Anti-osteoporotic Effects Research Articles

Decoding the synergistic potential of herbal medicine and dietary supplements for treating postmenopausal osteoporosis.

The exploration of the combined effects of FLL and quinoa presents an intriguing opportunity to enhance the efficacy of osteoporosis treatment. This study aimed to predict the potential anti-osteoporotic effects of FLL and quinoa using network pharmacology and subsequently verify these predictions through experimental investigation. Thirty rats were divided into five groups: sham operation group (SO), ovariectomized group (OVX), FLL group (FLL), quinoa group (Quinoa), and FLL combined with quinoa group (F&Q). The 12-week experiment involved measurements of bone density and microstructure, histological evaluation of femoral trabeculae and bone cortex, quantification of osteoclasts in the femur, assessment of osteoclast differentiation factor expression (NFATc1 and C-Fos), and measurement of collagen I carboxyl-terminal peptide (CTX-1). Additionally, intestinal flora analysis was performed. The results demonstrated reduced bone mineral density, compromised bone microarchitecture, increased osteoclast numbers and differentiation, and enhanced bone resorption in the OVX group, which were completely ameliorated by FLL, quinoa and F&Q interventions. F&Q exhibited superior improvement in bone density and microarchitecture compared to FLL and quinoa, although no significant differences were observed in their effects on osteoclasts and bone resorption. Gut flora analysis revealed that F&Q was more effective than FLL and quinoa in alleviating OVX-induced intestinal flora disorders, particularly in terms of enhancing intestinal flora diversity and function. The combo of FLL and quinoa was more effective in treating ovariectomy-induced osteoporosis and gut flora dysbiosis than FLL alone.

Bacoside A: A Promising Medication for Treatment of Various Disorders

Abstract: Bacoside A is a triterpenoid saponin and nootropic herb that can be extracted from Bacopa monnieri Linn., Scrophulariaceae. It is a glabrous and succulent herb used traditionally for centuries in treating various illnesses, mainly as a cardiotonic and nerve tonic, and has been considered an eminent Ayurvedic medicine. Various studies reported that the herb consists of a wide range of potentially bioactive, phytochemical constituents with synergistic effects. Bacoside A is a major constituent of B. monnieri, with diverse biological functions and significant therapeutic potential, as given by various researchers and preclinical studies. It possesses various biological activities such as hepatoprotective, anti-osteoporotic, anti-ulcerogenic, anti-inflammatory, anti-tumor, wound healing, and neuroprotective effects. This review compiled the preclinical evidence-based studies and present knowledge of bacoside A's potential benefits and fruitful impact on human health, and we provided a comprehensive perspective of bacoside A in various disease treatments.

S6K/FLNC/ITGβ3 signaling pathway regulates osteoclastogenesis and the inhibition of osteoclastogenesis by columbianadin

BackgroundOver-activation of osteoclastogenesis is a significant factor contributing to bone loss, leading to increased resorption of bone. Columbianadin (CBN), a compound derived from Angelicae Pubescentis Radix, has traditionally been used in Chinese medicine to treat bone-related disorders. However, the specific effects of CBN on bone loss are still poorly understood. Study designThis study aims to identify a novel target for inhibiting osteoclast differentiation and to elucidate the effects and underlying mechanisms of CBN on osteoclastogenesis. MethodsWe employed a transcriptomics approach to identify genes that undergo significant changes during osteoclast differentiation. These findings were validated using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB) analysis. Subsequently, we utilized adenoviral transfection to investigate the effects of target genes on osteoclast differentiation. Additionally, we employed proteomics to elucidate the signaling pathways that regulate osteoclast differentiation. We examined the effect of CBN on S6K/FLNC/ITGβ3 signaling pathway and osteoclast differentiation. ResultsOur results revealed a dramatic increase in filamin C (FLNC) levels during osteoclast differentiation. Inhibition of FLNC expression significantly suppressed markers of osteoclast differentiation such as tartrate-resistant acid phosphatase (TRAP), nuclear factor-activated T cell 1 (NFATc1), and c-Fos, as well as inhibited the activity of bone resorption. We further conducted a proteomic analysis and found S6K protein might be involved in this process. Then we utilized an S6K-specific inhibitor (PF-4708671) and demonstrated that inhibiting the S6K protein reduced FLNC expression and the interaction between FLNC and integrin β3 (ITGβ3) in osteoclasts. Finally, we found that CBN inhibited osteoclast differentiation and bone loss in ovariectomized mice by targeting the S6K/FLNC/ITGβ3 signaling pathway. ConclusionFLNC was identified as a critical protein in osteoclastogenesis. The S6K/FLNC/ITGβ3 signaling pathway played a significant role in osteoclast differentiation and bone loss. Furthermore, CBN exhibited anti-osteoporotic effects by inhibiting the S6K/FLNC/ITGβ3 signaling pathway.

The Acetylated 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-Glucoside Improved Pharmacokinetics and Enhanced Anti-Osteoporosis Effects

Background: Osteoporosis has emerged as a significant global public health concern, predominantly affecting postmenopausal women. Its pathogenesis is intricate and the disease course is protracted, imposing substantial medical burden on both society and individuals. Objective: To investigate the effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) and acetylated-TSG (Ac-TSG) on osteoblast viability, in vivo pharmacokinetics in rats and anti-osteoporotic effects in ovariectomized rat model. Methods: Ac-TSG was obtained by acetylation of TSG, and the purity and structure of Ac-TSG were determined by HPLC and 1H NMR. The effects of TSG and Ac-TSG on MC3T3-E1 cell viability, pharmacokinetics in rats, blood biochemical indexes of OVX model rats were detected. Hematoxylin–eosin (HE) staining was used to observe bone tissue morphology, tartrate-resistant acid phosphatase (TRAP) staining was used to observe osteoclast morphology, micro-CT was used to perform three-dimensional reconstruction of femur, and femur parameters were analyzed. Results: The structure of the compound is Ac-TSG and the purity is more than 98%. Both TSG and Ac-TSG could reduce the damage of oxidative stress to MC3T3-E1 cells and effectively improve the levels of Ca, P, ALP and BGP in serum of OVX rats. Compared with TSG, Ac-TSG has a longer action time in vivo and can improve the femoral structure, the number of trabecular bone and the number of osteoclasts in rats. Conclusion: Ac-TSG conferred protection to MC3T3-E1 cells against oxidative stress-induced damage and enhanced their bioavailability. Simultaneously, Ac-TSG ameliorated abnormal bone metabolism and mitigated bone microstructural changes in OVX rats, exhibiting a protective effect against osteoporosis.

Dihydromyricetin ameliorate postmenopausal osteoporosis in ovariectomized mice: Integrative microbiomic and metabolomic analysis.

The gut microbiota may help mitigate bone loss linked to postmenopausal osteoporosis by affecting the immune and inflammatory responses and the gut-bone axis. Dihydromyricetin (DMY), a natural flavonoid, has some anti-inflammatory and antioxidant properties. This study aimed to investigate the mechanisms underlying the amelioration of bone loss in ovariectomized (OVX) mice treated with various doses of DMY. Eight-week-old C57/BL6 mice underwent ovariectomy and received varying DMY doses over 8 weeks. Thereafter, femoral bone microarchitecture, serum biomarker levels, and colon samples were analyzed to assess bone metabolism and inflammatory and hormonal responses. Fecal samples were subjected to 16S rDNA sequencing, and short-chain fatty acids were quantified. An untargeted metabolomics approach was applied to both serum and fecal samples to investigate alterations in the intestinal microbiota and metabolic profiles following DMY treatment in the OVX mice. The results show high-dose DMY has anti-osteoporotic effects. Compared to the OVX group, the DMY-treated group showed enhanced bone mineral density and reduced inflammation and colonic damage levels. The DMY treatment altered the gut microbiota composition, including the relative abundances at both the phylum and genus levels. In addition, DMY treatment increased the production of acetate and propionate. Metabolomic analysis revealed differential regulation of 37 and 70 metabolites in the serum and feces samples, respectively, in the DMY-treated group compared to those in the OVX group, affecting the serotonergic signaling, arachidonic acid metabolism, and unsaturated fatty acid biosynthesis pathways. In conclusion, these findings indicate that DMY can ameliorate bone loss in OVX mice via the gut-bone axis.

Europium-Containing Nanospheres for Treating Ovariectomy-Induced Osteoporosis: Targeted Bone Remodeling and Macrophage Polarization Modulation.

Osteoporosis, characterized by reduced bone mass and structural deterioration, poses a significant healthcare challenge. Traditional treatments, while effective in reducing fracture risks, are often limited by side effects. This study introduces a novel nanocomplex, europium (Eu) ions-doped superparamagnetic iron oxide (SPIO) nanocrystals encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanospheres, abbreviated as SPIO:Eu@PLGA nanospheres, as a potential therapeutic agent for osteoporosis by modulating macrophage polarization, enhancing osteoblast differentiation and inhibiting osteoclastogenesis. SPIO and SPIO:Eu nanocrystals were synthesized through pyrolysis and encapsulated in PLGA using an emulsification method. To evaluate the impact of SPIO:Eu@PLGA nanospheres on macrophage reprogramming and reactive oxygen species (ROS) production, flow cytometry analysis was conducted. Furthermore, an ovariectomized (OVX) rat model was employed to assess the therapeutic efficacy of SPIO:Eu@PLGA nanospheres in preventing the deterioration of osteoporosis. In vitro, SPIO:Eu@PLGA nanospheres significantly attenuated M1 macrophage activation induced by lipopolysaccharides, promoting a shift towards the M2 phenotype. This action is linked to the modulation of ROS and the NF-κB pathway. Unlike free Eu ions, which do not achieve similar results when not incorporated into the SPIO nanocrystals. SPIO:Eu@PLGA nanospheres enhanced osteoblast differentiation and matrix mineralization while inhibiting RANKL-induced osteoclastogenesis. In vivo studies demonstrated that SPIO:Eu@PLGA nanospheres effectively targeted trabecular bone surfaces in OVX rats under magnetic guidance, preserving their structure and repairing trabecular bone loss by modulating macrophage polarization, thus restoring bone remodeling homeostasis. The study underscores the critical role of Eu doping in boosting the anti-osteoporotic effects of SPIO:Eu@PLGA nanospheres, evident at both cellular and tissue levels in vitro and in vivo. The inclusion of Eu into SPIO matrix suggests a novel approach for developing more effective osteoporosis treatments, particularly for conditions induced by OVX. This research provides essential insights into SPIO:Eu@PLGA nanospheres as an innovative osteoporosis treatment, addressing the limitations of conventional therapies through targeted delivery and macrophage polarization modulation.

Identification of novel RANKL inhibitors through in silico analysis

Receptor activator of nuclear factor-κB ligand (RANKL) is considered the principal regulator of osteoclast differentiation. Therefore, strategies interfering with the RANKL-RANK signaling pathway may effectively inhibit osteoclast differentiation and mitigate bone resorption. Consequently, RANKL has become a promising target for new drug design strategies. Despite extensive research on specific drugs and antibodies, only a few have shown efficacy in treating osteoporosis. To address this challenge, we aimed to explore new approaches for designing drugs for osteoporosis. In this study, a 3D quantitative structure–activity relationship (QSAR) pharmacophore model was built for RANKL with reference to known inhibitor IC50 values. The optimal pharmacophore model was then employed as a 3D query to screen databases for novel lead compounds. The obtained compounds were subjected to ADMET and TOPKAT analyses to predict drug pharmacokinetics and toxicity. Molecular docking and de novo evolution approaches were applied to verify the docking binding affinities of the compounds. Five candidate compounds were subjected to further in vitro analyses to assess their anti-osteoporotic effects, among which compound 4 demonstrated significant inhibitory activity, achieving an inhibitory rate of 92.6 % on osteoclastogenesis at a concentration of 10 μM. Subsequent molecular dynamics (MD) simulations to assess the stability and behavior of compound 4 and its evolved variant, ZINC00059014397_Evo, within the RANKL binding site revealed that the variant is a potential therapeutic agent for targeting osteoclasts. This study offers valuable insights for developing next generation RANKL inhibitors for osteoporosis treatments.

Oral Propolis Nanoemulsions Modulate Gut Microbiota to Balance Bone Remodeling for Enhanced Osteoporosis Therapy.

The discovery of the bone-gut axis linking bone metabolism to gut microbiota (GM) dysbiosis has revolutionized our understanding of managing degenerative skeletal diseases. Targeting GM regulation has emerged as a promising approach to osteoporosis treatment. Herein, we develop propolis nanoemulsions (PNEs) with enhanced gastrointestinal stability and oral bioavailability for GM-based osteoporosis therapy. Orally administered PNEs exhibit superior antiosteoporosis efficacy in an ovariectomized (OVX) mouse model by modulating the GM structure and metabolites and restoring the intestinal barrier function. Multiomics analysis reveals that a reduction in Streptococcus abundance and an increase in the GM metabolite l-arginine are key factors in osteoporosis management. These changes suppress osteoclast activity and enhance osteoblast function, leading to balanced bone remodeling and, thus, significant antiosteoporotic effects via the gut-bone axis. Our results deepen insights into the intricate relationship between GM and bone remodeling, suggesting a promising strategy that maintains the homeostasis of the GM structure and metabolite for osteoporosis treatment.

Anti-inflammatory, antiosteoporotic, and bone protective effect of hydroxysafflor yellow A against glucocorticoid-induced osteoporosis in rats.

Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.

Icariin as a Treatment Proposal in Mammalian Reproduction.

Icariin (ICA), one of the main active components of Herba Epimedii, is a natural prenylated flavonol glycoside that possesses a wide range of pharmacological effects, including antioxidant, antiosteoporotic, anti-aging, neuroprotective, immunomodulatory, antitumor, and aphrodisiac effects, and prevents numerous health disorders, such as cardiovascular diseases, osteoporosis, cancer, sexual dysfunction, menstrual disorders, neurodegenerative diseases, asthma, chronic inflammation, and diabetes. In the reproductive system, it has been observed that ICA may play a role in preserving fertility by regulating different signalling pathways, such as PI3K/AKT, which improves ovarian function, and ERα/Nrf2, which enhances testicular function and prevents ROS generation. In contrast, regulating the NF/kB signalling pathway causes anti-inflammatory effects, reducing spontaneous abortions. In this study, we review and examine the relevant literature on the therapeutic potential of ICA in reproduction, highlight the various mechanisms of action and limitations for the therapeutic applications of ICA, and summarise and highlight the existing preclinical research on its effects on male and female reproduction.

Vigeo Promotes Myotube Differentiation and Protects Dexamethasone-Induced Skeletal Muscle Atrophy via Regulating the Protein Degradation, AKT/mTOR, and AMPK/Sirt-1/PGC1α Signaling Pathway In Vitro and In Vivo.

Sarcopenia, a condition caused by an imbalance between muscle growth and loss, can severely affect the quality of life of elderly patients with metabolic, inflammatory, and cancer diseases. Vigeo, a nuruk-fermented extract of three plants (Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK)) has been reported to have anti-osteoporotic effects. However, evidence of the effects of Vigeo on muscle atrophy is not available. Here, in the in vivo model of dexamethasone (Dex)-induced muscle atrophy, Vigeo treatment significantly reversed Dex-induced decreases in calf muscle volume, gastrocnemius (GA) muscle weight, and histological cross-section area. In addition, in mRNA and protein analyses isolated from GA muscle, we observed that Vigeo significantly protected against Dex-induced mouse muscle atrophy by inhibiting protein degradation regulated by atrogin and MuRF-1. Moreover, we demonstrated that Vigeo significantly promoted C2C12 cell line differentiation, as evidenced by the increased width and length of myotubes, and the increased number of fused myotubes with three or more nuclei. Vigeo alleviated the formation of myotubes compared to the control group. Vigeo also significantly increased the mRNA and protein expression of myosin heavy chain (MyHC), MyoD, and myogenin compared to that in the control. Vigeo treatment significantly reduced the mRNA and protein expression of muscle degradation markers atrogin-1 and muscle RING Finger 1 (MuRF-1) in the C2C12 cell line in vitro. Vigeo also activated the AMP-activated protein kinase (AMPK)/silent information regulator 1 (Sirt-1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) mitochondrial biogenesis pathway and the Akt/mTOR protein synthesis signaling pathway in Dex-induced myotube atrophy. These findings suggest that Vigeo may have protective effects against Dex-induced muscle atrophy. Therefore, we propose Vigeo as a supplement or potential therapeutic agent to prevent or treat sarcopenia accompanied by muscle atrophy and degeneration.

Bu-Sui-Dan Enhances Osteoblast Differentiation by Upregulating VGLL4 to Counteract TEAD4-Mediated RUNX2 Transcription Suppression in Ovariectomized Rats

Ethnopharmacological relevancePostmenopausal osteoporosis (PMOP) has been considered as a major causative factor for bone-joint pain and inducing pathologic fractures. Bu-Sui-Dan (BSD), a classic ancient herbal formula, has been shown to exhibit osteoprotective effects by promoting bone marrow development and bone growth. However, the exact mechanism of BSD are still unexplored. Aim of studyThe study aimed to investigate the protective effect of BSD against osteoporotic injury, and to explore whether BSD regulated BMSCs’ osteogenic differentiation by targeting VGLL4, which in turn improved PMOP. Materials and methodsThe anti-osteoporotic effect of BSD was studied in ovariectomized (OVX) rats and bone marrow mesenchymal stem cells (BMSCs). Micro-CT imaging and HE staining were performed, and the levels of osteogenic protein RUNX2 and osteogenesis-related factor VGLL4 were determined. Co-immunoprecipitation (Co-IP) was further employed to delve into the effects of BSD on the interactions between TEAD4 and RUNX2. The key osteogenic factors 1ALP, COLl1A1, and Osterix expression were detected by RT-qPCR. Co-IP and proximity ligation assay (PLA) were employed to scrutinize the influence of BSD on TEAD4 and RUNX2 inter-binding. Moreover, VGLL4 knockdown in BMSCs was conducted to confirm the role of VGLL4 in the therapeutic mechanism of BSD. ResultsBSD showed a dose-dependent protective effect against osteoporotic injury, as evidenced by improvement in bone volume, bone microarchitecture, and histomorphometry. Additionally, BSD treatment increased the levels of RUNX2 and its downstream target genes including ALP, COL1A1, and Osterix. Moreover, BSD upregulated VGLL4 expression and lessened TEAD4-RUNX2 interactions. In BMSCs experiment, BSD-containing serum could promote osteogenic differentiation of BMSCs, boosted the expression of osteogenesis-related factors and VGLL4 level. The knockdown of VGLL4 in BMSCs diminished the promotion effect of BSD in osteoblast differentiation, suggesting that VGLL4 play a vital role in the therapeutic effects exerted by BSD. ConclusionBSD ameliorated osteoporosis injury and promoted osteoblast differentiation through upregulation of VGLL4 levels, which in turn antagonized TEAD4-mediated RUNX2 transcriptional repression. Our study implied that BSD may be an osteoporosis therapeutic agent.

Mechanistic Insights into the Anti-Osteoporotic Effects of Naringin via Network Pharmacology and Molecular Docking Studies

Background: Naringin, a natural flavonoid prevalent in citrus fruits, is known for its antioxidant, anti-inflammatory, and antitumor properties. Recent studies suggest its potential influence on bone metabolism, proposing it as an anti-osteoporotic agent. However, specific mechanisms of action remain unclear. Objective: This study aimed to validate the anti-osteoporotic effects of naringin by combining network pharmacology analysis and molecular docking validation. Methods: Employing network pharmacology and molecular docking, we constructed an analysis framework for "Naringin-Targets-GO and KEGG-Osteoporosis" using Cytoscape software and R software. This framework integrated various online public databases, Protein-Protein Interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking using AutoDock Vina software. Results: We identified 272 target genes associated with naringin and 5,785 target genes related to osteoporosis, with 197 overlapping genes. Further analysis led to the selection of eight core targets: TP53, TNF, JUN, STAT3, AKT1, ESR1, BCL2, and IL6. GO functional enrichment analysis and KEGG pathway enrichment analysis revealed that naringin might influence osteoporosis progression by regulating biological processes, such as apoptosis, cell proliferation, and inflammatory responses, as well as signaling pathways, such as TNF, FoxO, and PI3K-Akt. Molecular docking validation confirmed the high binding affinity of naringin to the eight core targets, with binding energies below 7.2 kcal/mol. Conclusion: The therapeutic mechanism of naringin against osteoporosis may involve the regulation of gene expression, including TP53, IL6, TNF, JUN, STAT3, AKT1, ESR1, and BCL2, and mediating signaling pathways such as TNF, FoxO, IL-17, PI3K-Akt, AMPK, and VEGF, thereby affecting multiple biological processes, such as bidirectional regulation of osteoblast proliferation and apoptosis, angiogenesis, and downregulation of inflammatory responses.

Qianggu Decoction Alleviated Osteoporosis by Promoting Osteogenesis of BMSCs through Mettl3-Mediated m6A Methylation.

Osteoporosis development is linked to abnormal bone marrow mesenchymal stem cells (BMSCs) differentiation. N6-methyladenosine (m6A), a prevalent mRNA modification, is known to influence BMSCs' osteogenic capacity. Qianggu decoction (QGD), a traditional Chinese medicine for osteoporosis, has unknown effects on BMSCs differentiation. This study investigates QGD's impact on BMSCs and its potential to ameliorate osteoporosis through m6A regulation. Using Sprague-Dawley (SD) rats with ovariectomy-induced osteoporosis, it is evaluated QGD's antiosteoporotic effects through micro-CT, histology, Western blotting, and osteoblastogenesis markers. QGD is found to enhance bone tissue growth and upregulate osteogenic markers Runx2, OPN, and OCN. It also promoted BMSCs osteogenic differentiation, as shown by increased calcium nodules and ALP activity. QGD treatment significantly increased m6A RNA levels and Mettl3 expression in BMSCs. Silencing Mettl3 with siRNA negated QGD's osteogenic effects. Collectively, QGD may improve BMSCs differentiation and mitigate osteoporosis, potentially through Mettl3-mediated m6A modification.

Royal Jelly: Biological Action and Health Benefits.

Royal jelly (RJ) is a highly nutritious natural product with great potential for use in medicine, cosmetics, and as a health-promoting food. This bee product is a mixture of important compounds, such as proteins, vitamins, lipids, minerals, hormones, neurotransmitters, flavonoids, and polyphenols, that underlie the remarkable biological and therapeutic activities of RJ. Various bioactive molecules like 10-hydroxy-2-decenoic acid (10-HDA), antibacterial protein, apisin, the major royal jelly proteins, and specific peptides such as apisimin, royalisin, royalactin, apidaecin, defensin-1, and jelleins are characteristic ingredients of RJ. RJ shows numerous physiological and pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, and anti-tumor effects. Moreover, RJ may reduce menopause symptoms and improve the health of the reproductive system, liver, and kidneys, and promote wound healing. This article provides an overview of the molecular mechanisms underlying the beneficial effects of RJ in various diseases, aging, and aging-related complications, with special emphasis on the bioactive components of RJ and their health-promoting properties. The data presented should be an incentive for future clinical studies that hopefully will advance our knowledge about the therapeutic potential of RJ and facilitate the development of novel RJ-based therapeutic opportunities for improving human health and well-being.

Anti-osteoporotic effects of enzymatic hydrolysates of mackerel Scomber japonicus byproduct in MC3T3-E1 cells and ovariectomized rat model

Anti-osteoporotic effects of enzymatic hydrolysates of mackerel Scomber japonicus byproduct in MC3T3-E1 cells and ovariectomized rat model

Effect of hyperoside on osteoporosis in ovariectomized mice through estrogen receptor α/ITGβ3 signaling pathway

Osteoporosis is a highly prevalent bone metabolic disease in menopause due to estrogen deficiency. Hyperoside is a main compound in Semen cuscutae. Our team previously reported that Semen cuscutae has anti osteoporosis effect on ovariectomized mice by inhibiting bone resorption of osteoclasts. However, it is still unclear whether hyperoside affects osteoclast differentiation and bone resorption, and whether its anti-osteoporosis effect is related to an estrogen-like effect. This study investigates the potential mechanism of hyperoside's anti-osteoporotic effect by examining its impact on osteoclast differentiation and its relationship with the estrogen receptor. DXA, Micro-CT, TRAP staining, HE, and ELISA were used to assess the impact of hyperoside on OVX-induced osteoporosis. The effect of hyperoside on octeoclast differentiation was evaluated using TRAP activity assay, TRAP staining, F-actin staining. The activation of the estrogen receptor by hyperoside and its relationship with osteoclast differentiation were detected using dual-luciferase reporter assay and estrogen receptor antagonists. Our findings revealed that hyperoside (20–80 mg/kg) protect against OVX-induced osteoporosis, including increasing BMD and BMC and improving bone microstructure. Hyperoside inhibited osteoclast differentiation in a concentration dependent manner, whereas estrogen receptor α antagonists reversed its inhibitory effect osteoclast differentiation. Western blot results suggested that hyperoside inhibited TRAP, RANKL, c-Fos and ITG β3 protein expression in osteoclast or femoral bone marrow of ovariectomized mice. Our findings suggest that hyperoside inhibits osteoclast differentiation and protects OVX-induced osteoporosis through the ERα/ITGβ3 signaling pathway.

Isolation, phytochemistry, characterization, biological activity, and application of Morinda officinalis How oligosaccharide: a review.

Morinda officinalis How oligosaccharide (MOO) stands as one of the principal active constituents of M. officinalis How, widely employed in traditional Chinese medicine. The methods for MOO extraction predominantly encompass hot water extraction, ethanol extraction, ultrasonic-assisted extraction, and microwave-assisted extraction. Distinct extraction techniques yield varying MOO quantities. MOO encompasses a diversity of oligosaccharides, including bajijiasu, sucrose, 1-kestose, nystose, mannose, 1F-fructofuranosylnystose, 1,1,1,1-kestohexose, fructoheptasaccharide, inulin-type hexasaccharide, inulin-type heptasaccharide, inulotriose, inulotetraose, inulopentaose, and mannose. MOO exhibits a wide spectrum of biological activities, exerting specific effects on the nervous system, cardiovascular system, motor system, reproductive system, and immune system. It demonstrates antidepressant properties, offers potential in mitigating Alzheimer's disease, stimulates angiogenesis, and possesses anti-osteoporotic and other pharmacological effects. Clinically, when combined with various antidepressants, MOO exhibits specific therapeutic efficacy across multiple forms of depression. As a naturally occurring plant oligosaccharide, MOO holds diverse pharmaceutical applications. This article conducts a review of the latest extraction and purification methodologies, structural characterization analysis, biological activity assessment, and clinical applications of MOO. Such a comprehensive analysis yields innovative insights for advancing the research and application of MOO in the future.

Restoring bone-fat equilibrium: Baicalin's impact on P38 MAPK pathway for treating diabetic osteoporosis

Diabetes can lead to a disorder of bone-fat balance, a significant cause of osteoporosis due to changes in environmental factors. Baicalin (Bai), an active ingredient of Scutellaria baicalensis, has been confirmed to possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, a comprehensive understanding of Bai's influence on diabetic osteoporosis (DOP), including its effects and underlying mechanisms, remains elusive. This study investigated Bai's impact on the bone-fat equilibrium in rats with DOP. The results indicated that Bai alleviated bone damage in DOP by promoting osteogenesis and inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested that Bai's mechanism of action might involve the P38-MAPK pathway. In vitro, Bai was found to enhance the development of bone marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation towards adipogenic lineages. It was discovered that Bai's promotion of BMSC osteogenic differentiation depends on the P38-MAPK pathway. Additionally, the synergistic effect mediated by Bai and P38-MAPK inhibitor suppressed BMSC adipogenic differentiation. Our research indicates that the P38-MAPK pathway play a role in Bai's effects on the osteogenic-adipogenic differentiation of BMSCs, showcasing the potential for DOP treatment. This study highlights Bai's ability to regulate the equilibrium between bone and fat, presenting a novel approach to adressing DOP.

Novel Peptides from Sturgeon Ovarian Protein Hydrolysates Prevent Oxidative Stress-Induced Dysfunction in Osteoblast Cells: Purification, Identification, and Characterization.

This study aimed to explore antioxidant peptides derived from sturgeon (Acipenser schrenckii) ovaries that exhibit antiosteoporotic effects in oxidative-induced MC3T3-E1 cells. The F3-15 component obtained from sturgeon ovarian protein hydrolysates (SOPHs) via gel filtration and RP-HPLC significantly increased the cell survival rate (from 49.38 ± 2.88 to 76.26 ± 2.09%). Two putative antioxidant-acting peptides, FDWDRL (FL6) and FEGPPFKF (FF8), were screened from the F3-15 faction via liquid chromatography-tandem mass spectrometry (LC-MS/MS) and through prediction by computer simulations. Molecular docking results indicated that the possible antioxidant mechanisms of FL6 and FF8 involved blocking the active site of human myeloperoxidase (hMPO). The in vitro tests showed that FL6 and FF8 were equally adept at reducing intracellular ROS levels, increasing the activity of antioxidant enzymes, and protecting cells from oxidative injuries by inhibiting the mitogen-activated protein kinase (MAPK) pathway and activating the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. Moreover, both peptides could increase differentiation and mineralization abilities in oxidatively damaged MC3T3-E1 cells. Furthermore, FF8 exhibited high resistance to pepsin and trypsin, showcasing potential for practical applications.