Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation.
Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S-linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1 was highly selective in inhibiting cyclooxygenase-2 (COX-2) enzyme by 60% at 100 microm with no activity against COX-1 enzyme. The IC(50) values of compound 1 against human gastric (AGS), breast (MCF-7), central nervous system (SF-268) and colon (HCT-116) cancer cell lines were in the range 0.74-3.63 microm. Both S-containing dimeric withanolides, 1 and 2, completely suppressed TNF-induced NF-kappaB activation when tested at 100 microm. The isolation of a withanolide sulfoxide from W. somnifera roots and its ability to inhibit COX-2 enzyme and to suppress human tumor cell proliferation are reported here for the first time. In addition, this is the first report on the abrogation of TNF-induced NF-kappaB activation for compounds 1 and 2.
Mulabagal
Vanisree
V
Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food, Safety and Toxicology Center, Michigan State University, East Lansing, Michigan, USA.
Subbaraju
Gottumukkala V
GV
Rao
Chirravuri V
CV
Sivaramakrishna
Chillara
C
Dewitt
David L
DL
Holmes
Daniel
D
Sung
Bokyung
B
Aggarwal
Bharat B
BB
Tsay
Hsin-Sheng
HS
Nair
Muraleedharan G
MG
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004875:Ergosterol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D013454:Sulfoxides / Q000302:isolation & purification / Q000494:pharmacology*; D032341:Withania / Q000737:chemistry; D054358:Withanolides / Q000302:isolation & purification / Q000494:pharmacology*
D016328:NF-kappa B; D010936:Plant Extracts; D013454:Sulfoxides; D054358:Withanolides; C516508:ashwagandhanolide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D004875:Ergosterol