Integrating network analysis and pharmacokinetics to investigate the mechanisms of Danzhi Tiaozhi Decoction in metabolic-associated fatty liver disease (MAFLD)

被引：5

作者：

Jiang, Xiaofei ^{[1
]}

Tang, Nannan ^{[2
]}

Liu, Yuyu ^{[2
]}

Wang, Zhiming ^{[3
]}

Chen, Jun ^{[3
]}

Liu, Fang ^{[3
]}

Zhang, Ping ^{[3
]}

Sui, Miao ^{[3
,5
]}

Xu, Wei ^{[4
,6
]}

机构：

[1] Nanjing Univ Chinese Med, Xuzhou City Hosp Tradit Chinese Med, Dept Gynecol, Xuzhou Tradit Chinese Med Hosp, Xuzhou 221003, Jiangsu, Peoples R China

[2] Grad Sch Anhui Univ Tradit Chinese Med, Hefei 230000, Anhui, Peoples R China

[3] Nanjing Univ Chinese Med, Xuzhou City Hosp Tradit Chinese Med, Dept Endocrinol, Xuzhou Tradit Chinese Med Hosp, Xuzhou 221003, Jiangsu, Peoples R China

[4] Nanjing Med Univ, Xuzhou Cent Hosp, Xuzhou Inst Med Sci, Affiliated Hosp,Med Sch,Southeast Univ,Xuzhou Clin, Xuzhou 221003, Jiangsu, Peoples R China

[5] Xuzhou City Hosp Chinese Med, 169 Zhongshan South Rd, Xuzhou 210029, Jiangsu, Peoples R China

[6] Xuzhou Cent Hosp, 199 Jiefang South Rd, Xuzhou 210029, Jiangsu, Peoples R China

来源：

JOURNAL OF ETHNOPHARMACOLOGY | 2024年 / 318卷

关键词：

Pharmacochemistry; Network pharmacology; Danzhi Tiaozhi Decoction; Metabolic associated fatty liver disease; Molecular docking; Experimental validation;

D O I：

10.1016/j.jep.2023.117008

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Ethnopharmacological relevance: Based on ancient classics, Danzhi Tiaozhi Decoction has been successfully used to treat nonalcoholic fatty liver disease for decades. However, its therapeutic mechanisms remain unclear.Aim of the study: This study aimed to investigate the effects of Danzhi Tiaozhi Decoction (DZTZD) on metabolic-associated fatty liver disease (MAFLD).Materials and methods: First, we identified the active ingredients of DZTZD and their potential targets in the Traditional Chinese Medicine System Pharmacology database. Using the overlapped genes, we selected the key MAFLD-associated genes, then conducted GO and KEGG pathway enrichment analyses. Furthermore, DZTZD was administered orally to rats, and their serum and liver tissues were examined for absorbed compounds using pharmacochemistry. UPLC-Q-Exactive Orbitrap/MS was used to determine the main compounds. Then, we validated the binding association of the key targets with their active compounds with AutoDock Tools and other software. Finally, the predicted hub targets were experimentally validated.Results: We found 254 active compounds in DZTZD corresponding to 208 targets. Sixteen key genes were identified, and the enrichment analysis revealed multiple signaling pathways, including the AGE-RAGE pathway in diabetic complications and the lipid and atherosclerosis signaling pathway. Next, 160 absorbed components and metabolites were characterized in vivo , and 53 absorbed components and metabolites were characterized in liver tissue. Thirteen parent compounds were identified, including coptisine, quercetin, luteolin, and aloeemodin. The molecular docking data demonstrated the strongest binding between the active compounds and the core proteins. Moreover, the animal experiments showed that DZTZD decreased body weight, liver weight, lipid accumulation, and ALT, AST, CRP, FFA, IL-6, PEPCK, G6P, TG, TC, and LDL-c serum levels, and increased serum HDL-c levels compared to high-fat induced rats. Besides, the RT-PCR and Western blot showed that DZTZD inhibited the SREBP1c and FAS and increased hyperlipidemia-induced CPT-1A levels. In the high-fat group, JNK phosphorylation increased, and AKT protein phosphorylation decreased, while DZTZD reversed these effects.Conclusion: Based on the pharmacological network analysis, pharmacochemistry, and experimental validation, DZTZD can potentially improve MAFLD via the JNK/AKT pathway.

引用

页数：13

共 34 条

[21] Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease [J].