2790 - Berberine Mitigates the Hypofunction of Salivary Gland after Radiotherapy Induced Injury
Presenter(s)
Q. Lian1, Y. Chen2, Y. Tian1, L. Li3, M. Fan4, Y. Huang5, D. Liu6, and M. Feng7,8; 1Sichuan Cancer Hospital & Institute, Chengdu, Sichuan, China, 2Sichuan Cancer Hospital, chengdu, SICHUAN, China, 3Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, 4Sichuan Cancer Hospital and Research Institute, University of Electronic Science and Technology of China, Chengdu, China, 5No. 55, Section 4, South Renmin Road, Chengdu, China, 6Sichuan Cancer Center, Chengdu, China, 7The Third People's Hospital of Sichuan Province, Chengdu, China, 8Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Cheng Du, China
Purpose/Objective(s): Radiotherapy is the widely adopted treatment for head and neck cancers. Patients receiving radiation would experience different degrees of xerostomia, which seriously affects their life quality after therapy. However, there is still lack of effective therapeutic drug for alleviating xerostomia. At the same time the mechanisms of salivary gland regeneration and repairing after radiotherapy have not been fully clarified. Therefore, it is urgent and necessary to explore a new effective drug. Berberine (BBR) is a natural isoquinoline alkaloid extracted from Coptis. As an important extract from traditional Chinese medicinal herb, BBR exhibits a variety of biological and pharmacological functions. In this study, we aimed to investigate the roles of BBR during the regeneration and repairing of submandibular gland (SMG) after ionizing radiation induced injury.
Materials/Methods: C57BL/6J mice were divided into 4 groups (5 mice per group), including Control group, BBR group, Head and Neck Radiation (HNR) group, HNR+BBR group. BBR was administered into BBR group mice by continuous daily intraperitoneal (i.p) injections. The histological expressions of Aquaporin 5 (AQP5) and Na-K-Cl cotransporter 1 (NKCC1), Mist1, PCNA, Caspase3, MUC2 were examined by immunohistochemistry (IHC). The relative mRNA expression levels of AQP5, NKCC1, PCNA, MUC2, and Mist1 were detected by qRT-PCR assay. The degree of inflammatory activity in SMG after a single fraction of 15Gy radiation injury was evaluated by detecting the mRNA expression levels of IL-1b, TNF-a, and TGF-ß.
Results: Interestingly, we found that both before and after HNR treatment, BBR was able to significantly boost the secretion of saliva (P <0.001). Accordingly, the molecular markers for secretion and proliferation in submandibular gland tissues were increased, including AQP5, NKCC1, PCNA, MUC2, and Mist1 after BBR treatment (P <0.05). Meanwhile, BBR greatly decreased the expression levels of inflammatory cytokines, such as IL-1b, TNF-a, and TGF-ß in SMG in both healthy and HNR mice.
Conclusion: This study identified that BBR could promote the saliva secretion in both healthy and pathological conditions after HNR via modulating cellular proliferation, reducing apoptosis, blocking inflammation, and enhancing the expression of MIST1. BBR might be a prospective drug for xerostomia. We are deciphering the exact mechanisms linking BBR and the mentioned therapeutic functions to provide new insights into the treatment of xerostomia.