Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG2through nuclear factor-κB pathway.
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.
Bio-organic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, 211007, India.
Amita
A
Verma
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India.
Bahar
B
Ahmed
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Firoz
F
Anwar
Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, 211007, India.
Mahfoozur
M
Rahman
Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, 211007, India.
Dinesh Kumar
DK
Patel
Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, UP, 226025, India.
Gaurav
G
Kaithwas
Clinical Laboratory Sciences, Sam Higginbottom University of Agriculture, technology & Sciences, Allahabad, Uttar Pradesh, 211007, India.
Ravi
R
Rani
Microbial and Pharmaceutical Biotechnology Laboratory, Centre for Advanced Research in Pharmaceutical Science, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India.
Prakash C
PC
Bhatt
Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, 211007, India. phvikas@gmail.com.
Vikas
V
Kumar
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000633:toxicity; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D031209:Wedelia
D006027:Glycosides; D016328:NF-kappa B; D010936:Plant Extracts; D004052:Diethylnitrosamine; D051546:Cyclooxygenase 2; D015232:Dinoprostone
Diethylnitrosamine; Ferric nitrilotriacetate; Inflammation; Pro-inflammatory cytokines; Reactive oxygen species