%0 Journal Article %T The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-κB/NLRP3 signaling %A Yang Fang-ming %A Fan Di %A Yang Xiao-qian %A Zhu Feng-hua %A Shao Mei-juan %A Li Qian %A Liu Yu-ting %A Lin Ze-min %A Cao Shi-qi %A Tang Wei %A He Shi-jun %A Zuo Jian-ping %J Acta Pharmacologica Sinica %D 2021 %B 2021 %9 %! The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-κB/NLRP3 signaling %K %X 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-κB/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. %U http://www.chinaphar.com/article/view/10302 %V 42 %N 4 %P 593–603 %@ 1745-7254