Mechanistic Potentials of Natural Herbal Medicines (NHMs) in Promoting Bone Regeneration: A Comprehensive Review.

Bone healing remains a major clinical challenge, especially in conditions such as osteoporosis, delayed unions, and critical-sized defects, where conventional therapies often prove inadequate. Current approaches, including growth factor therapies, autografts, and allografts, are limited by complications such as immunological reactions, donor-site morbidity, high cost, and poor long-term outcomes. In recent years, Natural Herbal Medicines (NHMs) have emerged as promising alternatives owing to their osteogenic, antioxidant, and anti-inflammatory properties. Phytoconstituents such as flavonoids, saponins, polyphenols, alkaloids, and minerals exert significant regulatory effects on key signaling pathways, including BMP/Smad, Wnt/β-catenin, MAPK, and RANK/RANKL/OPG, thereby restoring bone microarchitecture, suppressing osteoclastogenesis, and promoting osteoblast differentiation and mineralization. This review focuses on five medicinal plants with strong evidence in bone regeneration: Cissus quadrangularis, Dalbergia sissoo, Moringa oleifera, Withania somnifera, and Terminalia arjuna. Preclinical and clinical studies demonstrate their ability to enhance bone mineral density, collagen deposition, angiogenesis, and callus formation, while reducing oxidative stress and inflammation. Furthermore, synergistic effects have been reported in polyherbal formulations, and recent advances in biomaterials and nanotechnology-based carriers, such as scaffolds, hydrogels, and nanoparticles, offer targeted and sustained delivery, thereby improving therapeutic efficacy. Despite these promising findings, major barriers remain, including poor solubility, variability in phytochemical composition, lack of standardization, and limited large-scale clinical trials. Future research must integrate toxicological profiling, pharmacokinetic studies, and regulatory harmonization to ensure safe and effective translation of these therapies. Overall, NHMs represent an affordable, biocompatible, and culturally relevant adjunct or alternative to conventional bone-healing strategies, with the potential to revolutionize orthopedic regeneration when integrated with modern delivery platforms.