Gastrodin ameliorates Parkinson’s disease by downregulating connexin 43

Abstract

Abstract. Gastrodin, the predominant constituent of a Chinese herbal medicine, has been utilized in the prevention of Parkinson's disease (PD); however, its mechanism of action remains unknown. Astrocytes are involved in PD and are proposed to be coupled with gap junction connexin 43 (Cx43). To evaluate the effects of gastrodin on PD, the effect of gastrodin on Cx43 in astrocytes and in a PD model were observed. Different doses of gastrodin were added to the astrocyte culture medium or injected into the rotenone model of PD. The relative expression of Cx43 was determined by qPCR and western blot analysis, while gap junctional intercellular communication (GJIC) was quantified using fluorescence recovery after photobleaching (FRAP). The phosphorylated Cx43 was significantly inhibited by gastrodin and the quantity of GJIC was significantly downregulated compared with that of the control cells (P<0.05). In addition, in the rat model of PD induced by rotenone, phosphorylated Cx43 was selectively enhanced in the striatal and hippocampal regions. The enhanced activity was inhibited significantly by gastrodin treatment (P<0.01). Gastrodin results in the prevention of PD by reducing the expression of Cx43 and inhibiting the phosphorylation of Cx43; therefore, it may offer a potential therapeutic alternative for patients with PD.

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“…Some studies have shown that phosphorylated gap junction protein connexin 43 is selectively enhanced in the basal ganglia regions, which contain dopamine neurons or their terminal areas (striatum) [30,31]. PD is ameliorated by Gastrodin by downregulating connexin 43 [32]. …”

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“…In addition, GAS significantly attenuates the levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibiting the nuclear factor-κB signaling pathway and phosphorylation of mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-stimulated microglial cells (13). GAS also ameliorates Parkinson's disease by downregulating connexin 43 (14), and improves anxiety-like behaviors by decreasing the levels of interleukin (IL)-1β and inhibiting p38 MAPK phosphorylation in the hippocampus of a rat model of post-traumatic stress disorder (15). These findings indicated that GAS may exert beneficial effects on diseases of the central nervous system.…”