurs-12(13)-ene-28-oic acid-3-O-β-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 (PGE₂) expression via nuclear factor-kappa B (NF-κB) pathway.