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Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation.
Biochem Pharmacol. 2016 Apr 15; 106:70-81.BP

Abstract

Oroxyloside, as a metabolite of oroxylin A, may harbor various beneficial bioactivities which have rarely been reported in the previous studies. Here we established the dextran sulfate sodium (DSS)-induced experimental colitis and evaluated the anti-inflammatory effect of oroxyloside in vivo. As a result, oroxyloside attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, oroxyloside inhibited inflammatory cell infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well. The production of pro-inflammatory cytokines in serum and colon was also significantly reduced by oroxyloside. We unraveled the underlying mechanisms that oroxyloside inhibited NF-κB pathway by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) to attenuate DSS-induced colitis. Moreover, we investigated the anti-inflammatory effect and mechanisms of oroxyloside in the mouse macrophage cell line RAW264.7 and bone marrow derived macrophages (BMDM). Oroxyloside decreased several LPS-induced inflammatory cytokines, including IL-1β, IL-6 and TNF-α in RAW264.7 and BMDM. We also found that oroxyloside inhibited LPS-induced activation of NF-κB signaling pathway via activating PPARγ in RAW 264.7 and BMDM. Docking study showed that oroxyloside could bind with PPARγ. GW9662, the inhibitor of PPARγ, and PPARγ siRNA transfection blocked the effect of oroxyloside on PPARγ activation. Our study suggested that oroxyloside prevented DSS-induced colitis by inhibiting NF-κB pathway through PPARγ activation. Therefore, oroxyloside may be a promising and effective agent for inflammatory bowel disease (IBD).

Authors+Show Affiliations

Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: anticancer_drug@163.com.Jiangsu Key Laboratory of Carcinogenesis and Intervention, State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: zhaoli@cpu.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

26947454

Citation

Wang, Xiaoping, et al. "Oroxyloside Prevents Dextran Sulfate Sodium-induced Experimental Colitis in Mice By Inhibiting NF-κB Pathway Through PPARγ Activation." Biochemical Pharmacology, vol. 106, 2016, pp. 70-81.
Wang X, Sun Y, Zhao Y, et al. Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation. Biochem Pharmacol. 2016;106:70-81.
Wang, X., Sun, Y., Zhao, Y., Ding, Y., Zhang, X., Kong, L., Li, Z., Guo, Q., & Zhao, L. (2016). Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation. Biochemical Pharmacology, 106, 70-81. https://doi.org/10.1016/j.bcp.2016.02.019
Wang X, et al. Oroxyloside Prevents Dextran Sulfate Sodium-induced Experimental Colitis in Mice By Inhibiting NF-κB Pathway Through PPARγ Activation. Biochem Pharmacol. 2016 Apr 15;106:70-81. PubMed PMID: 26947454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation. AU - Wang,Xiaoping, AU - Sun,Yang, AU - Zhao,Yue, AU - Ding,Youxiang, AU - Zhang,Xiaobo, AU - Kong,Lingyi, AU - Li,Zhiyu, AU - Guo,Qinglong, AU - Zhao,Li, Y1 - 2016/03/04/ PY - 2015/11/18/received PY - 2016/02/26/accepted PY - 2016/3/8/entrez PY - 2016/3/8/pubmed PY - 2016/7/28/medline KW - 5-ASA (PubChem CID: 4075) KW - Colitis KW - DAPI (PubChem CID: 2954) KW - DMSO (PubChem CID: 679) KW - DSS sodium salt (PubChem CID: 5167273) KW - GW9662 (PubChem CID: 644213) KW - LPS (PubChem CID: 53481793) KW - MTT formazan (PubChem CID: 16218671) KW - NF-κB KW - Oroxyloside KW - Oroxyloside (PubChem CID: 91884769) KW - PPARγ SP - 70 EP - 81 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 106 N2 - Oroxyloside, as a metabolite of oroxylin A, may harbor various beneficial bioactivities which have rarely been reported in the previous studies. Here we established the dextran sulfate sodium (DSS)-induced experimental colitis and evaluated the anti-inflammatory effect of oroxyloside in vivo. As a result, oroxyloside attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, oroxyloside inhibited inflammatory cell infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well. The production of pro-inflammatory cytokines in serum and colon was also significantly reduced by oroxyloside. We unraveled the underlying mechanisms that oroxyloside inhibited NF-κB pathway by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) to attenuate DSS-induced colitis. Moreover, we investigated the anti-inflammatory effect and mechanisms of oroxyloside in the mouse macrophage cell line RAW264.7 and bone marrow derived macrophages (BMDM). Oroxyloside decreased several LPS-induced inflammatory cytokines, including IL-1β, IL-6 and TNF-α in RAW264.7 and BMDM. We also found that oroxyloside inhibited LPS-induced activation of NF-κB signaling pathway via activating PPARγ in RAW 264.7 and BMDM. Docking study showed that oroxyloside could bind with PPARγ. GW9662, the inhibitor of PPARγ, and PPARγ siRNA transfection blocked the effect of oroxyloside on PPARγ activation. Our study suggested that oroxyloside prevented DSS-induced colitis by inhibiting NF-κB pathway through PPARγ activation. Therefore, oroxyloside may be a promising and effective agent for inflammatory bowel disease (IBD). SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/26947454/Oroxyloside_prevents_dextran_sulfate_sodium_induced_experimental_colitis_in_mice_by_inhibiting_NF_κB_pathway_through_PPARγ_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(16)00133-7 DB - PRIME DP - Unbound Medicine ER -