PMID- 38138520 OWN - NLM STAT- MEDLINE DCOM- 20231225 LR - 20231225 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 28 IP - 24 DP - 2023 Dec 10 TI - Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification. LID - 10.3390/molecules28248030 [doi] LID - 8030 AB - Astragali Radix (AR) is a common Chinese medicine and food. This article aims to reveal the active role of AR in treating Type 2 diabetes mellitus (T2DM) and its renal protective mechanism. The hypoglycemic active fraction was screened by alpha-glucosidase and identified by UPLC-QE-Orbitrap-MS spectrometry. The targets and KEGG pathway were determined through the application of network pharmacology methodology. Molecular docking and molecular dynamics simulation technology were used for virtual verification. Subsequently, a mouse model of T2DM was established, and the blood glucose and renal function indexes of the mice after administration were analyzed to further prove the pharmacodynamic effect and mechanism of AR in the treatment of T2DM. HA was determined as the best hypoglycemic active fraction by the alpha-glucosidase method, with a total of 23 compounds identified. The main active components, such as calycoside-7-O-beta-D-glucoside, methylnisoline, and formononetin, were revealed by network pharmacology. In addition, the core targets and the pathway have also been determined. Molecular docking and molecular dynamics simulation techniques have verified that components and targets can be well combined. In vivo studies have shown that AR can reduce blood sugar levels in model mice, enhance the anti-inflammatory and antioxidant activities of kidney tissue, and alleviate kidney damage in mice. And it also has regulatory effects on proteins such as RAGE, PI3K, and AKT. AR has a good therapeutic effect on T2DM and can repair disease-induced renal injury by regulating the RAGE/PI3K/Akt signaling pathway. This study provides ideas for the development of new drugs or dietary interventions for the treatment of T2DM. FAU - Li, Chunnan AU - Li C AUID- ORCID: 0000-0002-4212-0428 AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. AD - Jilin Correction Pharmacy New Drug Development Co., Ltd., Changchun 130012, China. FAU - Zhang, Kaiyue AU - Zhang K AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Liu, Lu AU - Liu L AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Shen, Jiaming AU - Shen J AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Wang, Yuelong AU - Wang Y AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Tan, Yiying AU - Tan Y AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Feng, Xueqin AU - Feng X AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Liu, Wanjie AU - Liu W AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Zhang, Hui AU - Zhang H AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Sun, Jiaming AU - Sun J AD - Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China. LA - eng GR - YDZJ202301ZYTS172/Jilin Province Science and Technology Department/ GR - 2023, NO.36/Project supported by postdoctoral researchers in Jilin Province/ GR - QNKXJ2-2021+ZR17./Young Scientist Program of "XingLin Scholar Project" of Changchun University of Chinese Medicine/ PT - Journal Article DEP - 20231210 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.2.1.20 (alpha-Glucosidases) RN - 0 (Hypoglycemic Agents) RN - 0 (Drugs, Chinese Herbal) SB - IM MH - Animals MH - Mice MH - *Diabetes Mellitus, Type 2/drug therapy MH - Molecular Docking Simulation MH - Network Pharmacology MH - Phosphatidylinositol 3-Kinases MH - Proto-Oncogene Proteins c-akt MH - alpha-Glucosidases MH - Kidney MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - *Astragalus Plant MH - *Drugs, Chinese Herbal/pharmacology PMC - PMC10745890 OTO - NOTNLM OT - Astragali Radix OT - T2DM OT - UPLC-QE-Orbitrap-MS OT - mechanism OT - network pharmacology COIS- Author Chunnan Li was employed by the company Jilin Correction Pharmacy New Drug Development Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/12/23 12:44 MHDA- 2023/12/25 06:41 PMCR- 2023/12/10 CRDT- 2023/12/23 01:16 PHST- 2023/11/15 00:00 [received] PHST- 2023/11/26 00:00 [revised] PHST- 2023/12/07 00:00 [accepted] PHST- 2023/12/25 06:41 [medline] PHST- 2023/12/23 12:44 [pubmed] PHST- 2023/12/23 01:16 [entrez] PHST- 2023/12/10 00:00 [pmc-release] AID - molecules28248030 [pii] AID - molecules-28-08030 [pii] AID - 10.3390/molecules28248030 [doi] PST - epublish SO - Molecules. 2023 Dec 10;28(24):8030. doi: 10.3390/molecules28248030.