PMID- 35718494 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20220621 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 47 IP - 10 DP - 2022 May TI - [Mechanism of Astragali Radix-Puerariae Lobatae Radix combination in regulating type 2 diabetes mellitus through AMPK signaling pathway: based on network pharmacology and experimental verification]. PG - 2738-2749 LID - 10.19540/j.cnki.cjcmm.20211216.703 [doi] AB - This study aims to explore the mechanism of Astragali Radix-Puerariae Lobatae Radix(AP) combination in the treatment of type 2 diabetes mellitus(T2 DM) based on network pharmacology and experiment. The effective components and targets of the pair were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and targets of T2 DM from each disease database. On this basis, the common targets of the medicinals and the disease were screened out. The protein-protein interaction(PPI) network was established based on STRING. Then Cytoscape 3.7.1 was employed for visualization of the common targets and the network topology analysis of key targets, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of core targets by DAVID. Thereby, the possible molecular mechanism was unveiled. High-fat diet was combined with streptozotocin(STZ, injected into tail vein) for T2 DM rat modeling. Rats were classified into the normal group, model group, positive control group(metformin hydrochloride), AP high-dose, medium-dose, and low-dose groups. After 4 weeks of intragastric administration, serum fasting blood glucose(FBG), fasting insulin(FINS), aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), interleukin(IL)-6, and tumor necrosis factor(TNF)-alpha of rats in each group were measured. The expression of insulin receptor substrate-2(IRS-2), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), glucose 6 phosphatase(G6 Pase), and phosphoenolpyruvate carboxy kinase(Pepck) in rat liver was detected by Western blot. A total of 131 core targets of the combination in the treatment of T2 DM were screened out, among which protein kinase B(AKT) 1, mitogen-activated protein kinase(MAPK) 1, TNF-alpha, IL-6 were more critical. KEGG enrichment analysis suggested that the combination decreased blood glucose mainly through PI3 K/AKT signaling pathway, AMPK signaling pathway, TNF signaling pathway, and MAPK signaling pathway. The levels of FBG and FINS were lower and the glycogen level was higher in the AP high-dose and medium-dose groups than in the model group. The levels of AST, ALT, TG, and LDL-C in the three AP groups and the level of TC in AP high-dose and low-dose groups decreased compared with those in the model group. Levels of IL-6 and TNF-alpha were lower in AP high-dose and medium-dose groups than in the model group. The expression of IRS-2, AMPK, and p-AMPK was higher and that of G6 Pase and Pepck was lower in AP high-dose group than in the model group. Thus, the combination had multi-component, multi-target, and multi-pathway characteristics in the treatment of T2 DM. It may regulate AMPK signaling pathway through IL-6 and TNF-alpha to influence insulin resistance, glycogen synthesis, gluconeogenesis, islet beta cell transport, and inflammatory response, thereby exerting therapeutic effect on T2 DM. FAU - Wei, Shuang AU - Wei S AD - Heilongjiang University of Chinese Medicine Harbin 150040, China. FAU - Li, Ji AU - Li J AD - Heilongjiang University of Chinese Medicine Harbin 150040, China. FAU - Han, Dong-Wei AU - Han DW AD - Heilongjiang University of Chinese Medicine Harbin 150040, China. FAU - Fu, Qiang AU - Fu Q AD - Heilongjiang University of Chinese Medicine Harbin 150040, China. FAU - Hao, Feng AU - Hao F AD - Jiangxi University of Chinese Medicine Nanchang 330004, China. LA - chi PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 RN - 0 (Blood Glucose) RN - 0 (Cholesterol, LDL) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 5W494URQ81 (Streptozocin) RN - 9005-79-2 (Glycogen) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/genetics/metabolism MH - Animals MH - *Astragalus Plant/metabolism MH - Blood Glucose/metabolism MH - Cholesterol, LDL/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Drugs, Chinese Herbal/pharmacology/therapeutic use MH - Glycogen/therapeutic use MH - Interleukin-6/genetics MH - Network Pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism MH - *Pueraria MH - Rats MH - Signal Transduction MH - Streptozocin/therapeutic use MH - Tumor Necrosis Factor-alpha OTO - NOTNLM OT - AMPK signaling pathway OT - Astragali Radix-Puerariae Lobatae Radix combination OT - IL-6 OT - T2DM OT - TNF-alpha OT - network pharmacology EDAT- 2022/06/20 06:00 MHDA- 2022/06/22 06:00 CRDT- 2022/06/19 22:02 PHST- 2022/06/19 22:02 [entrez] PHST- 2022/06/20 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] AID - 10.19540/j.cnki.cjcmm.20211216.703 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2022 May;47(10):2738-2749. doi: 10.19540/j.cnki.cjcmm.20211216.703.