Pharmacological Research Progress on the Regulation of Bone Metabolism and Anti-osteoporosis by Active Ingredients of Rehmannia Glutinosa.

Osteoporosis, a common age-related bone metabolic disorder, poses a significant challenge in public health today. Existing chemical drugs are limited by long treatment durations and numerous side effects, making the search for safe and effective prevention and treatment strategies from traditional Chinese medicine a research hotspot. This narrative review synthesizes evidence primarily from preclinical studies to summarize the mechanisms of action of active ingredients in Rehmannia for treating osteoporosis based primarily on preclinical evidence, aiming to provide theoretical support for further research and new drug development. Studies have revealed that various natural compounds in Rehmannia exhibit potential against osteoporosis. Active components such as catalpol and verbascoside primarily promote bone formation through antioxidant stress reduction, inhibition of inflammatory responses, and regulation of osteogenic signaling pathways. (For instance,catalpol increased bone mineral density by approximately 25% in diabetic osteoporotic mouse models.) Meanwhile, compounds like oleanolic acid and ursolic acid appear to target the OPG/RANKL/RANK system and its downstream NF-κB and MAPK pathways, potentially suppressing osteoclast differentiation and bone resorption. These components collectively demonstrate a multi-target, bidirectional regulation characteristic in bone metabolism in experimental models. It is important to note that the current evidence is almost entirely preclinical, and the multi-pathway activity, while a potential advantage for holistic regulation, remains descriptive without clear hierarchical or comparative mechanistic prioritization. In summary, active ingredients from Rehmannia show clear preclinical potential in both promoting bone formation and inhibiting bone resorption, and are hypothesized to offer possibly offering better safety compared to conventional chemical drugs, although this claim lacks direct clinical comparative evidence. However, current evidence is mainly derived from preclinical studies, and the precise mechanisms and human efficacy require further clinical validation. The translational relevance of these findings is currently limited. Future research should focus on elucidating their molecular mechanisms with greater biological specificity, addressing pharmacokinetic challenges such as bioavailability,and accelerating clinical translation, thereby advancing Rehmannia-derived active ingredients as a potentially promising option for anti-osteoporosis drug development.