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| Mechanism of stilbene compounds on the improvement of insulin resistance of adipocytes by NLRP3 inflammasome |
| Hits 550 Download times 256 Received:January 25, 2025 |
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| DOI
10.11656/j.issn.1672-1519.2025.06.15 |
| Key Words
stilbene compounds;insulin resistance;NLRP3 inflammasome;inflammation;network pharmacology |
| Author Name | Affiliation | E-mail | | ZHANG Bo | School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | XU Yifang | School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | YUAN Yongkang | School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | CAO Shijie | State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | KANG Ning | School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | kangndd@163.com |
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| Abstract
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| [Objective] To investigate the mechanism of stilbene compounds，including resveratrol（Re），mulberroside A（SP），and polygonum multiflorum glycosides（HSW），from three traditional Chinese medicines on the improvement of insulin resistance（IR） of adipocytes. [Methods] Network pharmacology was used to predict the potential therapeutic targets of the tested compounds；insulin resistant 3T3-L1 adipocytes model（IR-3T3-L1） was established by the stimulation of tumor necrosis factor α（TNF-α）；after pretreated with NLRP3（NOD-like receptor pyrin domain containing 3） inhibitor MCC950，the growth inhibitory effect and glucose consumption of the tested compound on the IR-3T3-L1 cells were determined by thiazole blue（MTT） method and Glucose oxidase method，respectively；molecular docking and cell thermal shift assay（CETSA） were used to investigate the binding of NLRP3 with Re，SP and HSW；Western Blot was used to test the expression of NLRP3 inflammasome-related protein；reverse transcription-quantitative polymerase chain reaction（RT-qPCR） was performed to investigate the mRNA expression of inflammatory factors. [Results] The results of network pharmacology analysis indicated that NOD-like receptor signaling pathway might play an important role in the beneficial effects of Re，SP，and HSW on inflammation and diabetes mellitus；the addition of MCC950 further increased the glucose uptake compared with Re，SP，HSW alone treatment；the results of molecular docking and CETSA showed that SP，HSW could bind to NLRP3；compared with the control group，the protein expression of NLRP3 and cleaved caspase-1（cle-caspase 1） in the model group was upregulated，and the pro-caspase 1 protein was downregulated. Meanwhile TNF-α significantly upregulated the mRNA expression of interleukin-1β（IL-1β），interleukin-6（IL-6） and interleukin-18（IL-18），and downregulated the mRNA expression of adiponectin（Adipoq）；but compared with the model group，Re，SP and HSW could significantly decrease the protein expressions of NLRP3，while SP and HSW significantly increased the protein expression of pro-caspase 1，and HSW significantly reduced the protein expression of cle-caspase 1. In addition，compared with the model group，Re significantly inhibited the mRNA expression of IL-6，IL-18 and IL-1β，and SP decreased the mRNA expression of IL-6 and IL-18，and HSW significantly decreased the mRNA expression of IL-1β. [Conclusion] Re，SP and HSW exhibited anti-diabetic effects through suppressing inflammatory responses and improving IR of adipocytes by inhibition of NLRP3 inflammasome. |
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