Corylin

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.

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

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.

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.

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.

A green ultrasound-assisted deep eutectic solvent (UAE-DES) method was optimised for extracting flavonoid enzyme inhibitors from Blumea aromatica. Optimal conditions (choline chloride-1,4-butanediol 1:3 molar ratio, 43% water content, 50 mL/g liquid-to-solid ratio, 80 °C ultrasound for 48 min) yielded 3.15% total flavonoids, 45.2% higher than 50% ethanol extraction. Scanning electron microscopy confirmed cell wall disruption. The UAE-DES extract showed the strongest enzyme inhibition among all extracts tested (IC₅₀ 35.872 ± 0.294 µg/mL for α-glucosidase, 9.126 ± 0.285 μg/mL for tyrosinase), though the α-glucosidase inhibition was much weaker than acarbose, while tyrosinase inhibition was comparable to kojic acid. Six flavonoids were identified via UPLC-Q-Orbitrap HRMS, including scutellarein and corylin. Molecular docking revealed strong binding affinities (≤ -5 kcal/mol), with corylin showing the highest binding to both enzymes through hydrogen bonds and van der Waals interactions. This approach supports sustainable discovery of natural enzyme inhibitors for antidiabetic and skin-whitening applications.