Taohong Siwu dispensing granules alleviate rotenone-induced SH-SY5Y cellular cytotoxicity by rescuing mitochondrial dysfunction and amino acid metabolism disarrangements

doi:10.5246/jcps.2023.05.031

Abstract

Abstract:

As a progressive neurological disorder, Parkinson’s disease (PD) is characterized by tremors and slow movement. Mitochondrial dysfunction and amino acid (AA) metabolism are essential mechanisms of PD. Previous work has confirmed that the changes in amino acid contents in SH-SY5Y cells are earlier than the changes in cell viability. In the present study, we aimed to investigate whether Taohong Siwu dispensing granules (THSWDG) could alleviate rotenone-induced SH-SY5Y cytotoxicity by improving mitochondrial dysfunction and amino acid metabolism disorder. MTT assay was used to analyze the cell viability. JC-1 dye assay was used to measure mitochondrial membrane potential (MMP). HPLC was used to determine the content of amino acids (AAs) in SH-SY5Y cells. Principal component analysis was used to analyze the changes in the content of AAs. In order to further explore the PD-related biological functions involved in amino acid regulation, bioinformatics analysis tools were used to assess the biological processes involved in these protective effects. This study showed that the changes in AA contents in SH-SY5Y cells were earlier than the changes in cell activity. THSWDG dramatically increased cell viability and improved the rotenone-induced repression of MMP and abnormal metabolism of AAs. The results of the bioinformatic analysis suggested that the effects of THSWDG involved nine biological processes, including five AA metabolism regulations related to PD and four biological processes related to oxidative damage. The cellular AA process is a common biological process involved in the regulation of AA metabolism and oxidative damage. These results suggested that THSWDG exerted a cytoprotective effect on SH-SY5Y cells by rescuing mitochondrial dysfunction and AA metabolism disarrangements.

Key words: Parkinson’s disease, Taohong Siwu dispensing granules, Amino acid, Rotenone, Mitochondrial membrane potential

Supporting:

Shuang Li, Minggang Dong, Chunyan Guo, Shuangshuang Li, Sihan You, Ye Wan, Xinxing Liu. Taohong Siwu dispensing granules alleviate rotenone-induced SH-SY5Y cellular cytotoxicity by rescuing mitochondrial dysfunction and amino acid metabolism disarrangements[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(5): 360-378.

Figures/Tables 16

Table 1. Statistically significant AAs with VIP > 1 in THSWDG groups relative to SH-SY5Y cells in the model group.

Table 2. PD-related gene targets from the TTD database.

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