Systematic understanding of the mechanism and effects of Arctigenin attenuates inflammation in dextran sulfate sodium-induced acute colitis through suppression of NLRP3 inflammasome by SIRT1

  • Am J Transl Res. 2019 Jul 15;11(7):3992-4009.
Zhichen Pu  1 ,  Chengzheng Han  2 ,  Weiwei Zhang  3 ,  Maodi Xu  1 ,  Zijing Wu  1 ,  Yanhao Liu  1 ,  Min Wu  4 ,  Hui Sun  5 ,  Haitang Xie  1
Affiliations
  • 1. Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College Wuhu 241001, Anhui, China.
  • 2. Clinic of Integrated Traditional Chinese and Western Medicine, Yijishan Hospital of Wannan Medical College Wuhu 241001, Anhui, China.
  • 3. Department of Pharmacy, Fourth People's Hospital of Maanshan Maanshan 243031, Anhui, China.
  • 4. Department of Drug Consumption Supply, Wuhu Second People's Hospital Wuhu 241001, Anhui, China.
  • 5. State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University Tongjiaxiang 24, Nanjing 210009, China.
PMID: 31396314
Abstract

Arctigenin (ARC-G) is the main active ingredient extracted from Great Burdock Achene, with extensive pharmacological effects. In addition, ARC-G has been suggested to show excellent efficacy on inflammatory disease. This study aimed to defined that the function of Arctigenin attenuates inflammation in dextran sulfate sodium (DSS)-induced acute colitis, to determine its possible mechanism. Mice was induced by giving 2.0% DSS in the drinking water for DSS-induced acute colitis. Mice of acute colitis were injected intraperitoneally with 20 mg/kg per day of Arctigenin for 7 days. MPO activity levels were measured using MPO activity kits. Western Blot Analysis was used to determine the protein expression. Arctigenin prevents colitis and attenuates inflammation in DSS-induced acute colitis. Arctigenin suppressed NLRP3 inflammasome by SIRT1 in DSS-induced acute colitis. In THP-1 cell by LPS model, Arctigenin suppressed NLRP3, Caspase-1 and IL-1β protein expression by SIRT1. Si-NLRP3 increases the effects of Arctigenin on inflammation in THP-1 cell by LPS model. Si-SIRT1 decreases the effects of Arctigenin on inflammation in THP-1 cell by LPS model. INF39, NLRP3 Inhibitor also increased the effects of Arctigenin on inflammation in DSS-induced acute colitis. SIRT1 Inhibitor also decreases the effects of Arctigenin on inflammation in DSS-induced acute colitis. Taken together our results demonstrated that Arctigenin attenuates inflammation in DSS-induced acute colitis through suppression of NLRP3 inflammasome by SIRT1.

Keywords
Arctigenin; NLRP3; SIRT1; acute colitis.
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