2. Academic Validation
  3. Shengmai San attenuates irradiation-induced salivary gland injury and fibrosis by inhibiting the SPHK1-S1P-S1PR1 axis

Shengmai San attenuates irradiation-induced salivary gland injury and fibrosis by inhibiting the SPHK1-S1P-S1PR1 axis

  • Phytomedicine. 2025 Dec 27:150:157742. doi: 10.1016/j.phymed.2025.157742.
Honglin Li 1,  Guanru Wang 1,  Yuchen Fan 2,  Zhixuan Li 1,  Hongxuan Wei 1,  Suning Mao 2,  Cheng Miao 1,  Liu Liu 3,  Junsheng Chen 4,  Chunjie Li 1,  Zhangfan Ding 5,  Yubin Cao 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
  • 2 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
  • 3 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
  • 4 Developmental, Stem Cell and Cancer Biology Program, The Hospital for Sick Children, Toronto, Ontario 20017-3096, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario 20017-3096, Canada.
  • 5 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
PMID: 41483577 DOI: 10.1016/j.phymed.2025.157742
Abstract

Background: Radiation-induced salivary gland injury is a common complication of radiotherapy for head and neck tumors. The traditional Chinese herbal compound Shengmai San (SMS) can regulate Qi-Yin deficiency, promote fluid secretion, and alleviate thirst. However, its therapeutic effects on radiation-induced salivary gland damage remain unexplored.

Purpose: This study aimed to investigate the therapeutic efficacy of Shengmai San in irradiation-induced salivary gland injury, identify its active pharmaceutical components, and elucidate the underlying molecular mechanisms of radioprotection.

Material and methods: The natural drug components of Shengmai San were analyzed, and a murine model of irradiation-induced salivary gland injury was established. SMS extract was administered to irradiated mice, and the functional restoration of salivary glands was evaluated. Network pharmacology was employed to identify the active constituents of SMS, while molecular docking and protein-protein interaction analysis were used to screen key signaling pathways associated with glandular functional preservation. In vitro and in vivo experiments were conducted to validate these findings.

Results: Shengmai San significantly alleviated irradiation-induced salivary gland injury by promoting M2 macrophage polarization and reducing the levels of Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) in serum and salivary gland tissues. It also ameliorated glandular fibrosis and inflammation. Network pharmacology analysis revealed that ophiopogonanone E was one of the primary active components, and molecular docking demonstrated its strong interaction with sphingosine kinase 1 (SphK1) protein. In vivo experiments showed that SMS suppressed SphK1 activity and sphingosine-1-phosphate (S1P) production in irradiated salivary glands. Additionally, SMS effectively inhibited the downstream receptor S1PR1. In vitro studies confirmed that SMS attenuated mitochondrial damage in acinar cells by inhibiting the SPHK1-S1P-S1PR1 axis and reduced glandular inflammation and oxidative stress by suppressing Nucleotide-binding Oligomerization Domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation, thereby preserving salivary gland function.

Conclusion: Shengmai San effectively attenuates irradiation-induced salivary gland hypofunction and fibrosis, mainly through inhibition of the SPHK1-S1P-S1PR1 signaling pathway.

Keywords

Ophiopogonanone E; Radiation; Salivary gland injury; Shengmai San.

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