Maad Rayan Publishing Company Biomedical Research Bulletin 2980-9924 3 4 2025 12 29 Exploring the Osteoprotective Mechanisms of Sambucus Williamsii Hance: A Comprehensive Narrative Review 200 205 10.34172/biomedrb.9084 EN Amir Hossein Jahanbani Mohammad Safakhalaj Mohsen Pourebrahimi Zahra Saeidi Pakdel Reza Aletaha https://orcid.org/0000-0002-5392-9599 REVIEW 10.34172/biomedrb.9084 2025 11 30 2025 12 12 Background: Osteoporosis, marked by reduced bone density and increased fracture risk, remains a serious public health challenge. Sambucus williamsii Hance (SWH), a traditional Chinese medicine, has been traditionally used for bone disorders and may represent a natural alternative to pharmacological therapies. Accordingly, this review evaluated the therapeutic potential and mechanisms of SWH extracts in osteoporosis management. Methods: A narrative review was conducted, and PubMed, Scopus, and Web of Science databases were searched for studies investigating SWH and osteoporosis in preclinical and clinical environments, focusing on populations at risk for osteoporosis, including postmenopausal and diabetic individuals. Outcome Measures: The primary outcomes included the effects of SWH extracts on bone formation and resorption, molecular mechanisms involved, and impacts on metabolic risk factors affecting bone health. Results: In general, SWH extracts were found to promote bone formation while inhibiting bone loss through genomic and non-genomic estrogen receptor pathways, involving mitogen-activated protein kinase and cyclic guanosine monophosphate-mediated protein kinase G type-2 signaling. Additional benefits on dyslipidemia, insulin resistance, and inflammation were also observed, potentially contributing to improved bone health in high-risk populations. SWH may offer safety and efficacy advantages over conventional estrogen-based therapies. Conclusion: SWH appears to be a promising natural candidate for osteoporosis treatment, with multi-faceted benefits and a favorable safety profile. Nonetheless, further clinical research is needed to confirm these findings and define its role in clinical practices.