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Molecules 2019, 24(2), 252; https://doi.org/10.3390/molecules24020252

A Novel Synthetic Steroid of 2β,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia

1
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
2
School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, China
3
Guangzhou Cellprotek Pharmaceutical Co. Ltd., G Building F/4, 3 Lanyue Road, Science City, Guangzhou 510663, China
4
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 12 December 2018 / Revised: 29 December 2018 / Accepted: 8 January 2019 / Published: 11 January 2019
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Neuroinflammation has been well recognized as a key pathological event in acute glaucoma. The medical therapy of acute glaucoma mainly focuses on lowering intraocular pressure (IOP), while there are still scarce anti-inflammatory agents in the clinical treatment of acute glaucoma. Here we reported that β,3α,5α-trihydroxy-androst-6-one (sterone), a novel synthetic polyhydric steroid, blocked neuroinflammation mediated by microglia/macrophages and alleviated the loss of retinal ganglion cells (RGCs) caused by acute intraocular hypertension (AIH). The results showed that sterone significantly inhibited the morphological changes, the up-regulation of inflammatory biomarker ionized calcium-binding adapter molecule 1 (Iba-1), and the mRNA increase of proinflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in BV2 microglia and RAW264.7 macrophages. Moreover, immunofluorescence and western blotting analysis revealed that sterone markedly abrogated the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) p65 subunit. Furthermore, sterone significantly suppressed the inflammatory microglial activation and RGCs’ reduction caused by retinal ischemia/reperfusion (I/R) injury in a rat AIH model. These results suggest sterone may be a potential candidate in the treatment of acute glaucoma caused by microglial activation-mediated neuroinflammatory injury. View Full-Text
Keywords: 2β,3α,5α-trihydroxy-androst-6-one; lipopolysaccharide; microglial activation; nuclear factor-κ B; ischemia/reperfusion injury; acute glaucoma 2β,3α,5α-trihydroxy-androst-6-one; lipopolysaccharide; microglial activation; nuclear factor-κ B; ischemia/reperfusion injury; acute glaucoma
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Sun, H.-J.-Q.; Xue, D.-D.; Lu, B.-Z.; Li, Y.; Sheng, L.-X.; Zhu, Z.; Zhou, Y.-W.; Zhang, J.-X.; Lin, G.-J.; Lin, S.-Z.; Yan, G.-M.; Chen, Y.-P.; Yin, W. A Novel Synthetic Steroid of 2β,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia. Molecules 2019, 24, 252.

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