Research Paper Volume 13, Issue 21 pp 24290—24312
Decoding the chemical composition and pharmacological mechanisms of Jiedu Tongluo Tiaogan Formula using high-performance liquid chromatography coupled with network pharmacology-based investigation
- 1 Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, P.R. China
- 2 Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, Guangdong Province, P.R. China
- 3 Guang’anmen Hospital, China Academy of Chinese Medical Science, Beijing 100700, P.R. China
Received: July 19, 2021 Accepted: October 26, 2021 Published: November 5, 2021
https://doi.org/10.18632/aging.203679How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.
Abbreviations
T2DM: Type 2 diabetes mellitus; JDTL: Jiedu Tongluo Tiaogan Formula; PPI: protein-protein interaction; GO: Enrichment of Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; TCM: Traditional Chinese medicine; MW: Molecular Weight; LogP: Octanol-Water Partition Coefficient; Hdon: The Number of Donor Atoms For H-Bonds; Hacc: The Number of Acceptor Atoms For H-Bonds; OB: Oral Bioavailability; DL: Drug-Like; TCMSP: Traditional Chinese Medicine Systems Pharmacology; MTT: 3-(4;5-dimethylthiazol-2-yl)-2; 5-diphenyltetrazolium bromide; AKT1: RAC-alpha serine/threonine-protein kinase; IL-6: interleukin-6; VEGFA: vascular endothelial growth factor A; MAPK1: mitogen-activated protein kinase 1; MAPK8: mitogen-activated protein kinase8; JUN: Transcription factor AP-1; EGF: Pro-epidermal growth factor; EGFR: Epidermal growth factor receptor; CXCL8: Interleukin-8; IL1B: Interleukin-1 beta; MF: molecular function; CC: cellular composition; BP: biological process.