curcumin and Osteoporosis

Phenolic compounds are natural phytochemicals that have recently reported numerous health benefits. Resveratrol, curcumin, and quercetin have recently received the most attention among these molecules due to their documented antioxidant effects. The review aims to investigate the effects of these molecules on bone metabolism and their role in several diseases such as osteopenia and osteoporosis, bone tumours, and periodontitis. The PubMed/Medline, Web of Science, Google Scholar, Scopus, Cochrane Library, and Embase electronic databases were searched for papers in line with the study topic. According to an English language restriction, the screening period was from January 2012 to 3 July 2022, with the following Boolean keywords: ("resveratrol" AND "bone"); ("curcumin" AND "bone"); ("quercetin" AND "bone"). A total of 36 papers were identified as relevant to the purpose of our investigation. The studies reported the positive effects of the investigated phenolic compounds on bone metabolism and their potential application as adjuvant treatments for osteoporosis, bone tumours, and periodontitis. Furthermore, their use on the titanium surfaces of orthopaedic prostheses could represent a possible application to improve the osteogenic processes and osseointegration. According to the study findings, resveratrol, curcumin, and quercetin are reported to have a wide variety of beneficial effects as supplement therapies. The investigated phenolic compounds seem to positively mediate bone metabolism and osteoclast-related pathologies.

Topics: Curcumin; Dietary Supplements; Humans; Osteoporosis; Periodontitis; Quercetin; Resveratrol

Curcumin, an active component of the rhizome turmeric, has gained much attention as a plant-based compound with pleiotropic pharmacological properties. It possesses anti-inflammatory, antioxidant, hypoglycemic, antimicrobial, neuroprotective, and immunomodulatory activities. However, the health-promoting utility of curcumin is constrained due to its hydrophobic nature, water insolubility, poor bioavailability, rapid metabolism, and systemic elimination. Therefore, an innovative stride was taken, and complexes of metals with curcumin have been synthesized. Curcumin usually reacts with metals through the β-diketone moiety to generate metal-curcumin complexes. It is well established that curcumin strongly chelates several metal ions, including boron, cobalt, copper, gallium, gadolinium, gold, lanthanum, manganese, nickel, iron, palladium, platinum, ruthenium, silver, vanadium, and zinc. In this review, the pharmacological, chemopreventive, and therapeutic activities of metal-curcumin complexes are discussed. Metal-curcumin complexes increase the solubility, cellular uptake, and bioavailability and improve the antioxidant, anti-inflammatory, antimicrobial, and antiviral effects of curcumin. Metal-curcumin complexes have also demonstrated efficacy against various chronic diseases, including cancer, arthritis, osteoporosis, and neurological disorders such as Alzheimer's disease. These biological activities of metal-curcumin complexes were associated with the modulation of inflammatory mediators, transcription factors, protein kinases, antiapoptotic proteins, lipid peroxidation, and antioxidant enzymes. In addition, metal-curcumin complexes have shown usefulness in biological imaging and radioimaging. The future use of metal-curcumin complexes may represent a new approach in the prevention and treatment of chronic diseases.

Topics: Alzheimer Disease; Animals; Arthritis; Coordination Complexes; Curcumin; Humans; Nervous System Diseases; Osteoporosis

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (

Topics: Aging; Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Curcumin; Diabetes Mellitus; Humans; Inflammation; Molecular Structure; Neoplasms; Neurodegenerative Diseases; Osteoporosis

The Indian spice turmeric, in which the active and dominant biomolecule is curcumin, has been demonstrated to have significant medicinal properties, including anti-inflammatory and anti-neoplastic effects. This promise is potentially very applicable to musculoskeletal disorders, which are common causes of physician visits worldwide. Research at the laboratory, translational and clinical levels that supports the use of curcumin for various musculoskeletal disorders, such as osteoarthritis, osteoporosis, musculocartilaginous disorders, and sarcoma is here in comprehensively summarized. Though more phase I-III trials are clearly needed, thus far the existing data show that curcumin can indeed potentially be useful in treatment of the hundreds of millions worldwide who are afflicted by these musculoskeletal disorders.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Bone Density Conservation Agents; Cartilage Diseases; Curcumin; Humans; Muscular Atrophy; Musculoskeletal Diseases; Osteoarthritis; Osteoporosis; Sarcoma; Translational Research, Biomedical

During aging, bone marrow mesenchymal stromal cells (MSCs)-the precursors of osteoblasts-undergo cellular senescence, losing their osteogenic potential and acquiring a pro-inflammatory secretory phenotype. These dysfunctions cause bone loss and lead to osteoporosis. Prevention and intervention at an early stage of bone loss are important, and naturally active compounds could represent a valid help in addition to diet. Here, we tested the hypothesis that the combination of two pro-osteogenic factors, namely orthosilicic acid (OA) and vitamin K2 (VK2), and three other anti-inflammatory compounds, namely curcumin (CUR), polydatin (PD) and quercetin (QCT)-that mirror the nutraceutical BlastiMin Complex

Topics: Bone Diseases, Metabolic; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Curcumin; Humans; Mesenchymal Stem Cells; Osteogenesis; Osteoporosis; Quercetin; Vitamin K 2

The present study aimed to investigate the effect of phosphatidylserine liposomes containing curcumin (PSLs-Cur) on the development of osteoporosis induced by glucocorticoids (GCs) in the rat model. PSL-Cur, phosphatidylserine (PSL), curcumin (Cur), and alendronate (AL) drugs as a positive control were administrated orally to evaluate the beneficial effects of 3-week treatments on osteoporotic rats. The biochemical and biomechanical properties of bone parameters as well as gene expression were evaluated in treated rats. Moreover, histomorphometric examinations were performed on the bone tissues of the animals. The results revealed that PSL-Cur oral administration caused a significant improvement in serum markers, mechanical strength, and OPG gene expression rather than PSL or Cur administration in osteoporotic rats. Also, PSL-Cur significantly increased the thickness and volume of cortical and trabecular bone mass in comparison with the untreated osteoporotic group. The results of this study indicated that PSL-Cur had a more inhibitory effect on bone loss induced by GCs compared to AL standard drug. Our findings suggested that PSL-loaded Cur may be an appropriate alternative therapy for glucocorticoid-induced osteoporosis. PRACTICAL APPLICATIONS: Osteoporosis is one of the most serious metabolic chronic diseases that causes fragile bone due to decreased mineral density and microarchitectural deterioration in humans. The osteoprotective effects of curcumin and phosphatidylserine, as a food spice and supplementary diet, respectively, have been shown, previously. However, the low bioavailability of curcumin (Cur) due to its poor absorption, rapid metabolism, and fast systemic elimination, limits its benefits. This deficit can be modified with phosphatidylserine liposome (PSL) formulation that facilitates the gastrointestinal delivery of Cur. Moreover, PSL is known as an osteoprotective agent that may make synergy effect with Cur against GC-induced osteoporosis. In this study, daily oral administration of phosphatidylserine liposomes containing curcumin (PSL-Cur) for 3 weeks, considerably improved biochemical, biomechanical, and gene expression of bone parameters in the treated animals subjected to osteoporosis. PSL-Cur can significantly increase the thickness and volume of cortical and trabecular bone mass as well as the mechanical bone strength in animals. Experimental findings proposed PSL-Cur consumption as a proper and safe supplementary medication in th

Topics: Animals; Curcumin; Liposomes; Osteoporosis; Phosphatidylserines; Rats; Signal Transduction

Osteoporosis (OP) behaves in different manners in different parts of the skeleton. This study aims to investigate the effects of curcumin on bone mass of the mandibular and femur from ovariectomized OP rats and to validate whether enhancer of zeste homolog 2 (EZH2)/Wnt/β-Catenin pathway is involved in this process. Curcumin was administered intragastrically into ovariectomized rats for 12 weeks. The bone parameters and the morphology of the trabecular bone of the left mandible and left femur were assessed by micro-computed tomography assay. Morphological changes of the left mandible and left femur were evaluated by hematoxylin and eosin staining. The mRNA levels of EZH2, β-Catenin, and Runx2 in the right mandible and right femur were examined by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed to assess EZH2 expression. Both the mandible and femur exhibited OP-like changes in ovariectomized rats, while the mandible bone resorption was less than the femur bone resorption. Curcumin intragastric administration improved bone microstructure and promoted bone formation in the mandible and femur. Curcumin inhibited EZH2 mRNA level and induced that of β-Catenin and Runx2 in the mandible and femur. Collectively, curcumin exerts protective effects against OP, possibly by regulating the EZH2/Wnt/β-Catenin pathway.

Topics: Animals; beta Catenin; Bone Density; Curcumin; Enhancer of Zeste Homolog 2 Protein; Female; Femur; Mandible; Osteogenesis; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Wnt Proteins; Wnt Signaling Pathway; X-Ray Microtomography

Curcumin prevents bone loss in resorptive bone diseases and inhibits osteoclast formation, a key process driving bone loss. Curcumin circulates as an inactive glucuronide that can be deconjugated in situ by bone's high β-glucuronidase (GUSB) content, forming the active aglycone. Because curcumin is a common remedy for musculoskeletal disease, effects of microenvironmental changes consequent to skeletal development or disease on bone curcumin metabolism are explored.. Across sexual/skeletal development or between sexes in C57BL/6 mice ingesting curcumin (500 mg kg. Dietary polyphenols circulating as glucuronides may require in situ deconjugation for bone-protective effects, a process influenced by bone microenvironmental changes.

Topics: Aging; Animals; Bone and Bones; Bone Neoplasms; Curcumin; Female; Glucuronidase; Glucuronides; Male; Mice, Inbred C57BL; Osteogenesis; Osteolysis; Osteoporosis; Ovariectomy; Polyphenols; Quercetin

Curcumin can inhibit the osteoclastogenesis and the migration of several cells including macrophages. Osteoclast precursors (OCPs) are known to exist as bone marrow-derived macrophages (BMMs). This study aims to explore whether curcumin can prevent the fusion and differentiation of OCPs to mature osteoclasts by inhibiting OCP migration.. In this study, we investigated the role of curcumin in regulating the production of several chemokines (CCL2, CCL3 and CX3CL1) and the migration of OCPs by ELISA, Western blotting and Transwell assays. Furthermore, we explored the role of curcumin in the chemokines-related osteoclastogenesis using pharmacological intervention and virus infection, and used ovariectomized (OVX) mice (osteoporosis model) to explore the effect of curcumin on the production of specific chemokine in vivo.. The results showed that curcumin significantly reduced the production of CCL3 in OCPs. Moreover, curcumin-inhibited the migration of OCPs was not affected by CCR1 (Receptor of CCL3) overexpression. Remarkably, curcumin-reduced osteoclastogenesis was significantly reversed by CCL3 addition, while CCR1 overexpression did not increase the osteoclastogenesis in the presence of curcumin. Furthermore, in vivo assays also showed that curcumin significantly reduced the production of CCL3 in OCPs in the trabecular bone of OVX mice.. In conclusion, curcumin prevents the migration of OCPs by reducing CCL3 production, ultimately inhibiting the formation of mature osteoclasts. Therefore, our study provides the clues for improving the clinical strategies of osteoporosis, dental implantation or orthodontic treatment.

Topics: Animals; Cell Movement; Chemokines; Curcumin; Disease Models, Animal; Female; Macrophages; Mice; Mice, Inbred C57BL; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy

Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.

Topics: Alkaline Phosphatase; Animals; Bone and Bones; Bone Regeneration; Bone Resorption; Cell Line, Tumor; Cell Survival; Curcumin; Drug Delivery Systems; Female; Humans; In Vitro Techniques; Metals; Mice; Norpregnenes; Osteoblasts; Osteogenesis; Osteoporosis; Ovariectomy; Prostheses and Implants; Rats; Rats, Wistar; RAW 264.7 Cells; Surface Properties; Titanium

To study the effects of curcumin on EZH2 mRNA expression in the mandible and femur of ovariectomized osteoporosis rats,and to investigate its protective effect and mechanism.. Thirty female 6-month old SD rats were randomly divided into sham group,OVX group and experimental group. The rats in the experimental groups were given curcumin (110 mg/kg) by intragastric administration after ovariectomy, while rats in the sham group and OVX group were given the same dosage of carboxymethylcellulose sodium solution, once a day for 12 weeks. All rats were sacrificed after the last intragastric administration. The serum samples were collected for detemination of biochemistrical parameters. Micro-CT was used for bone parameters and the morphology of the trabecular bone of the left mandibles and femurs. The expression level of EZH2mRNA in right mandible and femurs tissue was detected by reverse transcription polymerase chain reaction (RT-PCR). SPSS22.0 software package was used for statistical analysis.. The expression of EZH2mRNA in the OVX group was significantly higher than the sham group (P<0.05). Compared with the OVX group,curcumin increased BMD and improved bone microstructure, decreased serum contents of alkaline phosphatase,and down-regulated the expression levels of EZH2mRNA in bone tissues of rats with osteoporosis (P<0.05).. Curcumin can effectively prevent the lose of bone volume of ovariectomized rats, and repaire bone microstructure. Its mechanism is related with down -regulation of EZH2mRNA.

Topics: Animals; Bone Density; Curcumin; Enhancer of Zeste Homolog 2 Protein; Enzyme Inhibitors; Female; Humans; Mandible; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; RNA, Messenger

The present study explored the effects of the combined herbal therapy consisting of curcumin (CUR) and Fructus Ligustri Lucidi (FLL) on aspects of bone regeneration.. Prior to analyzing the ability of this novel combined herbal therapy to promote aspects of bone regeneration, its cytotoxicity was determined using MC3T3-E1 cells (pre-osteoblast model). Cell proliferation was evaluated using phase-contrast microscopy and cell differentiation was estimated using alkaline phosphatase activity. The effect of the combined herbal therapy (CUR + FLL) was also assessed in terms of mineralization in the extracellular matrix (ECM) of cultured cells. Further, to explore the molecular mechanisms of bone formation, time-dependent expression of bone-regulating protein biomarkers was also evaluated.. Combined herbal therapy (CUR + FLL) significantly upregulated the viability, proliferation and differentiation of MC3T3-E1 cells compared to the monotherapy of CUR or FLL. The magnitude of ECM mineralization (calcium deposition) was also higher in MC3T3-E1 cells treated with combined therapy. The time-dependent expression of bone-forming protein biomarkers revealed that the tendency of expression of these bone-regulating proteins was remarkably higher in cells treated with combined therapy.. The co-administration of CUR and FLL had superior promotion of elements of bone regeneration in cultured cells, thus could be a promising alternative herbal therapy for the management of bone erosive disorders such as osteoporosis.

Topics: Animals; Bone and Bones; Calcium; Cell Line; Cell Proliferation; Core Binding Factor Alpha 1 Subunit; Curcuma; Curcumin; Drug Synergism; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Ligustrum; Mice; Mice, Inbred C57BL; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis

Osteopenia is a chronic bone condition characterized by decreased calcification, density, or bone mass that, if untreated, can lead to osteoporosis and bone fractures. Although its increasing prevalence, nowadays osteopenia is not adequately prevented and managed. In this study, we evaluated the efficacy, in term of changes in bone density, and safety of an oral formulation based on turmeric phytosome (Meriva®), in subjects suffering from low bone density.. 57 otherwise healthy subjects with low bone density were enrolled in this pilot, supplement study. Informed participants freely decided to follow either a standard management (SM) to control low bone density (control group=28) or SM associated with a curcumin-based oral supplementation (supplement group=29). The bone densities of heel, small finger and upper jaw were evaluated at inclusion and at different time points during the observational period (4, 12 and 24 weeks), in all subjects.. The bone density of the heel measured by the Sahara densitometer remarkably improved in the Meriva®-supplemented group, with a significant decrease of ultrasounds transmission values at week 12 (-18.4%) and at week 24 (-21.0%), compared with baseline values. The bone densities of small finger and upper jaw also significantly increased during the study in supplemented subjects, reaching +7.1% and +4.8%, respectively, at week 24, with respect to values at inclusion. Noteworthy, no significant changes of heel, small finger and upper jaw densities were observed in the control group. Last, no safety and tolerability issues were reported during the observational period.. This preliminary study suggests that a curcumin-based supplementation in combination with an appropriate lifestyle could be beneficial in the prevention and management of osteopenia.

Topics: Bone Density; Curcumin; Dietary Supplements; Humans; Osteoporosis; Pilot Projects

Curcumin, an active component of the rhizomes of Curcumin longa L., possesses broad anti-inflammation and anti-cancer properties. Curcumin was previously reported to be capable of protecting ovariectomized rats against osteoporosis. However, the effect of curcumin on glucocorticoid-induced osteoporosis (GIO) is not yet clear. The present study investigated the effects of curcumin on dexamethasone (Dex)-induced osteoporosis in vivo and Dex-induced osteoblast apoptosis in vivo and in vitro. The GIO rat model was induced by subcutaneous injection of Dex for 60 days and verified to be successful as evidenced by the significantly decreased bone mineral density (BMD) determined using dual X-ray absorptiometry. Subsequently, curcumin administration (100 mg/kg) for 60 days obviously increased BMD and bone-alkaline phosphatase, decreased carboxy-terminal collagen cross links, enhanced bone mechanical strength, and improved trabecular microstructure, thereby alleviating Dex-induced osteoporosis. Mechanically, curcumin remarkably reversed Dex-induced femoral osteoblast apoptosis in vivo. In cultured primary osteoblasts, pretreatment with curcumin concentration-dependently decreased the number of Dex-induced apoptotic osteoblasts by down-regulating the ratio of Bax/Bcl-2 as well as the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Moreover, curcumin pretreatment activated extracellular signal regulated kinase (ERK) signalling in Dex-induced osteoblasts by up-regulating the expression level of p-ERK1/2. Taken together, our study demonstrated that curcumin could ameliorate GIO by protecting osteoblasts from apoptosis, which was possibly related to the activation of the ERK pathway. The results suggest that curcumin may be a promising drug for prevention and treatment of GIO.

Topics: Animals; Apoptosis; Curcumin; Cytoprotection; Dexamethasone; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation; Glucocorticoids; Osteoblasts; Osteoporosis; Rats; Rats, Sprague-Dawley; Signal Transduction

It is known that prolonged glucocorticoid (GC) treatment results in osteoporosis. This study aimed to evaluate the protective effects of curcumin on the bones of rats with dexamethasone (DXM)-induced osteoporosis. In the present study, rats were administered DXM for 60 days to induce osteoporosis, and they were then treated with curcumin (100 mg/kg/day) for a further 60 days. H&E staining was used to observe the pathological changes in the femurs. Serum osteocalcin levels and collagen-type I fragments (CTX) were examined as bone metabolism markers. The results revealed that treatment with curcumin attenuated DXM-induced bone injury in femurs, increased the serum levels of osteocalcin and decreased the levels of CTX. In addition, in in vitro experiments, primary rat osteoblasts treated with curcumin at 0.5, 1 and 2 µM were exposed to 100 nM DXM. An MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase activity, and the mRNA expression levels of runt‑related transcription factor 2 (Runx2), osterix, osteocalcin, collagen, type 1, alpha 1 (Col1A1) and osteonectin were detected to assess transcription factor-associated osteogenic differentiation. The mRNA and protein expression levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-kappa B ligand (RANKL) were detected to assess cytokine-associated osteoclastogenesis. The results demonstrated that curcumin prevented the DXM-induced inhibition of the proliferative ability of the osteoblasts in a dose-dependent manner. In addition, curcumin upregulated the mRNA expression levels of transcription factors that favor osteoblast differentiation and increased the ratio of OPG to RANKL. Moreover, the effects of curcumin on the Wnt signaling pathway were also investigated. RT-qPCR and western blot analysis demonstrated that the Wnt signaling pathway, which was inhibited by DXM, was re-activated upon treatment with curcumin. Immunofluorescence staining revealed that curcumin restored the intranuclear staining of β-catenin in the DXM-stimulated osteoblasts. Collectively, our data demonstrate that curcumin may be a potential therapeutic agent for the treatment of GC-induced osteoporosis.

Topics: Animals; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Curcumin; Dexamethasone; Gene Expression Regulation; Glucocorticoids; Humans; Osteoblasts; Osteocalcin; Osteoporosis; Osteoprotegerin; RANK Ligand; Rats; RNA, Messenger; Wnt Signaling Pathway

Treatment with curcumin attenuated modeled microgravity-induced bone loss, possibly through abating oxidative stress and activating vitamin D receptor. Curcumin might be an effective countermeasure for microgravity-induced bone loss but remains to be tested in humans.. Bone loss is one of the most important complications for human crewmembers who are exposed to long-term microgravity in space and also for bedridden people. The aim of the current study was to elucidate whether treatment with curcumin attenuated bone loss induced by microgravity.. We used hind-limb suspension (HLS) and rotary wall vessel bioreactor (RWVB) to model microgravity in vivo and in vitro, respectively. We investigated the effects of curcumin consumption (40 mg kg(-1) body weight day(-1), via daily oral gavages) on Sprague-Dawley (SD) rats exposed to HLS for 6 weeks. Then, we investigated the effects of incubation with curcumin (4 μM) on MC3T3-E1 and RAW264.7 cells cultured in RWVB.. Curcumin alleviated HLS-induced reduction of bone mineral density in tibiae and preserved bone structure in tibiae and mechanical strength in femurs. Curcumin alleviated HLS-induced oxidative stress marked by reduced malondialdehyde content and increased total sulfhydryl content in femurs. In cultured MC3T3-E1 cells, curcumin inhibited modeled microgravity-induced reactive oxygen species (ROS) formation and enhanced osteoblastic differentiation. In cultured RAW264.7 cells, curcumin reduced modeled microgravity-induced ROS formation and attenuated osteoclastogenesis. In addition, curcumin upregulated vitamin D receptor (VDR) expression in femurs of rats exposed to HLS and MC3T3-E1 cells exposed to modeled microgravity.. Curcumin alleviated HLS-induced bone loss in rats, possibly via suppressing oxidative stress and upregulating VDR expression.

Topics: Animals; Antioxidants; Bone Density; Cell Differentiation; Cells, Cultured; Curcumin; Drug Evaluation, Preclinical; Femur; Gene Expression Regulation; Hindlimb Suspension; Male; Osteoblasts; Osteogenesis; Osteoporosis; Oxidative Stress; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptors, Calcitriol; RNA, Messenger; Tibia; Weightlessness

The present study aimed to investigate bone microarchitecture of the proximal tibia in glucocorticoid-induced osteoporosis (GIOP) mice, and the underlying molecular mechanisms of curcumin in DXM-induced osteoporosis were performed. DXM-treated facilitated to induce hypercalciuria in mice, and curcumin-treated showed a decrease in urine calcium. Curcumin reversed DXM-induced bone resorption, including an increase in serum OCN and a decrease in bone resorption markers CTX and TRAP-5b. H&E staining showed the increased disconnections and separation in trabecular bone network as well as the reduction of trabecular thickness throughout the proximal metaphysis of tibia in GIOP group. Importantly, curcumin reversed DXM-induced trabecular deleterious effects and stimulated bone remodeling. The further evidence showed that curcumin supplement significantly decreased the TRAP-positive stained area and inhibited the activity of OPG/RANKL/RANK signaling in the GIOP mice. Moreover, bioinformatics analysis suggested that miR-365 was a regulator of MMP9. The levels of miR-365 were markedly suppressed; however, curcumin treatment could reverse the downregulation of miR-365 in the tibia of GIOP mice. Simultaneously, the results demonstrated that the mRNA and protein expression of MMP-9 were significantly increased in GIOP mice compared with that of the control group. Curcumin treatment could suppress the expression of MMP-9 in the tibia of GIOP mice. The present study demonstrated the protective effects of curcumin against bone deteriorations in the experimentally DIOP mice, and the underlying mechanism was mediated, at least partially, through the activation of microRNA-365 via suppressing MMP9.

Topics: 3' Untranslated Regions; 3T3 Cells; Animals; Binding Sites; Bone Density Conservation Agents; Bone Remodeling; Computational Biology; Curcumin; Dexamethasone; Disease Models, Animal; Gene Expression Regulation, Enzymologic; Glucocorticoids; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; MicroRNAs; Osteoclasts; Osteoporosis; Osteoprotegerin; RANK Ligand; RAW 264.7 Cells; Receptor Activator of Nuclear Factor-kappa B; Signal Transduction; Tibia; Transfection; X-Ray Microtomography

The first reported homogenous rare earth curcumin (HCurc; ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione)) complexes with the formula ML3, where M(3+) is Eu(III), Gd(III) or Lu(III), were synthesized and characterized by mass spectrometry, infrared spectroscopy and, in the case of the lutetium complex, (1)H NMR spectroscopy. Most importantly an improved separation of the three curcuminoids, HCurc, HDMC ((1E,6E)-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-1,6-diene-3,5-dione) and HBDMC ((1E,6E)-1,7-bis(4-hydroxyphenyl)hepta-1,6-diene-3,5-dione) was realized using a combination of normal-phase column and phosphate-impregnated preparative-thin layer chromatographies. The toxicities of the metal curcumin complexes and ligands were investigated in MG-63 cells, an osteoblast-like cell line, for potential activity as antiosteoporotic agents.

Topics: Animals; Cell Survival; Cells, Cultured; Chemistry Techniques, Analytical; Chromatography, Thin Layer; Coordination Complexes; Curcumin; Humans; Metals, Rare Earth; Models, Molecular; Osteoblasts; Osteoporosis; Rats

Curcumin, an active ingredient of turmeric, is proved to be a potential candidate of controlling inflammation and bone resorption, but few reports are on the periodontitis. The purpose of this study was to evaluate whether the intra-gastric administration of curcumin could inhibit the inflammation and alveolar bone resorption in rats following ligature-induced experimental periodontitis.. Male Wistar rats were randomly divided into three groups: no ligature placement and administration of vehicle, ligature placement and administration of vehicle, ligature placement and administration of curcumin. After the animals were sacrificed, their mandibles were collected for morphological, histological and immunohistochemical analysis; their gingival tissues were collected for cytokine measurements.. Bone resorption was significantly higher in the experimental periodontitis animals treated with vehicle compared with the curcumin-treated group or the control group. Furthermore, receptor activator of nuclear factor-κB ligand (RANKL), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels were higher in the experimental periodontitis animals treated with vehicle compared with the curcumin treated group or the control group. CONCLUSIONS. Curcumin may decrease alveolar bone loss in the experimental periodontitis rats via suppressing the expression of RANKL/RANK/OPG and its anti-inflammatory properties.

Topics: Animals; Curcumin; Immunohistochemistry; Inflammation; Inflammation Mediators; Male; Osteoporosis; Periodontitis; Rats; Rats, Wistar

Curcuma comosa Roxb. is ginger-family plant used to relieve menopausal symptoms. Previous work showed that C. comosa extracts protect mice from ovariectomy-induced osteopenia with minimal effects on reproductive organs, and identified the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) as the major active component of C. comosa rhizomes. At 1-10μM, DPHD increased differentiation in transformed mouse osteoblasts, but the effect of DPHD on normal bone cells was unknown. We examined the concentration dependency and mechanism of action of DPHD relative to 17β-estradiol in nontransformed human osteoblasts (h-OB). The h-OB were 10-100 fold more sensitive to DPHD than transformed osteoblasts: DPHD increased h-OB proliferation at 10nM and, at 100nM, activated MAP kinase signaling within 30 min. In long-term differentiation assays, responses of h-OB to DPHD were significant at 10nM, and optimal response in most cases was at 100 nM. At 7-21 days, DPHD accelerated osteoblast differentiation, indicated by alkaline phosphatase activity and osteoblast-specific mRNA production. Effects of DPHD were eliminated by the estrogen receptor antagonist ICI182780. During differentiation, DPHD promoted early expression of osteoblast transcription factors, RUNX2 and osterix. Subsequently, DPHD accelerated production of bone structural genes, including COL1A1 and osteocalcin comparably to 17β-estradiol. In h-OB, DPHD increased the osteoprotegerin to RANKL ratio and supported mineralization more efficiently than 10nM 17β-estradiol. We conclude that DPHD promotes human osteoblast function in vitro effectively at nanomolar concentrations, making it a promising compound to protect bone in menopausal women.

Topics: Cell Differentiation; Cell Proliferation; Curcuma; Diarylheptanoids; Estradiol; Female; Heptanol; Humans; MAP Kinase Signaling System; Menopause; Osteoblasts; Osteocalcin; Osteoporosis; Osteoprotegerin; Phytoestrogens; Plant Extracts; RANK Ligand; Rhizome; RNA, Messenger

Delivery of therapeutic agents to bone is crucial in several diseases such as osteoporosis, Paget's disease, myeloproliferative diseases, multiple myeloma as well as skeletal metastasizing cancers. Prevention of cancer growth and lowering the cancer induced bone resorption is important in the treatment of bone metastasizing cancers. Keeping in mind the low diffusivity and availability of cell surface targets on cancer cells, we designed a targeted system to deliver chemotherapeutic agents to the bone microenvironment as an approach to tissue targeting using alendronate (Aln). We co-encapsulated curcumin and bortezomib in the PLGA nanoparticles to further enhance the therapeutic efficiency and overall clinical outcome. These multifunctional nanoparticles were characterized for particle size, morphology and drug encapsulation. The particles were spherical with smooth surface and had particle size of 235 ± 70.30 nm. We validated the bone targeting ability of these nanoparticles in vitro. Curcumin and bortezomib are known to have synergistic effect in inhibition of growth of cancer; however there was no synergism in the anti-osteoclastogenic activity of these agents. Surprisingly, curcumin by itself had significant inhibition of osteclastogenic activity. In vivo non-invasive bioimaging showed higher localization of Aln-coated nanoparticles to the bone compared to control groups, which was further confirmed by histological analysis. Aln-coated nanoparticles protected bone resorption and decreased the rate of tumor growth as compared to control groups in an intraosseous model of bone metastasis. Our data show efficient attachment of Aln on the surface of nanoparticles which could be used as a drug carrier for preferential delivery of multiple therapeutic agents to bone microenvironment.

Topics: Alendronate; Animals; Antineoplastic Agents; Bone and Bones; Bone Neoplasms; Boronic Acids; Bortezomib; Breast Neoplasms; Curcumin; Drug Carriers; Female; Humans; Lactic Acid; Mice; Mice, Nude; Nanoparticles; Neoplasm Metastasis; Osteoporosis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Pyrazines

The purpose of this study was to evaluate the therapeutic effects of combination therapy with curcumin and alendronate on bone remodeling after ovariectomy in rats.. Eighty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed amongst four groups: untreated OVX group, curcumin-administered group, alendronate-administered group, and the combination therapy group. At 8 and 12 weeks after surgery, rats from each of the groups were euthanized. Serum biochemical markers of bone turnover, including osteocalcin and alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX) were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.. Serum biochemical markers of bone turnover in the experiment groups (curcumin administered group, alendronate administered group, and the combination therapy group) were significantly lower than in the untreated OVX group (p < 0.05). The combination therapy group had lower ALP and CTX-1 concentrations at 12 weeks, which were statistically significant compared with the curcumin only and the alendronate only group (p < 0.05). The combination therapy group had a significant increase in BMD at 8 weeks and Cr.BMD at 12 weeks compared with the curcumin-only group (p = 0.005 and p = 0.013, respectively). The three point bending test showed that the 4th lumbar vertebrae of the combination therapy group had a significantly greater maximal load value compared to that of the curcumin only and the alendronate only group (p < 0.05).. The present study demonstrated that combination therapy with a high dose of curcumin and a standard dose of alendronate has therapeutic advantages over curcumin or alendronate monotherapy, in terms of the synergistic antiresorptive effect on bone remodeling, and improving bone mechanical strength.

Topics: Alendronate; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Bone Remodeling; Collagen Type I; Curcumin; Drug Synergism; Drug Therapy, Combination; Female; Lumbar Vertebrae; Osteocalcin; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley

Alzheimer's disease and osteoporosis are often observed to co-occur in clinical practice. The present study aimed to evaluate the bone microarchitecture and bone mineral density (BMD) of the proximal tibia in APP/PS1 transgenic mice by micro-computed tomography (micro-CT), and to search for evidence that curcumin can be used to reduce bone mineral losses and treat osteoporosis after senile dementia in these transgenic mice. Three-month-old female mice were divided into the following groups (n=9 per group): wild-type mice (WT group); APP/PS1 transgenic mice (APP group); and APP/PS1 transgenic mice with curcumin treatment (APP+Cur group). Between 9 and 12 months of age, the APP+Cur group were administered curcumin orally (600ppm). CT scans of the proximal tibia were taken at 6, 9 and 12 months. At 6 months, there were little differences in the structural parameters. At 9 months, the APP groups displayed loss of bone volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and connectivity density (Conn.D) and increases in trabecular separation (Tb.Sp) and geometric degree of anisotropy (DA) (P<0.05 or P<0.01), with significant changes in the BMD parameters. At 12 months, curcumin treatment led to constant increases in the trabecular bone mass of the metaphysis and clearly improved the BMD. By the same time, we measured the TNF-α and IL-6 in the serum among the different groups at 6, 9 and 12 months by enzyme-linked immunoassay(ELISA). These results suggest that APP/PS1 transgenic mice are susceptible to osteoporosis, and that curcumin can prevent further deterioration of the bone structure and produce beneficial changes in bone turnover. The change of inflammation cytokine, including TNF-α and IL-6, may play an important role in the mechanisms of action of curcumin, but the detail mechanism remains unknown.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Bone and Bones; Bone Density; Curcuma; Curcumin; Female; Interleukin-6; Mice; Mice, Inbred Strains; Mice, Transgenic; Osteoporosis; Phytotherapy; Plant Extracts; Tibia; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha

Curcumin has anti-oxidative activity. In view of the increasing evidence for a biochemical link between increased oxidative stress and reduced bone density we hypothesized that curcumin might increase bone density by elevating antioxidant activity in some target cell type. We measured bone density by Micro-CT, enzyme expression levels by quantitative PCR or enzyme activity, and osteoclast (OC) formation by tartrate-resistant acid phosphatase staining. The bone mineral density of the femurs of curcumin-administered mice was significantly higher than that of vehicle-treated mice after ovariectomy (OVX) and this was accompanied by reduced amounts of serum collagen-type I fragments, which are markers of bone resorption. Curcumin suppressed OC formation by increasing receptor activator of nuclear factor-κB ligand (RANKL)-induced glutathione peroxidase-1, and reversed the stimulatory effect of homocysteine, a known H(2) O(2) generator, on OC formation by restoring Gpx activity. Curcumin generated an aberrant RANKL signal characterized by reduced expression of nuclear factor of activated T cells 2 (NFAT2) and attenuated activation of mitogen-activated protein kinases (ERK, JNK, and p38). Curcumin thus inhibited OVX-induced bone loss, at least in part by reducing osteoclastogenesis as a result of increased antioxidant activity and impaired RANKL signaling. These findings suggest that bone loss associated with estrogen deficiency could be attenuated by curcumin administration.

Topics: Animals; Blotting, Western; Curcumin; Female; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Mice; Mice, Inbred C57BL; Osteoclasts; Osteoporosis; Ovariectomy; Polymerase Chain Reaction; RANK Ligand; Signal Transduction

Curcuma comosa Roxb. or Wan chak motluk is an indigenous medicinal herb and has traditionally been used among postmenopausal women for relief of unpleasant menopausal symptoms.. Estrogen deficiency is a causative factor in the development of osteoporosis in menopausal women. Phytoestrogens, non-steroidal plant-derived compounds which have an array of beneficial effects, are considered as an effective alternative compound in preventing bone loss caused by the deficiency of estrogen. The present study determined the potential effect of Curcuma comosa Roxb. (C. comosa) hexane extract containing phytoestrogens in protecting bone loss induced by ovariectomy in mice.. Mature Swiss albino female mice were ovariectomized and treated with the C. comosa extract for 5 weeks. Bone calcium content, bone mass density, histology, and bone markers were evaluated.. The ovariectomized mice showed a marked decrease in total bone calcium content and bone mass density of lumbar vertebrae 5-6, femur and tibia bone in comparison with the intact control mice. Bone histology demonstrated the poor development of endochondral bone formation in ovariectomized mice which correlated with a decrease in plasma bone alkaline phosphatase activity. Treatment with C. comosa protected against the loss of total bone calcium content and bone mass density in both trabecular and cortical bones, similar to results observed with estrogen treatment. In addition, C. comosa treatment resulted in less increase in uterine weight compared to estrogen treatment.. Our results suggest that C. comosa prevents bone loss induced by estrogen deficiency. Therefore, C. comosa would be a potential alternative treatment for prevention of postmenopausal osteoporosis.

Topics: Absorptiometry, Photon; Animals; Bone Density; Calcium; Curcuma; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Femur; Lumbar Vertebrae; Mice; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Extracts; Tibia; Uterus

To study the effects of Yifuning soft gelatin capsules (YFN) on pathology and biomechanical indexes of ovariectomied female rats.. Sixty female Sprague-Dawley rats without pregnancy and delivery were used,50 of them were ovariectomized and randomly divided into 5 groups: ovariectomy(OVX), OVX with diethylstilbestrol tables (DT), OVX with YFN (high dose,middle dose and low dose), the others were sham-operated group. The rats began to take the rats drugs in the fifth week after the operation. After 12 weeks of treat ment the rats were killed, and the bones were collected to inspect. The pathology of bone was observed with the HE stain and the area of trabecular was detected. The electronic testing device was used to detect the biomechanical properties.. The results indicated that the rat model of postmenopausal osteoporosis (PMO) was a success. Compared with the model group, after application of the drugs, the observation of HE showed different repairing around trabecular. The biomechanical parameters also increased significantly.. YFN can effectively prevent the loss of bone in OVX rats and strengthen bone quality, and has a good effect on PMO oostmenopausal osteoporosis.

Topics: Animals; Biomechanical Phenomena; Bone Density; Capsules; Curcuma; Drug Combinations; Female; Femur; Lumbar Vertebrae; Materia Medica; Oils, Volatile; Osteoporosis; Ovariectomy; Oviducts; Plants, Medicinal; Random Allocation; Ranidae; Rats; Rats, Sprague-Dawley

To study the effects of Yifuning soft capsules on postmenopausal osteoporosis in ovariectomized female rats.. 60 female sprague-dawley rats in 3-month were used, 50 of them were ovariectomized and randomly divided into 5 groups: ovariectomy (OVX), OVX with diethylstilbestrol tables (DT), OVX with YFN (high dose, middle dose and low dose), the others were sham-operated group. Began to give the rats drugs in the fifth week after the operation. After 12 weeks killed the rats. The blood,the uterus and bones were collected to inspect. The content of estrogen (E2) in serum was detected by radioimmunoassay method. The contents of Ca, P, ALP in serum were detected using the automic biochemistry-analyse device. The uterus were weight and the length, width, dry weight and net weight of the shoulder bone were measured. The contents of Ca, Mg, Zn, Mn in the bone were measured using the automic absorption spectrophotometer. The right femer and the third lumbar vertebra were detected for BMD using the dual-energy X-ray absorptiometry scanner and compression test using electronic testing device.. After using the drugs,the content of E2, Ca in serum, the weight of uterus, the contents of Ca, Mg, Zn, Mn in the bone and the BMD of right femer increased significantly, the content of P, ALP in serum decreased significantly.. Yifuning soft capsules has a good effect on postmenopausal osteoporosis, which provides evidence for clinical use.

Topics: Animals; Bone and Bones; Bone Density; Capsules; Curcuma; Drug Combinations; Drugs, Chinese Herbal; Estradiol; Female; Materia Medica; Osteoporosis; Ovariectomy; Plants, Medicinal; Rana temporaria; Random Allocation; Rats; Rats, Sprague-Dawley

The effects of berberine in senescence accelerated mice P6 (SAMP6) were investigated to learn whether the alkaloid affects bone mineral density (BMD). Oral administration of berberine (10 mg/kg/d) to male and female mice for 22 weeks resulted in an increase in BMD in both sexes. A decreased concentration of deoxypyridinoline (Dpd) in urine was only observed in female mice. There was no effect on body or tibia weight or on the concentration of procollagen type I carboxyterminal extension peptide (PICP) in serum.

Topics: Aging; Animals; Berberine; Bone Density; Disease Models, Animal; Female; Hydrastis; Male; Mice; Mice, Mutant Strains; Osteoporosis; Ranunculaceae