Systems pharmacology-based exploration reveals mechanisms of anti-steatotic effects of Jiang Zhi Granule on non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD), which is in parallel with the obesity epidemic, accounts for a large amount of all chronic liver disease. Jiang Zhi Granule (JZG), a clinically used herbal formula, is developed in accordance with traditional Chinese medicine (TCM) pathogenesis for treating patients with NAFLD. In previous studies, the anti-steatotic effects of JZG against NAFLD have been demonstrated, and in this study, a systems pharmacology approach was used to explore the pharmacological mechanisms of JZG by predicting the active compounds within the herbal formula and their corresponding therapeutic targets. Its therapeutic efficacy was confirmed in the beginning of this study, and JZG was shown to significantly improve hepatic dysfunction and lipid droplet accumulation in PA-treated hepatocytes. Systems pharmacology was then performed to identify the active compounds in as well as to predict the therapeutic targets of this Chinese herbal prescription. Enrichment analyses indicated that the mechanisms of the anti-steatotic effects of JZG against NAFLD might be associated with lipid droplet degradation via autophagy, and a series of in vitro and in vivo validation experiments was subsequently performed to confirm that JZG could activate autophagy though the mTOR signalling to improve NAFLD.

Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine

“…In Chinese clinical practice, TCM has unique advantages in the clinical treatment of NAFLD, and most patients with NAFLD received TCM treatment. TCM stresses the differentiation treatment [8]. In other words, there are different types of syndromes in different patients with NAFLD, thus, different prescriptions need to be adopted for each specific treatment.…”

“…As regards traditional Chinese medicine (TCM), its pathogenesis mainly includes stagnation of liver-qi and catharsis disorder, leading to hindrance of functional activities of qi, liver-qi perversion attacking the stomach, qi disease involving blood, and poor blood flow, which finally induce NAFLD [7]. Chinese and international scholars agree that NAFLD is caused by multiple factors including insulin resistance, lipid metabolism disorder, and oxidative stress in Western medicine [8].…”

Chinese Medicinal Herbs Targeting the Gut–Liver Axis and Adipose Tissue–Liver Axis for Non-Alcoholic Fatty Liver Disease Treatments: The Ancient Wisdom and Modern Science

“…It can predict the active compounds within the herbal formula JZG and their corresponding therapeutic targets and synergistic effects. The analysis has highlighted a number of signaling pathways that may be involved in therapeutic effects of JZG, they are ER-phagosome pathway, proteasomal ubiquitindependent protein catabolic process, TRAF6-mediated induction of pro-inflammatory cytokines, MAPK cascade, regulation of lipid metabolism including steroid biosynthesis, cholesterol transport and fatty acid metabolism (116). Indeed, mechanistic study also shows that JZG regulates lipid metabolism.…”

“…JZG also protects mitochondrial integrity against oxidative stress in the hepatocyte model (121). In the mouse model of NAFLD, JZG reduces hepatic lipid content and ameliorates inflammation, improves metabolic disorder and reduces liver injury (116,118,121). In CCl4-induced liver injury in NAFLD rat, JZG also significantly reduces hepatic inflammation, ER stress, hepatic necrosis, hepatic lipid, blood transaminases and blood lipids (122).…”

Identify Key Active Ingredients and Molecular Mechanisms of Jiangzhi Decoction on Non-alcoholic Fatty Liver Disease by Network Pharmacology Analysis

“…Epidemiological researches have reported that NAFLD is one of the three main causes of cirrhosis [4], and NASH is rapidly becoming the leading cause of end-stage liver disease [5,6]. However, except for lifestyle interventions, such as exercise and dietary, there is still no approved pharmacotherapy for NAFLD.…”