The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-kB/NLRP3 signaling
文献类型：期刊论文
| 作者 | Yang Fangming2; Fan Di2; Yang Xiaoqian1; Zhu Fenghua1; Shao Meijuan2; Li Qian1; Liu Yuting1; Lin Zemin1; Cao Shiqi1; Tang Wei1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2021 |
| 卷号 | 42期号:4页码:593 |
| 关键词 | dry eye disease artemisinin derivative β-aminoarteether maleate inflammation macrophages TLR4 inflammasome |
| ISSN号 | 1671-4083 |
| 英文摘要 | Dry eye disease (DED) is a multifactorial disorder of the tears and ocular surface characterized by manifestations of dryness and irritation. Although the pathogenesis is not fully illuminated, it is recognized that inflammation has a prominent role in the development and deterioration of DED. β-aminoarteether maleate (SM934) is a water-soluble artemisinin derivative with antiinflammatory and immunosuppressive activities. In this study, we established scopolamine hydrobromide (SCOP)-induced rodent model as well as benzalkonium chloride (BAC)-induced rat model to investigate the therapeutic potential of SM934 for DED. We showed that topical application of SM934 (0.1%, 0.5%) significantly increased tear secretion, maintained the number of conjunctival goblet cells, reduced corneal damage, and decreased the levels of inflammatory mediators (TNF-α IL-6, IL-10, or IL-1β) in conjunctiva in SCOP-induced and BAC-induced DED models. Moreover, SM934 treatment reduced the accumulation of TLR4-expressing macrophages in conjunctiva, and suppressed the expression of inflammasome components, i.e., myeloid differentiation factor88 (MyD88), Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and cleaved caspase 1. In LPS-treated RAW 264.7 cells, we demonstrated that pretreatment with SM934 (10 μM) impeded the upregulation of TLR4 and downstream NF-kB/NLRP3 signaling proteins. Collectively, artemisinin analog SM934 exerts therapeutic benefits on DED by simultaneously reserving the structural integrity of ocular surface and preventing the corneal and conjunctival inflammation, suggested a further application of SM934 in ophthalmic therapy, especially for DED. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304794]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院上海药物研究所 2.上海中医药大学 |
| 推荐引用方式 GB/T 7714 | Yang Fangming,Fan Di,Yang Xiaoqian,et al. The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-kB/NLRP3 signaling[J]. ACTA PHARMACOLOGICA SINICA,2021,42(4):593. |
| APA | Yang Fangming.,Fan Di.,Yang Xiaoqian.,Zhu Fenghua.,Shao Meijuan.,...&Zuo Jianping.(2021).The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-kB/NLRP3 signaling.ACTA PHARMACOLOGICA SINICA,42(4),593. |
| MLA | Yang Fangming,et al."The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-kB/NLRP3 signaling".ACTA PHARMACOLOGICA SINICA 42.4(2021):593. |
入库方式： OAI收割
来源：上海药物研究所
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