Academy of Chinese Medical Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, 450058, People's Republic of China.
Academy of Chinese Medical Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, 450058, People's Republic of China; College of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, 450058, People's Republic of China.
J Ethnopharmacol. 2023 Dec 5;317:116767. doi: 10.1016/j.jep.2023.116767. Epub 2023 Jun 16.
Inflammation and subepithelial fibrosis play major roles in the early pathology of eosinophilic esophagitis (EoE). However, there are currently no pharmacotherapeutic interventions that directly target eosinophilic esophagitis. Citri Reticulatae Pericarpium (CRP, known as Chen-Pi) is one of most frequently used qi-regulating drugs in Chinese medicine and nutrition. CRP is rich with flavonones and polymethoxy flavones, both of which exhibit superior anti-inflammatory, anti-allergic and anti-fibrosis effects. This study is to investigate intervention effect of CRP on EoE, to identify its active compounds and to explore its underlying mechanisms.
The CRP extract was obtained by liquid-liquid extraction with 70% ethanol, and its main components were identified by HPLC and TLC chromatography as hesperidin, nobiletin, tangeretin, and narirutin in turn. Furthermore, we evaluated its effect and underlying mechanisms in an PN (Peanut protein extract)-sensitized murine model of food allergy induced EoE.
CRP treatment attenuated EoE model mice symptomatology, blocked hypothermia, reduced the production of PN-specific IgE and IgG1 and T2 cytokines (interleukin (IL)-4 and IL-5), and increased the level of anti-inflammatory cytokines IL-10 and interferon (IFN)-γ. CRP treatment also significantly alleviated the pathological damage and reduced fibrosis in inflamed tissues like esophagus, lung, and intestine. These results were strongly associated with reducing the expression of p-p38 mitogen-activated protein kinase (MAPK), transforming growth factor beta1 (TGF-β1) and p-Smad 3 proteins.
CRP extract markedly inhibited T2 immune response and attenuated subepithelial fibrosis with a dose-dependent manner through down-regulating MAPK/TGF-β signaling pathway. It is suggested that CRP extract might serve as a potential therapy for food allergy-induced EoE like disease.
炎症和上皮下纤维化在嗜酸性食管炎（EoE）的早期病理中起主要作用。然而，目前没有针对嗜酸性食管炎的药物治疗干预措施。陈皮（CRP，又称陈皮）是中药和营养中使用最频繁的调气药物之一。CRP 富含类黄酮和多甲氧基黄酮，两者均具有优异的抗炎、抗过敏和抗纤维化作用。本研究旨在探讨 CRP 对 EoE 的干预作用，确定其活性化合物，并探讨其潜在机制。
采用 70%乙醇液-液萃取法提取 CRP 提取物，并用 HPLC 和 TLC 色谱法依次鉴定其主要成分橙皮苷、川陈皮素、桔皮素和诺米林。此外，我们评估了其在花生蛋白提取物（PN）致敏的食物过敏诱导 EoE 小鼠模型中的作用及其潜在机制。
CRP 治疗可减轻 EoE 模型小鼠的症状，阻断体温过低，减少 PN 特异性 IgE 和 IgG1 和 T2 细胞因子（白细胞介素（IL）-4 和 IL-5）的产生，并增加抗炎细胞因子 IL-10 和干扰素（IFN）-γ的水平。CRP 治疗还显著减轻了食管、肺和肠道等炎症组织的病理损伤和纤维化。这些结果与降低 p-p38 丝裂原活化蛋白激酶（MAPK）、转化生长因子β1（TGF-β1）和 p-Smad3 蛋白的表达密切相关。
CRP 提取物通过下调 MAPK/TGF-β 信号通路，以剂量依赖性方式显著抑制 T2 免疫反应并减轻上皮下纤维化。提示 CRP 提取物可能成为食物过敏诱导的 EoE 样疾病的潜在治疗方法。
