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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Nutritional Immunology

This article is part of the Research TopicHealth Effects of Natural Compounds from PlantsView all 24 articles

Berberine augments the secretory function of salivary gland in homeostasis and after radiation exposure

Provisionally accepted
Qihang  LianQihang Lian1Yue  TianYue Tian1Nan  WangNan Wang1Yikun  LuoYikun Luo2Xi  WangXi Wang1Banghui  LiuBanghui Liu1Hefei  TianHefei Tian1Xiangjun  LiuXiangjun Liu1Yin  Qing pingYin Qing ping3Zhenni  XuZhenni Xu1Yujun  HuangYujun Huang1Lingxiao  HuangLingxiao Huang1Xudan  LeiXudan Lei1Jinyi  LangJinyi Lang1Feng  MeiFeng Mei3*Dengqun  LiuDengqun Liu1*
  • 1Radiation Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Cancer Hospital and Institute, Chengdu, China
  • 2Sichuan Cancer Hospital and Institute, Chengdu, China
  • 3Affiliated Hospital of Sichuan Nursing Vocational College, Chengdu, China

The final, formatted version of the article will be published soon.

Introduction: Radiotherapy serves as an essential therapeutic modality for head and neck malignancies. However, many patients who undergo head and neck radiation (HNR) frequently experience different severities of xerostomia. Berberine (BBR) has a variety of pharmacological functions and has shown favorable clinical efficacy. However, its therapeutic potential and mechanistic basis in xerostomia have not been explored. Methods: The histological expressions of Aquaporin 5 (AQP5), Na-K-Cl cotransporter 1 (NKCC1), Muscle intestine stomach expression 1 (MIST1), Proliferating cell nuclear antigen (PCNA), Phospho-GSK-3beta (p-GSK3β) and β-Catenin were examined by immunohistochemistry (IHC). Mucin2 (MUC2), were examined by immunofluorescence. The degree of apoptosis was assessed by TUNEL. The mRNA expression levels of AQP5, NKCC1, PCNA, MUC2, and MIST1 were detected by qRT-PCR assay. The degree of inflammatory was evaluated by detecting the mRNA expression levels of Il1b, Tgfb1, Tnf, and Il10. The Proliferation level was performed by salivary gland organoids. Results: BBR significantly enhanced saliva secretion in normal physiological conditions and after radiation injury. Mechanistically, BBR upregulated the expression of AQP5, NKCC1 and MIST1. Moreover, BBR conferred its protection via the upregulation of mucin 2 (MUC2) expression, and qPCR analysis revealed elevated Bhlha15 levels. Additionally, BBR preserved cellular proliferation, decreased TUNEL+ apoptotic cells and the inflammatory response in SMG tissues and organoids in HNR-induced xerostomia models. Conclusion: In conclusion, this study demonstrates that BBR can increase saliva secretion in healthy and HNR mice, indicating its potentiality for the treatment of radiation-induced xerostomia.

Keywords: Berberine, Homeostasis, Inflammation, proliferation, Radiation, Submandibular Gland

Received: 13 Aug 2025; Accepted: 18 Dec 2025.

Copyright: © 2025 Lian, Tian, Wang, Luo, Wang, Liu, Tian, Liu, ping, Xu, Huang, Huang, Lei, Lang, Mei and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Feng Mei
Dengqun Liu

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