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Jiedu Tongluo Tiaogan Formula Modulates Glycolipid Metabolism in Type 2 Diabetes via Pyroptosis: Network Pharmacology

Su Jing1, Cui Zhenhai1, Han Xiao1

  • 1Changchun University of Chinese Medicine, Changchun, China.

Biomedical Chromatography : BMC
|April 12, 2025
PubMed

Insights

Jiedu Tongluo Tiaogan Formula (JTTF) reduces blood glucose and insulin resistance in type 2 diabetes by inhibiting pyroptosis, a key cell death pathway. This traditional Chinese medicine preserves pancreatic beta-cell function through multi-target mechanisms.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Immunology

Background:

  • Type 2 diabetes mellitus (T2DM) involves beta-cell dysfunction and insulin resistance.
  • Pyroptosis, a pro-inflammatory cell death, significantly contributes to beta-cell loss in T2DM.
  • The precise mechanisms of traditional Chinese medicine, like Jiedu Tongluo Tiaogan Formula (JTTF), in modulating pyroptosis for T2DM remain unclear.

Purpose of the Study:

  • To elucidate the anti-diabetic mechanisms of JTTF, focusing on its effects on pyroptosis in T2DM.
  • To identify active compounds in JTTF and their potential targets related to T2DM and pyroptosis.
  • To evaluate the efficacy of JTTF in improving glucose and lipid metabolism and preserving beta-cell function in a T2DM mouse model.

Main Methods:

  • Ultra-Performance Liquid Chromatography coupled with tandem Mass Spectrometry (UPLC-MS/MS) for compound identification.
  • Network pharmacology to predict JTTF's multi-target effects on T2DM-associated pyroptosis.
  • In vivo experiments using diabetic mice to assess JTTF's therapeutic effects and molecular mechanisms.

Main Results:

  • UPLC-MS/MS identified 441 compounds in JTTF, including alkaloids, flavonoids, phenols, and terpenoids.
  • Network pharmacology indicated JTTF targets the NLRP3/Caspase-1/GSDMD pathway central to pyroptosis in T2DM.
  • JTTF treatment dose-dependently improved glycemic control, insulin sensitivity, and lipid profiles, while restoring pancreatic beta-cell morphology by suppressing NLRP3 inflammasome activation and downstream inflammatory cytokine release.

Conclusions:

  • JTTF exhibits significant anti-diabetic effects by concurrently modulating glycolipid metabolism and inhibiting pyroptosis in T2DM.
  • This study provides the first evidence of JTTF's anti-pyroptotic action, highlighting its potential for preserving beta-cell function.
  • JTTF demonstrates translational promise for integrative T2DM therapies, warranting further clinical investigation and exploration of non-classical pyroptosis pathways.
Keywords:
JTTFNLRP3/Caspase‐1/GSDMD pathwaynetwork pharmacologypyroptosistype 2 diabetes mellitus

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