Int J Med Sci 2021; 18(1):53-64. doi:10.7150/ijms.50174 This issue

Research Paper

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

Hsin-Wen Liang1, Tsung-Yuan Yang2,3, Chia-Sheng Teng1, Yi-Ju Lee4,5, Meng-Hsun Yu1, Huei-Jane Lee1,6, Li-Sung Hsu1,3,7✉, Chau-Jong Wang8,9✉

1. Institute of Biochemistry, Microbiology, and Immunology, Chung Shan Medical University, Taichung, 402, Taiwan
2. Department of Internal Medicine, Chung-Shan Medical University Hospital, Taichung 402, Taiwan
3. School of Medicine, Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
4. Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung City 402, Taiwan
5. Department of Pathology, Chung Shan Medical University Hospital, Taichung City 402, Taiwan
6. Department of Biochemistry, School of Medicine, Medical College, Chung Shan Medical University, Taichung, 402, Taiwan
7. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, 402, Taiwan
8. Department of Health Diet and Industry Management, Chung Shan Medical University, Taichung 402, Taiwan
9. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, 402, Taiwan

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Citation:
Liang HW, Yang TY, Teng CS, Lee YJ, Yu MH, Lee HJ, Hsu LS, Wang CJ. Mulberry leaves extract ameliorates alcohol-induced liver damages through reduction of acetaldehyde toxicity and inhibition of apoptosis caused by oxidative stress signals. Int J Med Sci 2021; 18(1):53-64. doi:10.7150/ijms.50174. Available from https://www.medsci.org/v18p0053.htm

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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.

Keywords: alcohol liver disease, mulberry leaf extract, oxidative stress, inflammation, acetaldehyde, apoptosis