scholarly journals Chinese Herbal Tanshinol Prevents Osteoporosis via Coordinately Promoting Osteogenesis and Inhibiting Osteoclastogenesis

2021 ◽  
Author(s):  
tailin wu ◽  
jianchao wang ◽  
jianzhou luo ◽  
haitao lin ◽  
fei wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oral Delivery ◽  
Salvia Miltiorrhiza ◽  
Chinese Herb ◽  
Water Soluble ◽  
Control Group ◽  
Group Model ◽  
Three Dimension ◽  
Mineral Density ◽  
Water Soluble Compound

Abstract Background: Osteoporosis severely affects patients’ life quality due to increased risks of fragility fractures. Tanshinol is a primary water-soluble compound purified from the Chinese herb Salvia Miltiorrhiza, which exhibits potent antioxidant and anti-inflammatory properties. However, whether Tanshinol functions in preventing and protecting osteoporosis remains unknown. Thus, current study proposed to systematically investigate the protective effects and the underlying mechanisms of Tanshinol in bone marrow mesenchymal stem cells (BM-MSCs) and ovariectomized (OVX) mice model. Materials and methods: Different concentrations of Tanshinol were given to induce differentiation of BM-MSCs respectively, and detected the expression of key markers of osteoclast and osteogenesis. The C57BL/6 mice were divided into control group, model group, low (80 mg/kg×day, i.g), medium (160 mg/kg×day, i.g) and high (240 mg/kg×day, i.g) concentrations Tanshinol groups. After 6 weeks treatment of Tanshinol, mice distal femurs were taken to measure bone mineral density (BMD) and three dimension parameters.Results: In the present study, we for the first time showed that Tanshinol could promote osteogenesis in the mouse BM-MSCs, as seen from the increase of the osteogenic markers such as ALP activity and collagen I. Meanwhile, Tanshinol inhibited the RANKL induced osteoclastogenesis in the bone marrow monocytes (BMMs). Animal studies showed that oral delivery of Tanshinol could attenuate in ovariectomy induced osteoporosis. Molecularly, Tanshinol activated Wnt signal pathway in MSCs while inhibited Akt in BMMs, suggesting these pathways might be involved in the osteoporosis protective role of Tanshinol. Conclusions: our study has revealed a potential application of Salvia miltiorrhiza derivative Tanshinol in the treatment of osteoporosis.

Tanshinol Alleviates Osteoporosis and Myopathy in Glucocorticoid-Treated Rats

Planta Medica ◽  
2017 ◽  
Vol 83 (16) ◽  
pp. 1264-1273 ◽  
Author(s):  
Guanghua Chen ◽  
Xinle Zhang ◽  
Han Lin ◽  
Guizhi Huang ◽  
Yahui Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Salvia Miltiorrhiza ◽  
Healing Process ◽  
Water Soluble ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Model Group ◽  
Mineral Density

AbstractTanshinol is a major water-soluble active component of Salvia miltiorrhiza. In this study, we aimed to investigate whether tanshinol has potential therapeutic effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five groups: a control group, a model group, and three model groups treated with 25 or 50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone acetate for 90 days to induce glucocorticoid-induced osteoporosis. Afterwards, all animals underwent a surgical procedure to induce bone defects at the right proximal tibia. Prednisone treatment was stopped after surgery, but tanshinol or calcitriol treatment was continued to the endpoint. At the experimental endpoint, compared to the model group, 25 mg/kg tanshinol could significantly reverse glucocorticoid-induced loss of bone mineral density by 12.5 %, while enhancing mechanical bone strength, causing a significant 11 % increase in trabecular number, and reducing trabecular separation by 28 %. In addition, tanshinol improved the bone microarchitecture and prevented glucocorticoid-induced bone loss by promoting bone formation and inhibiting bone resorption. Moreover, results of bone defect repair and muscle weight measurements revealed that tanshinol accelerated the bone fracture healing process and attenuated muscle atrophy caused by glucocorticoid. Furthermore, qRT-PCR analysis showed a 1-fold upregulation in mRNA levels of transforming growth factor beta and roughly 6-fold increases in vascular endothelial growth factor mRNA expression in calluses from the tanshinol groups. Tanshinol also preserved muscular ubiquitin mRNA levels from glucocorticoid-induced elevation. These findings demonstrate the potential benefits of tanshinol against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy, which warrants further investigation in future studies.

Progranulin Promotes Osteogenic Differentiation and Osteosynthesis of Bone Marrow Mesenchymal Stem Cells and Alleviates Osteoporosis Through Phosphatidylinositol 3-Kinase/Protein Kinase B/Peroxisome Proliferator-Activated Receptor γ Pathway

2020 ◽  
Vol 10 (12) ◽  
pp. 1865-1870
Author(s):  
Yang Ying ◽  
Binghao Zhao ◽  
Wei Qian ◽  
Li Xu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Mrna Level ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Mineral Density ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential with multi-directional differentiation. Progranulin prevents bone degradation, inhibits inflammation and protects bone tissue. However, the role of Progranulin in osteoporotic BMSCs is unclear. Osteoporosis (OP) rat models were prepared by ovarian removal and treated with different doses (5 and 10 μM) of Progranulin followed by analysis of BMP-2 level by ELISA, bone mineral density and ALP activity. OP rat BMSCs were isolated and assigned into control group and Progranulin group followed by analysis of Progranulin level by ELISA, cell proliferation by MTT assay, RUNX2 and COL1A1 mRNA level by Real time PCR, and PI3K/Akt/PPARγ signaling protein level by Western blot. Progranulin treatment of OP rats dose-dependently increased BMP-2 expression, bone density and ALP activity. Compared with OP group, there were significant differences (P <0.05). Progranulin expression and BMSCs proliferation was increased, and RUNX2 and COL1A1 mRNA expression was elevated in Progranulin-treated OP group along with increased PI3K/Akt expression and decreased PPARγ protein expression. Compared with OP group, the difference was statistically significant, and the change was more significant with increasing concentration (P <0.05). Progranulin promotes BMSCs osteogenic differentiation and proliferation by regulating PI3K/Akt/PPARγ signaling pathway, which is beneficial for OP rats’ bone synthesis.

scholarly journals Development of Indirect Competitive ELISA for Lithospermic Acid B of Salvia miltiorrhiza with Its Specific Antibodies Generated via Artificial Oil Bodies

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1952 ◽  
Author(s):  
Yu-En Shih ◽  
Chao-Hsiang Chen ◽  
Nan-Hei Lin ◽  
Jason T.C. Tzen
Keyword(s):  
Metal Ion ◽  
Salvia Miltiorrhiza ◽  
Chinese Herb ◽  
Competitive Elisa ◽  
Water Soluble ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Effects ◽  
Oil Bodies ◽  
Body Protein ◽  
Indirect Competitive Elisa

Lithospermic acid B (LSB), the major water-soluble ingredient of Salvia miltiorrhiza (Danshen), has been shown to be an active ingredient responsible for the therapeutic effects of this traditional Chinese herb used to treat cardiac disorders. This study aimed to develop an indirect competitive enzyme linked immunosorbent assay (ELISA) for the detection of LSB. Firstly, LSB was chemically conjugated to a modified oil-body protein, lysine-enriched caleosin, recombinantly expressed in Escherichia coli. Antibodies against LSB (Ab-LSB) were successfully generated by immunizing hens with artificial oil bodies constituted with the LSB-conjugated caleosin. Western blotting showed that Ab-LSB specifically recognized LSB, but not the carrier protein, lysine-enriched caleosin. To detect LSB via indirect competitive ELISA, LSB was conjugated with bovine serum albumin (LSB-BSA) and coated on a microplate. The binding between Ab-LSB and LSB-BSA on the microplate was competed dose-dependently in the presence of free LSB with a concentration ranging from 5 to 5 × 104 ng/mL. The IC50 value was approximately determined to be 120 ng/mL for LSB regardless of its complex with a metal ion of Na+, K+ or Mg2+.

Microencapsulation of Coenzyme Q10 and bile acids using ionic gelation vibrational jet flow technology for oral delivery

2020 ◽  
Vol 11 (12) ◽  
pp. 791-805
Author(s):  
Melissa Jones ◽  
Daniel Walker ◽  
Corina Mihaela Ionescu ◽  
Bozica Kovacevic ◽  
Susbin Raj Wagle ◽  
...  
Keyword(s):  
Bile Acids ◽  
Coenzyme Q10 ◽  
Oral Delivery ◽  
Jet Flow ◽  
Water Soluble ◽  
Ionic Gelation ◽  
Drug Bioavailability ◽  
Water Soluble Compound ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

Developing new delivery dosage forms with robust delivery and safety profiles remains a challenge to the pharmaceutical industry in terms of optimum gut absorption, consistent dosing and bioavailability; particularly for orally administered drugs that are poorly water soluble. Coenzyme Q10 is an example of a poorly water-soluble compound with low bioavailability, and significant inter-individual variation after oral administration; limiting its optimum efficacy, as a powerful antioxidant with significant promise in treating hearing disorders. Microencapsulation technology is one way to optimize drug bioavailability and absorption profile. One example is Ionic Gelation Vibrational Jet Flow techniques, using new encapsulating parameters to determine the nature of formed capsules. Bile acids are an example of an excipient that can be used to improve membrane permeability; and will be examined. This review addresses the applications of microencapsulation technology on oral delivery and efficacy profiles of poorly water-soluble drugs, focusing on Coenzyme Q10.

Effect of Bone Marrow Stromal Stem Cells (BMSCs) Therapy on the Expression of Sodium Channel, Voltage-Gated, Type I, Alpha Subunit (SCN1A) in Temporal Lobe Epilepsy and Its Mechanism

2021 ◽  
Vol 11 (8) ◽  
pp. 1565-1570
Author(s):  
Gaolin Wang ◽  
Bo Sun ◽  
Xiangpeng Meng ◽  
Bin Ge
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Incubation Period ◽  
Control Group ◽  
Excitatory Postsynaptic Potential ◽  
Type I ◽  
Group Model ◽  
Model Group ◽  
Postsynaptic Potential ◽  
Stromal Stem Cells

SCN1A gene plays an indispensable role in several diseases. Bone marrow stromal stem cells (BMSCs) therapy is a potential target for treating epilepsy, but its therapeutic effect and mechanism is unclear. Our study aims to investigate the mechanism by how BMSCs affect epilepsy. Wistar rats were assigned into control group, model group (pilocarpine-induced TLE model), and BMSCs group followed by measuring the latency of field excitatory postsynaptic potential, pathological changes, SCN1A level by Real time PCR, NF-ĸB and TLR4 expression by Western blot, and HGMB1, TLR4, IL-1β and IL-6 secretion by ELISA. In model group, the incubation period of postsynaptic potential generation was significantly shortened and SCN1A level was significantly decreased, along with increased NF-ĸB expression and secretion of HMGB1, TLR-4, IL-1β and IL-6 (P < 0.05). After BMSCs treatment, the incubation period of postsynaptic potentials can be significantly prolonged and SCN1A was significantly upregulated, with ameliorated epilepsy injury and reduced secretion of related factors (P <0.05). Pilocarpine-induced TLE can reduce SCN1A expression and BMSCs therapy can up-regulate SCN1A expression by regulating NF-ĸB/HGMB1/TLR4 signaling pathway, thereby protecting neurons, reducing pathological damage, and ameliorating the development of epilepsy.

scholarly journals The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Peng-Fei Yu ◽  
Wen-Yan Wang ◽  
Gaowa Eerdun ◽  
Tian Wang ◽  
Lei-Ming Zhang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Brain Barrier ◽  
Saline Control ◽  
Control Group ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Danshensu (3-(3, 4-dihydroxyphenyl) lactic acid), a water-soluble active component isolated from the root ofSalvia miltiorrhizaBunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1(verapamil group) or the same volume of normal saline (control group). Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1) by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

LncRNA Urothelial Carcinoma-Associated 1 (UCA1) Regulates Rat Bone Marrow Mesenchymal Stem Cell Differentiation and Promotes Repair of Bone Defects

2019 ◽  
Vol 9 (10) ◽  
pp. 1441-1447
Author(s):  
Yucheng Li ◽  
Jiang Xin ◽  
Wencai Sun
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Bone Defect ◽  
Bone Mineral ◽  
Type Ii Collagen ◽  
Bone Defects ◽  
Control Group ◽  
Type Ii ◽  
Mineral Density ◽  
Alp Activity

Bone marrow mesenchymal stem cells (BMSCs) have characteristics of self-renewal and multidirectional differentiation. LncRNA UCA1 regulates BMSCs differentiation. Whether LncRNA UCA1 plays a role in bone defects remains unclear. BMSCs were randomly divided into control group, radiation group (6Gy), radiation + UCA1 group followed by analysis of the expression of LncRNA UCA1, RUNX2 and OPN by real time PCR, BMSCs proliferation by MTT assay as well as ALP activity. Healthy Sprague-Dawley rats were randomly divided into control group; bone defect group; UCA1 group, in which UCA1-transfected BMSCs were infused into bone defect rats followed by analysis of bone mineral density, ALP activity as well as the formation of type II collagen by ELISA. LncRNA UCA1 expression was significantly decreased in BMSCs of irradiated group, with decreased BMSCs proliferation, reduced expression of RUNX2 and OPN as well as decreased ALP activity (P < 0.05). Transfection of UCA1 significantly up-regulated LncRNA UCA1 expression in BMSCs, promoted BMSCs proliferation, increased the expression of RUNX2 and OPN, and the activity of ALP (P < 0.05). In addition, UCA1 promoted bone mineral density, increased ALP activity and type II collagen formation in rats with bone defect. LncRNA UCA1 promotes osteogenic differentiation of BMSCs, and targeting it might be a novel approach to promote bone remodeling at the bone defect site.

scholarly journals Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2398 ◽  
Author(s):  
Hongxing Zheng ◽  
Shanshan Qi ◽  
Chen Chen
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Bone Turnover ◽  
Diabetic Rats ◽  
Control Group ◽  
Diabetic Patients ◽  
Tartrate Resistant Acid Phosphatase ◽  
Sham Operation ◽  
Type I ◽  
Mineral Density

Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio.

scholarly journals Treatment of Urolithiasis with Medicinal Plant Salvia miltiorrhiza: A Nationwide Cohort Study

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Wen-Chi Chen ◽  
San-Yuan Wu ◽  
Po-Chi Liao ◽  
Tzu-Yang Chou ◽  
Huey-Yi Chen ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Medicinal Plant ◽  
Salvia Miltiorrhiza ◽  
Chinese Herb ◽  
Bleeding Risk ◽  
Percutaneous Nephrostomy ◽  
Initial Diagnosis ◽  
Control Group ◽  
Extracorporeal Shock Wave ◽  
Stone Treatment

Salvia miltiorrhiza Bunge (Danshen), a common medicinal plant in traditional Chinese medicine, has been tested effectively to prevent urolithiasis in animals; nevertheless, the clinical application for urolithiasis remains unclear. We thus investigated the clinical effect of Danshen by analyzing the database from the Taiwan National Institute of Health. The cohort “Danshen-users” was prescribed Chinese herb medicine Danshen after the initial diagnosis of calculus. The control group (non-Danshen-users) was not given Danshen after the initial diagnosis of calculus. The date of first using Danshen after new diagnosis date of calculus was considered as index date. The outcome variables were categorized into two categories: the first category included calculus surgical treatment, including extracorporeal shock wave lithotripsy, ureteroscopy, percutaneous nephrostomy with fragmentation, and ureterolithotomy; the second category included any bleeding disorders, including gastrointestinal bleeding, intracranial hemorrhage, and blood transfusions. The incidence of calculus surgical treatment in the Danshen-users was less than that in the non-Danshen-users: 1.071% in 1,000 person-years (200 people followed up for 5 years) and 3.142% in 1,000 person-years, respectively. The adjusted hazard ratio for calculus surgical treatment in the Danshen-users was 0.34 (95% confidence intervals: 0.31–0.38) as compared to the non-Danshen-users. When stratified by sex, the incidence of calculus surgical treatment in Danshen-users was 0.685% in 1,000 person-years and 1.575% in 1,000 person-years for women and men, respectively, which was lower than that in non-Danshen-users. Danshen decreased the ratio of subsequent stone treatment after the first treatment in the study population; there was no increased bleeding risk due to long-term Danshen use.

Utilization of Tofu Dregs Flour in Making Snack Bars for People with Diabetes Mellitus

2020 ◽  
Vol 7 (1) ◽  
pp. 27
Author(s):  
Ni Putu Diah Cahyani Subamia ◽  
Komang Ayu Nocianitri ◽  
I Dewa Gede Mayun Permana
Keyword(s):  
Diabetes Mellitus ◽  
Blood Sugar ◽  
Wheat Flour ◽  
Sugar Content ◽  
Type Ii Diabetes Mellitus ◽  
Positive Control ◽  
Water Soluble ◽  
Control Group ◽  
Unhealthy Lifestyle ◽  
Control Group Design

Type II diabetes mellitus due to an unhealthy lifestyle, one of which is the lack of fiber in daily food consumption. One food that has a high fiber content is tofu dregs. The purpose of this study was to determine substitution of wheat flour with tofu dregs flour to produce a snack bar with the best characteristics, and determine the effect of consumption of snack bar from tofu dregs on blood sugar content in rats. The research was conducted two steps. Step I: Formulation of snack bar using a completely randomized design with tofu dregs flour concentration of 0 %, 10 %, 20 %, 30 %, 40 %, and 50 %. The variables of this study were the content of water, ash, protein, fat, carbohydrates, sensory tests, and effectiveness tests. Step II: the best characteristic snack bar in the step I was used experimental rats. This step used true experimental design with pre-post test control group design. The variables of study were blood glucose levels before treatment and after treatment. The treatment group consisted of normal, negative, positive control, and snack bar. The results of the first step of the research showed that substitution of wheat flour with 40 % tofu dregs produced the best characteristic snack bar with 17.19 % water content, 1.33 % ash content, 11.03 % protein, 20.53 % fat, 49.92 % carbohydrate, light brown color, unpleasant aroma, distinctive soy taste, crumb texture, 0.63 % water soluble food fiber, 1.57 % water insoluble fiber, and total food fiber 2.36 %. The results of the second step of the study showed that the provision of substitution of wheat flour with tofu dregs flour 40 % could reduce blood sugar levels in diabetic mellitus rats until normal, start 290 mg/dl to 108.5 mg/dl. Tofu dregs flour can be used for snack bar formulations for people with diabetes mellitus.

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