Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)₂D₃/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety.

Tourism promotes the economic development of agro-cultural heritage sites while causing the problem of spatial alienation, so exploring the spatial alienation problems based on the integration of culture and tourism is of great significance for achieving the sustainable development of tourism in agro-cultural heritage sites. This study took the Yuanyang Hani Terrace agro-cultural heritage site as the research area, constructed the model of the spatial system of the agro-cultural heritage site based on the classical grounded theory, and analyzed the spatial characteristics of the agro-cultural heritage site. The results show that the spatial disorder of the agro-cultural heritage site is caused by the interaction of the imbalance of physical space, the fragmentation of cultural space and the complications of social space. Next, this study constructed the model for the spatial restructuring of the agro-cultural heritage site in the context of culture and tourism integration, with the integration of management systems as a guiding force, the integration of talent systems as a crucial force, the integration of agricultural, cultural and tourism resources as a core force, the integration of the cultural and tourism industries as a driving force, the integration of ecology and culture as a basic force, and the integration of digital scenes as an innovative force. This study expands and deepens the spatial theory of tourist destinations and the knowledge system of cultural heritage tourism, and provides a systematic implementation framework and management tools for the integration of culture and tourism and the high-quality development of agro-cultural heritage sites.

Osteoclasts are the only multinucleated cellsin vivoresponsible for bone resorption and are vital for regulating bone remodeling and maintaining bone mass. The RAW264.7 cell line is widely used to study osteoclastic differentiation and biological molecular mechanism. However, protocols for inducing osteoclast formation in RAW264.7 cells vary considerably between laboratories, hindering the replication of results. Therefore, we tested the influence of culture conditions on osteoclast differentiation, including cell density and receptor activator of nuclear factor kappa-B ligand (RANKL) concentrations with or without macrophage colony-stimulating factors (M-CSF). Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the morphology of osteoclasts. qPCR was used to detect gene expression of osteoclast-specific gene marker cathepsin K (CTSK), osteoclast transcription factors c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). The bone resorption function was evaluated by a scanning electron microscope (SEM). RANKL treatment increased multinucleated osteoclasts formation and increased CTSK, c-Fos and NFATc1 gene expression. Compared with RANKL treatment, M-CSF significantly decreased multinucleated osteoclasts formation, reduced CTSK gene expression and had little effect on c-Fos and NFATc1 gene expression. Concerning bone resorption activity, RANKL treatment increased bone resorption pits on bovine bone slices. Significantly higher levels of osteoclastogenesis were observed with RAW264.7-cell density of 2×10⁴cells/well in 24-well plates. Our results suggest that the addition of 50 ng/ml M-CSF has no positive effect on osteoclastogenesis. RANKL treatment and cell density contribute to osteoclast formation, and the optimal conditions are beneficial when exploring osteoclast function and mechanism.

Postmenopausal osteoporosis (PMOP) has increased in prevalence in recent years, thus researchers have evaluated alternative medicine therapies. Fructus Ligustri Lucidi (FLL) can inhibit bone loss, and ferroptosis serves an important role in osteoporosis. Therefore, the present study assessed the presence of ferroptosis in PMOP and whether FLL could inhibit ferroptosis to improve bone microstructure in ovariectomized rats. Ovariectomized rats were treated with FLL (1.56 g/kg/day) for 12 weeks. Micro‑CT was performed to evaluate the bone microstructure and bone mineral density. Western blotting and reverse transcription‑quantitative PCR were performed to assess the relative expression levels of proteins and mRNA. Subsequently, malondialdehyde (MDA) and Fe²⁺ assay kits were used to quantify the MDA and Fe²⁺ content, respectively. The results demonstrated that ovariectomy (OVX) resulted in iron overload and the accumulation of lipid peroxide. Furthermore, the expression of key factors that inhibited ferroptosis, glutathione peroxidase 4 and solute carrier family 7 member 11 was significantly downregulated in ovariectomized rats, which was significantly reversed by FLL treatment. Furthermore, bone formation was assessed using the expression of osteogenesis‑related genes, runt‑related transcription factor 2 and osterix, which revealed significantly higher levels in FLL‑treated rats compared with ovariectomized rats. The levels of nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) were also significantly recovered following FLL treatment. In the present study, OVX of postmenopausal osteoporotic rats was found to induce ferroptosis by enhancing lipid peroxidation and Fe²⁺ levels. FLL significantly suppressed ferroptosis, protected the osteogenic ability of ovariectomized rats and promoted the Nrf2/HO‑1 signaling pathway.