Gastrodin regulates expression of angiotensin-SirT3 and proinflammatory mediators in reactive astrocytes via activated microglia

Abstract

Abstract Use of Chinese herbal compounds have been widely explored in recent years to inhibit excessive proliferation and activation of astrocytes in brain injuries. Thus, it has been reported that Gastrodin, an anti-inflammatory agent, can effectively suppress microglia activation in rats with hypoxic-ischemia brain damage. This study was therefore aimed to determine if Gastrodin would exert a similar effect on reactive astrocytes and alleviate their inflammatory response through the renin-angiotensin system (RAS) and Sirtuin3 (SirT3). Expression of ATO, AT1 and SirT3 was detected in TNC-1 astrocytes, treated respectively with conditioned medium from BV-2 microglia with or without pretreatment of Gastrodin and lipopolysaccharide (LPS) by immunofluorescence and Western blotting. Along with this, expression of C3, S100A10, TNF-α and neurotrophic factors, including BDNF and IGF-1 expression was also evaluated. We showed here that TNC-1 astrocytes incubated in CM + LPS showed a marked increase in ATO, AT1, C3 and TNF-α when compared to cells in the BV-2 conditioned medium (CM), but that of S100A10 was reduced. Of note, TNC-1 astrocytes responded vigorously to conditioned medium derived from BV-2 microglia treated with Gastrodin + LPS when compared to the controls. This was evident by the decreased expression of the above-mentioned proteins, except for S100A10. As opposed to this, SirT3, IGF-1 and BDNF expression as determined by Western and immunofluorescence analysis was enhanced. The results suggest that Gastrodin inhibits the expression of RAS and proinflammatory mediators, but promotes the production of large amounts of neurotrophic factors in reactive astrocytes induced by LPS-stimulated activated microglia. Another novel finding of this study is the unequivocal demonstration that Gastrodin can promote the polarization of A2 phenotype that is regarded to be neuroprotective. This has added a new therapeutic perspective of this herbal compound that is gaining more attention in recent years.