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Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation.
Biochem Pharmacol. 2015 Mar 15; 94(2):142-54.BP

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+Show Affiliations

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.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.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.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.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.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.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25677765

Citation

Sun, Yang, et al. "Wogonoside Protects Against Dextran Sulfate Sodium-induced Experimental Colitis in Mice By Inhibiting NF-κB and NLRP3 Inflammasome Activation." Biochemical Pharmacology, vol. 94, no. 2, 2015, pp. 142-54.
Sun Y, Zhao Y, Yao J, et al. Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation. Biochem Pharmacol. 2015;94(2):142-54.
Sun, Y., Zhao, Y., Yao, J., Zhao, L., Wu, Z., Wang, Y., Pan, D., Miao, H., Guo, Q., & Lu, N. (2015). Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation. Biochemical Pharmacology, 94(2), 142-54. https://doi.org/10.1016/j.bcp.2015.02.002
Sun Y, et al. Wogonoside Protects Against Dextran Sulfate Sodium-induced Experimental Colitis in Mice By Inhibiting NF-κB and NLRP3 Inflammasome Activation. Biochem Pharmacol. 2015 Mar 15;94(2):142-54. PubMed PMID: 25677765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation. AU - Sun,Yang, AU - Zhao,Yue, AU - Yao,Jing, AU - Zhao,Li, AU - Wu,Zhaoqiu, AU - Wang,Yu, AU - Pan,Di, AU - Miao,Hanchi, AU - Guo,Qinglong, AU - Lu,Na, Y1 - 2015/02/10/ PY - 2014/11/07/received PY - 2015/02/02/revised PY - 2015/02/02/accepted PY - 2015/2/14/entrez PY - 2015/2/14/pubmed PY - 2015/5/1/medline KW - 5-ASA (PubChem CID: 4075) KW - CMC (PubChem CID: 6328154) KW - Colitis KW - DAPI (PubChem CID: 2954) KW - DMSO (PubChem CID: 679) KW - IL-1β KW - LPS (PubChem CID: 53481793) KW - NF-κB KW - NLRP3 inflammasome KW - PMA (PubChem CID: 27924) KW - Wogonoside KW - Wogonoside (PubChem CID: 29927693) SP - 142 EP - 54 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 94 IS - 2 N2 - 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. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/25677765/Wogonoside_protects_against_dextran_sulfate_sodium_induced_experimental_colitis_in_mice_by_inhibiting_NF_κB_and_NLRP3_inflammasome_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(15)00088-X DB - PRIME DP - Unbound Medicine ER -