Xia-Yu-Xue Decoction Inhibits Intestinal Epithelial Cell Apoptosis in CCl4-Induced Liver Fibrosis

Abstract

Background/Aims: Intestine-derived endotoxin is thought to play a role in the development of liver fibrosis. However, the pathological change in the intestine during liver fibrosis is still poorly understood. Here, we investigated the effects of Xia-yu-xue decoction (XYXD) on intestinal inflammation, apoptosis, and tight junction integrity in the carbon tetrachloride (CCl₄)-induced liver fibrosis. Methods: Murine liver fibrosis was developed by CCI₄ treatment three times per week over a 6-week period. The CCl₄-treated mice were divided into two groups: the CCl₄-water group (n=8, CCl₄) and the CCl₄-XYXD group (n=8, CCl₄+XYXD). The CCl₄+XYXD mice were treated with XYXD from the beginning of the first week. The expression of inflammatory cytokines and apoptotic molecules were examined using immunohistochemistry, real-time PCR, and western blot. The intestinal epithelial cell apoptosis was examined by TUNEL staining. The tight junction-related molecules, such as ZO-1, claudin, and occludin in the gut were measured by real-time PCR. Results: In CCl₄-treated mice damage of the intestinal epithelia and infiltration of inflammatory cells into the lamina propria and muscular layer were observed. Proinflammatory markers MCP-1, TNF-α, CXCL11, IL-6, and CD68 were significantly increased in the intestinal epithelia in CCI₄-treated mice. The expression of pro-apoptotic molecules including Fas and Bax was increased in the intestinal epithelia in CCI₄-treated mice compared with that in control. The number of TUNEL-positive intestinal epithelial cells was also markedly increased in CCl₄-treated mice. The expression of the tight junction proteins including ZO-1, claudin, and occludin was significantly decreased in CCI₄-treated mice compared with that in control mice. Notably, XYXD treatment ameliorated increased inflammatory markers and apoptosis-related molecules and decreased tight-junction proteins in CCl₄-treated mice. Conclusion: CCl₄-treatment increased expression of proinflammatory cytokines and pro-apoptotic molecules and disrupted tight junction integrity in the intestine. XYXD treatment ameliorated intestinal inflammation, cell death, and tight junction disintegrity induced by CCl₄ treatment, suggesting that XYXD inhibits CCl₄-mediated liver fibrosis at least in part by ameliorating the intestinal epithelial damage.

Dendrobium officinale Polysaccharide Protected CCl4-Induced Liver Fibrosis Through Intestinal Homeostasis and the LPS-TLR4-NF-κB Signaling Pathway

“…Destruction of TJ-related barrier integrity leads to increased intestinal permeability and increased inflammation (Wen et al, 2014). Previous studies have demonstrated that "Xia-Yu-Xue Decoction" reversed histological changes caused by CCl 4 and restored intestinal barrier integrity (Ma et al, 2017). We found that the expression of occludin and claudin-1 in the rat intestinal tract decreased significantly in CCl 4 -induced liver fibrosis rats, while DOP enhanced the expression of these proteins.…”

hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis

“…The liver fibrosis mouse model was established referring to the previous report [32]. C57BL/6 male mice of 6-8 weeks old and 20±2 g in weight were supplied by the Experimental Animal Center of Hubei University of Medicine.…”

Hepatoprotective effect of Xiayuxue decoction ethyl acetate fraction against carbon tetrachloride-induced liver fibrosis in mice via inducing apoptosis and suppressing activation of hepatic stellate cells

“…Furthermore, XYXD has been also reported to play a protective effect in renal injury induced by bile duct ligation (Liu et al 2015). In our previous studies confirmed that XYXD provides prominently anti-liver fibrotic effects in CCl 4 -induced rodents, which attenuated HSCs activation, collagen deposition, and LSECs defenestration (Zhang et al 2014;Ma et al 2017). However, the potential anti-liver fibrosis active constituents and XYXD possible mechanisms are still unclear.…”

“…In recent years, traditional Chinese medicine (TCM) has become popular for use in the treatment of many liver diseases, such as fibrosis (Zhou et al 2014;Ma et al 2017). Xiayuxue decoction (XYXD), a famous traditional Chinese herbal formulation consists of Rheum palmatum Linn (Polygonaceae), Prunus persica (Linn) Batsch (Rosaceae), and Eupolyphaga sinensis Walker (Corydiidae) was first found in Synopsis of the Golden Chamber in 200 AD.…”

“…Based on the clinical practice of traditional Chinese medicine, the core pathogenesis and the main syndrome pathogenesis of liver fibrosis and cirrhosis after hepatitis were the consensus of blood stasis, qi and yin deficiency, damp heat intrinsic (Lv et al 2012;Chi et al 2016). XYXD is often used in the treatment of liver fbrosis and cirrhosis in China (Chen 2013) and is reported to attenuate liver fibrosis and/or cirrhosis mediated by carbon tetrachloride (CCl 4 ) (Zhang et al 2014;Ma et al 2017), thioacetamide (Ding et al 2012), or pig serum (Chen et al 2012). Furthermore, XYXD has been also reported to play a protective effect in renal injury induced by bile duct ligation (Liu et al 2015).…”