Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective treatments.Nuciferine,an alkaloid found in lo...Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective treatments.Nuciferine,an alkaloid found in lotus leaf,has shown promising anti-inflammatory and anti-tumor effects,yet its efficacy in RA treatment remains unexplored.This study investigated the antiproliferative effects of nuciferine on the MH7A cell line,a human RA-derived fibroblast-like synoviocyte,revealing its ability to inhibit cell proliferation,promote apoptosis,induce apoptosis,and cause G1/S phase arrest.Additionally,nuciferine significantly reduced the migration and invasion capabilities of MH7A cells.The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis(CIA)rat model,where it markedly alleviated joint swelling,synovial hyperplasia,cartilage injury,and inflammatory infiltration.Nuciferine also improved collagen-induced bone erosion,decreased pro-inflammatory cytokines and serum immunoglobulins(IgG,IgG1,IgG2a),and restored the balance between T helper(Th)17 and regulatory T cells in the spleen of CIA rats.These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.展开更多
文摘目的探究芹菜素对雄激素性脱毛(androgenetic alopecia,AGA)小鼠的治疗作用及机制。方法将24只C57BL/6小鼠随机分为空白对照组、模型组、阳性对照组和芹菜素组。建立AGA小鼠模型,空白对照组和模型组小鼠背部涂抹1,2-丙二醇溶液,药物治疗组分别涂抹米诺地尔和芹菜素。观察实验期间小鼠皮毛生长情况,比较新生皮毛长度及质量;利用苏木精-伊红(hematoxylin-eosin,HE)染色观察小鼠毛囊状态及数量;通过蛋白质免疫印迹法(Western blot,WB)检测小鼠皮肤组织中Wnt/β-连环蛋白(Wnt/β-catenin)信号通路关键蛋白及细胞凋亡相关蛋白水平;通过皮肤组织免疫荧光染色检测β-catenin及核因子Ki-67(nuclear protein Ki-67)蛋白表达;使用分子对接软件对芹菜素及预测靶点进行对接分析。结果与模型组相比,芹菜素显著促进AGA模型小鼠皮毛新生,增加毛囊数量,促进毛囊由休止期向生长期转变。WB结果显示,芹菜素显著抑制Axis抑制蛋白1(axis inhibition protein 1,Axin1)、半胱天冬氨酸蛋白酶-3(cysteine-aspartic protease-3,Caspase-3)、Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax)表达,促进B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、β-catenin及磷酸化糖原合成酶激酶3β(phospho-glycogen synthase kinase 3β,p-GSK3β)/GSK3β蛋白表达,且显著增加小鼠皮肤Ki-67蛋白水平。此外,分子对接结果显示,β-catenin、GSK3β与芹菜素结合性良好。结论芹菜素具有促进AGA模型小鼠皮毛生长的作用,其作用机制可能与抑制毛囊细胞凋亡和激活Wnt/β-catenin信号通路相关。
基金supported by the National Natural Science Foundation of China(No.82274329,82304991)the China Postdoctoral Science Foundation(No,2023M732336)Shanghai Science and Technology Committee Sailing Program Foundation(No.23YF1442500)。
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective treatments.Nuciferine,an alkaloid found in lotus leaf,has shown promising anti-inflammatory and anti-tumor effects,yet its efficacy in RA treatment remains unexplored.This study investigated the antiproliferative effects of nuciferine on the MH7A cell line,a human RA-derived fibroblast-like synoviocyte,revealing its ability to inhibit cell proliferation,promote apoptosis,induce apoptosis,and cause G1/S phase arrest.Additionally,nuciferine significantly reduced the migration and invasion capabilities of MH7A cells.The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis(CIA)rat model,where it markedly alleviated joint swelling,synovial hyperplasia,cartilage injury,and inflammatory infiltration.Nuciferine also improved collagen-induced bone erosion,decreased pro-inflammatory cytokines and serum immunoglobulins(IgG,IgG1,IgG2a),and restored the balance between T helper(Th)17 and regulatory T cells in the spleen of CIA rats.These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.
