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image of Study on the Mechanism of Alpinia officinarum Hance in the Improvement of Insulin Resistance through Network Pharmacology, Molecular Docking and in vitro Experimental Verification

Abstract

Background

Research has elucidated that the pathophysiological underpinnings of non-alcoholic fatty liver disease and type 2 diabetes mellitus are intrinsically linked to insulin resistance (IR). However, there are currently no pharmacotherapies specifically approved for combating IR. Although Hance () can ameliorate diabetes, the detailed molecular mechanism through which it influences IR has not been fully clarified.

Aims

To predict the active components of and determine the mechanism by which affects IR.

Methods

The active compounds and molecular mechanism underlying the improvement of IR by were predicted via network pharmacology and molecular docking. To further substantiate these predictions, an model of IR was induced in HepG2 cells using high glucose concentrations. Cytotoxicity and oxidative stress levels were evaluated using Cell Counting Kit-8, reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) assay kits. The putative molecular mechanisms were corroborated through Western blot and RT-PCR analyses.

Results

Fourteen principal active components in , 133 potential anti-IR gene targets, and the top five targets with degree values were ALB, AKT1, TNF, IL6, and VEGFA. was posited to exert its pharmacological effects on IR through mechanisms involving lipid and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, the PI3K-AKT signaling pathway, fluid shear stress, and atherosclerosis. Intriguingly, network pharmacology analysis highlighted (4)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (A14) as the most active compound. Molecular docking studies further confirmed that A14 has a strong binding affinity for the main targets of PI3K, AKT, and Nrf2. The experiments demonstrated that A14 significantly diminished the ROS and MDA levels while augmenting the SOD activity. Moreover, A14 was found to elevate the protein expression of PI3K, AKT, Nrf2, and HO-1, and increase the mRNA levels of these targets as well as NQO1.

Conclusion

could play a therapeutic role in IR through multiple components, targets, and pathways. The most active component of responsible for combating IR is A14, which has the ability to regulate oxidative stress in IR-HepG2 cells by activating the PI3K/AKT/Nrf2 pathway. These findings suggest a potential pharmacological intervention strategy for the treatment of IR.

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2024-11-01
2025-01-29

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Study on the Mechanism of Alpinia officinarum Hance in the Improvement of Insulin Resistance through Network Pharmacology, Molecular Docking and in vitro Experimental Verification
Bentham Science Publishers ; https://doi.org/10.2174/0115734099325919241025023026
/content/journals/cad/10.2174/0115734099325919241025023026
/content/journals/cad/10.2174/0115734099325919241025023026
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  • Article Type:     Research Article
Keywords: insulin resistance ; network pharmacology ; oxidative stress ; Alpinia officinarum Hance ; molecular docking

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