Effects of Extracts from Trifolium medium

Some plant species belonging to Trifolium L. genus are a source of isoflavones considered to exert phytoestrogenic activities. The aim of the present study was to examine the effects of standardized extract obtained from aerial parts of Trifolium medium L., in comparison with the extract of Trifolium pratense L., on the development of estrogen deficiency-induced osteoporosis in rats. Both Trifolium extracts, at doses corresponding to 10 and 20 mg/kg of isoflavone aglycones daily, or estradiol (0.2 mg/kg daily), were administered orally to ovariectomized (OVX) rats for 4 weeks. Serum bone turnover markers, bone mass, mineralization, and mechanical properties were studied. In OVX control rats, mechanical properties of the tibial metaphysis and femoral neck were strongly worsened in comparison with sham-operated control rats, and those of femoral diaphysis were unaffected. Estradiol counteracted the worsening of the tibial strength and increases in bone turnover markers. Both extracts significantly increased the strength of the femoral diaphysis and calcium and phosphorus content in the bone mineral, but only T. pratense extract increased the strength of the tibial metaphysis. In conclusion, effects of both Trifolium extracts differed from those of estradiol. It is possible that other than isoflavone extract constituents contributed to their skeletal effects

Negligible Effect of Estrogen Deficiency on Development of Skeletal Changes Induced by Type 1 Diabetes in Experimental Rat Models

Although postmenopausal osteoporosis often occurs concurrently with diabetes, little is known about interactions between estrogen deficiency and hyperglycemia in the skeletal system. In the present study, the effects of estrogen deficiency on the development of biochemical, microstructural, and mechanical changes induced by streptozotocin-induced diabetes mellitus (DM) in the rat skeletal system were investigated. The experiments were carried out on nonovariectomized (NOVX) and ovariectomized (OVX) control and diabetic mature female Wistar rats. Serum levels of bone turnover markers (CTX-I and osteocalcin) and 23 cytokines, bone mass and mineralization, histomorphometric parameters, and mechanical properties of cancellous and compact bone were determined. The results were subjected to two-way ANOVA and principal component analysis (PCA). Estrogen deficiency induced osteoporotic changes, with increased bone resorption and formation, and worsening of microstructure (femoral metaphyseal BV/TV decreased by 13.0%) and mechanical properties of cancellous bone (the maximum load in the proximal tibial metaphysis decreased by 34.2%). DM in both the NOVX and OVX rats decreased bone mass, increased bone resorption and decreased bone formation, and worsened cancellous bone microarchitecture (for example, the femoral metaphyseal BV/TV decreased by 17.3% and 18.1%, respectively, in relation to the NOVX controls) and strength (the maximum load in the proximal tibial metaphysis decreased by 35.4% and 48.1%, respectively, in relation to the NOVX controls). Only in the diabetic rats, profound increases in some cytokine levels were noted. In conclusion, the changes induced by DM in female rats were only slightly intensified by estrogen deficiency. Despite similar effects on bone microstructure and strength, the influence of DM on the skeletal system was based on more profound systemic homeostasis changes than those induced by estrogen deficiency

Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System

Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone

Natural phenolic acids may increase serum estradiol level in ovariectomized rats

Natural phenolic acids are commonly present in plants consumed in the diet. Recently we have observed that different natural phenolic acids exert differential effects on the body mass gain in ovariectomized and non-ovariectomized female rats. The aim of the present study was to investigate the effects of ferulic, caffeic, p-coumaric and chlorogenic acids on serum estradiol and total cholesterol levels in ovariectomized and non-ovariectomized rats. The experiments were carried out on 3-month old female Wistar Cmd:(WI)WU rats, divided into following groups (n=8 in each group): non-ovariectomized control rats and non-ovariectomized rats receiving ferulic, caffeic, p-coumaric or chlorogenic acids, sham-operated control rats, ovariectomized control rats and ovariectomized rats receiving the same phenolic acids. The phenolic acids were administered at a dose of 10 mg/kg p.o. daily for 4 weeks. Serum estradiol and total cholesterol levels on the next day after the last administration of the phenolic acids were examined. The phenolic acids did not affect serum estradiol or total cholesterol levels in non-ovariectomized rats. In ovariectomized rats, caffeic acid and to a lesser extent p-coumaric acid increased serum estradiol level, which effect correlated with a decreased body mass gain. All the phenolic acids decreased serum cholesterol level in ovariectomized rats. Concluding, the anti-obesity activity of some phenolic acids may be, at least partially, connected with estrogenic pathways

RANKL and osteoprotegerin, factors regulating metabolic processes in the skeletal system, in the pathogenesis of atherosclerosis

W ostatnich latach została wykazana korelacja między występowaniem osteoporozy i miażdżycy z wapnieniem naczyń. Jak się wydaje, najważniejszymi czynnikami łączącymi miażdżycę z osteoporozą są czynnik jądrowy țB i układ: ligand receptora aktywującego czynnik jądrowy țB (RANKL)/receptor aktywujący czynnik jądrowy țB (RANK)/osteoprotegeryna (OPG), jeden z podstawowych mechanizmów regulujących procesy metaboliczne w układzie kostnym. Większość danych eksperymentalnych wskazuje na niekorzystne działanie RANKL i ochronne działanie OPG w rozwoju wapnienia i destabilizacji blaszki miażdżycowej, należy jednak brać pod uwagę także możliwość niekorzystnego udziału nadmiaru OPG w patomechanizmie miażdżycy. W pracy przedstawiono rolę RANKL i OPG w patogenezie osteoporozy i miażdżycy.A correlation between occurrence of osteoporosis and atherosclerosis with vascular calcification has been found in recent years. The most significant link between atherosclerosis and osteoporosis seem to be nuclear factor țB and the receptor activator of nuclear factor țB ligand (RANKL)/receptor activator of nuclear factor țB (RANK)/osteoprotegerin (OPG) system – one of the fundamental mechanisms regulating metabolic processes in the skeletal system. Most experimental data indicate a negative effect of RANKL and protective effect of OPG in development of calcification and destabilization of atherosclerotic plaque. However, a potential unfavourable role of excessive OPG in the pathomechanism of atherosclerosis also needs to be considered. The role of RANKL and OPG in pathogenesis of osteoporosis and atherosclerosis has been presented in the study

The Effects of Sinapic Acid on the Development of Metabolic Disorders Induced by Estrogen Deficiency in Rats

Sinapic acid is a natural phenolic acid found in fruits, vegetables, and cereals, exerting numerous pharmacological effects. The aim of the study was to investigate the influence of sinapic acid on biochemical parameters related to glucose and lipid metabolism, as well as markers of antioxidant abilities and parameters of oxidative damage in the blood serum in estrogen-deficient rats. The study was performed on 3-month-old female Wistar rats, divided into 5 groups, including sham-operated control rats, ovariectomized control rats, and ovariectomized rats administered orally with estradiol (0.2 mg/kg) or sinapic acid (5 and 25 mg/kg) for 28 days. The levels of estradiol, progesterone, interleukin 18, insulin, glucose, fructosamine, lipids, and enzymatic and nonenzymatic antioxidants (superoxide dismutase, catalase, and glutathione); total antioxidant capacity; and oxidative damage parameters (thiobarbituric acid-reactive substances, protein carbonyl groups, and advanced oxidation protein products) were determined in the serum. Estradiol counteracted the carbohydrate and cholesterol metabolism disorders induced by estrogen deficiency. Sinapic acid increased the serum estradiol concentration; decreased insulin resistance and the triglyceride and total cholesterol concentrations; and favorably affected the parameters of antioxidant abilities (reduced glutathione, superoxide dismutase) and oxidative damage (advanced oxidation protein products)