lignans and Osteoporosis

From a nutritional point of view, several factors are involved in ensuring optimal bone health. The most documented of these are calcium and vitamin D. However, it is now well acknowledged that some phytochemicals, also known as phytonutrients, which are plant-based compounds that are present in our daily diet, can positively regulate a number of physiological functions in mammalian systems involved in chronic diseases such as osteoporosis. Indeed, emerging data in animal models of postmenopausal osteoporosis has shown that exposure to some of these naturally plant-derived compounds (e.g. flavonoids) positively influences bone metabolism through preserved bone mineral density. In vitro experiments with bone cells have reported cellular and molecular mechanisms of phytonutrients involved in bone metabolism. Indeed, phytonutrients and especially polyphenols can act on both osteoblasts and osteoclasts to modulate bone metabolism, a balance between both cell type activities being required for bone health maintenance. To date, most studies investigating the effects of polyphenols on osteoblast cells have reported involvement of complex networks of anabolic signalling pathways such as BMPs or estrogen receptor mediated pathways. This review will report on the interaction between phytochemicals and bone metabolism in cell or animal models with a particular focus on the molecular mechanisms involved in the bone anabolic response.

Topics: Bone and Bones; Bone Density; Carotenoids; Catechin; Flavonoids; Humans; Lignans; Osteoporosis; Plants; Polyphenols; Signal Transduction; Stilbenes

Phytoestrogens have been investigated at the epidemiological, clinical and molecular levels to determine their potential health benefits. The two major groups of phytoestrogens, isoflavones and lignans, are abundant in soy products and flax respectively, but are also present in a variety of other foods. It is thought that these estrogen-like compounds may protect against chronic diseases, such as hormone-dependent cancers, cardiovascular disease and osteoporosis. Furthermore, phytoestrogens are used as a natural alternative to hormone replacement therapy and to reduce menopausal symptoms. Phytoestrogens have been shown to induce both estrogenic and anti-estrogenic effects but their biological relevance and potency have not been well characterized. In children, consumption of soy-based formulas and soy milk can lead to high levels of exposure to phytoestrogens with only limited data available concerning potential benefits or adverse effects. Phytoestrogens are considered good candidates for use in natural therapies and as chemopreventive agents in adults. Safe and efficacious levels have yet to be established.

Topics: Biological Availability; Breast Neoplasms; Cardiovascular Diseases; Diet; Estrogens, Non-Steroidal; Female; Food Analysis; Humans; Isoflavones; Lignans; Male; Menopause; Osteoporosis; Phytoestrogens; Plant Preparations; Plants; Prostatic Neoplasms

Phytoestrogens represent a family of plant compounds that have been shown to have both estrogenic and antiestrogenic properties. A variety of these plant compounds and their mammalian metabolic products have been identified in various human body fluids and fall under two main categories: isoflavones and lignans. A wide range of commonly consumed foods contain appreciable amounts of these different phytoestrogens. For example, soy and flax products are particularly good sources of isoflavones and lignans, respectively. Accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials suggests that phytoestrogens may potentially confer health benefits related to cardiovascular diseases, cancer, osteoporosis, and menopausal symptoms. These potential health benefits are consistent with the epidemiological evidence that rates of heart disease, various cancers, osteoporotic fractures, and menopausal symptoms are more favorable among populations that consume plant-based diets, particularly among cultures with diets that are traditionally high in soy products. The evidence reviewed here will facilitate the identification of what is known in this area, the gaps that exist, and the future research that holds the most potential and promise.

Topics: Cardiovascular Diseases; Diet; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Lignans; Male; Neoplasms; Osteoporosis; Plants, Edible

Incidences of breast, colorectal and prostate cancer are high in the Western world compared to countries in Asia. We have postulated that the Western diet compared to the semivegetarian diet in some Asian countries may alter hormone production, metabolism or action at the cellular level by some biochemical mechanisms. Our interest has been focused on two groups of hormone-like diphenolic phyto-oestrogens of dietary origin, the lignans and isoflavonoids abundant in plasma of subjects living in areas with low cancer incidence. The precursors of the biologically active compounds detected in man are found in soybean products, whole-grain cereal food, seeds, and berries. The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds. The weakly oestrogenic diphenols formed influence sex-hormone production, metabolism and biological activity, intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, cell adhesion and angiogenesis in such a way as to make them strong candidates for a role as natural cancer-protective compounds. Their effect on some of the most important steroid biosynthetic enzymes may result in beneficial modulation of hormone concentrations and action in the cells preventing development of cancer. Owing to their oestrogenic activity they reduce hot flushes and vaginal dryness in postmenopausal women and may to some degree inhibit osteoporosis, but alone they may be insufficient for complete protection. Soy intake prevents oxidation of the low-density lipoproteins in vitro when isolated from soy-treated individuals and affect favourably plasma lipid concentrations. Animal experiments provide evidence suggesting that both lignans and isoflavonoids may prevent the development of cancer as well as atherosclerosis. However, in some of these experiments it has not been possible to separate the phyto-oestrogen effect from the effect of other components in the food. The isoflavonoids and lignans may play a significant inhibitory role in cancer development particularly in the promotional phase of the disease, but recent evidence points also to a role in the initiation stage of carcinogenesis. At present, however, no definite recommendations can be made as to the dietary amounts needed for prevention of disease. This review deals with all the above-mentioned aspects of phyto-oestrogens.

Topics: Diet; Estrogens; Female; Heart Diseases; Humans; Lignans; Male; Menopause; Neoplasms; Osteoporosis; Plant Growth Regulators; Plants, Edible; Western World

A randomized double-blind placebo controlled study design was used to assess the effects of flaxseed lignan complex supplementation during exercise training on a metabolic syndrome composite score and osteoporosis risk in older adults. A total of 100 subjects (>or=50 years) were randomized to receive flaxseed lignan (543 mg.day-1 in a 4050 mg complex) or placebo while completing a 6 month walking program (30-60 min.day-1, 5-6 days.week-1). Fasting serum glucose, triacylglycerol (TAG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, total cholesterol, interleukin-6, and tumor necrosis factor-alpha were measured every 2 months, while body composition, bone mineral density, and resting blood pressure were assessed at baseline and at 6 months. A composite Z score of 6 risk factors for metabolic syndrome (fasting glucose, HDL cholesterol, TAG, abdominal adiposity, blood pressure, and inflammatory cytokines) was calculated at baseline and at 6 months. Men taking placebo increased metabolic syndrome composite Z score (p < 0.05), but there were no changes in the other groups. A significant group x sex x time interaction was noted for TAG (p = 0.017) and diastolic blood pressure (p = 0.046), with men taking flaxseed lignan decreasing diastolic blood pressure relative to men taking placebo, and men taking placebo increasing TAG relative to men taking flax lignan. There were no differences between groups for change in bone measures, body composition, lipoproteins, or cytokines. Males taking the flaxseed lignan complex reduced metabolic syndrome score relative to men taking placebo, but a similar trend was not seen in females. Flaxseed lignan had no effect on bone mineral density or content, body composition, lipoproteins, glucose, or inflammation.

Topics: Biomarkers; Blood Glucose; Blood Pressure; Body Composition; Calcification, Physiologic; Combined Modality Therapy; Cytokines; Dietary Supplements; Double-Blind Method; Exercise Therapy; Female; Flax; Humans; Lignans; Lipids; Male; Medication Adherence; Metabolic Syndrome; Middle Aged; Osteoporosis; Risk Factors; Time Factors; Treatment Outcome

BACKGROUND Osteoporosis is a metabolic osteopathy characterized by abnormal bone mass and microstructure that has become a public health problem worldwide. Cuscutae semen (CS) is a traditional Chinese medicine (TCM) that has a positive effect on the prevention and treatment of osteoporosis. However, the mechanism of CS is unclear. Therefore, this study aimed to reveal the possible molecular mechanism involved in the effects of CS on osteoporosis based on a network pharmacology approach. MATERIAL AND METHODS The inactive and active ingredients of CS were identified by searching the pharmacology analysis platform of the Chinese medicine system (TCMSP), and the targets of osteoporosis were screened in the relevant databases, such as GeneCards, PubMed, and the Comparative Toxicogenomics Database (CTD). The network of "medicine-ingredients-disease-targets (M-I-D-T)" was established by means of network pharmacology, and the key targets and core pathways were determined by R analysis. Molecular docking methods were used to evaluate the binding activity between the target and the active ingredients of CS. RESULTS Eleven active ingredients were identified in CS, and 175 potential targets of the active ingredients were also identified from the TCMSP. Moreover, we revealed 22 539 targets related to osteoporosis in the 3 well-established databases, and we determined the intersection of the disease targets and the potential targets of the active ingredients; 107 common targets were identified and used in further analysis. Additionally, biological processes and signaling pathways involved in target action, such as fluid shear stress, atherosclerosis, cancer pathways, and the TNF signaling pathway, were determined. Finally, we chose the top 5 common targets, CCND1, EGFR, IL6, MAPK8, and VEGFA, for molecular docking with the 11 active ingredients of CS. CONCLUSIONS This study suggested that CS has multiple ingredients and multiple targets relevant to the treatment of osteoporosis. We determined that the active ingredient, sesamin, may be the most crucial ingredient of CS for the treatment of osteoporosis. Additionally, the network pharmacology method provided a novel research approach to analyze the function of complex ingredients.

Topics: Catalytic Domain; Cyclins; Dioxoles; Drugs, Chinese Herbal; ErbB Receptors; Gene Ontology; Humans; Interleukin-6; Lignans; Mitogen-Activated Protein Kinase 8; Molecular Docking Simulation; Molecular Targeted Therapy; Osteoporosis; Protein Interaction Maps; Thermodynamics; Vascular Endothelial Growth Factor A

BACKGROUND Osteoporosis is a common osteopathy, resulting in fractures, especially in elder people. Sesamin has many pharmacological effects, including supplying calcium. However, how sesamin might prevent osteoporosis is still under study. MATERIAL AND METHODS Bone marrow stromal cells (BMSCs) extracted from rat femur were induced for osteoblastic differentiation. Cell proliferation, alkaline phosphatase (ALP), osterix (OSX), SRY-box 9 (SOX9), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), ß-catenin, low density lipoprotein receptor-related protein 5 (LRP5), and glycogen synthase kinase-3ß (GSK-3ß) levels in BMSCs were detected in the presence or absence of sesamin (1 μM or 10 µM). In addition, FH535 (1 μM) was used to silence Wnt/ß-catenin in vitro. Ovariectomized (OVX) rats were established and intragastrically administrated sesamin (80 mg/kg), and then the rat bones were analyzed by micro-computed tomography. Osteocalcin and collagen type I were measured in the rat femurs. RESULTS Sesamin had no influence on BMSC proliferation. Higher sesamin concentration promoted Wnt/ß-catenin activity and enhanced more expressions of ALP, OSX, SOX9, RUNX2, and OCN, gradually and significantly (P<0.05). Silencing Wnt/ß-catenin weakened the enhancement on RUNX2 and OCN expression. Sesamin (80 mg/kg) promoted bone structure in ovariectomized rats, and significantly enhanced osteocalcin and collage type I expression (P<0.05). CONCLUSIONS Sesamin promoted osteoblastic differentiation of rat BMSCs by regulating the Wnt/ß-catenin pathway, and improved rat bone structure. Sesamin could have therapeutic and preventive effects on osteoporosis.

Topics: Alkaline Phosphatase; Animals; beta Catenin; Bone and Bones; Cell Differentiation; Cell Proliferation; China; Collagen Type I; Dioxoles; Female; Lignans; Mesenchymal Stem Cells; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Wnt Signaling Pathway

Two new lignans, zanthoxyloside C (

Topics: Antioxidants; Flavonoids; Humans; Lignans; Osteoporosis; Oxygen Radical Absorbance Capacity; Peroxides; Phenols; Plant Extracts; Tartrate-Resistant Acid Phosphatase; Zanthoxylum

Matairesinol is a plant lignan present in a wide variety of foodstuffs such as seeds, vegetables and fruits. It has various biological functions including anti-angiogenic, anti-cancer and anti-fungal activities, but its anti-osteoporotic activity, if any, is unknown.. For osteoclast differentiation, primary mouse bone marrow-derived macrophage cells (BMMs) were cultured for 4 days in the presence of RANKL and M-CSF with the vehicle (DMSO) or matairesinol. Cell cytotoxicity was examined by CCK-8 assay. Gene expression of NFATc1, TRAP, OSCAR, v-ATPasev0d2 were observed in the presence or absence of matairesinol (10 μM) for the indicated times. For evaluating the involvement of NFATc1 in the anti-osteoclastogenic action of matairesinol, BMMs were infected with pMX-IRES-GFP or pMX-IRES-CA-NFATc1-GFP for 8 h with polybrene, and then infected BMMs were cultured with M-CSF and RANKL for 4 days in the presence or absence of matairesinol (10 μM). MAPK signaling activation was examined by immunoblotting. For measuring the resorptive activity of mature osteoclasts, osteoclasts and osteoblasts were co-cultured on BioCoat Osteologic MultiTest slides, and treated with matairesinol for 24 h.. Here we show that matairesinol dose-dependently inhibited the RANKL-induced differentiation of BMMs into osteoclasts by downregulating RANKL-induced expression and activity of NFATc1. Ectopic overexpression of NFATc1 blunted the anti-osteoclastogenic effect of matairesinol implicating NFATc1 in the action of matairesinol. Additionally, matairesinol blocked the RANKL-induced activation of p38 and ERK in BMMs, but had no effect on bone resorption activity in mature osteoclasts.. Taken together, our results suggest that the anti-osteoporotic activity of matairesinol could arise from its anti-osteoclastogenic potential via p38/ERK-NFATc1 signaling, but not by way of anti-resorptive action.

Topics: Animals; Bone Resorption; Cell Differentiation; Down-Regulation; Extracellular Signal-Regulated MAP Kinases; Furans; Lignans; Macrophage Colony-Stimulating Factor; Macrophages; Male; Mice, Inbred ICR; NFATC Transcription Factors; Osteoblasts; Osteoclasts; Osteoporosis; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Phytotherapy; Plant Extracts; Plants, Edible; RANK Ligand; Signal Transduction; Transcription Factors

The present study systematically investigate the in vivo and in vitro effect of total lignans (TL) extracted from Eucommia ulmoides Oliv. barks on bone formation using ovariectomy rat model and primary cultures of rat osteoblasts.. Eighty 3-month-old female Sprague-Dawley rats were used and randomly assigned into sham-operated group (SHAM) and five ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX); OVX with 17α-ethinylestradiol (E2, 25 μg/kg/day); OVX with TL of graded doses (20, 40, or 80 mg/kg/day). The treatment began 4 weeks after the surgery and lasted for 16 weeks. in vitro experiments were performed to determine the potential mechanisms of the anti-osteoporotic effect of TL.. Treatment with TL significantly prevent OVX-induced decrease in biomechanical quality of femur such as maximum stress and Young׳s modulus. The mechanical changes were associated with the prevention of a further BMD decrease or even with some improvements in microarchitecture. TL inhibited BMD decrease in the femur caused by OVX, which was accompanied by a significant decrease in skeletal remodeling, as was evidenced by the decreased levels of the bone turnover markers. μCT analysis of the femoral metaphysis showed how to prevent the deterioration of trabecular microarchitecture. TL induced primary osteoblastic cell proliferation and differentiation, inhibition of osteoclastogenesis through an increase in osteoprotegrin (OPG) and a decrease in NF-κB ligand (RANKL) expression in vitro.. We concluded that TL treatment can effectively suppress the loss of bone mass induced by OVX and in vitro evidence suggests this could be through actions on both osteoblasts and osteoclasts.

Topics: Animals; Bone Density; Bone Remodeling; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Drug; Eucommiaceae; Female; Lignans; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; RANK Ligand; Rats; Rats, Sprague-Dawley

Antimycin A treatment of cells blocks the mitochondrial electron transport chain and leads to elevated ROS generation. In the present study, we investigated the protective effects of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells. Osteoblastic MC3T3-E1 cells were pre-incubated with magnolol before treatment with antimycin A. Cell viability and mineralization of osteoblasts were assessed by MTT assay and Alizarin Red staining, respectively. Mitochondrial dysfunction in cells was measured by mitochondrial membrane potential (MMP), complex IV activity, and ATP level. The cellular antioxidant effect of magnolol in osteoblastic MC3T3-E1 cells was assessed by measuring cardiolipin oxidation, mitochondrial superoxide levels, and nitrotyrosine content. Phosphorylated cAMP-response element-binding protein (CREB ) was evaluated using ELISA assay. Pretreatment with magnolol prior to antimycin A exposure significantly reduced antimycin A-induced osteoblast dysfunction by preventing MMP dissipation, ATP loss, and CREB inactivation. Magnolol also reduced cardiolipin peroxidation, mitochondrial superoxide, and nitrotyrosine production induced by antimycin A. These results suggest that magnolol has a protective effect against antimycin A-induced cell damage by its antioxidant effects and the attenuation of mitochondrial dysfunction. All these data indicate that magnolol may reduce or prevent osteoblast degeneration in osteoporosis or other degenerative disorders.

Topics: Animals; Antimycin A; Antioxidants; Biphenyl Compounds; Cardiolipins; Cell Line; CREB-Binding Protein; Electron Transport; Lignans; Magnolia; Membrane Potential, Mitochondrial; Mice; Mitochondria; Osteoblasts; Osteoporosis; Oxidative Stress; Plant Extracts; Protective Agents; Reactive Oxygen Species; Tyrosine

Osteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function.. Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting.. Sesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19.. The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy.

Topics: Cell Differentiation; Dioxoles; Female; Gene Expression; Humans; Lignans; MAP Kinase Signaling System; Osteoblasts; Osteoporosis; p38 Mitogen-Activated Protein Kinases; Sesamum; Up-Regulation

There has been a strong interest in searching for natural therapies for osteoporosis. Honokiol is a phenolic compound isolated from the bark of Magnolia officinalis, a plant widely used in traditional medicine. In the present study, the effects of honokiol on the function of osteoblastic MC3T3-E1 cells were studied. Honokiol caused a significant elevation of cell growth, alkaline phosphatase activity, collagen synthesis, mineralization, glutathione content, and osteoprotegerin release in the cells (P<0.05). Moreover, honokiol significantly (P<0.05) decreased the production of osteoclast differentiation inducing factors such as TNF-α, IL-6, and receptor activator of nuclear factor-kB ligand (RANKL) in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as a ROS generator. These results demonstrate that honokiol may have positive effects on skeletal structure.

Topics: Alkaline Phosphatase; Animals; Antimycin A; Biphenyl Compounds; Bone Resorption; Calcification, Physiologic; Cell Growth Processes; Cell Line; Collagen; Glutathione; Humans; Interleukin-6; Lignans; Magnolia; Mice; Osteoblasts; Osteoporosis; Osteoprotegerin; Phytotherapy; RANK Ligand; Tumor Necrosis Factor-alpha

Flaxseed, rich in the phytoestrogen lignan secoisolariciresinol diglycoside (SDG), provides protection against bone loss at the lumbar vertebrae primarily when combined with low-dose estrogen therapy in the ovariectomized rat model of postmenopausal osteoporosis. Whether SDG metabolites are accessible to skeletal tissue, and thus have the potential to interact with low-dose estrogen therapy to exert direct local action on bone metabolism, is unknown. The objective of this study was to determine whether metabolites of SDG are accessible to the skeleton of ovariectomized rats and to compare the distribution of SDG metabolites in skeletal tissue with that in other tissues. Rats were fed a 10% flaxseed diet and gavaged daily with tritium-labeled SDG (7.4 kBq/g of body weight) in deionized water (500 μL) (n=3) or deionized water alone (n=3) for 7 days, after which tissues were collected for liquid scintillation counting. Radioactivity was detected in similar concentrations in the lumbar vertebrae, femurs, and tibias. Compared with non-skeletal tissues, total radioactivity in the skeleton was significantly lower than in the liver, heart, kidney, thymus, and brain (P < .001). There were no significant differences in levels of radioactivity between skeletal tissue versus the spleen, lung, bladder, uterus, vagina, and mammary gland. In conclusion, SDG metabolites are accessible to skeletal tissue of ovariectomized rats. Thus, it is biologically plausible that SDG metabolites may play a direct role in the protective effects of flaxseed combined with low-dose estrogen therapy against the loss of bone mass and bone strength in the ovariectomized rat model of postmenopausal osteoporosis.

Topics: Animals; Butylene Glycols; Disease Models, Animal; Female; Femur; Flax; Lignans; Lumbar Vertebrae; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Tibia

Magnolia officinalis, a component of Asian herbal teas, has long been employed in traditional Japanese and Chinese medicine to treat numerous maladies. Honokiol, a biphenolic compound, is now considered to be one of the major active ingredients of Magnolia extract, and is under intense investigation for its anti-angiogenic, anti-inflammatory, anti-tumor and neuroprotective properties. Biochemically, honokiol has been recognized to modulate the nuclear factor κ B (NF-κB) signal transduction pathway suggesting that it possesses anti-inflammatory properties. Inflammation is intimately associated with bone turnover and skeletal deterioration and consequently, anti-inflammatory drugs may hold significant promise as bone protective agents to stem bone loss in osteoporotic conditions. We and others have demonstrated that suppression of NF-κB blunts osteoclastic bone resorption, but promotes osteoblastic bone formation. Indeed previous studies have demonstrated the anti-osteoclastogenic effects of honokiol, however, activities on osteoblast differentiation and activity have yet to be investigated. In this study, we show that honokiol is a potent inducer of in vitro osteoblast differentiation by virtue of its capacity to suppress basal and tumor necrosis factor alpha (TNFα)-induced NF-κB activation and to alleviate the suppressive action of TNFα on bone morphogenetic protein (BMP)-2-induced Smad activation. Our data confirm that honokiol may have considerable promise as a dual anabolic/anti-catabolic agent for the amelioration of multiple osteoporotic diseases.

Topics: Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Blotting, Western; Bone Morphogenetic Protein 2; Bone Resorption; Cell Differentiation; Cell Line; Drugs, Chinese Herbal; Humans; Lignans; Magnolia; Mice; NF-kappa B; Osteoclasts; Osteogenesis; Osteoporosis; Signal Transduction; Smad Proteins; Tumor Necrosis Factor-alpha

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.

Topics: Animals; Body Weight; Bone Density; Dose-Response Relationship, Drug; Female; Lignans; Molecular Structure; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Taxus

Topics: Animals; Diet; Female; Glycine max; Humans; In Vitro Techniques; Isoflavones; Lignans; Menopause; Neoplasms; Osteoporosis; Plant Growth Regulators; Plants, Edible