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

Kaiping Wang,Zhijing Wu,Ruxu You,Yu Zhang,Qiang Li,Hongjing Wang,Hao Mei,Xiawen Yang

doi:10.3389/fphar.2020.00240

Abstract

We explored the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on CCl4-induced liver fibrosis with respect to the intestinal hepatic axis using a rat model. Histopathological staining results showed that DOP alleviated extensive fibrous tissue proliferation in interstitium and lessened intestinal mucosal damage. Western blot and PCR results showed that DOP maintained intestinal balance by upregulating the expression of tight junction proteins such as occludin, claudin-1, ZO-1, and Bcl-2 proteins while downregulating the expression of Bax and caspase-3 proteins in the intestine. The transepithelial electrical resistance (TEER) value of the LPS-induced Caco-2 monolayer cell model was increased after DOP administration. These illustrated that DOP can protect the intestinal mucosal barrier function. DOP also inhibited activation of the LPS-TLR4-NF-κB signaling pathway to reduce the contents of inflammatory factors TGF-β and TNF-α, increased the expression of anti-inflammatory factor IL-10, and significantly decreased α-SMA and collagen I expression. These results indicated that DOP maintained intestinal homeostasis by enhancing tight junctions between intestinal cells and reducing apoptosis, thereby inhibiting activation of the LPS-TLR4-NF-κB signaling pathway to protect against liver fibrosis.

Highlights

Liver fibrosis is a common disease related to viral hepatitis, alcoholic liver, autoimmune disease, metabolic disease and cholestasis liver disease, that often leads to the gradual loss of liver function (Friedman, 2003; Shiha et al, 2017)
The Institute of Biochemistry and Cell Biology provided us with Caco-2 cell line (Shanghai, China), The aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (AKP) kits were obtained from Jiancheng Bioengineering Institute (Nanjing, China)
We found that the expression of occludin and claudin-1 in the rat intestinal tract decreased significantly in carbon tetrachloride (CCl4)-induced liver fibrosis rats, while Dendrobium officinale polysaccharide (DOP) enhanced the expression of these proteins

Summary

Introduction

Liver fibrosis is a common disease related to viral hepatitis, alcoholic liver, autoimmune disease, metabolic disease and cholestasis liver disease, that often leads to the gradual loss of liver function (Friedman, 2003; Shiha et al, 2017). Liver fibrosis is due to the excessive deposition of extracellular matrix (ECM), mainly from activated hepatic stellate cells (HSCs) (Gan et al, 2018). Collagen I is the most abundant extracellular matrix component in fibrosis (Schuppan, 2015). HSC cells are the most activated cells in liver fibrosis and involve in collagen synthesis, and alpha-smooth muscle actin (α-SMA) is the sign of HSC cell activation (Chiu et al, 2014). Inflammation promotes the activation of HSC cells and aggravates liver fibrosis, leading to cirrhosis of the liver, which endangers human life (Mitra et al, 2014). The prevention and treatment of liver fibrosis are important steps in liver cirrhosis clinical therapy

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