title: The Anti-inflammatory Activities of Two Major Withanolides from Physalis minima Via Acting on NF-κB, STAT3, and HO-1 in LPS-Stimulated RAW264.7 Cells.
abstract: Physalis minima has been traditionally used as a folk herbal medicine in China for the treatment of many inflammatory diseases. However, little is known about its anti-inflammatory constituents and associated molecular mechanisms. In our study, withaphysalin A (WA) and 2, 3-dihydro-withaphysalin C (WC), two major withanolide-type compounds, were obtained from the anti-inflammatory fraction of P. minima. Both WA and WC significantly inhibited the production of nitrite oxide (NO), prostaglandin E2(PGE2), and several pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Further research indicated that they downregulated the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, they also suppressed nuclear translocation of NF-κB p65, phosphorylation of STAT3, and upregulated HO-1 expression. Intriguingly, the activation of MAPKs was suppressed by WA but was not altered by WC. Taken together, these data provide scientific evidence for elucidating the major bioactive constituents and related molecular mechanisms for the traditional use of P. minima and suggest that WA and WC can be attractive therapeutic candidates for various inflammatory diseases.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. luojun1981ly@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. cpu_lykong@126.com.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D032321:Physalis / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012632:Secosteroids / Q000302:isolation & purification / Q000494:pharmacology*; D054358:Withanolides / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D012632:Secosteroids; D054358:Withanolides; C000617973:withaphysalin A; C012610:withaphysalin C; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D051546:Cyclooxygenase 2; D004875:Ergosterol
keywords: 2, 3-dihydro-withaphysalin C; RAW264.7; inflammatory diseases; lipopolysaccharide; nitric oxide; withaphysalin A