Gastrodin regulates the expression of renin‐angiotensin system–SIRT3 and proinflammatory mediators in reactive astrocytes via activated microglia

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 (AT1) and type 2 (AT2) 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, AT1, 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 AT2 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 AT2 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 AT1. Additionally, azilsartan (a specific inhibitor of AT1) 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. Angiotensin II receptor subtype AT1 is involved in the regulation of phenotypic changes in reactive astrocytes. Gastrodin reduces the inflammatory response of activated microglia‐mediated reactive astrocytes through RAS–SIRT3 signalling and affects the phenotypic changes of reactive astrocytes.