Transcriptome Analysis of Protection by <i>Dendrobium nobile</i> Alkaloids (DNLA) against Chronic Alcoholic Liver Injury in Mice
Xianyu Huang,
Shan Yang,
Jian Sun,
Xia Li,
Shao-Yu Zhou,
Jing-Shan Shi,
Jie Liu,
Qin Wu
Affiliations
Xianyu Huang
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Shan Yang
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Jian Sun
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Xia Li
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Shao-Yu Zhou
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Jing-Shan Shi
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Jie Liu
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Qin Wu
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China
Objective: To investigate the protective effects of Dendrobium nobile Lindl. alkaloids (DNLA) against chronic alcoholic liver injury. C57BL/6J mice were fed with the Lieber–DeCarli alcohol diet to induce chronic alcoholic liver injury. DNLA (20 mg/kg/day) was gavaged along with the alcohol diet for 28 days. Liver injury was evaluated by serum enzymes. Triglyceride levels, histopathology, and transcriptome changes were examined by RNA-Seq and qPCR. DNLA decreased serum triglyceride levels in mice receiving alcohol. Hepatocyte degeneration and steatosis were ameliorated by DNLA, as evidenced by H&E and Oil-red O staining. DNLA brought the alcohol-induced aberrant gene expression pattern towards normal. Alcohol induced 787 differentially expressed genes (padj < 0.01). DNLA induced 280 differentially expressed genes to a much less extent. Ingenuity pathway analysis showed that DNLA ameliorated alcohol-induced oxidative stress and xenobiotic metabolism disruption. qPCR verified that DNLA alleviated over-activation of Cyp2a4, Cyp2b10, and Abcc4; attenuated oxidative stress (Hmox1, Gstm3, Nupr1), reduced the expression of Nrf2 genes (Nqo1, Gclc, Vldlr); and rescued some metabolic genes (Insig1, Xbp1, Socs3, Slc10a2). In conclusion, DNLA was effective against alcohol-induced fatty liver disease, and the protection may be attributed to alleviated oxidative stress and restored metabolism homeostasis, probably through modulating nuclear receptor CAR-, PXR-, and Nrf2-mediated gene expression pathways.
