PMID- 34740995 OWN - NLM STAT- MEDLINE DCOM- 20220201 LR - 20220201 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 13 IP - 21 DP - 2021 Nov 5 TI - Decoding the chemical composition and pharmacological mechanisms of Jiedu Tongluo Tiaogan Formula using high-performance liquid chromatography coupled with network pharmacology-based investigation. PG - 24290-24312 LID - 10.18632/aging.203679 [doi] AB - Type 2 diabetes mellitus (T2DM), a chronic low-grade inflammatory disease with high morbidity and mortality, is a serious threat to public health. Previously we demonstrated that a traditional Chinese medicine formulation, Jiedu Tongluo Tiaogan Formula (JDTL), exerted a favorable hypoglycemic effect due to unknown molecular mechanisms involving interactions among JDTL compounds and various cellular components. This study aimed to explore JDTL mechanisms for alleviating hyperglycemia using an integrated strategy incorporating system pharmacology, bioinformatics analysis, and experimental verification. This strategy entailed initial elucidation of JDTL chemical composition using fingerprint analysis via high performance liquid chromatography (HPLC). Next, functions of putative shared target genes and associated pathways were deduced using GO and KEGG pathway enrichment and molecular docking analyses. Ultimately, targets associated with JTDL anti-T2DM effects were found to be functionally associated with biological functions related to lipopolysaccharide and cytokine receptor binding. These results implicated PI3K-Akt signaling pathway involvement in JDTL anti-T2DM effects, as this pathway had been previously shown to play significant roles in glucose and lipid metabolism-related diseases. Furthermore, addition of JDTL to INS-1 and HepG2 cell cultures stimulated cellular mRNA-level and protein-level expression leading to enhanced production of IRS1, Akt, and PI3K. In summary, here JDTL bioactive ingredients, potential targets, and molecular mechanisms underlying JDTL anti-T2DM effects were identified using a multi-component, multi-target, and multi-channel analytical approach, thus providing an important scientific foundation to facilitate development of new drugs mechanistic strategies for preventing and treating T2DM. FAU - Zhang, Qi AU - Zhang Q AD - Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, P.R. China. FAU - Piao, Chunli AU - Piao C AD - Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, Guangdong Province, P.R. China. FAU - Jin, Wenqi AU - Jin W AD - Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, P.R. China. FAU - Jin, De AU - Jin D AD - Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100700, P.R. China. FAU - Wang, Han AU - Wang H AD - Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100700, P.R. China. FAU - Tang, Cheng AU - Tang C AD - Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, P.R. China. FAU - Zhao, Xiaohua AU - Zhao X AD - Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, Guangdong Province, P.R. China. FAU - Zhang, Naiwen AU - Zhang N AD - Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, Guangdong Province, P.R. China. FAU - Gao, Shengnan AU - Gao S AD - Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, Guangdong Province, P.R. China. FAU - Lian, Fengmei AU - Lian F AD - Guang'anmen Hospital, China Academy of Chinese Medical Science, Beijing 100700, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211105 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Drugs, Chinese Herbal) SB - IM MH - Chromatography, High Pressure Liquid/*methods MH - Diabetes Mellitus, Type 2/metabolism MH - *Drugs, Chinese Herbal/analysis/chemistry/pharmacology MH - Humans MH - Molecular Docking Simulation MH - Network Pharmacology/*methods MH - Protein Interaction Maps/drug effects PMC - PMC8610129 OTO - NOTNLM OT - Jiedu Tongluo Tiaogan Formula OT - PI3K/Akt signaling pathway OT - network pharmacology OT - traditional Chinese medicine OT - type 2 diabetes mellitus COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest. EDAT- 2021/11/07 06:00 MHDA- 2022/02/02 06:00 PMCR- 2021/11/15 CRDT- 2021/11/06 05:39 PHST- 2021/07/19 00:00 [received] PHST- 2021/10/26 00:00 [accepted] PHST- 2021/11/07 06:00 [pubmed] PHST- 2022/02/02 06:00 [medline] PHST- 2021/11/06 05:39 [entrez] PHST- 2021/11/15 00:00 [pmc-release] AID - 203679 [pii] AID - 10.18632/aging.203679 [doi] PST - ppublish SO - Aging (Albany NY). 2021 Nov 5;13(21):24290-24312. doi: 10.18632/aging.203679. Epub 2021 Nov 5.