Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Center for Converging Humanities, Kyung Hee University, Seoul 02447, Korea.
Molecules. 2019 Apr 15;24(8):1484. doi: 10.3390/molecules24081484.
Physcion is well known for the treatment of carcinoma. However, the therapeutic effect of physcion on atopic dermatitis (AD) through the inhibition of thymic stromal lymphopoietin (TSLP) level remains largely unknown. In this study, we investigated the anti-AD effect of physcion using HMC-1 cells, splenocytes, and a murine model. Treatment with physcion decreased production and mRNA expression levels of TSLP, IL-6, TNF-ɑ, and IL-1β in activated HMC-1 cells. Physcion reduced the expression levels of RIP2/caspase-1 and phospho (p)ERK/pJNK/pp38 in activated HMC-1 cells. Physcion suppressed the expression levels of pIKKβ/NF-κB/pIkB in activated HMC-1 cells. Moreover, physcion attenuated the production levels of TSLP, IL-4, IL-6, TNF-, and IFN-γ from activated splenocytes. Oral administration of physcion improved the severity of 2,4-dinitrochlorobenzene-induced AD-like lesional skin through reducing infiltration of inflammatory cells and mast cells, and the protein and mRNA levels of TSLP, IL-4, and IL-6 in the lesional skin tissues. Physcion attenuated histamine, IgE, TSLP, IL-4, IL-6, and TNF- levels in serum. In addition, physcion inhibited caspase-1 activation in the lesional skin tissues. These findings indicate that physcion could ameliorate AD-like skin lesions by inhibiting TSLP levels via caspase-1/MAPKs/NF-kB signalings, which would provide experimental evidence of the therapeutic potential of physcion for AD.
大黄素有治疗癌的功效已众所周知。然而,其通过抑制胸腺基质淋巴细胞生成素(TSLP)水平治疗特应性皮炎(AD)的疗效在很大程度上尚未可知。在这项研究中,我们使用 HMC-1 细胞、脾细胞和小鼠模型来研究大黄素的抗 AD 作用。大黄素处理可降低激活的 HMC-1 细胞中 TSLP、IL-6、TNF-ɑ和 IL-1β的产生和 mRNA 表达水平。大黄素降低了激活的 HMC-1 细胞中 RIP2/caspase-1 和磷酸化(p)ERK/pJNK/pp38 的表达水平。大黄素抑制了激活的 HMC-1 细胞中 pIKKβ/NF-κB/pIkB 的表达水平。此外,大黄素可降低激活的脾细胞中 TSLP、IL-4、IL-6、TNF-α和 IFN-γ的产生水平。口服大黄素可通过减少炎症细胞和肥大细胞的浸润以及减轻病变皮肤组织中 TSLP、IL-4 和 IL-6 的蛋白和 mRNA 水平,改善 2,4-二硝基氯苯诱导的 AD 样病变皮肤的严重程度。大黄素可降低血清中的组胺、IgE、TSLP、IL-4、IL-6 和 TNF-α水平。此外,大黄素抑制了病变皮肤组织中 caspase-1 的激活。这些发现表明,大黄素通过 caspase-1/MAPKs/NF-kB 信号通路抑制 TSLP 水平来改善 AD 样皮肤损伤,为大黄素治疗 AD 的治疗潜力提供了实验依据。