A Study on the Therapeutic Efficacy of San Zi Yang Qin Decoction for Non-Alcoholic Fatty Liver Disease and the Underlying Mechanism Based on Network Pharmacology

Abstract

Objective. This study aims to explore the therapeutic efficacy of San Zi Yang Qin Decoction (SZ) and its potential mechanism in the treatment of non-alcoholic fatty liver disease (NAFLD) based on network pharmacology and in vivo experiments. Methods. Effective chemicals and targets of SZ were searched in online databases, according to the drug-likeness of compounds and the binomial distribution of targets. A disease-target-chemical network was established using NAFLD-associated genes screened through GeneCards database, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, animal experiments were conducted to verify the efficacy and mechanism of SZ predicted by network pharmacology. The NAFLD mouse model was established with C57BL/6J mice fed with a high-fat diet for 22 weeks. The mice in the control group were fed with a chow diet. From the 23rd week, the NAFLD mice were treated with intragastric SZ or normal saline for 8 weeks. After the glucose tolerance was measured, the mice were sacrificed, followed by the collection of serum and liver tissues. Pathological changes in liver tissues were examined by H&E staining. Additionally, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum fast blood glucose, and insulin levels were detected. Expression levels of TNF-α of serum and liver tissues were determined by ELISA and qRT-PCR, respectively. Western blot was used to detect the activation of AKT in liver tissues. Results. A total of 27 effective compounds and 20 targets of SZ were screened. GO analysis uncovered a significant correlation between the targets of SZ and those of NAFLD. KEGG analysis presented the signaling pathways enriched in SZ and NAFLD, including NAFLD, TNF-α, and apoptosis pathways. The area under the curve of major GO and KEGG pathways indicated the potential role of SZ in improving NAFLD. In vivo experiments demonstrated that SZ significantly alleviated hepatosteatosis and inflammatory cell infiltration in liver tissues, reduced serum transaminases, and improved insulin resistance and glucose tolerance of NAFLD mice. The protein level of phospho-AKT was upregulated by SZ. Additionally, SZ treatment obviously impaired the TNF-α level in the serum and liver tissue of NAFLD mice. Conclusions. According to the network pharmacology analysis and in vivo experiments, SZ could have therapeutic efficacy for NALFD. The mechanism mainly involves pathways relative to insulin resistance, TNF-α, and apoptosis. Our results provide a scientific basis for SZ in the clinical treatment of NAFLD.

Therapeutic potential of traditional Chinese medicine for the treatment of NAFLD: A promising drug Potentilla discolor Bunge

“…The syndromes in patients with NAFLD can be classified into the following types 41 : (i) spleen-deficiency and phlegm-turbid stagnation; (ii) stagnation of liver-qi; (iii) accumulated damp-heat; (iv) stasis blocking channels and (v) deficiency of liver and kidney. According to these TCM syndromes, the treatment principle and the relevant classical formulas to treat NAFLD are as follows: (i) formulas for invigorating spleen, removing dampness and phlegm: shenlingbaizhu powder (Tai Ping Hui Min He Ji Ju Fang) 42 , 43 , simiao powder (Cheng Fang Bian Du) 44 , sanziyangqin decoction (Han Shi Yi Tong) 45 ; (ii) formulas for relieving liver and regulating qi: xiaochaihu decoction ( Shang Han Lun ) 46 , chaihushugan powder ( Jingyue Complete Library ) 47 , 48 , 49 ; (iii) formulas for clearing heat, promoting dampness and dispersing knot: dachaihu decoction ( Treatise on Febrile Disease ) 50 , 51 , yinchenhao decoction ( Shang Han Lun ) 52 ; (iv) formulas for promoting blood circulation and dissipating blood stasis: taohongsiwu decoction ( The Golden Mirror of Medicine ) 53 ; (v) formulas for warming yng and invigorating spleen: chaihulizhong decoction (Shang Han Lun) 54 , lingguizhugan decoction ( Jin Gui Yao Lue ) 55 , 56 , 57 , fuzilizhong decoction (San Yin Ji – Bing Zheng Fang Lun) 58 , sini powder (Shang Han Lun) 59 , 60 , 61 , ganjianglingzhu decoction ( Jin Gui Yao Lue ) 62 . The regulatory effects and relevant mechanisms of the classical formulas of TCM treating NAFLD are shown in Table 1 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ,…”

“… Treatment principle Chinese medicinal formula Model Effects of TCM treating NAFLD Ref. Invigorate spleen, remove dampness and phlegm Shenlingbaizhu powder (SLBZS) HFD-induced NAFLD rats CDAA-fed rats ↓ Hepatic injury ↓ Lipid accumulation ↓ The serum level of endotoxin, TNF- α , IL-1 β ↓ TLR4, TRAF6 in the liver tissue ↑ The abundance of intestinal microbiota ↑ The abundance of short-chain fatty acid ↑ Adiponection ↓ SREBP-1c, FAS 42 , 43 Simiao powder (SMS) HFHS-induced NAFLD mice ↓ Acly , Fas , Acc , Scd1 ↓ IL-1 β , NLRP-3 ↓ The biosynthesis of fatty acids ↑ Insulin secretion pathway ↑ Gut microbiota composition 44 Sanziyangqin decoction (SZYQT) HFD-induced NAFLD mice ↓ Hepatosteatosis ↓ TNF- α ↓ Inflammatory cell infiltration in liver tissues ↑ Insulin resistance ↑ p-AKT; ↓ apoptosis 45 Relieve liver and regulate Qi Xiaochaihu decoction (XCHT) Patients with NAFLD ↑ Lipid metabolism 46 Chaihushugan powder (CHSGS) HFD-induced NAFLD/NASH rats High fat and sugar emulsion-induced NAFLD rats ↓ Enterobacteriaceae, Staphylococcaceae families and Veillonella genus ↑ Anaeroplasma genus ↓ Fat accumulation ↓ Inflammatory factors (TNF- α , IL-1 β , IL-18, IL-6) ↓ NLRP3, ASC, CASPASE-1 ↓ TLR4, p-p38 MAPK ↑ Adiponectin; ↓ leptin 47 , 48 , 49 Clear heat, promote dampness and disperse knot Dachaihu decoction (DCHT) Patients with NAFLD High-fat high-fructosediet-induced NAFLD rats ↓ TNF- α , TGF- β , NF- κ B, TLR4 50 , 51 Yinchenhao decoction (YCHT) …”