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| Improvement of palmitic acid-induced insulin resistance in the L6 myoblast cells by withanolides through Akt/mTOR and Sirt 3 signal pathways |
| Hits 314 Download times 121 Received:July 30, 2025 |
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| DOI
10.11656/j.issn.1672-1519.2025.11.12 |
| Key Words
Physalis genus;withanolides;insulin resistance;ROS;autophagy;Akt/mTOR signal pathway;Sirt3 signal pathway |
| Author Name | Affiliation | E-mail | | YANG Qing | School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | LIU Yalu | School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | LI Zhipeng | 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 | | | CAO Shijie | State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | shijiecao0421@hotmail.com | | 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 the effects of withanolides from the medicinal plants of Physalis genus on improving insulin resistance. [Methods] L6 rat myoblasts were incubated with palmitic acid（PA） for 9 h to build the insulin resistance cell model（IR-L6）. The glucose oxidase assay and the Methylthiazolyldiphenyl-tetrazolium bromide（MTT） assay were used to measure the glucose consumption and cell viability of IR-L6 cells treated with 15 withanolides. Flow cytometry after stained with 2’，7’-Dichlorodihydrofluorescein diacetate（DCFH-DA） or Monodansylcadaverine（MDC） were used to test the production of Reactive oxygen species（ROS） and the proportion of autophagy cells，respectively. Western blot was used to measure the expression of the proteins related with phosphatidylinositol-3 kinase（PI3K）/protein kinase B（AKT）/the mammalian target of rapamycin（mTOR），Sirtuin 3（Sirt3） signal pathways and autophagy-related proteins. [Results] The 6 active components at the concentration of 10 μmol/L significantly promoted glucose uptake in the IR-L6 cells with low toxic. Compared with the control group，the levels of ROS and the proportion of autophagic cells were higher，but 6 withanolides could reversed these changes. Meanwhile，the protein expression of microtubule-associated protein-light chain 3 Ⅱ（LC3Ⅱ）and coiled-coil，myosin-like BCL2-interacting protein（Beclin 1） were up-regulated in the model group，but the relative expression of p-Akt/Akt and Sirt3 were down-regulated. In addition，ZM6，ZM11，XGY21，XGY24 and XGY29 down-regulated the expression of LC3Ⅱ and Beclin1，while the ratio of the expression of p-p-Akt/Akt and p-mTOR/mTOR were reduced by XGY21，XGY24 and XGY29. Meanwhile，ZM3，XGY21 and XGY24 promoted the expression of Sirt3. [Conclusion] The withanolides from Physalis alleviated insulin resistance by reducing ROS and autophagy，which may be related to Akt/mTOR and Sirt3 signal pathway. |
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