2. Academic Validation
  3. Corylin ameliorates diabetic osteoporosis by inhibiting inflammation via targeting RAG1

Corylin ameliorates diabetic osteoporosis by inhibiting inflammation via targeting RAG1

  • Phytomedicine. 2025 Dec 5:150:157671. doi: 10.1016/j.phymed.2025.157671.
Zhi-Rou Lin 1,  Hao Yin 2,  Teng-Fei Wan 3,  Zhe Ruan 4,  Jing-Yi Mao 5,  Zi-Yun Pan 6,  Yan Huang 5,  Shi-Yu Zeng 5,  Li Ran 5,  Jiang-Hua Liu 5,  Xin-Hua Xiao 7,  Hui Xie 8,  Yin Hu 9
Affiliations

Affiliations

  • 1 Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Pharmacology Xiangya School of Pharmaceutical, Sciences Central South University Changsha, 410013, China.
  • 2 Rehabilitation medicine center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • 3 Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • 4 Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • 5 Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 6 Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Clinical Laboratory Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 7 Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: [email protected].
  • 8 Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: [email protected].
  • 9 Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: [email protected].
PMID: 41385948 DOI: 10.1016/j.phymed.2025.157671
Abstract

Background: Diabetic osteoporosis (DOP), a severe complication of diabetes mellitus, arises primarily from hyperglycemia-induced chronic inflammation and remains challenging to treat. Corylin, a flavonoid isolated from Psoralea corylifolia l., has been reported to possess anti-inflammatory properties; however, its therapeutic potential for DOP remains unknown.

Purpose: This study aimed to determine the therapeutic potential of corylin on DOP and to elucidate its underlying mechanisms preliminarily.

Methods: The effects of corylin on lipopolysaccharide-induced inflammatory responses in macrophages, as well as its impacts on the anti-osteoblastic and pro-osteoclastic abilities of activated macrophages, were assessed by quantitative Real-Time PCR analysis and cytochemical staining. In vivo, the effects of corylin in a streptozotocin-induced DOP mouse model were evaluated using microcomputed tomography, biomechanical testing, immunohistochemistry, and immunofluorescence. Molecular docking analysis was employed to identify potential targets of corylin. Surface plasmon resonance experiments were performed to validate the docking-predicted corylin-target interactions and to quantify binding affinity and kinetics. Subsequently, the roles of the potential target in the regulatory effects of corylin on osteogenesis, osteoclastogenesis, and inflammation were evaluated by using small interfering RNA in bone marrow mesenchymal stem cells, bone marrow macrophages, and RAW264.7 cells, as well as by using recombinant adeno-associated virus in mice.

Results: In vitro, corylin not only enhanced osteoblast differentiation and suppressed osteoclast formation, but also reduced the secretion of pro-inflammatory cytokines in lipopolysaccharide-activated macrophages, thereby impairing their anti-osteoblastic and pro-osteoclastic activities. Consistently, in vivo studies demonstrated that intragastric administration of corylin significantly improved bone mass and microarchitecture in streptozotocin-induced DOP mice by promoting bone formation, inhibiting bone resorption, and alleviating local and systemic inflammation. Mechanistically, these beneficial effects depended on recombination-activating gene 1 (RAG1), as RAG1 knockdown abolished corylin's effects on bone metabolism and inflammation, both in vitro and in vivo.

Conclusion: This study provides the first evidence of corylin's efficacy in a diabetic osteoporosis model and identifies RAG1 as its direct binding target, highlighting a previously unrecognized role of RAG1 in regulating bone metabolism and inflammation.

Keywords

Corylin; Diabetes mellitus; Inflammation; Osteoporosis; RAG1.

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