Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Beom-Rak Choi,Dae-Geon Lee,Ki-Moon Park,Su-Jin Jung,Il-Je Cho,Sae-Kwang Ku,Jae-Kwang Kim

doi:10.3390/app11010390

Abstract

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

Highlights

Oxidative stress remains central to the onset and progression of liver disease regardless of disease etiology, with effects seen in drug- and alcohol-induced liver injury, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, cirrhosis, and cancer [2,4]
In parallel with our previous report [16], we showed that hepatic lipid peroxidation (e.g., 4-hydroxynonenal and malondialdehyde) and nitrotyrosine levels were increased in the CCl4 -treated mice, suggesting that CCl4 induces hepatic oxidative stress, which was synergistically attenuated by MLD administration
Our preliminary results using HepG2 cells indicate that MLD significantly transactivated antioxidant response element-harboring reporter genes and induced the mRNA level of NAD(P)H: quinone oxidoreductase 1 in a concentration-dependent manner [23]. These results indicate that MLD synergistically restored impaired nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression as well as antioxidant defense responses, suggesting that MLD-mediated Nrf2 activation protects against CCl4 -mediated liver injury by alleviating oxidative stress

Summary

Introduction

The production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS under normal physiological conditions act as secondary messengers responsible for the regulation of diverse cellular processes including cell proliferation, gene expression, and antimicrobial defenses [1]. Oxidative and nitrosative stress, caused by an imbalance of redox homeostasis resulting in an excessive and chronic accumulation of ROS/RNS, inhibits the function of various biomolecules and changes the permeability of plasma and subcellular membranes, which in turn triggers cell death [2]. Due to the high consumption of oxygen when metabolizing xenobiotic or endogenous substances, the liver is one of the primary organs susceptible to oxidative damage [4]. Oxidative stress remains central to the onset and progression of liver disease regardless of disease etiology, with effects seen in drug- and alcohol-induced liver injury, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, cirrhosis, and cancer [2,4]

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Conclusion