Research Square · Oct 22, 2026

Comparative pharmacodynamic effects of processed Ligustri Lucidi Fructus against postmenopausal osteoporosis and potential mechanisms associated with the wine-steamed preparation: Integrating multidimensional pharmacodynamics, serum chemistry, and spatial metabolomics

By Zhou B, Lu S, Wang R et al.

Ligustri Lucidi Fructus (LLF), a traditional Chinese medicine widely used for osteoporosis-related disorders, undergoes processing procedures that may alter its chemical composition and pharmacological properties. However, the comparative pharmacological profiles of different processed LLF preparations and the potential mechanisms associated with processing-enhanced effects remain insufficiently understood. In this study, five LLF preparations, including raw, steamed, wine-steamed, vinegar-steamed, and salt-steamed LLF, were systematically evaluated in ovariectomized (OVX) rats through an integrated strategy combining multidimensional pharmacodynamic assessment, serum pharmacochemistry, spectrum–efficacy correlation analysis, and desorption electrospray ionization mass spectrometry imaging (DESI-MSI)-based spatial metabolomics. Among the tested preparations, wine-steamed LLF (JLLF) exhibited the most comprehensive improvements in bone biomechanical properties, bone turnover markers, inflammatory responses, lipid metabolism, and marrow adiposity under the experimental conditions. Serum pharmacochemistry analysis identified 129 serum-exposed components, and 25 JLLF-characteristic candidate constituents, including 16 prototype compounds and 9 phase I/II metabolites, were prioritized through integrated component–efficacy analyses. DESI-MSI revealed distinct spatial distributions of JLLF-derived constituents in renal tissues and demonstrated that JLLF treatment was associated with the modulation of OVX-induced alterations in renal tryptophan metabolism and secondary bile acid biosynthesis. Collectively, this study provides comparative evidence regarding the pharmacological differences among processed LLF preparations and identifies candidate constituents and metabolic alterations associated with the enhanced effects of wine-steaming processing against postmenopausal osteoporosis.

doi.org/10.21203/rs.3.rs-11156039/v1 Open access Interventions