Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha, 410208, Hunan, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha, 410208, Hunan, China.
J Ethnopharmacol. 2021 Oct 5;278:114212. doi: 10.1016/j.jep.2021.114212. Epub 2021 Jun 1.
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.
人参是一种有价值的药用植物和“替代”疗法，可预防和治疗抑郁症。星形胶质细胞中连接蛋白 43（Cx43）-缝隙连接的功能障碍易导致抑郁症的发生。从人参中提取的主要生物活性成分人参皂苷 Rg1（Rg1）通过上调 Cx43 的含量在治疗抑郁症方面非常有效。我们之前的研究结果表明，Rg1 预处理可显著改善皮质酮（CORT）处理的星形胶质细胞中的 Cx43 缝隙连接。然而，Rg1 如何上调星形胶质细胞中的 Cx43 缝隙连接的抗抑郁机制尚未提出。
剖析 Rg1 控制原代星形胶质细胞中 Cx43 水平的机制。
我们检测了 Cx43 mRNA 水平的变化、Cx43 的降解以及 Cx43 的泛素-蛋白酶体和自噬-溶酶体降解途径，然后在大鼠原代星形胶质细胞中用 Rg1 预处理皮质酮（CORT），这些星形胶质细胞是从前额皮质和海马中分离出来的。此外，采用划痕加载/染料转移法检测 Cx43 缝隙连接功能，这是抗抑郁作用的一个重要指标。
Rg1 预处理可逆转 CORT 诱导的 Cx43 生物合成下调、Cx43 降解加速以及原代星形胶质细胞中两条 Cx43 降解途径的上调。
本研究结果首次提供了证据，强调 Rg1 通过上调 Cx43 mRNA 和下调 Cx43 降解来增加 Cx43 蛋白水平，这可能归因于 Rg1 对 Cx43 泛素-蛋白酶体和自噬-溶酶体降解途径的影响。
