Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China; Dermatology Department, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, Guangdong, China.
Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China; Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, Guangdong, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510120, Guangdong, China.
Int Immunopharmacol. 2019 Apr;69:270-278. doi: 10.1016/j.intimp.2019.01.054. Epub 2019 Feb 8.
Psoriasis is a chronic recurrent skin inflammatory disease, and inhibition of inflammation may be an effective means of treating psoriasis. The flavonoid genistein has a clear anti-inflammatory effect. However, the anti-psoriatic effects of genistein and their underlying mechanisms remain unclear. In this study, we investigated the effects of genistein on imiquimod (IMQ)-induced psoriasis-like skin lesions in vivo and explored the mechanisms underlying those effects in vitro. It was found that genistein can significantly improve IMQ-induced pathological scores of cutaneous skin lesions in mice, reduce epidermal thickness, and inhibit the expression of inflammatory factors，including interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2), IL-17 and IL-23. In vitro studies, genistein inhibited the proliferation of human keratinocyte HaCaT cells and inhibited the expression of inflammatory factors in a dose-dependent manner which induced by TNFα. Further researches showed that genistein could also significantly inhibit phosphorylated STAT3 (pSAT3) expression in IMQ mice dorsal skin and in TNF-α-induced HaCaT cells. The inhibitory effect of genistein on the expression of IL-6, IL-23 and TNF-α was weakened after Stat3 siRNA in HaCaT cells. Genistein could also significantly inhibit TNF-α induced the nuclear translocation of NF-κB, and inhibit the phosphorylation of I-kBα (pI-kBα). After combining with NF-κB blocker BAY 11-7082, the effect of genistein down-regulate the expression of TNF-α and VEGFA was attenuated in HaCaT cells. The results suggest that genistein may be developed for the treatment of psoriasis lesions.
银屑病是一种慢性复发性皮肤炎症性疾病，抑制炎症可能是治疗银屑病的有效手段。黄酮类化合物染料木黄酮具有明显的抗炎作用。然而，染料木黄酮的抗银屑病作用及其潜在机制尚不清楚。在本研究中，我们研究了染料木黄酮对咪喹莫特（IMQ）诱导的银屑病样皮肤损伤的体内作用，并探讨了其在体外的作用机制。结果发现，染料木黄酮能显著改善 IMQ 诱导的小鼠皮肤病变的病理评分，降低表皮厚度，并抑制炎症因子的表达，包括白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）、趋化因子配体 2（CCL2）、IL-17 和 IL-23。体外研究表明，染料木黄酮能抑制人角质形成细胞 HaCaT 细胞的增殖，并呈剂量依赖性抑制 TNFα诱导的炎症因子表达。进一步研究表明，染料木黄酮还能显著抑制 IMQ 小鼠背部皮肤和 TNF-α诱导的 HaCaT 细胞中磷酸化 STAT3（pSTAT3）的表达。在 HaCaT 细胞中沉默 Stat3 后，染料木黄酮对 IL-6、IL-23 和 TNF-α表达的抑制作用减弱。染料木黄酮还能显著抑制 TNF-α诱导的 NF-κB 核转位，并抑制 I-kBα（pI-kBα）的磷酸化。与 NF-κB 阻滞剂 BAY 11-7082 结合后，染料木黄酮下调 HaCaT 细胞中 TNF-α和 VEGFA 表达的作用减弱。这些结果表明，染料木黄酮可能被开发用于治疗银屑病皮损。
