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ArgL 可能靶向 COVID-19 相关的炎症小体诱导的 ARDS 和细胞因子风暴。

Arglabin could target inflammasome-induced ARDS and cytokine storm associated with COVID-19.

机构信息

Faculty of Pharmacy, Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

Mol Biol Rep. 2021 Dec;48(12):8221-8225. doi: 10.1007/s11033-021-06827-7. Epub 2021 Oct 15.

Abstract

Arglabin (l(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),ll(13)-dien-6,12-olide), is a natural sesquiterpene γ-lactone which was first isolated from Artemisia glabella. The compound has been shown to possess anti-inflammatory activity through inhibition of the NLR Family pyrin domain-containing 3 (NLRP3) inflammasome and production of proinflammatory cytokines including interleukin (IL)-1β and IL-18. A more hydrophilic derivative of the compound also exhibited antitumor activity in the breast, colon, ovarian, and lung cancer. Some other synthetic derivatives of the compound have also been synthesized with antitumor, cytotoxic, antibacterial, and antifungal activities. Since both NLRP3 inflammasome and cytokine storm are associated with the pathogenesis of COVID-19 and its lethality, compounds like arglabin might have therapeutic potential to attenuate the inflammasome-induced acute respiratory distress syndrome and/or the cytokine storm associated with COVID-19.

摘要

阿格雷巴宾(l(R),10(S)-环氧-5(S),5(S),7(S)-愈创木-3(4),11(13)-二烯-6,12-内酯),是一种天然倍半萜 γ-内酯,最初从青蒿中分离得到。该化合物已被证明具有抗炎活性,可通过抑制NLR 家族吡喃结构域包含蛋白 3(NLRP3)炎症小体和产生包括白细胞介素(IL)-1β和 IL-18 在内的促炎细胞因子。该化合物的一种更亲水的衍生物也在乳腺癌、结肠癌、卵巢癌和肺癌中表现出抗肿瘤活性。该化合物的一些其他合成衍生物也具有抗肿瘤、细胞毒性、抗菌和抗真菌活性。由于 NLRP3 炎症小体和细胞因子风暴都与 COVID-19 的发病机制及其致死率有关,因此像阿格雷巴宾这样的化合物可能具有治疗潜力,可减轻炎症小体诱导的急性呼吸窘迫综合征和/或与 COVID-19 相关的细胞因子风暴。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cbf/8519322/f7f4cc644740/11033_2021_6827_Fig1_HTML.jpg

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