Novel antidepressant mechanism of ginsenoside Rg1: Regulating biosynthesis and degradation of connexin43

• Published in: Journal of ethnopharmacology 2021-10, Vol.278, p.114212-114212, Article 114212
• Main Authors: Wang, Hui-Qin, Yang, Song-Wei, Gao, Yan, Liu, Ying-Jiao, Li, Xun, Ai, Qi-Di, Lin, Mei-Yu, Yang, Yan-Tao, Zeng, Qi, Zhang, Yi, Wang, Zhen-Zhen, Chen, Nai-Hong
• Format: Article
• Language: English
• Subjects: Antidepressant; Biosynthesis; Connexin 43; Degradation; Degradation pathways; Depression; Ginsenoside Rg1
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2021.114212

Panax ginseng C. A. Meyer is a valuable medicinal herb and “alternative” remedy for the prevention and treatment of depression. Dysfunction of connexin43 (Cx43)-gap junction in astrocytes is predisposed to the precipitation of depression. Ginsenoside Rg1 (Rg1), the main bioactive constituent extracted from ginseng, is efficacious in the management of depression by upregulating the content of Cx43. Our previous results indicated that pretreatment with Rg1 significantly improved Cx43-gap junction in corticosterone (CORT)-treated astrocytes. However, the antidepressant mechanism underlying how Rg1 upregulates Cx43-gap junction in astrocytes hasn't been proposed. To dissect the mechanisms of Rg1 controlling Cx43 levels in primary astrocytes. We examined the changes of the level of Cx43 mRNA, the degradation of Cx43, as well as the ubiquitin-proteasomal and autophagy-lysosomal degradation pathways of Cx43 followed by Rg1 prior to CORT in rat primary astrocytes isolated from prefrontal cortex and hippocampus. Furthermore, the recognized method of scrape loading/dye transfer was performed to detect Cx43-gap junctional function, an essencial indicator of the antidepressant effect. Pretreatment with Rg1 could reverse CORT-induced downregulation of Cx43 biosynthesis, acceleration of Cx43 degradation, and upregulation of two Cx43 degradation pathways in primary astrocytes. The findings in the present study provide the first evidence highlighting that Rg1 increases Cx43 protein levels through the upregulation of Cx43 mRNA and downregulation of Cx43 degradation, which may be attributed to the effect of Rg1 on the ubiquitin-proteasomal and autophagy-lysosomal degradation pathways of Cx43. [Display omitted] •Rg1 reversed CORT-induced reduction of Cx43 expression in rat primary astrocytes.•Rg1 increased Cx43 mRNA levels in rat primary astrocytes exposed to CORT.•CORT accelerated the degradation of Cx43, while Rg1 reduced Cx43 degradation.•Rg1 reduced the ubiquitin and autophagy degradation pathways of Cx43.