Puerarin Ameliorates Experimental Alcoholic Liver Injury by Inhibition of Endotoxin Gut Leakage, Kupffer Cell Activation, and Endotoxin Receptors Expression

Abstract

Puerarin, an isoflavone component extracted from Kudzu (Pueraria lobata), has been demonstrated to alleviate alcoholrelated disorders. Our study examined whether puerarin ameliorates chronic alcoholic liver injury through inhibition of endotoxin gut leakage, the subsequent Kupffer cell activation, and endotoxin receptors expression. Rats were provided with the Liber-DeCarli liquid diet for 8 weeks. Puerarin (90 mg/kg or 180 mg/kg daily) was orally administered from the beginning of the third week until the end of the experiment. Chronic alcohol intake caused increased serum alanine aminotransferase, aspartate aminotransferase, hepatic gamma-glutamyl transpeptidase, and triglyceride levels as well as fatty liver and neutrophil infiltration in hepatic lobules as determined by biochemical and histologic assays. A significant increase of liver tumor necrosis factor a was detected by enzyme-linked immunosorbent assay. These pathologic effects correlated with increased endotoxin level in portal vein and upregulated protein expression of hepatic CD68, lipopolysaccharide-binding protein, CD14, Toll-like receptor 2, and Toll-like receptor 4. Meanwhile, the intestinal microvilli were observed to be sparse, shortened, and irregularity in distribution under the transmission electron microscope in conjunction with the downregulated intestinal zonula occludens-1 protein expression. These hepatic pathologic changes were significantly inhibited in puerarintreated animals as were the endotoxin levels and hepatic CD68 and endotoxin receptors. Moreover, the pathologic changes in intestinal microvillus and the decreased intestinal zonula occludens-1 were also ameliorated with puerarin treatment. These results thus demonstrate that puerarin inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression is involved in the alleviation of chronic alcoholic liver injury in rats.

Berberine Exerts a Protective Effect on Gut-Vascular Barrier via the Modulation of the Wnt/Beta-Catenin Signaling Pathway During Sepsis

“…It has been reported that subcutaneous challenge of mice with LPS produces a gut microvascular lesions characterized by the damage of endothelial cell, microthrombi in the venules and capillaries of mucosal lamina propria [3]. LPS not only damages gut vascular integrity and increases permeability [4][5][6], but also reduces tight junction (TJ) and adherens junction (AJ) protein production in vascular endothelial cells [7,8]. In the intestine, the vascular permeability is strictly regulated and thus vascular endothelial layer possesses barrier properties.…”

Liver Injury Induced by Herbal Extracts Containing Mistletoe and Kudzu

“…Puerarin, an isoflavone and a bioactive ingredient in kudzu, has been found to be effective in protecting against alcohol-induced liver disease in animal models by inhibiting oxidative stress. [12][13][14][15] However, eliminating kudzu as a potential cause of the liver injury in the present case may not be appropriate because there are only limited reports regarding the protective effects of kudzu on the liver in humans. One pilot study with 10 heavy drinkers showed that a kudzu-containing product significantly reduced their scores on the Alcohol Use Disorders Identification Test.…”

“…In particular, puerarin, a major bioactive constituent in kudzu, has been shown to exert a protective effect in animal models of acute alcohol liver injury through the inhibition of oxidative stress. [12][13][14][15] The true incidence of herbal hepatotoxicity are not exactly known. Some herbals, such as dittany bark (Dictamnus dasycarpus) and ma-huang (Ephedra sinica), are intrinsically toxic and frequently reported as hepatotoxins.…”

Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

“…Liver inflammation can be associated with activation of Kupffer cells (KCs) and phagocytes where these macrophages excrete proinflammatory mediators [40]. CD68 expressed by activated tissue macrophages was determined as a special marker of activated KCs [41].…”