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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 25–100mg/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$\mu$M of geniposide for 4h. Myeloperoxidase (MPO) activity and Interleukin-1$\beta$ (IL-1$\beta )$ levels were measured using MPO activity kits and IL-1$\beta$ 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.

Blockade of the NOD-like receptor protein 3 (NLRP3) inflammasome has been shown to be effective in halting the progression of non-alcoholic steatohepatitis (NASH). Antrodia cinnamomea is a well-known indigenous medicine used by Taiwanese aboriginal tribes. However, its effect on NASH remains unclear. This study aimed to examine the mechanistic insight of Antrodia cinnamomea extract (ACE) in both in vitro and in vivo models of NASH. Murine RAW264.7 macrophages and human hepatocellular carcinoma HepG2 cells were treated with the indicated concentration of ACE 30 minutes prior to stimulation with lipopolysaccharide (LPS) for 24 h. Levels of inflammatory markers, NLRP3 inflammasome, components, and endoplasmic reticulum (ER) stress markers were analyzed by Western blotting. For the in vivo experiments, male C57BL/6 mice weighing 21–25 g were fed a methionine/choline deficient (MCD) diet along with vehicle or ACE (100 mg/kg) for 10 consecutive days. The serum glutamate pyruvate transaminase (SGPT) levels of the mice were measured. The liver tissues from the mice underwent histological analysis (hematoxylin and eosin staining), and the levels of inflammatory markers, NLRP3 inflammasome components, and autophagy-related proteins were evaluated. ACE significantly inhibited NLRP3 inflammasome activation in vitro and in vivo. In addition, ACE attenuated the severity of MCD-induced steatohepatitis, reduced the levels of oxidative stress markers, and ameliorated inflammatory responses, but restored autophagic flux. Based on these findings, Antrodia cinnamomea could be developed into an anti-non-alcoholic fatty liver disease/NASH agent.

Chronic pancreatitis (CP) is a multifactorial, inflammatory syndrome characterized by acinar atrophy and fibrosis. Activation of NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome is a central mediator of multiple chronic inflammatory responses and chronic fibrosis including pancreatic fibrosis in CP. The Psidium guajavaleaf is widely used in traditional medicine for the treatment of chronic inflammation, but the anti-inflammatory effect of Psidium guajavaleaf on CP has not yet been revealed. In this study, we investigated whether the extract of total flavonoids from Psidium guajava leaves (TFPGL) plays a therapeutic mechanism on CP through NLRP3 inflammasome signaling pathway in a mouse CP model. The H&E and acid-Sirius red staining indicted that TFPGL attenuated the inflammatory cell infiltration and fibrosis significantly. The results of immunohistological staining, western blot and RT-qPCR showed that the expressions of NLRP3 and caspase-1 were significantly increased in the CP model group, while TFPGL significantly decreased the NLRP3 and caspase-1 expression at both the gene and protein levels. Moreover, ELISA assay was used to examine the levels of NLRP3 inflammasome target genes, such as caspase-1, IL-1$\beta$ and IL-18. We found that TFPGL treatment decreased the expression of caspase-1, IL-1$\beta$ and IL-18, which is critical for the NLRP3 inflammasome signaling pathway and inflammation response significantly. These results demonstrated that TFPGL attenuated pancreatic inflammation and fibrosis via preventing NLRP3 inflammasome activation and TFPGL can be used as a potential therapeutic agent for CP.