scholarly journals Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice

2019 ◽  
Vol 20 (6) ◽  
pp. 1298 ◽  
Author(s):  
Ju Ham ◽  
Ra-Yeong Choi ◽  
Hae-In Lee ◽  
Mi-Kyung Lee

This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen (0.02%, w/w) was applied to diabetic mice that were provided with a high-fat diet and streptozotocin. Bone mineral density (BMD) and microarchitecture quality were significantly reduced in the diabetic control group; however, both bergapten and methoxsalen reversed serum osteocalcin, bone-alkaline phosphatase and femur BMD. These coumarin derivatives significantly increased bone volume density and trabecular number, whereas they decreased the structure model index of femur tissue in diabetic mice. Conversely, tartrate-resistant acid phosphatase 5 (TRAP) staining revealed that these derivatives reduced osteoclast numbers and formation in diabetic bone tissue. Additionally, both bergapten and methoxsalen tended to downregulate the expression of osteoclast-related genes such as receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear of activated T-cells, cytoplasmic 1 (NFATc1) and TRAP in diabetic femurs, with NFATc1 and TRAP expression showing significant reductions. Our data suggest that both bergapten and methoxsalen prevent diabetic osteoporosis by suppressing bone resorption.

2021 ◽  
Author(s):  
I.S. Al-Amri ◽  
F. Mabood ◽  
I.T. Kadim ◽  
A.Y. Alkindi ◽  
A. Al-Harrasi ◽  
...  

ABSTRACTThis study was designed to develop a rapid, sensitive, accurate, and inexpensive Fourier Transform Infrared Reflectance (FT-IR) Spectroscopy coupled with Principle Component Analysis (PCA) as a detection technique to evaluate the solubility of 11-Keto-β-Boswellic acid (KBA), from the gum resin extracted from the Omani frankincense, (Boswellia sacra) in the liver of STZ induced diabetic mice. This study also investigated the effect of KBA on the histological changes of hepatocytes of diabetic mice. Liver tissue samples from three groups of mice included normal control group, diabetic control group and diabetic group treated IP with KBA were scanned with FT-IR spectrophotometer in the reflection mode. FT-IR Spectra were collected in the wavenumber range from 400 to 4000cm-1 using ATR accessorry. The results of FT-IR Spectra were analyzed by using multivariate method Principle Component Analysis. The PCA score plot is an exploratory multivariate method indicated that there was a complete segregation among the three groups of liver samples based on change in variation of position of wavenumber in FT-IR spectra, which revealed that there is a clear effect of KBA solubility on treatments. The histological features showed an improvement in the liver tissues with normal structures of hepatocytes with exhibiting mild vacuolations in their cytoplasm. In conclusion, reflectance FT-IR spectroscopy coupled with PCA could be deployed as a new detection method for rapid, low cost and non-destructive method for evaluating of treatment effects in diseased liver tissue based on the solubility of KBA. Histological findings demonstrated the protective effective of KBA on improving the morphology of liver tissue in diabetic mice which resulted in complete recovery to the damage observed in diabetic control group.Summary StatementReflectance FT-IR spectroscopy coupled with PCA has been deployed as a new rapid, inexpensive and non-destructive detection method to examine the solubility of 11-keto-β-Boswellic acid (KBA) in streptozotocin (STZ) induced-diabetes mice liver tissue following intraperitoneal treatment. Moreover, microscopic study of liver tissue histopathology revealed that KBA has a protecting effect against STZ damage.


2021 ◽  
Vol 28 (4) ◽  
pp. 307-316
Author(s):  
Majed G. Alrowaili ◽  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Mohamed S. Serria ◽  
Hussein Abdellatif ◽  
...  

Background: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model.Methods: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC).Results: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05).Conclusions: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 11-11
Author(s):  
Jie Huang ◽  
Lei Zhang ◽  
Zhongxin Zhou

Abstract Icariin, a flavonol glycoside, is one of major active ingredients of the traditional Chinese medicine Herba epimedii. Icariin has been reported to successfully treat the osteoporosis of the rat. However, effects of icariin on the osteoporosis in caged laying hens are still unkown. This study present the effects of dietary icariin supplementation on the laying performance, the egg quality and the bone metabolism in caged laying hens. A total of 216 Lohmann pink-shell laying hens of 54-week-old from a commercial farm in the Hubei province of China were randomly assigned to 3 treatment groups with 6 replications per group and 12 birds per replication. The control group was fed a corn-soybean meal basal diet, and the experimental groups were fed basal diets supplemented with 500 and 2000 mg/kg icariin for 90 d. Layer performance responses, egg quality parameters, the bone mineral density and serum biochemical indicators were measured at the end of the experiment. Results showed that feed/egg ratio decreased as the supplied icariin level increased. The laying rate and the average egg weight were increased compared to the control group. However, no significant effect was observed on the egg quality. The bone mineral density of the tibia was measured by the dual-energy X-ray absorptiometry, indicating that icariin can increase the bone mineral density. Serum biochemical analysis showed that icariin decreased the level of alkaline phosphatase, tartrate-resistant acid phosphatase, osteocalcin and calcitonin. Our observations provided evidences that dietary supplementation of icariin increased the bone mineral density and improved the laying performance, and icariin can be used for the prevention of the osteoporosis in caged laying hens.


2020 ◽  
Vol 21 (5) ◽  
pp. 1870
Author(s):  
Do Yeon Kim ◽  
Sang Ryong Kim ◽  
Un Ju Jung

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic β-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes—fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.


Open Medicine ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. 425-434 ◽  
Author(s):  
Xiao Chen ◽  
Guoying Zhu ◽  
Taiyi Jin ◽  
Shuzhu Gu ◽  
Mingguang Tan ◽  
...  

AbstractFourteen Sprague-Dawley male rats were randomly divided into 2 groups which were given CdCl2 at the doses of 0 and 1.5 mg /kg for 12 weeks. Before sacrifice, microCT scanning were performed on the proximal tibia and urine were collected for cadmium and N-acetyl-beta-D-glucosaminidase assay, then all of rats were sacrificed and blood was collected for biomarkers measurement; bone tissues were collected for bone mass, histology and biomechanical analysis. The cadmium in blood, urine, bone and kidney of rats treated with cadmium was significantly higher than those in the control group. The bone mineral density, and bone mineral ability of rats treated with cadmium were obviously decreased by 20%–50% compared to controls. Bone microstructure index and trabecular separation of rats treated with cadmium were obviously lower (−50%) and significantly higher (+150%) than that in the control group. Bone biomechanical property decreased by 30%–60% in cadmium treated rats compared to control. Tartrate-resistant acid phosphatase 5b and alkaline phosphatase levels of rats treated with cadmium were significantly higher than those in control, but serum osteocalcin level decreased greatly by cadmium. Obvious proximal tubule damage occurred after cadmium exposure. These observations gave clear and comprehensive evidence that cadmium exposure could induce itai-itai-like syndrome in male rats.


2021 ◽  
pp. 1797-1803
Author(s):  
Issa Al Amri ◽  
Fazal Mabood ◽  
Isam T. Kadim ◽  
Abdulaziz Alkindi ◽  
A. Al-Harrasi ◽  
...  

Background and Aim: The literature is scant on the effect of 11-keto-β-boswellic acid (KBA) on the liver of diabetes-induced mice. This study was designed to develop a rapid, sensitive, accurate, and inexpensive detection technique for evaluating the solubility of KBA obtained from the gum resin of Omani frankincense (Boswellia sacra) in the liver of streptozotocin-induced diabetic mice using Fourier transform infrared (FTIR) reflectance spectroscopy coupled with principal components analysis (PCA). It also aimed to investigate the effect of KBA on histological changes in the hepatocytes of diabetic mice. Materials and Methods: Eighteen mice were assigned to the healthy control group, the diabetic control group, or the KBA-treated diabetic group. Liver tissue samples from all groups were scanned using an FTIR reflectance spectrophotometer in reflection mode. FTIR reflectance spectra were collected in the wavenumber range of 400-4000 cm-1 using an attenuated total reflectance apparatus. Results: FTIR reflectance spectra were analyzed using PCA. The PCA score plot, which is an exploratory multivariate data set, revealed complete segregation among the three groups' liver samples based on changes in the variation of wavenumber position in the FTIR reflectance spectra, which indicated a clear effect of KBA solubility on treatments. Histological analysis showed an improvement in the liver tissues, with normal structures of hepatocytes exhibiting mild vacuolation in their cytoplasm. Conclusion: KBA improved the morphology of liver tissues in the diabetic mice and led to complete recovery of the damage observed in the diabetic control group. FTIR reflectance spectroscopy coupled with PCA could be deployed as a rapid, low-cost, and non-destructive detection method for evaluating treatment effects in diseased liver tissue based on the solubility of KBA.


Author(s):  
Yosuke Nakagawa ◽  
Hirotaka Komaba ◽  
Naoto Hamano ◽  
Hisae Tanaka ◽  
Takehiko Wada ◽  
...  

Abstract Context Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure, but its role in the pathogenesis of renal bone disease remains unknown. Objective To explore the association of serum sclerostin with bone metabolism in patients undergoing hemodialysis, with a particular focus on parathyroid hormone (PTH)-dependent and PTH-independent pathways. Design Cross-sectional and prospective cohort study. Setting and participants 654 patients undergoing hemodialysis at 10 facilities in Japan. Main outcome measures We employed multivariable linear regression to explore whether sclerostin levels were associated with metacarpal bone mineral density (BMD), intact PTH, bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b). We employed mediation analyses to explore whether and to what extent the association of PTH with bone turnover markers is mediated by sclerostin. We also compared sclerostin levels between patients with and without previous or incident fractures. Results The median sclerostin level in hemodialysis patients was 3–4-fold higher than that in healthy individuals. Higher sclerostin levels were associated with higher metacarpal BMD and lower levels of intact PTH, BAP, and TRACP-5b. However, the relationships of sclerostin with bone turnover markers were substantially attenuated after adjustment for PTH. Mediation analysis suggested that the effects of PTH on bone turnover markers were mainly direct rather than mediated by sclerostin. Sclerostin levels were not associated with previous or incident fractures. Conclusions These findings suggest that in patients undergoing dialysis, sclerostin has only a limited role in bone metabolism and may not mediate the effect of PTH on bone turnover.


2011 ◽  
Vol 80 (4) ◽  
pp. 391-396 ◽  
Author(s):  
Iveta Gradošová ◽  
Helena Živná ◽  
Klára Švejkovská ◽  
Vladimír Palička ◽  
Aleš Tichý ◽  
...  

Amlodipine (dihydropyridine-type calcium channel blocker) is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage) was administered to 8 rats for 8 weeks. Control group (n = 8) received aqua pro inj. (0.2 ml/100 g body weight; gavage). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I) and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP) in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p = 0.0009) and CTX-I (p = 0.003), and the content of BALP in bone homogenate (p = 0.026) compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2.


Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 201 ◽  
Author(s):  
Ngoc Hong Nguyen ◽  
Quang Thang Pham ◽  
Thi Ngoc Han Luong ◽  
Hoang Khai Le ◽  
Van Giau Vo

Adenosma bracteosum Bonati. (A. bracteosum) has been used in traditional and modern medicine in Vietnam for curing hepatitis. In this study, ethanol and aqueous extracts of A. bracteosum were evaluated for their α-glucosidase inhibitory activities and anti-hyperglycemic effects on glucose loaded hyperglycemic and streptozotocin (STZ) induced diabetic mice. The α-glucosidase inhibition of the extracts was evaluated by colorimetric assays, and the anti-diabetic activity was tested on a STZ-induced diabetic mice model. The ethanol and aqueous extracts showed a significant α-glucosidase inhibitory activity, which was more effective than acarbose at the same concentration. In the STZ-induced diabetic mice, both extracts showed a strong anti-hyperglycemic activity, with the group receiving 50 mg/kg of ethanol extract and the group receiving 50 mg/kg of aqueous extract presenting 64.42% and 57.69% reductions, respectively, in the blood glucose levels when compared with the diabetic control group, on day 21 (p > 0.05). Isoscutellarein-8-O-β-D-glucopyranoside (IG) was identified from the ethanol extract, which showed a strong inhibitory activity against α-glucosidase, with a ten times higher potency compared with the positive control acarbose. The anti-hyperglycemic effect of IG was effectively similar to the standard drug, glibenclamide, at the same dose of 10 mg/kg (p > 0.05). These results indicated that A. bracteosum has a great antidiabetic potential.


2011 ◽  
Vol 236 (11) ◽  
pp. 1298-1305 ◽  
Author(s):  
Xiao Chen ◽  
Guoying Zhu ◽  
Chunlin Shao ◽  
Taiyi Jin ◽  
Mingguang Tan ◽  
...  

This study investigated the effects of cadmium on bone microstructure and serum tartrate-resistant acid phosphatase 5b (Tracp 5b) in male rats. Sprague-Dawley male rats were divided into three groups that were given CdCl2 by subcutaneous injection at doses of 0, 0.1 and 0.5 mg/kg body weight (bw) for 12 weeks, respectively. Before killing at the 12th week, microcomputed tomography scanning was performed on the proximal tibia, and urine samples were collected from all of the rats. All rats were then killed, and their blood was collected for biomarkers assay. Bone tissues were dissected for mineral density determinations and histology. The concentration of cadmium in the blood, urine and bone of rats treated with cadmium were significantly higher than in the control group. The bone mineral density, bone mineral concentrations and bone microstructure index of rats treated with cadmium at 0.5 mg/kg bw were clearly lower than in the control rats. Histological investigation also revealed damage to the bone microstructure caused by cadmium. Tracp 5b concentrations in rats treated with cadmium were dose dependently higher than the control. The concentration of cadmium in blood, urine and bone was significantly correlated with Tracp 5b and bone microstructure parameters. Cadmium was shown to induce bone microstructure damage, especially to trabecular bone. The elevated concentrations of serum Tracp 5b suggest that bone resorption mediated via osteoclasts is an important mechanism for the toxic effects of cadmium on bone.


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