Hawthorn Herbal Preparation from Crataegus oxyacantha Attenuates In Vivo Carbon Tetrachloride -Induced Hepatic Fibrosis via Modulating Oxidative Stress and Inflammation.

Alaaeldin Ahmed Hamza,Youssef Abdalla,Soha Osama Hassanin,Mona Gamel,Fawzy Mohamed Lashin,Amr Amin

doi:10.3390/antiox9121173

Abstract

Hawthorn (HAW) is a herbal preparation extracted from Crataegus oxyacantha. HAW has cardioprotective, antioxidants, anti-inflammatory, and anti-hypotensive effects. HAW’s effect on hepatic fibrosis remains, however, unknown. This study evaluated the impact of HAW on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats and elucidated its mechanisms. HAW reduced liver index and the serum liver enzyme markers and reduced liver damage, and fibrosis as confirmed by histopathological scoring of hematoxylin-eosin staining. Collagen deposition was reduced in HAW group compared to CCl4 group as confirmed by Masson staining, hydroxyproline content, and both mRNA and protein levels of alpha-smooth muscle actin, collagen 1 and 3. HAW also down regulated the gene expressions of inflammatory markers including interleukin-IL-1β, tumor necrosis factor-α, transforming growth factor-β 1, nuclear factor kappa-B, and cyclooxygenase-2 and decreased the myeloperoxidase activity. The effects of HAW was also associated with decreased levels of hepatic oxidative stress markers (malondialdehyde and P.Carbonyl) and with increased activity of superoxide dismutase. Those effects are possibly mediated by blocking the pro-oxidant machinery and down regulating the inflammatory and profibrotic responses. Finally, chlorogenic acid, epicatechin, rutin, vitexin quercetin, and iso quercetin were identified as the major species of polyphenols of the HAW herbal preparation used here. Therefore, HAW’s potent protecting effects against liver fibrosis predicts a significant beneficial application.

Highlights

Liver fibrosis and cirrhosis are the main contributors to chronic liver-associated morbidity and mortality [1]
Evident changes were observed in liver tissues of CCl4-treated group including necrosis, and inflammatory cells infiltration and diffuse fatty changes (Figure 1A,B)
Compared to SIL-treated group, rats treated with HAW revealed the best effects in terms of necrosis and fibrosis scores and for serum AST, ALT activities, and for serum albumin levels

Summary

Introduction

Liver fibrosis and cirrhosis are the main contributors to chronic liver-associated morbidity and mortality [1]. Extended liver injury can be induced by a range of stimuli including viral infection, metabolic disorders, and exposure to drugs and toxic substances [2,4,5] This chronic liver damage triggers the activation of hepatic macrophages [6] and monocyte-derived macrophages [1,2]. Activation of liver inflammatory cells, in turn, release reactive oxygen species (ROS) [7] in addition to a range of cytokines and other soluble factors These fibrogenic signals activate hepatic stellate cells (HSC) [2,4,5,8]. Those cells are proliferative, contractile, chemotactic, and can synthesize a large amount of ECM including collagen and alpha-smooth muscle actin (α-SMA) [9]. Several cellular mediators of HSC activation and fibrosis in injured/inflamed hepatic tissue include a broad range of fibrogenic and pro-inflammatory factors, such as tumor necrosis factor (TNF-α), nuclear factor kappa-B (NF-κB), cyclooxygenase-2 (COX-2), interleukin-IL-1β and tumor growth factor- β1 (TGFβ1) [1,3,10]

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Discussion

Conclusion