Using Network Pharmacology for Systematic Understanding of Geniposide in Ameliorating Inflammatory Responses in Colitis Through Suppression of NLRP3 Inflammasome in Macrophage by AMPK/Sirt1 Dependent Signaling.

Ulcerative colitis is a chronic and recurrent inflammatory bowel disease mediated by immune response. Geniposide is the main active ingredient extracted from Gardenia jasminoides, which has been suggested to exert excellent efficacy on inflammatory disease. Herein, in this study, we aimed to uncover the systematic understanding of the mechanism and effects of geniposide in ameliorating inflammatory responses in colitis. In brief, the TCMSP server and GEO DataSets were used to analyze the systematic understanding of the mechanism and effects of geniposide in ameliorating inflammatory responses in colitis. Dextran Sulfate Sodium (DSS)-induced acute colitis of mice were administered with 25-100[Formula: see text]mg/kg of geniposide for 7 days by gavage. Lipopolysaccharide (LPS)-induced Bone Marrow Derived Macrophage (BMDM) cell or RAW264.7 cell models were treated with 20, 50 and 100[Formula: see text][Formula: see text]M of geniposide for 4[Formula: see text]h. Myeloperoxidase (MPO) activity and Interleukin-1[Formula: see text] (IL-1[Formula: see text] levels were measured using MPO activity kits and IL-1[Formula: see text] levels enzyme-linked immunosorbent assay (ELISA) kits, respectively. Additionally, Western blot was used to determine the relevant protein expression. As a result, Geniposide could ameliorate inflammatory responses and prevent colitis in DSS-induced acute colitis of mice by activating AMP-activated protein kinase (AMPK)/Transcription 1 (Sirt1) dependent signaling via the suppression of nod-like receptor protein 3 (NLRP3) inflammasome. Geniposide attenuated macrophage differentiation in DSS-induced acute colitis of mice. Geniposide suppressed NLRP3 inflammasome and induced AMPK/Sirt1 signaling in LPS-induced BMDM cell or RAW264.7 cell models. In mechanism studies, the inhibition of AMPK/Sirt1 attenuated the anti-inflammatory effects of geniposide in colitis. The activation of NLRP3 attenuated the anti-inflammatory effects of geniposide in colitis. Taken together, our results demonstrated that geniposide ameliorated inflammatory responses in colitis vai the suppression of NLRP3 inflammasome in macrophages by AMPK/Sirt1-dependent signaling.

[1]  Wenjian Tang,et al.  Antidepressant-like effects of penta-acetyl geniposide in chronic unpredictable mild stress-induced depression rat model: Involvement of inhibiting neuroinflammation in prefrontal cortex and regulating hypothalamic-pituitaryadrenal axis. , 2020, International immunopharmacology.

[2]  P. Dhawan,et al.  Curcumin use in ulcerative colitis: is it ready for prime time? A systematic review and meta-analysis of clinical trials , 2019, Annals of gastroenterology.

[3]  S. Piao,et al.  Protectin DX attenuates IL-1β-induced inflammation via the AMPK/NF-κB pathway in chondrocytes and ameliorates osteoarthritis progression in a rat model. , 2019, International immunopharmacology.

[4]  Zhitao Feng,et al.  Efficacy of herbal medicine (Gegen Qinlian Decoction) on ulcerative colitis , 2019, Medicine.

[5]  Yanjiang Qiao,et al.  Optimization of PLS modeling parameters via quality by design concept for Gardenia jasminoides Ellis using online NIR sensor. , 2019, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[6]  S. Targan,et al.  Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. , 2019, The New England journal of medicine.

[7]  Yiming Lin,et al.  Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways , 2019, World journal of gastroenterology.

[8]  Li Yingchao,et al.  Effect of Tripterygium wilfordii Polycoride on the NOXs-ROS-NLRP3 Inflammasome Signaling Pathway in Mice with Ulcerative Colitis , 2019, Evidence-based complementary and alternative medicine : eCAM.

[9]  N. Soliman,et al.  Mechanistic evaluation of AMPK/SIRT1/FXR signaling axis, inflammation, and redox status in thioacetamide-induced liver cirrhosis: The role of Cichorium intybus linn (chicory)-supplemented diet. , 2019, Journal of food biochemistry.

[10]  K. Tufekci,et al.  Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway , 2019, Front. Immunol..

[11]  Chao Liu,et al.  Catechin attenuates TNF-α induced inflammatory response via AMPK-SIRT1 pathway in 3T3-L1 adipocytes , 2019, PloS one.

[12]  Zhenzhong Wang,et al.  Comparative analysis of sixteen active compounds and antioxidant and anti-influenza properties of Gardenia jasminoides fruits at different times and application to the determination of the appropriate harvest period with hierarchical cluster analysis. , 2019, Journal of ethnopharmacology.

[13]  Hu Zhang,et al.  NLRP3 Inflammasome and Inflammatory Bowel Disease , 2019, Front. Immunol..

[14]  Maodi Xu,et al.  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. , 2019, American journal of translational research.

[15]  R. Eri,et al.  NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis , 2018, International journal of molecular sciences.

[16]  C. Kong,et al.  Geniposide Protects against Obesity-Related Cardiac Injury through AMPKα- and Sirt1-Dependent Mechanisms , 2018, Oxidative medicine and cellular longevity.

[17]  Bangshun He,et al.  Ginsenoside Rd ameliorates colitis by inducing p62‐driven mitophagy‐mediated NLRP3 inflammasome inactivation in mice , 2018, Biochemical pharmacology.

[18]  C. Kong,et al.  Geniposide Alleviates Isoproterenol-Induced Cardiac Fibrosis Partially via SIRT1 Activation in vivo and in vitro , 2018, Front. Pharmacol..

[19]  K. Schroder,et al.  MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice , 2018, Scientific Reports.

[20]  Ming Xu,et al.  Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function , 2017, Acta Pharmacologica Sinica.

[21]  S. Chiou,et al.  Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis. , 2014, Biochemical pharmacology.

[22]  Fengqin Wang,et al.  Selenium‑enriched exopolysaccharides produced by Enterobacter cloacae Z0206 alleviate adipose inflammation in diabetic KKAy mice through the AMPK/SirT1 pathway. , 2014, Molecular medicine reports.

[23]  F. Fan,et al.  Resveratrol Inhibits Ionising Irradiation-Induced Inflammation in MSCs by Activating SIRT1 and Limiting NLRP-3 Inflammasome Activation , 2013, International journal of molecular sciences.