Withaferin A attenuates bleomycin-induced scleroderma by targeting FoxO3a and NF- signaling: Connecting fibrosis and inflammation
Withaferin A attenuates bleomycin-induced scleroderma by targeting FoxO3a and NF- signaling: Connecting fibrosis and inflammation
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DOI：
10.1002/biof.1446
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发表时间：
2018-11-01
期刊：
影响因子：
6
通讯作者：
Godugu, Chandraiah
中科院分区：
文献类型：
--
作者：
Bale, Swarna;Pulivendala, Gauthami;Godugu, Chandraiah
硬皮病是一种炎症性自身免疫性疾病，始于组织损伤引起的炎症，进展为细胞外基质的进行性积累，导致皮肤瘢痕和硬化。炎症是对多种因素引起的组织损伤的有益反应。虽然炎症是系统性伤口愈合所必需的，但失调的慢性炎症常常导致组织瘢痕。炎症在病理和生理上的突出作用使其成为一把双刃剑。本研究的目的是探讨Withaferin A（一种来自Withania somnifera的甾体内酯）在博莱霉素诱导的实验性硬皮病小鼠模型中的作用。以2和4 mg/kg两种剂量腹腔注射Withaferin A，连续28天。在研究结束时，我们观察到背部皮肤厚度明显减少。我们的研究结果表明，WFA能够充分抑制纤维化的促炎期、TGF-/Smad信号传导，并显著抑制成纤维细胞向肌成纤维细胞的转化。此外，我们的研究还表明，WFA调节foxo3a - akt依赖的NF-/ ikk介导的炎症级联反应，这是纤维形成的主要信号通路。本研究结果表明，枸杞多糖是一种抗纤维化药物，对硬皮病有良好的治疗效果。(c)中国生物医学工程学报，2018,35 (6):557 - 557,2018
Scleroderma is an inflammatory autoimmune disease which begins with inflammation due to tissue injury and advances to progressive accumulation of extracellular matrix resulting in scarring and hardening of the skin. Inflammation is a salutary response to tissue injury caused by varied factors. While inflammation is required for systematic wound healing, dysregulated chronic inflammation often leads to tissue scarring. Prominent role of inflammation in pathology and physiology makes it a double edge sword. The objective of this study was to investigate the role of Withaferin A (WFA), a steroidal lactone from Withania somnifera in a 28-day murine model of bleomycin-induced experimental scleroderma. Withaferin A was administered at two doses 2 and 4 mg/kg intraperitoneally for 28 days. At the time of study termination, we observed significant reduction in dorsal skin thickness. Our results indicate that WFA was able to sufficiently suppress pro-inflammatory phase of fibrosis, TGF-/Smad signaling and also significantly repressed fibroblast conversion to myofibroblasts. Additionally, our study also demonstrated that WFA modulates FoxO3a-Akt-dependent NF-/IKK-mediated inflammatory cascade, which is a prime signaling pathway in fibrogenesis. The findings of this study are persuasive of WFA as an antifibrotic agent with promising therapeutic effects in scleroderma. (c) 2018 BioFactors, 44(6):507-517, 2018