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Although radix Salviae miltiorrhizae (RSM) is reported to exhibit the antiosteoporotic effect in preclinical study, the underlying mechanism is unclear. To this end, ovariectomized (OVX) rats were employed with administration of RSM (5 g/kg) for 14 weeks. The disturbed serum levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), tartrate-resistant acid phosphatase, and receptor activator of nuclear factor-κB ligand (RANKL) in OVX rats were improved by RSM treatment. Furthermore, supplement of RSM to OVX rats resulted in an increase in femoral bone mineral density and bone strength as well as an improvement in bone microstructures. Moreover, the decreased expression of phosphor (p)-LRP6, insulin-like growth factor-1(IGF-1), ALP, and OPG, as well as increased expression of RANKL and cathepsin K in the tibias and femurs of OVX rats were shifted by RSM treatment. Additionally, RSM reversed the decreased ratio of p-glycogen synthase kinase 3β (GSK3β) to GSK3β and increased ratio of p-β-catenin to β-catenin in OVX rats. Altogether, it is suggestive that RSM improves bone quantity and quality by favoring Wnt/β-catenin and OPG/RANKL/cathepsin K signaling pathways in OVX rats thereby suggesting the potential of this herb to be a novel source of antiosteoporosis drugs.

Cinnamaldehyde, one of the active components derived from Cinnamon, has been used as a natural flavorant and fragrance agent in kitchen and industry. Emerging studies have been performed over the past decades to evaluate its beneficial role in management of diabetes and its complications. This review highlights recent advances of cinnamaldehyde in its glucolipid lowering effects, its pharmacokinetics, and its safety by consulting the Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, National Science and Technology Library, Wanfang Data, and the Web of Science Databases. For the inquiries, keywords such as Cinnamon, cinnamaldehyde, property, synthesis, diabetes, obesity, pharmacokinetics, and safety were used in various combinations. Accumulating evidence supports the notion that cinnamaldehyde exhibits glucolipid lowering effects in diabetic animals by increasing glucose uptake and improving insulin sensitivity in adipose and skeletal muscle tissues, improving glycogen synthesis in liver, restoring pancreatic islets dysfunction, slowing gastric emptying rates, and improving diabetic renal and brain disorders. Cinnamaldehyde exerts these effects through its action on multiple signaling pathways, including PPARs, AMPK, PI3K/IRS-1, RBP4-GLUT4, and ERK/JNK/p38MAPK, TRPA1-ghrelin and Nrf2 pathways. In addition, cinnamaldehyde seems to regulate the activities of PTP1B and α-amylase. Furthermore, cinnamaldehyde has the potential of metalizing into cinnamyl alcohol and methyl cinnamate and cinnamic acid in the body. Finally, there is a potential toxicity concern about this compound. In summary, cinnamaldehyde supplementation is shown to improve glucose and lipid homeostasis in diabetic animals, which may provide a new option for diabetic intervention. To this end, further scientific evidences are required from clinical trials on its glucose regulating effects and safety.

Salvia miltiorrhiza Bunge, also known as Danshen in Chinese, has been widely used to treat cardiovascular diseases (CVD) in China and other Asia countries. Here, we summarize literatures of the historical traditional Chinese medicine (TCM) interpretation of the action of Salvia miltiorrhiza, its use in current clinical trials, its main phytochemical constituents and its pharmacological findings by consulting Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, and the Web of Science Databases. Since 2000, 39 clinical trials have been identified that used S. miltiorrhiza in TCM prescriptions alone or with other herbs for the treatment of patients with CVD. More than 200 individual compounds have been isolated and characterized from S. miltiorrhiza, which exhibited various pharmacological activities targeting different pathways for the treatment of CVD in various animal and cell models. The isolated compounds may provide new perspectives in alternative treatment regimes and reveal novel chemical scaffolds for the development of anti-CVD drugs. Meanwhile, there are also some rising concerns of the potential side effects and drug-drug interactions of this plant. The insights gained from this study will help us to better understanding of the actions of this herb for management of cardiovascular disorders. As an herb of red root, S. miltiorrhiza will act as a potential red light to prevent the development of CVD.

Purpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats. Methods: Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias. Results: Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ. Conclusions: This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats.

Aim. In routine histopathology, decalcification is an essential step for mineralized tissues. The purpose of this study is to evaluate the effects of different decalcification solutions on the morphological and antigenicity preservation in Sprague Dawley (SD) rat femurs. Materials and Methods. Four different decalcification solutions were employed to remove the mineral substances from rat femurs, including 10% neutral buffered EDTA, 3% nitric acid, 5% nitric acid, and 8% hydrochloric acid/formic acid. Shaking and low temperature were used to process the samples. The stainings of hematoxylin-eosin (HE) and immunohistochemical (IHC) were employed to evaluate the bone morphology and antigenicity. Key Findings. Different decalcification solutions may affect the quality of morphology and the staining of paraffin-embedded sections in pathological examinations. Among four decalcifying solutions, 3% nitric acid is the best decalcifying agent for HE staining. 10% neutral buffered EDTA and 5% nitric acid are the preferred decalcifying agents for IHC staining. Significance. The current study investigated the effects of different decalcifying agents on the preservation of the bone structure and antigenicity, which will help to develop suitable protocols for the analyses of the bony tissue.

Estrogen receptor (ER) is expressed in most Breast cancer (BC) patients. G protein-coupled estrogen receptor (GPER), which is a membrane-bound estrogen receptor, is associated with the tumor development and progression in BC. Shikonin (SK) is a natural compound that is known to have anti-tumor effects. This study aims to assess the effects of shikonin on the cell proliferation, cell cycle and cell apoptosis of BC and whether the effects are related to ER/GPER signaling pathway. The results demonstrated that shikonin inhibited the cellular proliferation of MCF-7 BC cells via G0/G1 arrest and apoptosis in concentration-dependent manner. The anti-proliferative effect of SK on SK-BR-3 BC cells was associated with apoptosis. Both ERα and GPER were expressed in MCF-7 cells, while ERα were negative and GPER were positive in SK-BR-3 cells. Furthermore, shikonin downregulated the expression of ERα and GPER, and this effect was not affected by the estrogen environment. In addition, shikonin downregulated the EGFR and p-ERK expression in MCF-7 and SK-BR-3, which was also not affected by the estrogen environment. EGFR and p-ERK were still suppressed by co-treatment with the selective GPER against G1 or antagonist G15. In conclusion, these results suggest that shikonin shows anti-tumor effects on MCF-7 and SK-BR-3 cells. The effects seem to be associated with EGFR/p-ERK downregulation via ERα and GPER inhibition.

Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process. Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis. Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG. Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis.

Although radix Salviae miltiorrhizae (RSM) is reported to exhibit the antiosteoporotic effect in preclinical study, the underlying mechanism is unclear. To this end, ovariectomized (OVX) rats were employed with administration of RSM (5 g/kg) for 14 weeks. The disturbed serum levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), tartrate-resistant acid phosphatase, and receptor activator of nuclear factor-κB ligand (RANKL) in OVX rats were improved by RSM treatment. Furthermore, supplement of RSM to OVX rats resulted in an increase in femoral bone mineral density and bone strength as well as an improvement in bone microstructures. Moreover, the decreased expression of phosphor (p)-LRP6, insulin-like growth factor-1(IGF-1), ALP, and OPG, as well as increased expression of RANKL and cathepsin K in the tibias and femurs of OVX rats were shifted by RSM treatment. Additionally, RSM reversed the decreased ratio of p-glycogen synthase kinase 3β (GSK3β) to GSK3β and increased ratio of p-β-catenin to β-catenin in OVX rats. Altogether, it is suggestive that RSM improves bone quantity and quality by favoring Wnt/β-catenin and OPG/RANKL/cathepsin K signaling pathways in OVX rats thereby suggesting the potential of this herb to be a novel source of antiosteoporosis drugs.

Rehmanniae Radix Preparata (RRP) improves bone quality in OVX rats through the regulation of bone homeostasis via increasing osteoblastogenesis and decreasing osteoclastogenesis, suggesting it has a potential for the development of new anti-osteoporotic drugs.Determine the anti-osteoporotic effect of RRP in ovariectomized (OVX) rats and identify the signaling pathway involved in this process.OVX rats were treated with RRP aqueous extract for 14 weeks. The serum levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear factor kappa-Β ligand (RANKL), alkaline phosphatase (ALP), and osteoprotegerin (OPG) were determined by ELISA. Bone histopathological alterations were evaluated by HE, Alizarin red S, and Safranin O staining. Bone mineral density (BMD) and bone microstructure in rat femurs and lumbar bones were determined by dual-energy X-ray absorptiometry and micro-computed tomography. Femoral bone strength was detected by a three-point bending assay. The expression of Phospho-glycogen synthase kinase 3 beta (p-GSK-3β), GSK-3β, Dickkopf-related protein 1 (DKK1), cathepsin K, OPG, RANKL, IGF-1, Runx2, β-catenin, and p-β-catenin was determined by western blot and/or immunohistochemical staining.Treatment of OVX rats with RRP aqueous extract rebuilt bone homeostasis demonstrated by increasing the levels of OPG as well as decreasing the levels of TRAP, RANKL, and ALP in serum. Furthermore, RRP treatment preserved BMD and mechanical strength by increasing cortical bone thickness and epiphyseal thickness as well as improving trabecular distribution in the femurs of OVX rats. In addition, RRP downregulated the expression of DKK1, sclerostin, RANKL, cathepsin K, and the ratio of p-β-catenin to β-catenin, along with upregulating the expression of IGF-1, β-catenin, and Runx2 and the ratio of p-GSK-3β to GSK-3β in the tibias and femurs of OVX rats. Echinacoside, jionoside A1/A2, acetoside, isoacetoside, jionoside B1, and jionoside B2 were identified in the RRP aqueous extract.RRP attenuates bone loss and improves bone quality in OVX rats partly through its regulation of the canonical Wnt/β-catenin signaling pathway, suggesting that RRP has the potential to provide a new source of anti-osteoporotic drugs.

Background/Aim: Recent studies have demonstrated that circulating fibrocytes contribute to the formation and development of fibrosis. Curcumin, a polyphenolic compound isolated from turmeric, has been shown to have anti-fibrotic effects in various organs. We and others have demonstrated that curcumin beneficially affects the development of fibrosis. However the effect of curcumin on circulating fibrocytes has not been reported. Methods: Human circulating fibrocytes were isolated from leukocyte concentrates of healthy human donors and identified based on the expression of CD34, CD45, collagen I (COLI), and chemokine receptor CCR7 (CCR7) via flow cytometry. Cell Counting Kit-8 was used to evaluate cell viability. The effect of curcumin on the differentiation and migration of human circulating fibrocytes was evaluated by immunofluorescence staining, flow cytometry and a transwell migration assay. Transforming growth factor (TGF)-β1 secretion was examined by ELISA. Results: Curcumin treatment (72 h; 20 μM) significantly decreased the expression of COL I, α-SMA and CCR7, as well as TGF-βl secretion, in human circulating fibrocytes. The inhibitory effect of curcumin on the differentiation and migration of human circulating fibrocytes is likely via regulating the CCR7/CCL21 signaling pathway, in particular by reducing CCR7 expression. These observed effects may be beneficial in resolving fibrosis by suppressing TGF-β1 secretion. Conclusion: Our results suggest that curcumin has the potential to suppress the differentiation and migration of circulating fibrocytes, which would provide new explanation for curcumin's application in the development of fibrosis in various organs.

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

Background Accumulating evidence suggests that Fructus Ligustri Lucidi (FLL) plays a beneficial role in preventing the development of osteoporosis. However, the effects of FLL on estrogen receptor (ER) α and ERβ expressions remain unknown. Therefore, in the current study we attempted to probe into the effects of FLL on ERα and ERβ expressions in femurs, tibias and uteri of ovariectomized (OVX) rats. Methods The OVX rats were orally administrated with FLL water extract (3.5 g/kg/day) for 12 weeks. The uteri, femurs, tibias and serum were harvested from rats. The serum levels of estrogen (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by ELISA. The expressions of ERα and ERβ in the femurs and tibias as well as uteri were analysed by western blot and immunohistochemical staining. Results FLL treatment did not increase uterus relative weight in OVX rats. Further, FLL treatment increased ERα expression in the femurs and tibias, and enhanced ERβ expression in the uteri of OVX rats. However, the resulted expression of ERα was stronger than that of ERβ in OVX rats in response to FLL treatment. Meanwhile, administration with FLL to OVX rats increased FSH and LH but did not increase E2 level in the serum. Conclusion FLL treatment shows tissue selection on ERα and ERβ expressions in the femurs and tibias as well as uteri of OVX rats without uterotrophic effect, which may offer the scientific evidence of the efficiency and safety of its clinical application.

Ethnopharmacological relevance Emerging clinical usage and pharmacological effects have been achieved in using Rehmanniae Radix either singly or in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM) in the recent years. This study is aimed to provide a comprehensive review about the historical TCM interpretation of the action of Rehmanniae Radix in osteoporosis, its usage in clinical trials and osteoporotic models, its main phytochemical constituents, and its pharmacokinetics. Materials and methods Several databases included PubMed, China Knowledge Resource Integrated Database, China Science and Technology Journal Database, National Science and Technology Library and the Web of Science Database were consulted to locate the publications pertaining to Rehmanniae Radix . The initial inquiry was conducted for the presence of the following terms combinations in the abstracts: Rehmanniae Radix , Dihuang, phytochemistry, pharmacokinetics, osteoporosis, bone, osteoclast and osteoblast. About 330 research papers and reviews were consulted. Results In TCM, Rehmanniae Radix exerts the anti-osteoporotic effect via regulating the functions of kidney and liver as well as improving blood circulation. 107 clinical trials are identified that used Rehmanniae Radix in combination with other herbs to treat post-menopausal, senile and secondary osteoporosis. Most of the clinical trials are characterized by high efficacy and no obvious adverse effects. However, the efficacies of these clinical trials are limited because of small patient sample size, short treatment duration and poor clinical design. In addition, TCM herbs under the clinical study are not clear because of a lack of standardization and authentication. The pharmacokinetics data demonstrate that the ingredients of Rehmanniae Radix are widely distributed after administration, and that catalpol and ajugol as well as acetoside are supposed to be the active constituents. More than 140 individual compounds have been currently isolated from this plant and reported to show pleiotropic effects on various diseases. Rehmanniae Radix displays bone protecting features in the osteoporosis models via the delicate balance between osteoclastogenesis and osteoblastogenesis through single herb extracts and its isolated compounds. Conclusions The successful inclusion of Rehmanniae Radix in clinical trials and preclinical studies for the management of osteoporosis has attracted rising attentions for identifying potential anti-osteoporotic candidates from this plant and clinical existing TCM formulas, which will further speed up anti-osteoporosis drug discovery processes. Properly designed and well controlled prospective studies are still needed to further demonstrate bone protective actions and safe use of this herb and its ingredients

Oxidative stress with reactive oxygen species (ROS) can contribute to the pathogenesis of idiopathic pulmonary fibrosis. Antioxidant enzymes, such as extracellular superoxide dismutase (ECSOD), may modulate the injury and repair components of the fibrogenic response. Here we determined whether ECSOD could attenuate experimental TGF-β1-induced persistent lung fibrosis. In this study, primary human lung fibroblasts, MRC-5 fibroblasts and A549 epithelial cells were exposed to recombinant active TGF-β1. An adenovirus vector that expresses human ECSOD (AdECSOD) was constructed and rats were endotracheally intubated with an adenoviral vector encoding active TGF-β1 (AdTGF-β1), AdECSOD or a control vector (AdDL70) alone or in combinations AdTGF-β1/AdDL70 or AdTGF-β1/AdECSOD. TGF-β1 alone induced fibrotic responses and significantly down-regulated endogenous ECSOD gene expression both in vitro and in vivo and caused oxidative stress in rat lung, associated with increased levels of activated TGF-β1 in lung fluid and tissue. ECSOD protein was markedly reduced in the interstitium and fibrotic foci in TGF-β1 induced experimental lung fibrosis. The fibrotic response caused by AdTGF-β1 was markedly attenuated by concomitant gene transfer using AdECSOD, detected by lung function measurements, histologic and morphometric analysis, hydroxyproline content and fibrosis-related gene expression. In addition, the oxidative stress and increased presence of activated TGF-β1 in rat lung induced by AdTGF-β1 was significantly reduced by ECSOD gene transfer. These findings suggest a substantial role for oxidative stress in the pathogenesis of TGF-β1 driven persistent pulmonary fibrosis and enhanced presence of ECSOD can inhibit latent TGF-β1 activation by ROS and diminish subsequent fibrotic responses.

Herba Epimedii (HEP) known as YinYangHuo in Chinese is the dried leaf of the Epimediium, and has been historically used in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM). Here, we review the historical TCM interpretation of the action of HEP, its use in clinical trials, its main phytochemical constituents and its pharmacological findings. 85 clinical trials were identified which used HEP in TCM prescriptions with other herbs to treat primary and secondary osteoporosis from 2005 to now. More than 60 individual compounds were isolated and characterized from HEP and studied in various animal and cell models. HEP and its constituents exhibited a variety of anti-resorptive and bone formation-stimulating effects, which target different pathways in the bone remodeling cycle. These compounds may provide new perspectives in alternative treatment regimes and reveal novel chemical scaffolds for the development of anti-osteoporotic drugs. These approaches are also useful for guiding our research to employ an integrative therapeutic approach to treat complex diseases such as osteoporosis diseases which could be superior to the conventional single target – single drug approach.

Recent studies have confirmed that circulating fiobrocytes may play important roles in the formation and development of fibrosis. Curcumin, a polyphenolic compound isolated from turmeric (Zingibera...

Ethnopharmacological relevance Red sage (Salvia miltiorrhiza Bunge), also known as Danshen in Chinese, has been used historically and is currently exploited in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM). With the advance of modern analytical technology, a multitude of bone-targeting, pharmaceutically active, compounds has been isolated and characterized from various sources of TCM including those produced in Salvia miltiorrhiza root. The aim of the review is to provide a comprehensive overview about the historical TCM interpretation of the action of Salvia miltiorrhiza in osteoporosis, its use clinical trials, its main phytochemical constituents, and its action on bone-resorptive and bone formation-stimulating mechanisms in in vitro and in vivo studies. Materials and methods Literature sources used were Pubmed, CNKI.net, Cqvip.com, PubChem, and the Web of Science. For the inquiry, keywords such as Salvia, danshen, osteoporosis, bone, osteoclast and osteoblast were used in various combinations. About 130 research papers and reviews were consulted. Results In TCM, the anti-osteopororotic effect of Salvia miltiorrhiza is ascribed to its action on liver and blood stasis as main therapeutic targets defining osteoporosis. 36 clinical trials were identified which used Salvia miltiorrhiza in combination with other herbs and components to treat post-menopausal, senile, and secondary osteoporosis. On average the trials were characterized by high efficacy (>80%) and low toxicity problems. However, various limitations such as small patient samples, short treatment duration, frequent lack of detailed numerical data, and no clear endpoints must be taken into consideration. To date, more than 100 individual compounds have been isolated from this plant and tested in various animal models and biochemical assays. Compounds display anti-resorptive and bone formation-stimulating features targeting different pathways in the bone remodeling cycle. Pathways affected include the activation of osteoblasts, the modulation of osteoclastogenesis, and the inhibition of collagen degradation by cathepsin K. Conclusions The inclusion of Salvia miltiorrhiza in more than 30% of all herbal clinical trials successfully targeting osteoporosis has stimulated significant interest in the identification and characterization of individual constituents of this herb. The review highlights the anti-osteoporotic potential of Salvia miltiorrhiza in clinical applications and the potential of the herb to provide potent compounds targeting specific pathways in bone resorption and bone formation.

Postmenopausal osteoporosis is one of the commonest systemic bone metabolism diseases among menopausal women, mainly caused by lowering internal estrogen. Although Hormone Replacement Therapy (HRT) is an effective method in clinical practice for years, it shows side-effect in increasing gynecological carcinoma. It has already been proved by clinical tests that multiple traditional Chinese medicine formulas and their monomer ingredients and phytoestrogen-like active constituents contained in traditional Chinese medicines are effective on treating osteoporosis with relatively less side-effects comparing with HRT. They show protective and therapeutic effects by acting on estrogen receptors of targeted tissues and targeted cells and then affecting expressions of bone metabolism-related regulatory proteins and factors in downstream signal conduct paths. Recent studies on estrogen related receptor (ERR) provide new possibilities and pathways for mechanism of traditional Chinese medicine and their active constituents in osteoporosis.

Objective To explore the Zedoary oil on A549 cell line of collagen deposition cat D and cat K expression. Method The A549 cell line were treat by Zedoary oil on four different concentrations (0, 40, 80, 120 mg x L(-1)) in different time. Dynamic changes of collagen in A549 cell using Picric-sirius red method. Cat D and Cat K expression of level were detected by using western blot. Result The collagen content showed that Zedoary oil had an inhibitory effect on the deposition of A549 cells. The results of western blot showed that the expression of cat D and cat K were up-regulated significangly in A549 cells of Zedoary oil groups compared with that in controls. Conclusion A549 cell of collagen deposition were reduced by Zedoary oil. The effects may due to the up-regulation of cat D and cat K.

To study the total glucosides of Radix Paeoniae Rubra induced K562 tumor cell apoptosis of signaling pathways and related gene changes.By MTT and flow cytometric, real-time quantitatie polymerase chain reaction (PCR) and Western blot methods researched the level of genes and proteins.The total glucosides of Radix Paeoniae Rubra could inhibit K562 cell growth by MTT method, there was the relationship of concentration-time between them, TGC prompted K562 cell translocation of phosphatidylserine, may be apoptosis through non-receptor-dependent pathways because caspase-3 mRNA, caspase-9 mRNA and cytochrome C increased, caspase-8 mRNA had no significant change. The expression of Bcl-2 protein and Bcl-X1 protein could decreased, the expression of Bax protein could increased by regulating gene expression.TGC induced K562 cell apoptosis that might be through the mitochondria pathway, when cell apoptosis occured, Bcl-2 or Bcl-XI proteins combination of Bax protein would be displacement, then the mitochondrial membrane became permeable to release a series of material, then lead to cell death.

Background Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycin-induced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression and activity of cathepsins which have been implicated in the development of fibrotic lung diseases. Methods We investigated the effects of curcumin administration to bleomycin stimulated C57BL/6 mice and human fetal lung fibroblasts (HFL-1) on the expression of cathepsins K and L which have been implicated in matrix degradation, TGF-β1 modulation, and apoptosis. Lung tissues were evaluated for their contents of cathepsins K and L, collagen, and TGF-β1. HFL-1 cells were used to investigate the effects of curcumin and cathepsin inhibition on cell proliferation, migration, apoptosis, and the expression of cathepsins K and L and TGF-β1. Results Collagen deposition in lungs was decreased by 17-28% after curcumin treatment which was accompanied by increased expression levels of cathepsins L (25%-39%) and K (41%-76%) and a 30% decrease in TGF-β1 expression. Moreover, Tunel staining of lung tissue revealed a 33-41% increase in apoptotic cells after curcumin treatment. These in vivo data correlated well with data obtained from the human fibroblast line, HFL-1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGF-β1 decreased by 34%. Furthermore, curcumin significantly decreased cell proliferation and migration and increased the expression of surrogate markers of apoptosis. In contrast, these curcumin effects were partly reversed by a potent cathepsin inhibitor. Conclusion This study demonstrates that curcumin increases the expression of cathepsins K and L in lung which an effect on lung fibroblast cell behavior such as proliferation, migration and apoptosis rates and on the expression of TGF-β1 in mouse lung and HFL-1 cells. These results suggest that cathepsin-inducing drugs such as curcumin may be beneficial in the treatment of lung fibrosis.

OBJECTIVE To study the total glucosides of Radix Paeoniae Rubra induced K562 tumor cell apoptosis of signaling pathways and related gene changes. METHOD By MTT and flow cytometric, real-time quantitatie polymerase chain reaction (PCR) and Western blot methods researched the level of genes and proteins. RESULT The total glucosides of Radix Paeoniae Rubra could inhibit K562 cell growth by MTT method, there was the relationship of concentration-time between them, TGC prompted K562 cell translocation of phosphatidylserine, may be apoptosis through non-receptor-dependent pathways because caspase-3 mRNA, caspase-9 mRNA and cytochrome C increased, caspase-8 mRNA had no significant change. The expression of Bcl-2 protein and Bcl-X1 protein could decreased, the expression of Bax protein could increased by regulating gene expression. CONCLUSION TGC induced K562 cell apoptosis that might be through the mitochondria pathway, when cell apoptosis occured, Bcl-2 or Bcl-XI proteins combination of Bax protein would be displacement, then the mitochondrial membrane became permeable to release a series of material, then lead to cell death.

Objective Research on the phytoestrogenic effect and its possible mechanism of formononetin. Method To evaluate the estrogenic effect and mechanisms of formononetin through the test of its influence on proliferation and ER subtype expression of T47D cells. Result The proliferation rates of T47D cells treated with 1 x 10(-7) -1 x 10(-6) mol x L(-1) formononetin were not increased. On the influence of ICI182, 780, the proliferation rates of T47D cells treated with 1 x 10(-7) 1 x 10(-6) mol x L(-1) formononetin were decreased. Formonenetin could induce the augment of ERalpha expression significantly of T47D. Conclusion Formonenetin has phytoestrogenic effect Formonenetin can not accelerate ER(+) T47D cell proliferation. But the expression level of ERalpha subtype in T47D cells change significantly with certain concentrations of formonenetin.

Objective To investigate phytoestrogenic effects of ferulic acid in ER-positive T47D and ER-negative MDA-MB231 cells in culture. Method T47D and MDA-MB231 human breast cancer cells were treated with ferulic acid and examined cell proliferation by means of MTT assay. Cell cycle distribution, ERalpha and ERbeta expression were treated by flow cytometer. The pS2 mRNA expressions were detected by real-time fluorescence quantitative PCR. Result The proliferations were enhanced significantly by treatment with ferulic acid on T47D cells and the proliferation effects were inhibited by adding Faslodex (1 x 10(-8) mol x L(-1)). However, there was no significant difference on the proliferation in MDA-MB-231 cells compared with solvent control group by both treatment with ferulic acid and co-treatment with Faslodex (1 x 10(-8) mol x L(-1)). Ferulic acid stimulated the amount of T47D cells in phase S and proliferation index increased significantly. The effects were inhibited by treatment with Faslodex (1 x 10(-8) mol x L(-1)), and the amount of cells in phase S and proliferation index decreased, the amount of cells in G0/G1 phase increased, cell cycle of T47D was arrested in G0/G1 phase. Ferulic acid up-regulated pS2 mRNA expressions and increased the level of ERalpha protein expression in T47D cells. Ferulic acid did not show remarkable effect to the level of ERbeta protein expression in T47D cells. Conclusion Ferulic acid possessed phytoestrogenic effect by up-regulating pS2 gene expression and the receptor subtype of ERalpha.

OBJECTIVE To evaluate the protective effects of siwuheji on cisplatin-induced ovarian impairing and explore its possible mechanisms in mice. METHOD The mice received cisplatin ip (7 mg kg(-1)) for 7 days, while fed with siwuheji for 14 days. The changes of estrous cycle, ovary and uterus coefficient, levels of estrogen in serum and morphology of ovary were recorded. RESULT From the third day of cisplatin injection, the estrous cycle of the model group stagnated in interphase. On the thirteenth day, part of the mice fed with siquheji started with change of estrous cycle. The ovary coefficient of the model group was less than the control group, the experimental groups were no differences compared with the control group and had significant differences with the model group. The levels of E2 and P of model group were lower than the control group, but no statistical significance. The level of E2 with high-dose Siwuheji group was higher than model group, and the level of P of the low-dose group was higher than model group, but both no statistical significances. The FSH/LH ratio of model group was significantly higher than the control group, low-dose group and medium-dose group of siwuheji resumed to normal levels, and had a significantly change compared with the model group. Ovarian biopsy of model group showed the decrease in the number of developing follicle at all levels, and increase in the number of Atresia of ovarian. There were more growing follicte in the large, medium-dose group. CONCLUSION Cisplatin can induce mice ovarian injury and functional decline, on the other hand, siwuheji can improve cisplatin-induced ovarian dysfunction.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To examine the efficacy and safety of acupuncture therapy in patients with MS, compared with no treatment, sham/placebo acupuncture, medication or other treatment.

To study the phytoestrogenic effects and their possible mechanisms of Jiaoai tang and Shenqi Jiaoai tang through the tests in mice and ER (+) MCF7 cells.Sixty kunming mice weighing 9-12 g were randomly divided into 6 groups: solvent control group (administrated equal dose of diswater), diethylstilbestrol control group (administrated diethylstilbestrol at a dose of 0.35 mg x kg(-1) x d(-1) and 4 Chinese medicine treated groups (administrated low or high doses of Jiaoai tang and Shenqi Jiaoai tang at 2.5 g x kg(-1) x d(-1) or 5.0 g x kg(-1) x d(-1) respectively). After administration for 4 days, the mice were sacrificed; uterus was removed and weighed, uterus rate was calculated. The blood serum was also separated. The proliferation rate of MCF7 cells influenced by Jiaoai tang and Shenqi Jiaoai tang was determined by MIT assay. PS2, ERalpha and ERbeta mRNA expression was quantified by Real-time PCR assay. Estrogen receptor antagonist ICI182, 780 was employed as a tool.Administration of Jiaoai tang and Shenqi Jiaoai tang at high dose significantly increased uterus rate in mice (P0. 05). The pharmacological serum from two high-dosage groups of Chinese herbal medicine decoction significantly enhanced proliferation rate of MCF7 cells (P0.05 or 0.01), while their effects were blocked by ICI182, 780 (P0.05 or 0.01). The pharmacological serum could cause elevation of pS2 level (P0.01) which would be obviously inhibited by ICI182, 780 (P0.01). ERalpha and ERbeta mRNA levels were also elevated significantly (P0.05 and P0.01 respectively).Jiaoai tang and Shenqi Jiaoai tang have phytoestrogenic effects, which were attained via ER pathway. They can also increase the mRNA levels of estrogen receptor subtypes, especially ERbeta.

To explore the phytoestrogenic-like effects of four kinds of Chinese medicine including Radix rehmanniae preparata, Radix Paeoniae Alba, Radix Angelicae Sinensis, Rhizoma Chuanxiong.Sixty immature female SD rats weighting (70 +/- 5) g were randomly divided into six groups: normal control group, positive control group and 4 Chinese medicine groups. The rats in different groups were treated for 4 days. On the fifth day, animals were sacrificed and uteri were separated solely and weighed. The blood was collected, and serum was separated. The effect of the pharmacological serum on proliferation assay with human breast cancer cell line (MCF7) by MTT method. Cell-cycle analyses were carried out with propidium iodide staining by flow cytometer. The expressions of subtypes-estrogen receptor-alpha (ERalpha) were detected by flow cytometry.Radix Rehmanniae Preparata, Radix Paeoniae Alba and Radix Angelicae Sinensis could increase the immature rat's uterus wet weight and the ratio of uterus to body weight (P0.05). The pharmacological serum of the four kinds of Chinese medicine stimulated proliferation of MCF7 cell respectively compared with normal control group (P0.01). The cell cycle was impulsed from G1 to S, DNA synthesizing was inhanced, and PI was also increased. The pharmacological serum of Radix Angelicae Sinensis and Rhizoma Chuanxiong could increase the expressions of (ERalpha) (P0.05).Radix Rehmanniae Preparata, Radix Paeoniae Alba and Radix Angelicae sinensis have phytoestrogenic effects. But the data werent consistent with in vitro and in vivo assay of Rhizoma Chuanxiong.