network-pharmacological-analysis-tcm-formulae-based-on-syndrome

Network Pharmacological Analysis of TCM Formulae Based on the Syndrome Ontology and Multidimensional Quantitative Association Computing Platform

Current network pharmacology methods for TCM formulae predict potential active ingredients and mechanisms of action for specific diseases by constructing ...

Sichuan University

Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education

The global obese population is rapidly increasing, urgently requiring the development of effective and safe weight-loss medications. The classic Chinese medicine formulation Lingguizhugan Decoction has exerted a significant anti-obesity effect. However, the underlying mechanism is still unclear.

Lingguizhugan Decoction Improved Obesity by Modulating the Gut Microbiota and its Metabolites in Mice.

As a classical traditional Chinese patent medicine, Shugan Yipi Granule is widely used in China to treat non-alcoholic fatty liver disease (NAFLD) recently. Our previous study confirmed that Shugan Yipi Granule are effective in NAFLD. However, its underlying mechanism is still unknown. This study aims to investigate the mechanism of Shugan Yipi Granule on NAFLD based on network pharmacology prediction, liquid chromatography-mass spectrometry (LC-MS) analysis and in vitro verification. We obtained the active ingredients and targets of Shugan Yipi Granule and NAFLD from 6 traditional Chinese medicine databases, and the crucial components and targets screened by protein-protein interaction (PPI) network were used for molecular docking. Plasma metabolomics of NAFLD patients treated with Shugan Yipi Granule for one month was analyzed using LC-MS methods and MetaboAnalyst 4.0 to obtain significant differential metabolites and pathways. Finally, free fatty acid (FFA) induced HepG2 cells were treated with different concentrations of quercetin and kaempferol, then oil red o (ORO) and triglyceride (TG) level were tested to verify the lipid deposition of the cell. Network pharmacology analysis showed that the main active ingredients of Shugan Yipi Granule include quercetin, kaempferol and other 58 ones, as well as 188 potential targets. PI3K/Akt signaling pathway was found to be the most relevant pathway for the treatment of NAFLD. Non-targeted metabolomics showed that quercetin and kaempferol were significantly up-regulated differential metabolites and were involved in metabolic pathways such as thyroid hormone signaling. In vitro results showed that quercetin, kaempferol were effective in reducing lipid deposition and TG content by inhibiting cellular fatty acid uptake. Ultimately, with the network pharmacology and serum metabolomics analysis, quercetin and kaempferol were found to be the important active ingredients and significantly up-regulated differential metabolites of Shugan Yipi Granule against NAFLD, which we inferred that they may regulate NAFLD through PI3K/Akt signaling pathway and thyroid hormone metabolism pathway. The in vitro experiment verification results showed that quercetin and kaempferol attenuated the lipid accumulation and TG content by inhibiting the fatty acid uptake in the FFA-induced HepG2 cell. Current study provides the necessary experimental basis for subsequent in-depth mechanism research.

Mechanism investigation of anti-NAFLD of Shugan Yipi Granule based on network pharmacology analysis and experimental verification.

The research and development of new anti-cancer drugs face challenges such as high costs, lengthy development cycles, and limited data on side effects. In contrast, the clinical safety and side effects of traditional drugs have been well established through long-term use. The development or repurposing of traditional drugs with potential applications in cancer treatment offers an economical, feasible, and promising strategy for new drug development. This article reviews the novel applications of traditional drugs in tumor immunotherapy, discussing how they can enhance tumor treatment efficacy through functional repositioning, while also reducing development time and costs. Recent advancements in cancer immunotherapy have revolutionized treatment options, but resistance to ICIs remains a significant challenge. Drug repurposing has emerged as a promising strategy to identify novel agents that can enhance the efficacy of immunotherapies by overcoming ICI resistance. A study suggests that drug repositioning has the potential to modulate immune cell activity or alter the tumor microenvironment, thereby circumventing the resistance mechanisms associated with immune checkpoint blockade. This approach provides a rapid and cost-effective pathway for identifying therapeutic candidates that can be quickly transitioned into clinical trials. To improve the effectiveness of tumor immunotherapy, it is crucial to explore systematic methods for identifying repurposed drug candidates. Methods such as high-throughput screening, computational drug repositioning, and bioinformatic analysis have been employed to efficiently identify potential candidates for cancer treatment. Furthermore, leveraging databases related to immunotherapy and drug repurposing can provide valuable resources for drug discovery and facilitate the identification of promising compounds. It focuses on the latest advancements in the use of antidiabetic drugs, antihypertensive agents, weight-loss medications, antifungal agents, and antiviral drugs in tumor immunotherapy, examining their mechanisms of action, clinical application prospects, and associated challenges. In this context, our aim is to explore these strategies and highlight their potential for expanding the therapeutic options available for cancer immunotherapy, providing valuable references for cancer research and treatment.

Article	Year
Lingguizhugan Decoction Improved Obesity by Modulating the Gut Microbiota and its Metabolites in Mice. Current drug metabolism\| PubMed ID: 38982915	2024
Mechanism investigation of anti-NAFLD of Shugan Yipi Granule based on network pharmacology analysis and experimental verification. Heliyon\| PubMed ID: 39170438	2024
Drug functional remapping: a new promise for tumor immunotherapy. Frontiers in oncology\| PubMed ID: 40161377	2025

Yang Yubin

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