Geniposide and Chlorogenic Acid Combination Ameliorates Non-alcoholic Steatohepatitis Involving the Protection on the Gut Barrier Function in Mouse Induced by High-Fat Diet

Abstract

Gut-liver axis is increasingly recognized to be involved in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD). The gut microbiota and intestinal permeability have been demonstrated to be the key players in the gut-liver cross talk in NAFLD. Geniposide and chlorogenic acid (GC) combination is derived from a traditional Chinese medicine, Qushi Huayu Decoction (QHD), which has been used in clinic for NAFLD treatment for decades in China and validated in multiple animal models of NAFLD. GC combination previously has been demonstrated to treat NAFLD via modulation on the gut microbiota composition. In the present study, the effects of GC combination on gut barrier function in NAFLD were evaluated, and QHD and sodium butyrate (NaB), the intestinal mucosa protectant, were used as positive control. The therapeutic effect of GC combination on NAFLD were confirmed by amelioration on non-alcoholic steatohepatitis (NASH) induced by high-fat diet (HFD) in mouse, which was comparable to that of QHD. Simultaneously, GC combination was found to reduce the signaling of gut-derived lipopolysaccharide (LPS) including hepatic LPS binding protein, Toll like receptor 4, interleukin-1β, tumor necrosis factor –α, and Kupffer cells infiltration. Furthermore, GC combination reduced LPS and D-lactate in plasma, restoring the colonic tight junction (TJ) expression and inhibited colonic TJs disassembly by down-regulation on RhoA/ROCK signaling in NASH induced by HFD. On the other hand, NASH was also alleviated in NaB group. The results of the present study suggested the important role of protection on gut barrier function in NAFLD treatment, which contributed to the therapeutic effects of GC combination on NASH.

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

“…However, we, for the first time, demonstrated the neuroprotective effects of geniposide against LPS injury. Besides this, the neuroprotective effects of geniposide may attribute to its anti-apoptotic and anti-inflammatory properties, which were in line with findings reported elsewhere [26,27]. More interestingly, in vitro data displayed that geniposide was able to increase the viability of LPS-injured cells.…”

Supplemental Plant Extracts From Flos lonicerae in Combination With Baikal skullcap Attenuate Intestinal Disruption and Modulate Gut Microbiota in Laying Hens Challenged by Salmonella pullorum

“…It was also reported that chlorogenic acid or baicalin addition modulated immune responses and improved intestinal homeostasis in pigs and mice (Chen et al, 2018b; Wu S.C. et al, 2018). A combination of the supplementation of chlorogenic acid and geniposide (a kind of glycoside that similar to baicalin in structure) was demonstrated to mitigate high-fat diet-induced intestinal inflammation and barrier dysfunction in mice (Peng et al, 2018). Accordingly, addition of the extracts from Flos lonicerae and Baikal skullcap may exert active roles in protecting the intestinal tract in chickens.…”

Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

“…Geniposide (GE), an iridoid glycoside derived from the gardenia plant, has a series of pharmacological effects, including antioxidative stress, antiapoptosis, anti-inflammatory, anti-ER stress, and other pharmacological effects [20–22]. Our previous study demonstrated that GE could attenuate the development of pressure overload-induced cardiac hypertrophy and prevent obesity-related cardiac complications via activation of AMPK α [16, 17].…”