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. 2024 Jul 30;10(15):e35423.
doi: 10.1016/j.heliyon.2024.e35423. eCollection 2024 Aug 15.

Jie-Du-Tong-Luo formula protects C2C12 myotubes against high glucose and palmitic acid injury by activating the PI3K/Akt/PPARγ pathway in vitro

Manying Wang  1 , Xuenan Chen  1 , Xiuci Yan  2 , Changjiu Cai  3 , Limei Ren  3 , Shuai Zhang  4 , Fangbing Liu  4
Affiliations

Jie-Du-Tong-Luo formula protects C2C12 myotubes against high glucose and palmitic acid injury by activating the PI3K/Akt/PPARγ pathway in vitro

Manying Wang et al. Heliyon. .

Abstract

Introduction: In prior reports, Jie-Du-Tong-Luo (JDTL) was reported to help control insulin secretion and blood glucose in patients with diabetes, while also protecting liver and pancreatic islet cells against injury caused by exposure to high glucose (HG) levels. This study was thus developed to assess the effects of JDTL on HG and palmitic acid (PA)-induced muscle injury and to explore the mechanistic basis for these effects.

Methods: A model of muscle injury was established using mouse C2C12 myotubes treated with HG + PA. A proteomics approach was used to assess changes in protein levels following JDTL treatment, after which Western immunoblotting was employed to validate significantly affected pathways.

Results: JDTL was able to protect against HG + PA-induced muscle cell injury in this experimental system, altering lipid metabolism and inflammatory activity in these injured C2C12 myotubes. Western blotting suggested that JDTL is capable of activating PI3K/Akt/PPARγ signaling to control lipid metabolism without any corresponding impact on the inflammatory NF-κB pathway.

Conclusions: These data highlight the ability of JDTL to protect against HG + PA-induced injury to muscle cells, and suggest that the underlying basis for such efficacy is related to the PI3K/Akt/PPARγ pathway-mediated modulation of lipid metabolism.

Keywords: C2C12 myotubes; High glucose; Jie-Du-Tong-Luo formula; PI3K/Akt/PPARγ; Palmitic acid.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Total ion chromatograms for JDTL generated using an UHPLC-Q-Exactive HF platform in (A) positive and (B) negative ion modes.
Fig. 2
Fig. 2
The impact of JDTL on injury to C2C12 myotubes induced by exposure to HG and/or PA. (A–F) An MTT assay approach was used to assess the viability of C2C12 myotubes exposed to JDTL (A), HG (B), mannitol (C), PA (D), HG + PA (E), and HG + PA and JDTL. *p < 0.05, **p < 0.01, ***p < 0.001 vs. CON; #p < 0.05, ##p < 0.01 vs. HG + PA.
Fig. 3
Fig. 3
Screening for differentially abundant proteins in JDTL-treated C2C12 myotubes injured with HG + PA. (A) Principal component analysis. (B) Volcano plot. (C) Heat map. (D) Column chart analysis.
Fig. 4
Fig. 4
Gene Ontology analyses of JDTL-treated HG + PA injured C2C12 myotubes. (A) Biological process terms. (B) Cellular component terms. (C) Molecular function terms. (D) KEGG pathway.
Fig. 5
Fig. 5
JDTL activates PI3K/Akt/PPARγ pathway signaling in C2C12 myotubes injured with HG + PA. (A–C) Following JDTL treatment for 24 h, p-PI3K/PI3K and p-Akt/Akt levels were assessed in HG + PA injured C2C12 myotubes via Western immunoblotting (A), with corresponding densitometric quantification of levels of p-PI3K/PI3K and p-Akt/Akt (B) and p-p65/p65, p-IκBα/IκBα, and PPARγ (C) Data are means ± SD (n = 3). *p < 0.05, **p < 0.01, ***p < 0.001 vs. CON; #p < 0.05, ##p < 0.01 vs. HG + PA.
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