Osteogenic potential of Ricinus communis seed extract: Phytochemical profiling, in vitro and in silico evaluation

Abstract

Osteoporosis is a prevalent metabolic bone disease characterized by reduced bone mass, impaired bone microarchitecture, and an increased risk of fragility fractures. Ricinus communis L., a medicinal plant rich in bioactive phytochemicals, has recently attracted attention for its potential role in bone health. This study comprehensively investigated the osteogenic potential of Ricinus communis seed extract using integrated phytochemical, in vitro, and computational approaches. Phytochemical profiling of the ethanolic seed extract was performed using gas chromatography-mass spectrometry (GC-MS), while its osteogenic activity was evaluated in primary osteoblast cells through cell viability, alkaline phosphatase (ALP) activity, and mineralization assays. Molecular docking and molecular dynamics (MD) simulation were conducted against key membrane-bound osteogenic receptors, including bone morphogenetic protein receptor-2 (BMPR2), parathyroid hormone receptor-1 (PTHr1), and lipoprotein receptor-related protein 1 (LRP1). GC-MS analysis identified 37 phytoconstituents, predominantly fatty acid esters, phytosterols, tocopherols, and hydrocarbons. The extract significantly enhanced osteoblast proliferation, ALP activity, and mineralized nodule formation in a dose-dependent manner (25-100 μg/mL), indicating its osteogenic potential. Molecular docking demonstrated that stigmasterol, isofucosterol, γ-sitosterol, campesterol, δ-tocopherol, γ-sitostenone, hexadecanoic acid ethyl ester, and β-tocopherol exhibited strong binding affinities toward BMPR2, PTHR1, and LRP1. Furthermore, MD simulation, principal component analysis, and free-energy landscape assessments confirmed the structural stability of the BMPR2-stigmasterol, PTHr1-stigmasterol, and LRP-isofucosterol complexes. Most identified phytoconstituents also exhibited favorable pharmacokinetic, physicochemical, and drug-likeness characteristics. These findings provide preliminary evidence that Ricinus communis seed extract is a promising source of osteogenic phytochemicals with potential application in osteoporosis management, warranting further mechanistic and in vivo validation.