Journal Article Ppublish
PubMed: 40183499 DOI: 10.1177/17448069251335230
Puerarin improves the comorbidity of chronic pain and depression by binding with Bax and reducing mitochondrial dysfunction.
Mol Pain 21:17448069251335230
Authors: Gege Sheng, Yin Wu, Lixin Yao, Hongyan Liu, Peigen Zhang, Cancan Song, Ganlin Wu, Haili Zhu
Affiliations
- Hubei Key Laboratory of Diabetes and Angiopathy, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, China.
- College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, Hubei, China.
- School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, China.
Abstract
Depression is a common comorbidity of chronic pain. The comorbidity of pain and depression causes longer symptoms and poorer patient prognosis. Periaqueductal gray (PAG) is the key region for the regulation of pain and depression. Puerarin (Pue) is a natural isoflavone compound that has a neuroprotective effect, but the mechanisms on the comorbidity of chronic pain and depression remain unclear. In this study, the spared nerve injury (SNI) produced mechanical allodynia and depressive-like behaviors and elevated the neurological damage in ventrolateral (vl) PAG. Meanwhile, at the 8 weeks following injury, mitochondrial dysfunctions including the dysregulated protein levels, the decreased Mn-SOD activity and the reduced ATP contents were observed in vlPAG of SNI model mice. Pue administration improved mechanical pain, motor coordination, and depression-like behaviors, decreased the neuronal activity and neuroinflammation, and elevated the mitochondrial function in vlPAG. Database analysis and experimental assay showed that Pue bound with Bax at the affinity of 2.4 ± 0.1 μM via D102 residue, and decreased Bax level in vlPAG of mice and in primary astrocytic cells. In addition, Pue also recovered levels of mitochondrial membrane potential and reactive oxygen species, and decreased inflammation in primary astrocytic cells. These results suggest that Pue improves the comorbidity of chronic pain and depression by targeting Bax and reducing mitochondrial dysfunction in vlPAG. This study may provide a theoretical basis for Pue application in improving the comorbidity of chronic pain and depression.
MeSH
Depression, Cells, Comorbidity, Chronic Pain, Pain