背景:黄芪,一种用途广泛的传统中草药,有丰富的历史可以追溯到“盛农的草药经典”。它已被用于临床实践,以解决各种疾病,包括抑郁症。它的主要活性成分之一,黄芪总黄酮(TFA),在其潜在的抗抑郁特性方面仍未被探索。本研究使用经受慢性不可预测的轻度应激(CUMS)的小鼠模型深入研究TFA的抗抑郁作用。
目的:这项研究旨在调查TFA如何影响抑郁行为,海马中皮质酮和谷氨酸水平,以及CUMS小鼠中髓磷脂相关蛋白的表达。此外,它试图探索Wnt/β-catenin/Olig2/Sox10信号轴的参与,这是TFA的潜在抗抑郁机制。
方法:使雄性C57BL/6小鼠经受CUMS以诱导抑郁行为。以两种不同的剂量(50mg/kg和100mg/kg)口服给予TFA。一系列行为测试,生化分析,免疫组织化学,UPLC-MS/MS,实时PCR,和Western印迹用于评估TFA的抗抑郁潜力。通过MO3.13细胞验证了Wnt/β-catenin/Olig2/Sox10信号轴在TFA抗抑郁机制中的作用。
结果:TFA给药可显着减轻CUMS小鼠的抑郁行为,正如蔗糖偏好改善所证明的那样,减少尾部悬挂和强迫游泳测试中的不动,和增加的运动活动在开放领域的测试。此外,TFA可有效降低CUMS小鼠海马皮质酮和谷氨酸水平,促进海马髓鞘形成。然后,TFA增加了CUMS小鼠海马中Olig2和Sox10的表达,同时抑制了Wnt/β-catenin通路。最后,我们进一步证实了TFA在MO3.13细胞中通过Wnt/β-catenin/Olig2/Sox10信号轴促进髓鞘再生中的作用。
结论:TFA在CUMS小鼠模型中显示有希望的抗抑郁作用,由髓鞘的恢复和皮质酮的调节促进,谷氨酸,Olig2、Sox10和Wnt/β-catenin途径。这项研究为TFA治疗抑郁症的潜在治疗应用提供了有价值的见解。尽管需要进一步的研究来充分阐明潜在的分子机制和临床相关性。
BACKGROUND: Radix Astragali, a versatile traditional Chinese medicinal herb, has a rich history dating back to \"Sheng Nong\'s herbal classic\". It has been employed in clinical practice to address various ailments, including depression. One of its primary active components, total flavonoids from Astragalus (TFA), remains unexplored in terms of its potential antidepressant properties. This study delves into the antidepressant effects of TFA using a mouse model subjected to chronic unpredictable mild stress (CUMS).
OBJECTIVE: The study aimed to scrutinize how TFA influenced depressive behaviors, corticosterone and glutamate levels in the hippocampus, as well as myelin-related protein expression in CUMS mice. Additionally, it sought to explore the involvement of the Wnt/β-catenin/Olig2/Sox10 signaling axis as a potential antidepressant mechanism of TFA.
METHODS: Male C57BL/6 mice were subjected to CUMS to induce depressive behaviors. TFA were orally administered at two different doses (50 mg/kg and 100 mg/kg). A battery of behavioral tests, biochemical analyses, immunohistochemistry, UPLC-MS/MS, real-time PCR, and Western blotting were employed to evaluate the antidepressant potential of TFA. The role of the Wnt/β-catenin/Olig2/Sox10 signaling axis in the antidepressant mechanism of TFA was validated through MO3.13 cells.
RESULTS: TFA administration significantly alleviated depressive behaviors in CUMS mice, as evidenced by improved sucrose preference, reduced immobility in tail suspension and forced swimming tests, and increased locomotor activity in the open field test. Moreover, TFA effectively reduced hippocampal corticosterone and glutamate levels and promoted myelin formation in the hippocampus of CUMS mice. Then, TFA increased Olig2 and Sox10 expression while inhibiting the Wnt/β-catenin pathway in the hippocampus of CUMS mice. Finally, we further confirmed the role of TFA in promoting myelin regeneration through the Wnt/β-catenin/Olig2/Sox10 signaling axis in MO3.13 cells.
CONCLUSIONS: TFA exhibited promising antidepressant effects in the CUMS mouse model, facilitated by the restoration of myelin sheaths and regulation of corticosterone, glutamate, Olig2, Sox10, and the Wnt/β-catenin pathway. This research provides valuable insights into the potential therapeutic application of TFA in treating depression, although further investigations are required to fully elucidate the underlying molecular mechanisms and clinical relevance.