Balaha Mohamed F, Ahmed Nehad J, Almalki Ziyad S, Alahmari Abdullah K, Alshehri Ahmed M, Soliman Gamal A, Hamad Abubaker M
Clinical Pharmacy Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Tanta 31527, Egypt.
Clinical Pharmacy Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Life Sci. 2022 Aug 1;302:120653. doi: 10.1016/j.lfs.2022.120653. Epub 2022 May 19.
The present study aimed to investigate the potential of epimedin A to ameliorate DNFB-induced allergic contact dermatitis (CD) and reveal its potential underlying mechanisms of action, emphasizing its role in modulating NF-κB/NLRP3, Nrf2/HO-1 pathways, and inflammation.
Seven-week-old BALB/c mice received epimedin A orally for 11 days at doses of 5, 10, or 20 mg/kg/day, starting from the seventh day of DNFB-inducing CD.
Epimedin A dose-dependently ameliorated DNFB-induced CD, as revealed by the repression of the mice's scratching behavior, dermatitis score, ear thickness and weight, and ear tissue's histopathological changes, and area percent of collagen fibers induced by DNFB. These potentials were due to the NF-κB/NLRP3 pathway suppression and the Nrf2 pathway enhancement, as demonstrated by the reduction of NF-κB, NLRP3, ASC, caspase-1, and 8 mRNA expression, and NF-κBp65, IL-1β, MDA levels, and NF-κBp65 binding activity, along with the enhancement of the Nrf2, HO-1, IκB-α, GSH levels, SOD activity, and Nrf2 binding activity. Besides, it suppressed ear tissues' NLRP3 and caspase-8 induced pyroptosis by suppressing the ear tissues' caspase-1, 8, GSDMD upregulation, and LDH activity. Additionally, it repressed the local inflammatory reaction of ear tissue, as evidenced by the reduction of the elevated inflammatory cytokines (IL-1β, IL-6, Il-4, TNF-α, and IFN-γ), the serum level of t-IgE, DNFB s-IgE, s-IgE/t-IgE ratio, and the abrogation of the ear tissues histopathological changes.
Epimedin A is a novel, hopeful, natural therapeutic agent for CD by modulating NF-κB/NLRP3, Nrf2 pathways, and inflammation.
本研究旨在探讨淫羊藿苷A改善二硝基氟苯（DNFB）诱导的过敏性接触性皮炎（CD）的潜力，并揭示其潜在的作用机制，重点研究其在调节核因子κB（NF-κB）/NOD样受体蛋白3（NLRP3）、核因子E2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路及炎症反应中的作用。
7周龄BALB/c小鼠从DNFB诱导CD的第7天开始，以5、10或20mg/kg/天的剂量口服淫羊藿苷A，持续11天。
淫羊藿苷A剂量依赖性地改善了DNFB诱导的CD，表现为小鼠搔抓行为、皮炎评分、耳厚度和重量的降低，耳组织组织病理学变化的减轻，以及DNFB诱导的胶原纤维面积百分比的减少。这些作用可能是由于抑制了NF-κB/NLRP3信号通路并增强了Nrf2信号通路，表现为NF-κB、NLRP3、凋亡相关斑点样蛋白（ASC）、半胱天冬酶-1和8的mRNA表达降低，NF-κBp65、白细胞介素-1β（IL-1β）、丙二醛（MDA）水平及NF-κBp65结合活性降低，同时Nrf2、HO-1、核因子κB抑制蛋白α（IκB-α）、谷胱甘肽（GSH）水平、超氧化物歧化酶（SOD）活性及Nrf2结合活性增强。此外，它通过抑制耳组织中半胱天冬酶-1、8、gasdermin D（GSDMD）的上调及乳酸脱氢酶（LDH）活性，抑制了耳组织中NLRP3和半胱天冬酶-8诱导的细胞焦亡。此外，它还抑制了耳组织的局部炎症反应，表现为炎症细胞因子（IL-1β、IL-6、白细胞介素-4、肿瘤坏死因子-α和干扰素-γ）水平降低、血清总免疫球蛋白E（t-IgE）、DNFB特异性免疫球蛋白E（s-IgE）水平及s-IgE/t-IgE比值降低，以及耳组织组织病理学变化的消除。
淫羊藿苷A是一种新型、有前景的天然治疗CD的药物，可通过调节NF-κB/NLRP3、Nrf2信号通路及炎症反应发挥作用。
