Dahuang Zexie Decoction Protects against High‐Fat Diet‐Induced NAFLD by Modulating Gut Microbiota‐Mediated Toll‐Like Receptor 4 Signaling Activation and Loss of Intestinal Barrier

Abstract

Increasing evidence suggests that intestinal dysbiosis, intestinal barrier dysfunction, and activated Toll-like receptor 4 (TLR4) signaling play key roles in the pathogenesis of NAFLD. Dahuang Zexie Decoction (DZD) has been verified to be effective for treating NAFLD, but the mechanisms remain unclear. In this study, we investigated the effects of DZD on NAFLD rats and determined whether such effects were associated with change of the gut microbiota, downregulated activity of the TLR4 signaling pathway, and increased expressions of tight junction (TJ) proteins in the gut. Male Sprague Dawley rats were fed high-fat diet (HFD) for 16 weeks to induce NAFLD and then given DZD intervention for 4 weeks. We found that DZD reduced body and liver weights of NAFLD rats, improved serum lipid levels and liver function parameters, and relieved NAFLD. We further found that DZD changed intestinal bacterial communities, inhibited the intestinal TLR4 signaling pathway, and restored the expressions of TJ proteins in the gut. Meanwhile ten potential components of DZD had been identified. These findings suggest that DZD may protects against NAFLD by modulating gut microbiota-mediated TLR4 signaling activation and loss of intestinal barrier. However, further studies are needed to clarify the mechanism by which DZD treats NAFLD.

Combined effect of a farnesoid X receptor agonist and dipeptidyl peptidase‐4 inhibitor on hepatic fibrosis

“…We previously showed that TLR4‐mediated signaling in intestinal epithelial cells regulated hepatic fibrogenesis in porcine serum‐treated diabetic rats . Activation of TLR4 in the intestine induces intestinal mucosal inflammation by mediating ERK and c‐Jun NH2‐terminal kinase phosphorylations in high‐fat diet‐fed Sprague–Dawley rats . Moreover, OCA reduces bacterial translocation along with intestinal mucosal TLR4 signaling and inhibits intestinal inflammation in a CCl4‐induced hepatic cirrhosis rat model .…”

“…33 Activation of TLR4 in the intestine induces intestinal mucosal inflammation by mediating ERK and c-Jun NH2-terminal kinase phosphorylations in high-fat diet-fed Sprague-Dawley rats. 35 Moreover, OCA reduces bacterial translocation along with intestinal mucosal TLR4 signaling and inhibits intestinal inflammation in a CCl4-induced hepatic cirrhosis rat model. 11 The reason for the difference in the role of intestinal TLR4 signaling between these models remains indiscernible but could be related to the fact that intestinal epithelial cell expression of TLR4 differs among strains and species.…”

Role of Chrysophanol in Epithelial‐Mesenchymal Transition in Oral Cancer Cell Lines via a Wnt‐3‐Dependent Pathway

“…Therefore, ROS may be considered as a therapeutic target in the progression of oral cancer. Dahuang, the roots of Rheum palmatum , a well-known traditional Chinese herb used for chronic kidney disease and liver disease [ 9 , 10 ]. Chrysophanol, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, has been reported to inhibit proliferation and induces apoptosis through the NF- κ B/cyclin D1 and NF- κ B/Bcl-2 signaling cascade in breast cancer cell lines [ 11 ].…”

Chrysophanol Prevents Lipopolysaccharide‐Induced Hepatic Stellate Cell Activation by Upregulating Apoptosis, Oxidative Stress, and the Unfolded Protein Response

“…Dahuang, the root of Rheum palmatum L., is a wellknown traditional Chinese herbal medicine that has been used to treat chronic liver disease and inflammation [9,10]. Chrysophanol is an anthraquinone derivative isolated from the rhizomes of R. palmatum L. Previous studies demonstrated that chrysophanol shows anticancer, hepatoprotective, neuroprotective, anti-inflammatory, antiulcer, and antimicrobial activities [11][12][13].…”

“…Dahuang, the root of Rheum palmatum L ., is a well-known traditional Chinese herbal medicine that has been used to treat chronic liver disease and inflammation [ 9 , 10 ]. Chrysophanol is an anthraquinone derivative isolated from the rhizomes of R. palmatum L .…”