Molecular Mechanisms and Therapeutic Potential of Puerariae Lobatae Radix in Bone Metabolism: A Comprehensive Review

Dysregulated bone metabolism is the core pathological trigger of osteoporosis (OP) and other orthopedic disorders. Puerariae Lobatae Radix (PLR; kudzu) is a classic traditional Chinese medicinal herb, and its bioactive constituents including isoflavonoids and triterpenoid saponins exert well-documented bone-modulating effects. However, the specific mechanisms underlying PLR's regulation of bone metabolism have not been systematically elucidated, due to the complexity of bone metabolic signaling networks. Based on 127 relevant literature retrieved from Web of Science, Scopus and PubMed, this review systematically summarizes the molecular mechanisms of PLR and its core active components in regulating bone metabolism. We focus on PLR's regulation of pathways implicated in metabolic bone diseases (MBDs), including NF-κB, RANKL/RANK/OPG, PI3K/AKT, and MAPK, via multiple mechanisms including anti-inflammation, anti-oxidative stress, modulation of ferroptotic signaling, ie, regulation of iron-dependent lipid peroxidation-related cell death, autophagy modulation, and osteoimmune regulation, ie, modulation of interactions between immune responses and bone cells. This review suggests that PLR regulates bone homeostasis through multi-component and multi-pathway mechanisms, with potential effects on inhibiting osteoclast activity, promoting osteoblast function and maintaining bone microenvironment stability. It also provides a theoretical reference for further research on PLR, and highlights that future studies should focus on high-quality clinical trials and multi-omics exploration of signaling crosstalk to promote its clinical translation in MBDs.