The improvement of modified Si-Miao granule on hepatic insulin resistance and glycogen synthesis in type 2 diabetes mellitus involves the inhibition of TNF-α/JNK1/IRS-2 pathway: network pharmacology, molecular docking, and experimental validation
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View abstract on PubMed
Summary
This summary is machine-generated.Modified Si-Miao granule (mSMG) improves insulin resistance (IR) in type 2 diabetes by inhibiting the TNF-α/JNK1/IRS-2 pathway. This traditional Chinese medicine enhances glucose metabolism and glycogen synthesis, offering a potential therapeutic strategy for IR.
Area Of Science
- Pharmacology
- Traditional Chinese Medicine
- Metabolic Disease Research
Background
- Modified Si-Miao granule (mSMG) shows promise for type 2 diabetes (T2DM) and insulin resistance (IR).
- The precise molecular mechanisms underlying mSMG's therapeutic effects on IR remain largely unexplored.
Purpose Of The Study
- To elucidate the mechanism of mSMG in treating hepatic IR in T2DM using network pharmacology and molecular docking.
- To validate the predicted mechanisms through in vivo and in vitro experiments.
Main Methods
- Network pharmacology was employed to identify mSMG compounds, their targets, and pathways relevant to IR in T2DM.
- Molecular docking was used to assess the binding affinity between mSMG compounds and key targets, particularly TNF-α.
- Experimental validation was conducted in KK-Ay mice and HepG2 cells to confirm the effects on IR and related signaling pathways.
Main Results
- Network pharmacology identified 50 compounds and 170 targets for mSMG against IR, highlighting TNF and MAPK8 as hub targets.
- mSMG treatment ameliorated hyperglycemia, IR, and TNF-α levels, while enhancing glucose consumption and glycogen synthesis in KK-Ay mice.
- In vitro studies demonstrated that mSMG and berberine significantly increased glucose consumption and glycogen synthesis and modulated the TNF-α/JNK1/IRS-2 pathway in IR-HepG2 cells.
Conclusions
- Network pharmacology and molecular docking are effective tools for predicting the mechanisms of traditional Chinese medicines like mSMG.
- mSMG, and its compound berberine, demonstrate efficacy in improving hepatic IR and glycogen synthesis.
- The therapeutic mechanism of mSMG in IR is associated with the inhibition of the TNF-α/JNK1/IRS-2 signaling pathway.
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