Protective effects of essential oil from Fructus Alpiniae zerumbet on retinal Müller gliosis via the PPAR-γ-p-CREB signaling pathway

BACKGROUND: Diabetic retinopathy (DR) involves extensive retinal damage and is one of the most common and serious complications of diabetes mellitus. Hyperglycemia is the major pathological trigger for diabetic complications. Müller cell gliosis, a key pathophysiological process in DR, could finally lead to vision loss. Our previous finding revealed that the essential oil of Fructus Alpiniae zerumbet (EOFAZ) protects human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced injury via the PPAR-γ signal. However, Whether EOFAZ could prevent HG-induced Müller cell gliosis through the PPAR signaling remains unclear. METHODS: The neuroprotective effects of EOFAZ were evaluated in HG-treated rat retinal Müller cells (RMCs) and DR rat model. RESULT: GFAP and VEGF upregulation is the biomarker of Müller glial reactivity gliosis. Results suggested that EOFAZ could remarkably ameliorate retinal reactive gliosis by suppressing p-CREB and GFAP and VEGF downstream effectors. Its effects on PPAR-γ, a major target for currently available anti-diabetes drugs, were also investigated. EOFAZ treatment remarkably attenuated the reduction of PPAR-γ and high level of p-CaMK II and p-CREB in HG-treated RMCs and diabetic rats. Furthermore, the activation and ectopic expression of PPAR-γ downregulated p-CREB and p-CaMK II in HG-treated RMCs. By contrast, CaMK II inhibitor KN93 and CREB gene silencing did not significantly affect the PPAR-γ expression. CONCLUSIONS: A novel PPAR-γ-p-CREB signaling pathway accounts for the inhibitory effect of EOFAZ on RMCs gliosis. These findings provide scientific evidence for the potential use of EOFAZ as a complementary and alternative medicine for DR prevention and treatment in the future. [Image: see text]