Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China.
Eur J Neurosci. 2024 Jul;60(1):3677-3693. doi: 10.1111/ejn.16371. Epub 2024 May 6.
Gastrodin, an anti-inflammatory herbal agent, is known to suppress microglia activation. Here, we investigated whether it would exert a similar effect in reactive astrocytes and whether it might act through the renin-angiotensin system (RAS) and sirtuin 3 (SIRT3). Angiotensinogen (ATO), angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT) and type 2 (AT) receptor and SIRT3 expression was detected in TNC-1 astrocytes treated with BV-2 microglia conditioned medium (CM) with or without gastrodin and lipopolysaccharide (LPS) pre-treatment by RT-PCR, immunofluorescence and western blotting analysis. Expression of C3 (A1 astrocyte marker), S100A10 (A2 astrocyte marker), proinflammatory cytokines and neurotrophic factors was then evaluated. The results showed a significant increase of ATO, ACE, AT, SIRT3, C3, proinflammatory cytokines and neurotrophic factors expression in TNC-1 astrocytes incubated in CM + LPS when compared with cells incubated in the CM, but AT and S100A10 expression was reduced. TNC-1 astrocytes responded vigorously to BV-2 CM treated with gastrodin + LPS as compared with the control. This was evident by the decreased expression of the abovementioned protein markers, except for AT and S100A10. Interestingly, SIRT3, IGF-1 and BDNF expression was enhanced, suggesting that gastrodin inhibited the expression of RAS and proinflammatory mediators but promoted the expression of neurotrophic factors. And gastrodin regulated the phenotypic changes of astrocytes through AT. Additionally, azilsartan (a specific inhibitor of AT) inhibited the expression of C3 and S100A10, which remained unaffected in gastrodin and azilsartan combination treatment. These findings provide evidence that gastrodin may have a therapeutic effect via regulating RAS-SIRT3.
天麻，一种抗炎草药，已知可抑制小胶质细胞的激活。在这里，我们研究了它是否会对反应性星形胶质细胞产生类似的作用，以及它是否可能通过肾素-血管紧张素系统 (RAS) 和沉默调节蛋白 3 (SIRT3) 起作用。通过 RT-PCR、免疫荧光和 Western blot 分析，检测了用 BV-2 小胶质细胞条件培养基 (CM) 预处理并用天麻和脂多糖 (LPS) 处理的 TNC-1 星形胶质细胞中血管紧张素原 (ATO)、血管紧张素转换酶 (ACE)、血管紧张素 II 型 1 (AT) 和 2 (AT) 受体和 SIRT3 的表达。然后评估了 C3 (A1 星形胶质细胞标志物)、S100A10 (A2 星形胶质细胞标志物)、促炎细胞因子和神经营养因子的表达。结果显示，与在 CM 中孵育的细胞相比，在 CM+LPS 中孵育的 TNC-1 星形胶质细胞中 ATO、ACE、AT、SIRT3、C3、促炎细胞因子和神经营养因子的表达显著增加，但 AT 和 S100A10 的表达减少。与对照相比，用天麻+LPS 处理的 BV-2 CM 处理的 TNC-1 星形胶质细胞反应强烈。这可以通过降低上述蛋白标志物的表达来证明，除了 AT 和 S100A10。有趣的是，SIRT3、IGF-1 和 BDNF 的表达增强，表明天麻抑制了 RAS 和促炎介质的表达，但促进了神经营养因子的表达。并且天麻通过 AT 调节星形胶质细胞的表型变化。此外，阿齐沙坦 (AT 的特异性抑制剂) 抑制了 C3 和 S100A10 的表达，但在天麻和阿齐沙坦联合治疗中不受影响。这些发现提供了证据，表明天麻可能通过调节 RAS-SIRT3 发挥治疗作用。
