Qiangji Jianli Decoction Alleviates Hydrogen Peroxide-Induced Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics and Biogenesis in L6 Myoblasts.

Jingwei Song,Lanqi Li,Huafeng Pan,Aidong Ji,Qun Du,Jian Liang,Jinqiu Li,Zhiwei Chen,Yafang Song,Yanwu Li,Lingling Ke,Qing Li,Wei Jiao,Jos L Quiles

doi:10.1155/2021/6660616

Jingwei Song, Lanqi Li + Show 12 more

Open Access

https://doi.org/10.1155/2021/6660616

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Abstract

Oxidative stress can cause the excessive generation of reactive oxygen species (ROS) and has various adverse effects on muscular mitochondria. Qiangji Jianli decoction (QJJLD) is an effective traditional Chinese medicine (TCM) that is widely applied to improve muscle weakness, and it has active constituents that prevent mitochondrial dysfunction. To investigate the protective mechanism of QJJLD against hydrogen peroxide- (H2O2-) mediated mitochondrial dysfunction in L6 myoblasts. Cell viability was determined with MTT assay. Mitochondrial ultrastructure was detected by transmission electron microscope (TEM). ROS and mitochondrial membrane potential (MMP) were analyzed by fluorescence microscope and flow cytometry. The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) level were determined by WST-1, TBA, and DTNB methods, respectively. The mRNA and protein levels were measured by quantitative real-time PCR (qRT-PCR) and Western blot. The cell viability was decreased, and the cellular ROS level was increased when L6 myoblasts were exposed to H2O2. After treatment with QJJLD-containing serum, the SOD and GSH-Px activities were increased. MDA level was decreased concurrently. ROS level was decreased while respiratory chain complex activity and ATP content were increased in L6 myoblasts. MMP loss was attenuated. Mitochondrial ultrastructure was also improved. Simultaneously, the protein expressions of p-AMPK, PGC-1α, NRF1, and TFAM were upregulated. The mRNA and protein expressions of Mfn1/2 and Opa1 were also upregulated while Drp1 and Fis1 were downregulated. These results suggest that QJJLD may alleviate mitochondrial dysfunction through the regulation of mitochondrial dynamics and biogenesis, the inhibition of ROS generation, and the promotion of mitochondrial energy metabolism.

Highlights

Mitochondria have great impact on longevity and stress resistance [1]
The results indicated that cell viability of the model group was reduced by approximately 50% (p < 0:01), and this reduction was dramatically protected by QJJLDcontaining serum in a concentration-dependent manner (p < 0:01) (Figure 1(d))
To pose a hypothesis to explain the observations of our results, we suggest that Qiangji Jianli decoction (QJJLD) can upregulate the p-AMPK, PGC-1α, NRF1, and TFAM to promote mitochondrial biogenesis

Summary

Introduction

Mitochondria have great impact on longevity and stress resistance [1]. Yu and Yang have demonstrated that AMPK played a key role in mitochondrial energy metabolism by modulating PGC-1α [2]. They found PGC-1α acted as a master transcription factor for mitochondrial biogenesis by increasing the expression of NRF1 and TFAM, and PGC-1α is . Oxidative Medicine and Cellular Longevity important for the expression of nuclear genes that encode respiratory chain subunits. Both mitochondrial biogenesis and the activities of the mitochondrial respiratory chain are important for the increase in intracellular ATP levels

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