title: Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation.
abstract: Previous studies have demonstrated that wogonoside, the glucuronide metabolite of wogonin, has anti-inflammatory, anti-angiogenic and anticancer effects. However, the anti-inflammatory mechanism of wogonoside has not been fully elucidated. Recently, NLRP3 inflammasome has been reported to be correlated with inflammatory bowel disease for its ability to induce IL-1β release. Nevertheless, there are few drug candidates targeting NLRP3 inflammasome for this disease. In this study, we investigated the anti-inflammatory effect of wogonoside in dextran sulfate sodium (DSS)-induced murine colitis and further revealed the underlying mechanisms by targeting NF-κB and NLRP3 inflammasome. Wogonoside treatment dose-dependently attenuated DSS-induced body weight loss and colon length shortening. Moreover, wogonoside prevented DSS-induced colonic pathological damage, remarkably inhibited inflammatory cells infiltration and significantly decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities. The production of pro-inflammatory mediators in serum and colon was also significantly reduced by wogonoside. The underlying mechanisms for the protective effect of wogonoside in DSS-induced colitis may be attributed to its inhibition on NF-κB and NLRP3 inflammasome activation in colons. Furthermore, wogonoside markedly decreased production of IL-1β, TNF-α and IL-6 and suppressed mRNA expression of pro-IL-1β and NLRP3 in phorbol myristate acetate (PMA)-differentiated monocytic THP-1 cells via inhibiting the activation of NF-κB and NLRP3 inflammasome. In conclusion, our study demonstrated that wogonoside may exert its anti-inflammatory effect via dual inhibition of NF-κB and NLRP3 inflammasome, suggesting that wogonoside might be a potential effective drug for inflammatory bowel diseases.
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Yang
authors: Y
authors: Sun
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Yue
authors: Y
authors: Zhao
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Jing
authors: J
authors: Yao
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Li
authors: L
authors: Zhao
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Zhaoqiu
authors: Z
authors: Wu
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Yu
authors: Y
authors: Wang
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Di
authors: D
authors: Pan
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Hanchi
authors: H
authors: Miao
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: anticancer_drug@163.com.
authors: Qinglong
authors: Q
authors: Guo
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Na
authors: N
authors: Lu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D017931:DNA Primers; D016264:Dextran Sulfate / Q000633:toxicity*; D044950:Flavanones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D044950:Flavanones; D005960:Glucosides; D058847:Inflammasomes; D018836:Inflammation Mediators; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D016264:Dextran Sulfate; C473995:wogonoside
keywords: 5-ASA (PubChem CID: 4075); CMC (PubChem CID: 6328154); Colitis; DAPI (PubChem CID: 2954); DMSO (PubChem CID: 679); IL-1β; LPS (PubChem CID: 53481793); NF-κB; NLRP3 inflammasome; PMA (PubChem CID: 27924); Wogonoside; Wogonoside (PubChem CID: 29927693)