Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Molecules. 2024 May 2;29(9):2107. doi: 10.3390/molecules29092107.
Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant L. is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria. contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of and tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and teas reduced fibroblast viability 4 d post-treatment in up to 80% of their respective controls. After 4 d of treatment, AS DHA and teas downregulated up to 10 fold while ART had no significant effect, and AM increased viability by 10%. and were upregulated by AS, 17.5 and 32.6 fold, respectively, and by DHA, 8 and 51.8 fold, respectively. ART had no effect, but and teas increased 5 and 16-fold, respectively. Although tea increased 5 fold, decreased >7 fold with no change in either transcript by tea. Although contains ART, it had a significantly greater anti-fibrotic effect than ART alone but was less effective than . Immunofluorescent staining for smooth-muscle α-actin (α-SMA) correlated well with the transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts, with evidence also of remodeling of fibrotic ECM.
纤维化是一种普遍存在的病理学，先前的研究表明，各种青蒿素（ART）衍生物（包括青蒿琥酯（AS）、青蒿素（AM）和二氢青蒿素（DHA））可以减少体外和体内的纤维化。药用植物 L. 是 ART 的天然来源，被广泛使用，尤其是在欠发达国家，用于治疗各种疾病，包括疟疾。 不含 ART，但也具有抗疟作用。我们使用人真皮成纤维细胞（CRL-2097），比较了 和 茶提取物、ART、AS、AM、DHA 和 ART 的一种肝代谢物脱氧 ART（dART）对成纤维细胞活力和关键纤维化标记基因表达的影响，治疗 1 天和 4 天后。AS、DHA 和 茶在高达 80%的各自对照中在治疗后 4 天降低了成纤维细胞活力。经过 4 天的治疗，AS、DHA 和 茶将下调高达 10 倍，而 ART 则没有显著影响，AM 则增加了 10%的活力。 和 分别被 AS 上调了 17.5 和 32.6 倍，被 DHA 上调了 8 和 51.8 倍，ART 没有作用，但 和 茶分别上调了 5 倍和 16 倍。虽然 茶使 增加了 5 倍，但 茶使 减少了>7 倍，而 茶对两种转录物均无影响。虽然 茶含有 ART，但它的抗纤维化效果明显优于单独的 ART，但不如 茶有效。平滑肌α-肌动蛋白（α-SMA）的免疫荧光染色与药物处理的成纤维细胞的转录反应密切相关。综上所述，增殖、qPCR 和免疫荧光结果表明，ART、AS、DHA 和两种 茶的治疗导致人真皮成纤维细胞产生不同的反应，包括与纤维化相关的反应，并且还存在纤维化 ECM 的重塑。
