Protective effects of water fraction of Fructus Ligustri Lucidi extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice

Zhang, Yan; Diao, Teng Yue; Wang, Liang; Tao, Chun; Wong, Man Sau

doi:10.1016/j.jep.2014.10.025

Cited by 24 publications

(14 citation statements)

References 31 publications

(45 reference statements)

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“…We and others demonstrate that FLL improves Bone mineral density (BMD) and bone microstructure as well as bone mechanical strength in both aged (Ko et al, 2010) and growing female rats (Feng et al, 2014) as well as ovariectomized (OVX) rats (Zhang et al, 2006; Lyu et al, 2014; Guo et al, 2016a). FLL exhibited bone protective effects by improving calcium absorption and balance via increasing gene expression of transient receptor potential vanilloid 6 and calcium-binding protein-9k, and by decreasing renal calcium-sensing receptor gene expression (Zhang Y. et al, 2014; Zhang et al, 2015) via stimulating 1.25(OH) 2 D 3 /vitamin D receptor signaling (Feng et al, 2014) through inducing the activity of renal 25-hydroxyvitamin D-1α hydroxylase (Dong et al, 2010), as well as by stimulating parathyroid hormone production in mature normal female rats (Dong et al, 2012) and in type 1 diabetic mice (Zhang Y. et al, 2014). Meanwhile, FLL was also demonstrated to promote osteogenesis by stimulating the alkaline phosphatase (ALP) activity and accelerating the mineralization in human mesenchymal stem cells (Li et al, 2010) and UMR-106 cells (Wang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

Wang

Guo

et al. 2017

Front. Pharmacol.

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Purpose: This study is designed to explore whether Fructus ligustri lucidi (FLL) exhibits antioxidant effect in ovariectomized (OVX) rats, and to identify the signaling pathway involved in this process.Methods: OVX rats were treated with FLL aqueous extract (3.5 g/kg) for 12 weeks. Serum, uteri, and tibias were harvested from the rats and the levels of total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were determined. Changes in the levels of NF-κB-p65, phosphorylation of NF-κB-p65 (NF-κB-pp65), NF-κB inhibitor alpha (IκBα), phosphorylation of IκBα (p-IκBα), and NADPH oxidase 4 (Nox4) in uteri and tibias were determined by western blot, immunofluorescent and immunohistochemical analysis, respectively. In addition, the expression of cytochrome C (Cyto-C) and B-cell lymphoma-2 (Bcl-2) were determined in the tibias of rats. Histopathological changes in the bones were evaluated by hematoxylin-eosin staining. Bone mineral density (BMD) was determined in rat femurs by dual X-ray absorptiometry.Results: Treatment of OVX rats with FLL aqueous extract improved redox homeostasis by increasing the levels of TAC and NO as well as decreasing the levels of MDA and 8-OHdG in serum, tibias, and uteri. Further, FLL extract also downregulated the expression of Nox4, NF-κB-p65, NF-κB-pp65, and p-IκBα in the uteri and tibias. Furthermore, administration of FLL–OVX rats increased Bcl-2 expression and prevented cytoplasmic release of mitochondrial Cyto-C in the tibias. In addition, FLL treatment also improved bone microstructure and increased cortical bone thickness as well as increased BMD values in the femurs of OVX rats.Conclusions: FLL treatment may suppress oxidative stress response in OVX rats via regulating the Nox4/ROS/NF-κB signaling pathway. These results suggest the potential of using FLL as a natural antioxidant agent in preventing the development of osteoporosis.

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Section: Introductionmentioning

confidence: 99%

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

Wang

Guo

et al. 2017

Front. Pharmacol.

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“…Despite the known importance of insulin signaling in osteoblasts to bone mass accrual (Fulzele et al, 2010, Thrailkill et al, 2014), insulin co-therapy is not always included in pre-clinical studies investigating the effect of bone- or glucose-targeting therapies on preventing the T1D-related decrease in bone strength (Altan et al, 2007, Glorie et al, 2014, Maycas et al, 2016, Thrailkill et al, 2016, Zhang et al, 2014). In early rat studies, daily subcutaneous injections of insulin improved the structural strength of the femur mid-shaft (Dixit and Ekstrom, 1980) and femoral neck (Hou et al, 1993) when compared to untreated alloxan-induced T1D rats.…”

Section: Introductionmentioning

confidence: 99%

Preserving and restoring bone with continuous insulin infusion therapy in a mouse model of type 1 diabetes

et al. 2017

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Those with type 1 diabetes (T1D) are more likely to suffer a fracture than age- and sex-matched individuals without diabetes, despite daily insulin therapy. In rodent studies examining the effect of bone- or glucose-targeting therapies on preventing the T1D-related decrease in bone strength, insulin co-therapy is often not included, despite the known importance of insulin signaling to bone mass accrual. Therefore, working toward a relevant pre-clinical model of diabetic bone disease, we assessed the effect of continuous subcutaneous insulin infusion (CSII) therapy at escalating doses on preserving bone and the effect of delayed CSII on rescuing the T1D-related bone deterioration in an established murine model of T1D. Osmotic minipumps were implanted in male DBA/2 J mice 2 weeks (prevention study) and 6 weeks (rescue study) after the first injection of streptozotocin (STZ) to deliver insulin at 0, 0.0625, 0.125, or 0.25 IU/day (prevention study; n = 4–5 per dose) and 0 or 0.25 IU/day (rescue study; n = 10 per group). CSII lasted 4 weeks in both studies, which also included age-matched, non-diabetic DBA/2 J mice (n = 8–12 per study). As the insulin dose increased, blood glucose decreased, body weight increased, a serum maker of bone resorption decreased, and a serum marker of bone formation increased such that each end-point characteristic was linearly correlated with dose. There were insulin dose-dependent relationships (femur diaphysis) with cross-sectional area of cortical bone and cortical thickness (micro-computed tomography) as well as structural strength (peak force endured by the mid-shaft during three-point bending). Likewise, trabecular bone volume fraction (BV/TV), thickness, and number (distal femur metaphysis) increased as the insulin dose increased. Delayed CSII improved glycated hemoglobin (HbA1c), but blood glucose levels remained relatively high (well above non-diabetic levels). Interestingly, it returned the resorption and formation markers to similar levels as those seen in non-T1D control mice. This apparent return after 4 weeks of CSII translated to a partial rescue of the structural strength of the femur mid-shaft. Delayed CSII also increased Tb.Th to levels seen in non-T1D controls but did not fully restore BV/TV. The use of exogenous insulin should be considered in pre-clinical studies investigating the effect of T1D on bone as insulin therapy maintains bone structure without necessarily lowering glucose below diabetic levels.

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“…In vivo studies demonstrated that, in contrast to the non-treated rabbits or mice, the DEX-injected subjects exhibited the typical features of GIOP as shown by the measurement of the basic biomechanical parameters, including reductions in BMD, and the increased disconnections and separation of the trabecular bone network (29,30). It has been found that these pathological changes in bone metabolism correlate with disturbances of calcium homeostasis (31). As expected, DEX significantly upregulated the urine calcium concentration and downregulated the levels of serum calcium in the mice.…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate

Zhang

Shao

Wang

et al. 2016

International Journal of Molecular Medicine

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Abstract. The present study was performed in order to examine bone loss and calcium homeostasis in mice with glucocorticoid (GC)-induced osteoporosis (GIOP) following treatment with the aqueous extract of pomegranate seed (AE-PS). In addition, a comparative study with alendronate was performed. Biomarkers in the serum and the urine were measured. The tibias, kidney and duodenum were removed in order to measure the levels of bone calcium, protein expression as well as to perform histomorphological analysis of the bone. GC treatment facilitated the induction of hypercalciuria in the mice, and the AE-PS-treated mice exhibited a greater increase in serum calcium and a decrease in urine calcium. The AE-PS reversed the deleterious effects on the trabecular bone induced by DXM and stimulated bone remodeling, including an increase in bone calcium and alkaline phosphatase-b (ALP-b) and a decrease in a the critical bone resorption markers C-terminal telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase-5b (TRAP-5b). Hematoxylin and eosin (H&E) staining revealed the increased disconnections and separation between the growth plate and the trabecular bone network as well as the reduction in the trabecular bone mass of the primary and secondary spongiosa throughout the proximal metaphysis of the tibia in the DXM group. Moreover, the decreased protein expression of transient receptor potential vanilloid (TRPV)5, TRPV6 and calbindin-D9k (CaBP-9k) was reversed by the AE-PS or alendronate supplementation in the kidneys and the duodenum as well as plasma membrane Ca 2+ -ATPase1 (PMCA1) expression in the kidneys of mice with GIOP. There was no marked difference in pharmacological effectiveness between alendronate and the AE-PS. Taken together, these findings suggest that the AE-PS may be an alternative therapy suitable for use in the management of secondary osteoporosis.

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Protective effects of water fraction of Fructus Ligustri Lucidi extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice

Cited by 24 publications

References 31 publications

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

Preserving and restoring bone with continuous insulin infusion therapy in a mouse model of type 1 diabetes

Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate

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