Mulberry leaves extract ameliorates alcohol-induced liver damages through reduction of acetaldehyde toxicity and inhibition of apoptosis caused by oxidative stress signals

Abstract

Mulberry leaves (Morus alba L.), which are traditional Chinese herbs, exert several biological functions, such as antioxidant, anti-inflammation, antidiabetic, and antitumor. Alcohol intake increases inflammation and oxidative stress, and this increase causes liver injury and leads to liver steatosis, cirrhosis, and hepatocellular carcinoma, which are major health problems worldwide. Previous report indicated that mulberry leaf extract (MLE) exited hepatoprotection effects against chronic alcohol-induced liver damages. In this present study, we investigated the effects of MLE on acute alcohol and liver injury induced by its metabolized compound called acetaldehyde (ACE) by using in vivo and in vitro models. Administration of MLE reversed acute alcohol-induced liver damages, increased acetaldehyde (ACE) level, and decreased aldehyde dehydrogenase activity in a dose-dependent manner. Acute alcohol exposure-induced leukocyte infiltration and pro-inflammation factors, including cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were blocked by MLE in proportion to MLE concentration. MLE prevented alcohol-induced liver apoptosis via enhanced caveolin-1 expression and attenuated EGFR/STAT3/iNOS pathway using immunohistochemical analysis. ACE induced proteins, such as iNOS, COX-2, TNF-α, and IL-6, and inhibited superoxide dismutase expression, whereas co-treated with MLE reversed these proteins expression. MLE also recovered alcohol-induced apoptosis in cultured Hep G2 cells. Overall, our findings indicated that MLE ameliorated acute alcohol-induced liver damages by reducing ACE toxicity and inhibiting apoptosis caused by oxidative stress signals. Our results implied that MLE might be a potential agent for treating alcohol liver disease.

Ethanol Metabolism in the Liver, the Induction of Oxidant Stress, and the Antioxidant Defense System

“…It has also been reported that mulberry leaves raise the peroxisome-proliferator-activated receptor-α; these leaves reduce chronic alcohol-induced liver oxidative stress; increase the expression of caveolin-1; and shut-down the epidermal growth factor receptor (EGFR), the signal transducer activator of transcription 3 (STAT3), and iNOS by diminishing alcohol-induced liver damage. Hence, it has been proposed that mulberry leaves can reverse the alcohol-induced liver injury [ 151 ].…”

Biological activities of Egyptian grape and mulberry by-products and their potential use as natural sources of food additives and nutraceuticals foods

“…Mulberry leaves and grape-derived polyphenols have a wide range of biological activity (pleiotropic), as well as possible health-promoting effects [6,55], they have anti-inflammatory, anti-amyloidogenic, anti-cholinesterase, anti-amnesic, hypolipidemic, anti-aging agents and immunomodulatory and they are dietary supplements that can help delay the neurocognitive deterioration that occurs with age and Alzheimer's disease (AD) [56,57]. Mulberry leaves polyphenols reduced acetaldehyde toxicity and oxidative stress-induced apoptosis, suggesting that they could be used to treat alcohol-induced liver disease [58]. Several studies and clinical trials have established the importance of polyphenols in controlling numerous human illnesses, including SARS and MERS, which are related to COVID-19, by enhancing the host immune response to viral infections through multiple biological processes [20].…”

Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds

“…Many in vitro and in vivo studies confirmed that fruits such as the mango [ 144 ], grape [ 145 ], blueberry [ 110 ], mulberry [ 146 ], persimmon [ 147 ], pomegranate [ 148 ], cranberry [ 149 ], and wolfberry [ 150 ] play an important role against ALD. This ameliorative effect on ALD was mainly due to the presence of a tangible amount of bioactive compounds in fruits.…”

“…A previous study confirmed that mulberry possessed hepatoprotective effects in both animals and humans [ 157 ]. It was also reported that mulberry fruits and leaves could mitigate ALD via multiple pathways such as reducing lipid accumulation and lipid synthesis, decreasing OS, increasing fatty acid transport and fatty acid oxidation responses, and exerting an anti-inflammatory effect [ 146 , 158 ]. Gao et al [ 150 ] confirmed that wolfberry-derived zeaxanthin dipalmitate can protect the liver from alcohol-induced toxicity and concluded that daily intake of wolfberry may have a positive impact on ALD.…”