Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing 100010, China; Beijing University of Chinese Medicine, Beijing 100029, China.
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing 100010, China.
Life Sci. 2019 Feb 15;219:311-321. doi: 10.1016/j.lfs.2019.01.019. Epub 2019 Jan 15.
To evaluate the therapeutic benefits of Hesperidin (Hes) using an imiquimod (IMQ)-induced psoriasis-like mouse model and human immortalized keratinocytes (HaCaT) cells stimulated with lipopolysaccharide (LPS).
Mice were treated with IMQ and orally administered Hes (125-500 mg/kg/day), methotrexate (MTX) 1 mg/kg/day or distilled water. HaCaT cells were stimulated with LPS (1 μg/mL) and relevant indices were measured after administration with different concentrations of Hes (5-20 μg/mL) for 24 h. Inflammatory skin lesions in IMQ mice were evaluated using the psoriasis area severity index (PASI) and pathological staining. Proteins in the IRS-1/ERK1/2 pathway and inflammatory factors were assessed using western blotting or quantitative real-time PCR. In addition, factors related to IRS-1 secretion levels were assessed by enzyme-linked immunosorbent assays. Extracellular flux (XF) analysis was used to assess cellular metabolic levels.
Hes significantly improved psoriasis-like skin lesions of IMQ-treated mice and inhibited LPS-induced HaCaT cell proliferation. In addition, Hes remarkably decreased PASI scores, reduced epidermal thickness, decreased proliferation and differentiation of epidermal cells, inhibited mRNA expression of inflammatory factors, reduced local skin lesions and serum insulin and glucose levels. Furthermore, Hes modulated the secretion levels of serum Leptin, Adiponectin and Resistin, and inhibited the activation of the IRS-1/ERK1/2 signaling pathway and regulated HaCaT cells metabolism.
This study demonstrated that Hes administration could have significant therapeutic value for the prevention and clinical treatment of psoriasis.
通过咪喹莫特（IMQ）诱导的银屑病样小鼠模型和脂多糖（LPS）刺激的人永生化角质形成细胞（HaCaT），评估橙皮苷（Hes）的治疗益处。
用 IMQ 处理小鼠，并口服给予 Hes（125-500mg/kg/天）、甲氨蝶呤（MTX）1mg/kg/天或蒸馏水。用 LPS（1μg/mL）刺激 HaCaT 细胞，给予不同浓度的 Hes（5-20μg/mL）24h 后测量相关指标。用银屑病面积严重程度指数（PASI）和病理染色评估 IMQ 小鼠的炎症性皮肤损伤。用 Western blot 或实时定量 PCR 评估 IRS-1/ERK1/2 通路和炎症因子中的蛋白。此外，通过酶联免疫吸附试验评估与 IRS-1 分泌水平相关的因素。使用细胞外通量（XF）分析来评估细胞代谢水平。
Hes 显著改善了 IMQ 处理小鼠的银屑病样皮肤损伤，抑制了 LPS 诱导的 HaCaT 细胞增殖。此外，Hes 显著降低了 PASI 评分，减少了表皮厚度，抑制了表皮细胞的增殖和分化，降低了炎症因子的 mRNA 表达，减少了局部皮肤损伤和血清胰岛素及葡萄糖水平。此外，Hes 调节了血清瘦素、脂联素和抵抗素的分泌水平，抑制了 IRS-1/ERK1/2 信号通路的激活，并调节了 HaCaT 细胞的代谢。
本研究表明，Hes 给药可能对预防和临床治疗银屑病具有重要的治疗价值。
