Reduction of Th2 Inflammation and Fibrosis in Eosinophilic Esophagitis in a Murine Model by Citri Reticulatae Pericarpium

Authors

Mingzhuo Cao, Academy of Chinese Medical Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, 450058, People's Republic of China.
Zeqian Wang, 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.
Yuan Wang, 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.
Heyun Jing, Academy of Chinese Medical Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, 450058, People's Republic of China.
Yijia Meng, 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.
Yu Geng, College of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, 450058, People's Republic of China.
Xiu-Min Li, Department of Microbiology and Immunology, and Otolaryngology, New York Medical College, Valhalla, NY, 10595, USA. Electronic address: Xiu-Min_Li@nymc.edu.
Mingsan Miao, Academy of Chinese Medical Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, 450058, People's Republic of China. Electronic address: miaomingsan@hactcm.edu.cn.

Author Type(s)

Faculty

DOI

10.1016/j.jep.2023.116767

Journal Title

Journal of Ethnopharmacology

First Page

116767

Document Type

Article

Publication Date

12-5-2023

Department

Pathology, Microbiology and Immunology

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Recommended Citation

Cao, M., Wang, Z., Wang, Y., Jing, H., Meng, Y., Geng, Y., Li, X., & Miao, M. (2023). Reduction of Th2 Inflammation and Fibrosis in Eosinophilic Esophagitis in a Murine Model by Citri Reticulatae Pericarpium. Journal of Ethnopharmacology, 317, 116767. https://doi.org/10.1016/j.jep.2023.116767