山奈酚通过抑制 MAPK 信号通路缓解 BALB/c 小鼠银屑病样皮炎的炎症反应。
Orientin alleviates the inflammatory response in psoriasis like dermatitis in BALB/c mice by inhibiting the MAPK signaling pathway.
机构信息
School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550000, China; Molecular Biology Laboratory, Guizhou Medical University, Guiyang, Guizhou 550000, China.
Department of Dermatology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, China.
出版信息
Int Immunopharmacol. 2024 Jun 15;134:112261. doi: 10.1016/j.intimp.2024.112261. Epub 2024 May 17.
BACKGROUND
Psoriasis, a chronic inflammatory condition of the skin, is characterized by an atypical proliferation of epidermal keratinocytes and immune cell infiltration. Orientin is a flavonoid monomer with potent anti-inflammatory activities. However, the therapeutic effects of orientin on psoriasis and the underlying mechanisms have not been elucidated.
OBJECTIVE
To investigate the therapeutic effect of orientin on psoriasis and the underlying mechanisms using network pharmacology and experimental studies.
METHODS
A psoriasis-like mouse model was established using imiquimod (IMQ). Lipopolysaccharide (LPS) was used to stimulate the RAW264.7 and HaCaT cells in vitro. The therapeutic effects of orientin and the underlying mechanism were analyzed using histopathological, immunohistochemical, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, flow cytometry, and western blotting analyses.
RESULTS
Orientin ameliorated skin lesions and suppressed keratinocyte proliferation and immune cell infiltration in the IMQ-induced psoriasis-like mouse model. Additionally, orientin inhibited the secretion of the pro-inflammatory factors interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-17, and IL-23 in the psoriasis-like mouse model and LPS-induced RAW264.7 and HaCaT cells. Furthermore, orientin mitigated the LPS-induced upregulation of reactive oxygen species and downregulation of IL-10 and glutathione levels. Orientin alleviated inflammation by downregulating the MAPK signaling pathway.
CONCLUSION
Orientin alleviated psoriasis-like dermatitis by suppressing the MAPK signaling pathway, suggesting that orientin is a potential therapeutic for psoriasis.
背景
银屑病是一种皮肤慢性炎症性疾病,其特征为表皮角质形成细胞的非典型增生和免疫细胞浸润。橙皮苷是一种具有强大抗炎活性的类黄酮单体。然而,橙皮苷对银屑病的治疗作用及其潜在机制尚未阐明。
目的
采用网络药理学和实验研究探讨橙皮苷治疗银屑病的作用及其潜在机制。
方法
采用咪喹莫特(IMQ)建立银屑病样小鼠模型。脂多糖(LPS)体外刺激 RAW264.7 和 HaCaT 细胞。采用组织病理学、免疫组织化学、实时定量聚合酶链反应、酶联免疫吸附试验、流式细胞术和蛋白质印迹分析方法分析橙皮苷的治疗效果及其潜在机制。
结果
橙皮苷改善了 IMQ 诱导的银屑病样小鼠模型的皮肤损伤,抑制了角质形成细胞增殖和免疫细胞浸润。此外,橙皮苷抑制了银屑病样小鼠模型和 LPS 诱导的 RAW264.7 和 HaCaT 细胞中促炎因子白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α、IL-6、IL-8、IL-17 和 IL-23 的分泌。此外,橙皮苷减轻了 LPS 诱导的活性氧增加和 IL-10 和谷胱甘肽水平降低。橙皮苷通过下调 MAPK 信号通路缓解炎症。
结论
橙皮苷通过抑制 MAPK 信号通路缓解银屑病样皮炎,提示橙皮苷可能是一种治疗银屑病的潜在药物。