Du Pei, Zhang Wenqian, Cui Haobo, He Wei, Lu Shuang, Jia Sujie, Zhao Ming
Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2022 Jan 21;13:805508. doi: 10.3389/fphar.2022.805508. eCollection 2022.
Sulforaphane, which is found in cruciferous vegetables, has been reported to have anti-inflammatory, antioxidant, and antitumour activities. However, whether sulforaphane has therapeutic effects on inflammatory or autoimmune skin diseases, including psoriasis and systemic lupus erythematosus (SLE), is unclear. The therapeutic effects of sulforaphane were analyzed in Imiquimod (IMQ)-induced psoriasis-like mice and lupus-prone MRL/lpr mice. In IMQ-induced psoriasis-like mice treated with sulforaphane (55.3 and 110.6 μmol/kg) or vehicle control, the pathological phenotypes were assessed by the psoriasis area and severity index (PASI) score, haematoxylin-eosin staining (H&E) and quantifying of acanthosis and dermal inflammatory cell infiltration. The proportions of T cell subsets in draining lymph nodes (dLNs) and spleens were examined by flow cytometry. In MRL/lpr mice treated with sulforaphane (82.9 μmol/kg) or vehicle control, mortality and proteinuria were observed, and the glomerular pathology was examined by H&E staining. C3 and IgG depositions in kidney sections were examined by immunofluorescence staining. The proportions of plasma cells, follicular helper T (Tfh) cells, neutrophils and dendritic cells in the dLNs and spleens were examined by flow cytometry. Finally, we examined the Malondialdehyde (MDA) concentration by thiobarbituric acid reactive substance assay and the expression of , , , and by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Sulforaphane ameliorated the skin lesions in IMQ-induced psoriasis-like mice and the renal damage in lupus-prone MRL/lpr mice. In IMQ-induced psoriasis-like mice, sulforaphane reduced the proportions of Th1 and Th17 cells and increased the expression of antioxidant gene . In lupus-prone MRL/lpr mice, sulforaphane increased the lifespan and the expression of , and decreased the proportions of plasma cells, Tfh cells, neutrophils, and dendritic cells in the dLNs and spleens and the concentration of MDA. Sulforaphane has significant therapeutic effects on IMQ-induced psoriasis-like mice and lupus-like MRL/Lpr mice by reducing inflammatory and autoimmune-related cells and oxidative stress. These findings provide new evidence for developing natural products to treat inflammatory and autoimmune diseases.
萝卜硫素存在于十字花科蔬菜中,据报道具有抗炎、抗氧化和抗肿瘤活性。然而,萝卜硫素对包括银屑病和系统性红斑狼疮(SLE)在内的炎症性或自身免疫性皮肤病是否具有治疗作用尚不清楚。我们在咪喹莫特(IMQ)诱导的银屑病样小鼠和狼疮易感MRL/lpr小鼠中分析了萝卜硫素的治疗效果。在用萝卜硫素(55.3和110.6 μmol/kg)或载体对照处理的IMQ诱导的银屑病样小鼠中,通过银屑病面积和严重程度指数(PASI)评分、苏木精-伊红染色(H&E)以及棘层肥厚和真皮炎症细胞浸润的定量来评估病理表型。通过流式细胞术检测引流淋巴结(dLNs)和脾脏中T细胞亚群的比例。在用萝卜硫素(82.9 μmol/kg)或载体对照处理的MRL/lpr小鼠中,观察死亡率和蛋白尿,并通过H&E染色检查肾小球病理。通过免疫荧光染色检查肾切片中的C3和IgG沉积。通过流式细胞术检测dLNs和脾脏中浆细胞、滤泡辅助性T(Tfh)细胞、中性粒细胞和树突状细胞的比例。最后,我们通过硫代巴比妥酸反应性物质测定法检测丙二醛(MDA)浓度,并通过逆转录定量聚合酶链反应(RT-qPCR)检测 、 、 和 的表达。萝卜硫素改善了IMQ诱导的银屑病样小鼠的皮肤病变和狼疮易感MRL/lpr小鼠的肾损伤。在IMQ诱导的银屑病样小鼠中,萝卜硫素降低了Th1和Th17细胞的比例,并增加了抗氧化基因的表达。在狼疮易感MRL/lpr小鼠中,萝卜硫素延长了寿命并增加了 的表达,降低了dLNs和脾脏中浆细胞、Tfh细胞、中性粒细胞和树突状细胞的比例以及MDA浓度。萝卜硫素通过减少炎症和自身免疫相关细胞以及氧化应激,对IMQ诱导的银屑病样小鼠和狼疮样MRL/Lpr小鼠具有显著的治疗作用。这些发现为开发治疗炎症性和自身免疫性疾病的天然产物提供了新的证据。