Screening and functional validation of active natural products against osteoporosis based on osteoimmunology
ZHANG Wenjuan
REN Tingting
JIANG Yao
BAI Wei
ZHAO Xin
ZHANG Genyang
QIAN Airong
Abstract：Objective To screen active natural products targeting osteoimmunology-related genes in osteoporosis using systems pharmacology,and to investigate their anti-osteoporotic functions.Methods Osteoimmunology-related genes were obtained from osteoporosis patient microarray datasets in the GEO database and the GeneCards database.Active natural products targeting these osteoimmunology-related genes were screened using the SysDT model.Potential anti-osteoporotic active natural products were further screened according to oral bioavailability ≥ 30％and drug-likeness ≥ 0.18.Furthermore,the pre-osteoblastic cell line MC3T3-E1 was used to investigate the effects of the screened active natural products,farrerol and rutaecarpine,on osteoblast differentiation.A rat model of disuse osteoporosis was established using the hindlimb unloading,and the preventive and therapeutic effects of the active natural product farrerol on disuse osteoporosis were explored.Results Microarray data analysis of osteoporosis patients identified 272 osteoimmunology-related genes.Further screening revealed two potential active natural products,farrerol and rutaecarpine,which target osteoimmunology-related genes.In vitro experiments revealed that both farrerol and rutaecarpine upregulated the expression of alkaline phosphatase and osteogenic differentiation-related genes in osteoblasts(P＜0.05,P＜0.01).These findings indicated that both farrerol and rutaecarpine facilitated osteoblast differentiation,with farrerol exhibiting a superior effect compared to rutaecarpine.Further in vivo experiments demonstrated that farrerol significantly increased bone mineral density and bone mineral content(P＜0.05),improved bone biomechanical properties(P＜0.01),and regulated the expression of bone immune factors including tumor necrosis factor-α,interleukin-4 and interleukin-10 in tail-suspended rats.Conclusion The active natural product farrerol,screened based on osteoimmunology-related genes,exerts anti-osteoporotic effects by promoting osteoblast differentiation,which may provide novel insights for the research and development of new drugs against osteoporosis.
Keywords：osteoimmunologyADME screeninganti-osteoporosisactive natural productssystems pharmacologyhindlimb unloadingfarrerolosteoblast differentiation
Publication Date：2026-07-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 978-984 )