PMID- 33505505 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240330 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2021 DP - 2021 TI - 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. PG - 8819245 LID - 10.1155/2021/8819245 [doi] LID - 8819245 AB - 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 23(rd) 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-alpha 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-alpha, 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-alpha 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-alpha, and apoptosis. Our results provide a scientific basis for SZ in the clinical treatment of NAFLD. CI - Copyright (c) 2021 Yiping Li et al. FAU - Li, Yiping AU - Li Y AUID- ORCID: 0000-0001-5611-9877 AD - Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping Road, Shanghai 200032, China. FAU - Liu, Yang AU - Liu Y AUID- ORCID: 0000-0003-3957-2754 AD - Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping Road, Shanghai 200032, China. FAU - Yang, Ming AU - Yang M AUID- ORCID: 0000-0001-8246-4797 AD - Office of National Drug Clinical Trial, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. FAU - Wang, Qianlei AU - Wang Q AUID- ORCID: 0000-0001-7733-8438 AD - Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping Road, Shanghai 200032, China. FAU - Zheng, Yu AU - Zheng Y AUID- ORCID: 0000-0003-0985-5163 AD - Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China. FAU - Xu, Jiaoya AU - Xu J AUID- ORCID: 0000-0001-6957-0106 AD - Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping Road, Shanghai 200032, China. FAU - Zheng, Peiyong AU - Zheng P AUID- ORCID: 0000-0003-1084-5317 AD - Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping Road, Shanghai 200032, China. FAU - Song, Haiyan AU - Song H AUID- ORCID: 0000-0003-2155-8110 AD - Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping Road, Shanghai 200032, China. LA - eng PT - Journal Article DEP - 20210108 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC7810527 COIS- The authors declare no conflicts of interest. EDAT- 2021/01/29 06:00 MHDA- 2021/01/29 06:01 PMCR- 2021/01/08 CRDT- 2021/01/28 05:42 PHST- 2020/09/19 00:00 [received] PHST- 2020/12/16 00:00 [revised] PHST- 2020/12/22 00:00 [accepted] PHST- 2021/01/28 05:42 [entrez] PHST- 2021/01/29 06:00 [pubmed] PHST- 2021/01/29 06:01 [medline] PHST- 2021/01/08 00:00 [pmc-release] AID - 10.1155/2021/8819245 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2021 Jan 8;2021:8819245. doi: 10.1155/2021/8819245. eCollection 2021.