Gushukang exerts osteopreserve effects by regulating vitamin D and calcium metabolism in ovariectomized mice.

Calcium homeostasis plays vital roles in the management of bone health. Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis. This study aimed to explore the osteoprotective effects of GSK and its roles in maintaining calcium homeostasis in ovariectomized (OVX) mice. The OVX mice were orally treated with low (0.38 g/kg), middle (0.76 g/kg) and high (1.52 g/kg) dose of GSK for 8 weeks. GSK treatment dramatically increased serum calcium level and decreased urinary calcium excretion as well as enhanced calcium content in bone of OVX mice. Serum level of 25-hydroxyvitamin D was significantly increased in OVX mice with exposure to GSK. Treatment with GSK improved bone mass and micro-structure of trabecular bone at distal metaphysis of femur and proximal metaphysis of tibia in OVX mice shown by safranin O staining and micro-CT measurement. GSK treatment at all doses up-regulated mRNA expression of calcium-binding protein-28k and vitamin D receptor in kidney of OVX mice, and dose-dependently decreased mRNA expression of claudin-14 and elevated mRNA expression of claudin-16 in duodenum of OVX mice. Taken together, GSK exerted beneficial effects on trabecular bone of OVX mice by improving calcium homeostasis via regulating paracellular calcium absorption in duodenum and transcellular calcium reabsorption in kidney.

A Naringin- and Icariin-Contained Herbal Formula, Gushukang, Ameliorated Aged Osteoporosis of Aged Mice with High Calcium Intake.

Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis and showed osteoprotective effect in ovariectomized rodent animals and regulatory action on calcium transporters. This study aimed to determine if GSK could ameliorate aged osteoporosis by modulating serum level of calciotropic hormones and improving calcium balance. 18-month-old male mice were orally administered with either GSK (0.38[Formula: see text]g/kg body weight) or calcitriol (1[Formula: see text][Formula: see text]g/kg body weight) combined with high calcium diet (HCD, 1.2% Ca) for 60 days. The aged mice fed with normal calcium diet (NCD, 0.6% Ca) were a negative control. Trabecular bone and cortical bone properties as well as calcium balance were determined. Treatment with GSK significantly increased 25(OH)D and 1,25-(OH)2D levels in serum, moreover, it markedly attenuated trabecular bone micro-architectural deteriorations and elevated trabecular bone mass as well as strengthened cortical bone mechanical properties shown by the increase in maximal bending load and elastic modulus. Calcium balance, including urinary Ca excretion, fecal Ca level and net calcium retention, was remarkably improved by GSK, which up-regulated TRPV6 expression in duodenum and TRPV5 expression in kidney and down-regulated claudin-14 expression in duodenum and kidney. Additionally, 1-OHase and 24-OHase expression was significantly decreased (vs. NCD group) and increased (vs. HCD group), respectively, in kidney of GSK- and calcitriol-treated mice. Taken together, this study demonstrated the ameliorative effects of Gushukang on aged osteoporosis by effectively stimulating vitamin D production and improving calcium balance of aged mice with high dietary calcium supplement.

TRB3 gene silencing alleviates diabetic cardiomyopathy in a type 2 diabetic rat model.

OBJECTIVE: Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (DCM). We sought to determine whether TRB3 plays a major role in modulating DCM and the mechanisms involved. RESEARCH DESIGN AND METHODS: The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of type 2 DCM by serial echocardiography and metabolite tests, Western blot analysis for TRB3 expression, and histopathologic analyses of cardiomyocyte density, lipids accumulation, cardiac inflammation, and fibrosis area. We then used gene silencing to investigate the role of TRB3 in the pathophysiologic features of DCM. RESULTS: Rats with DCM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, fibrosis, and TRB3 overexpression. We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased. CONCLUSIONS: TRB3 gene silencing may exert a protective effect on DCM by improving selective insulin resistance, implicating its potential role for treatment of human DCM.