Extraction of Soybean and Pea Protein Isolates to Evaluate Therapeutic Potential Against Dexamethasone‐Induced Osteoporosis: In Vivo and in Silico Insights

ABSTRACT Soybean and pea protein isolates contain essential amino acid that may support bone health, skeletal function and muscle performance. The current research examines the amino acid profile of SPI and PPI and evaluates their impact on bone health in vivo and in silico . Female Sprague‐Dawley rats were randomly assigned to four groups: T 0 (Standard diet + without osteoporosis), T 1 (Standard diet + osteoporosis), T 2 (2 g/kg bw of SPI+ 2 g/kg bw of PPI), and T 3 (3 g/kg bw of SPI+ 3 g/kg bw of PPI). Biochemical parameters and histopathology of bone (femur and tibia), liver, and kidney were evaluated. The amino acid profile demonstrated higher levels of glutamic and aspartic acids and a lower level of sulfur‐containing amino acids. PPI exhibited higher content of arginine, lysine, and leucine than SPI. T 3 significantly reduced the severity of disease compared with all other groups, as reflected in increased the osteocalcin levels (9.50 ± 1.85 ng/mL), Ca (9.10 ± 1.06 mg/dL), P (3.30 ± 0.08 mg/dL), and lowering inflammatory levels of CRP (0.70 ± 0.04 mg/L) and ESR (15.70 ± 1.58 mm/h) in the respective treatment groups. Histological studies revealed no changes in bone, liver, and kidney tissues. Furthermore, molecular docking demonstrated potential interactions between gamma‐carboxylase and ligands, such as genistein, β‐sitosterol, glycitein, kaempferol, and quercetin, with binding affinities of −8.3, −9.0, −7.6, −7.6, and −8.1 kcal/mol, respectively. These findings support the therapeutic potential of plant protein isolates in osteoporosis management; however, long‐term in vivo trials are required to validate the safety of isolates before moving toward human trials.