Connexin 43: A novel ginsenoside Rg1-sensitive target in a rat model of depression

Xia, Changfa; Wang, Zhenzhen; Wang, Huiqin; Ren, Siyu; Lou, Yuxia; Jin, Chen; Qu, Tiange; Feng, Sitong; Zhang, Yi; Chu, Shifeng; Chen, Nai‐Hong

doi:10.1016/j.neuropharm.2020.108041

Cited by 15 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The SPT was conducted as previously described ( Xia et al, 2020 ). In brief, rats were accustomed to 1% sucrose solution for 48 h. After water deprivation for 24 h, they were exposed to two identical bottles full of either sucrose solution or water for 1 h, and the bottle positions were changed during the test to prevent the interference of bottle position on the experiment.…”

Section: Methodsmentioning

confidence: 99%

Ginsenoside Rg1 Ameliorates Neuroinflammation via Suppression of Connexin43 Ubiquitination to Attenuate Depression

Wang

Yang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Depression is an inflammation-associated disease that results in major depression as inflammation increases and progresses. Ginsenoside Rg1 (Rg1), the major bioactive ingredient derived from ginseng, possesses remarkable anti-depressant and anti-inflammatory effects. Our previous studies showed that the pathogenesis of depression was concomitant with the acceleration of connexin43 (Cx43) ubiquitin degradation, while Rg1 could upregulate Cx43 expression to attenuate depression. However, whether the ubiquitination of Cx43 is the specific correlation between depression and inflammation, and how Rg1 ameliorates neuroinflammation to attenuate depression, are still under investigation. In in vivo experiments, Rg1 treatment significantly ameliorated depression-like behaviors in rats subjected to chronic unpredictable stress (CUS). Moreover, these CUS rats treated with Rg1 exhibited attenuated neuroinflammation, together with the suppression of Cx43 ubiquitination. In in vitro experiments, Rg1 reduced the secretion of inflammatory cytokines and the ubiquitination of Cx43 in lipopolysaccharide-induced glial cells. Furthermore, treatment with ubiquitin-proteasome inhibitor MG132 suppressing the ubiquitination of Cx43 ameliorated lipopolysaccharide-induced neuroinflammation. The results suggest that Rg1 attenuates depression-like behavioral performances in CUS-exposed rats; and the main mechanism of the antidepressant-like effects of Rg1 appears to involve protection against neuroinflammation via suppression of Cx43 ubiquitination. In conclusion, Rg1 could ameliorate neuroinflammation via suppression of Cx43 ubiquitination to attenuate depression, which represents the perspective of an innovative therapy of Rg1 in the treatment of inflammation-associated depression.

show abstract

Section: Methodsmentioning

confidence: 99%

Ginsenoside Rg1 Ameliorates Neuroinflammation via Suppression of Connexin43 Ubiquitination to Attenuate Depression

Wang

Yang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…The astrocytes in the prefrontal cortex and hippocampus of main rats were treated with CORT and cultured for 24 h to induce gap junction damage. Rg1 pretreatment extensively improved Cx43 gap junctions of CORT-treated astrocytes, reversed the CORT-induced down-regulation of Cx43 biosynthesis, accelerated Cx43 degradation, and enhanced the two primary astrocytes cell Cx43 degradation pathway ( Xia et al, 2020 ; Lenfant et al, 2021 ). Depression can be efficiently treated by raising Cx43 content, which may be owing to the effect of Rg1 on the degradation of ubiquitin-proteasome and autophagy-lysosome Cx43 pathways ( Wang H. Q. et al, 2021 ).…”

Section: Antidepressant Active Ingredients From Panax Notog...mentioning

confidence: 93%

“…However, the effect of Rg1 ( Lou et al, 2020 )can be reversed by injecting the gap junction blocker carbenoxolone (CBX) into the CA1 area of the hippocampus on both sides. Moreover, Rg1 significantly improved antidepressant susceptibility caused by injecting phenoxyketone or Gap26 (a selective inhibitor of Cx43) into the animal’s PFC ( Xia et al, 2020 ).…”

Section: Antidepressant Active Ingredients From Panax Notog...mentioning

confidence: 99%

Antidepressant Active Ingredients From Chinese Traditional Herb Panax Notoginseng: A Pharmacological Mechanism Review

Guo

Huang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Depression is one of the most common mental illnesses in the world and is highly disabling, lethal, and seriously endangers social stability. The side effects of clinical drugs used to treat depression are obvious, and the onset time is longer. Therefore, there is a great demand for antidepressant drugs with better curative effects, fewer side effects, and shorter onset time. Panax notoginseng, a Chinese herbal medication, has been used to treat depression for thousands of years and shown to have a therapeutic effect on depression. This review surveyed PubMed’s most recent 20 years of research on Panax notoginseng’s use for treating depression. We mainly highlight animal model research and outlined the pathways influenced by medicines. We provide a narrative review of recent empirical evidence of the anti-depressive effects of Panax Notoginseng and novel ideas for developing innovative clinical antidepressants with fewer side effects.

show abstract

“…Since infusion of gap26 into the rats, PFC induces dysfunction of gap junctions (Sun et al, 2012). Xia et al (Xia et al, 2020) established an in vitro depression rat model with corticosterone and found that ginsenoside Rg1 increased the expression of Cx43 compared with the gap26 group. Thus, the antidepressant-like effects of ginsenoside Rg1 were mainly mediated by Cx43-formed gap junctions.…”

Section: Protecting Astrocytes and Their Gap Junctionsmentioning

confidence: 99%

Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics

Xian

et al. 2022

Phytotherapy Research

View full text Add to dashboard Cite

The nervous system is one of the most complex physiological systems, and central nervous system diseases (CNSDs) are serious diseases that affect human health. Ginseng (Panax L.), the root of Panax species, are famous Chinese herbs that have been used for various diseases in China, Japan, and Korea since ancient times, and remain a popular natural medicine used worldwide in modern times. Ginsenosides are the main active components of ginseng, and increasing evidence has demonstrated that ginsenosides can prevent CNSDs, including neurodegenerative diseases, memory and cognitive impairment, cerebral ischemia injury, depression, brain glioma, multiple sclerosis, which has been confirmed in numerous studies. Therefore, this review summarizes the potential pathways by which ginsenosides affect the pathogenesis of CNSDs mainly including antioxidant effects, anti-inflammatory effects, anti-apoptotic effects, and nerve protection, which provides novel ideas for the treatment of CNSDs.

show abstract

Connexin 43: A novel ginsenoside Rg1-sensitive target in a rat model of depression

Cited by 15 publications

References 40 publications

Ginsenoside Rg1 Ameliorates Neuroinflammation via Suppression of Connexin43 Ubiquitination to Attenuate Depression

Ginsenoside Rg1 Ameliorates Neuroinflammation via Suppression of Connexin43 Ubiquitination to Attenuate Depression

Antidepressant Active Ingredients From Chinese Traditional Herb Panax Notoginseng: A Pharmacological Mechanism Review

Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics

Contact Info

Product

Resources

About