Bone protective effects of purified extract from Ruscus aculeatus on ovariectomy-induced osteoporosis in rats.

Ruscus aculeatus is a source of steroidal saponins that could mimic sex hormones and could help alleviate the risk of fracture in osteoporotic patients. The aim of the present study was to evaluate the in vitro effects of an extract from R. aculeatus (ERA) on the proliferation of human osteoblast-like SaOS-2 cell line and to investigate the effects of the ERA administered orally for 10 weeks at three doses (50, 100 and 200 mg/kg) on the bone structure of rats with estrogen deficiency induced by bilateral ovariectomy. Bone turnover markers, hormones, histopathological and radiological disturbances were evidenced in the ovariectomized rats. ERA recovered most of the affected parameters in a dose-dependent manner similar to diosgenin and alendronate used as positive comparators. The main active compounds of ERA (ruscogenin and neoruscogenin) were docked into the Vit. D receptor and oestrogen receptors alpha and beta, and stable complexes were found with binding scores equal to those of estradiol and diosgenin. The findings of this study provide for the first time an insight into the effects of ERA on bone structure and suggest that ERA could be developed as a potential candidate for the prevention of postmenopausal osteoporotic complications.

Hepatoprotective and antioxidant effects of alcesefoliside from Astragalus monspessulanus

Abstract The hepatoprotective potential of alcesefoliside (AF) from Astragalus monspessulanus was investigated. Iron sulphate/ascorbic acid (Fe2+/AA) lipid peroxidation was induced in rat liver microsomes and pre-incubated with AF and silybin (100, 10 and 1 µmol). Pronounced effects were observed in 100 µmol. In vivo experiments were carried out on rats, challenged orally with carbon tetrachloride (CCl4) alone and after pre-treatment and followed by curative treatment with AF (10 mg/kg). The activity of the serum and antioxidant enzymes, together with reduced glutathione (GSH) levels and malonedialdehyde (MDA) quantity were measured. Microsomal incubation with Fe2+/AA increased MDA production. The pre-incubation with AF reduced the formation of MDA, comparable to silybin. These findings were supported by the in vivo study where CCl4-induced liver damage was discerned by significant increase in serum enzymes and in MDA production as well as by GSH depletion and reduced antioxidant enzymes activity. The AF pre-treatment and consecutive curative treatment normalizes the activity of the serum and antioxidant enzymes alike, as well as the levels of GSH and MDA. Histological examination of AF-treated livers showed a decrease in the abnormal accumulation of lipids in hepatocytes as well as reduced alterative changes in their structure in a model of CCl4-induced toxicity.

Experimental liver protection of n-butanolic extract of Astragalus monspessulanus L. on carbon tetrachloride model of toxicity in rat.

OBJECTIVE: To investigate the hepatoprotective potential of n-butanolic extract of Astragalus monspessulanus L. (EAM) against in-vitro/in-vivo carbon tetrachloride (CCl4)-induced liver damage in rats. Silymarin was used as a positive control. METHODS AND RESULTS: The in-vitro experiments were carried out in primary isolated rat hepatocytes first incubated with CCl4 (86 µmol/l). Hepatic injury was discerned by a decrease in cell viability and cell glutathione (GSH) levels, an increase in lactate dehydrogenase leakage into the medium, and an elevation in malondialdehyde (MDA) quantity. Cell pre-incubation with EAM (1 µg/ml and 10 µg/ml) significantly ameliorated the CCl4-induced liver damage. In-vivo rats were challenged orally with CCl4 (10% solution in olive oil) alone and after 7 days pre-treatment with EAM (100 mg/kg body weight per day, oral gavage). CCl4 damage was judged by an increased production of MDA, depletion of cell GSH, and a decrease in cell antioxidant defense system. EAM pre-treatment normalizes the activities of the antioxidant enzymes and the levels of GSH and MDA. These data are supported by the histopathological examination. CONCLUSION: These results indicate that EAM has a similar significant protective effect, in vitro and in vivo, against CCl4 induced hepatotoxicity in rat as silymarin.This may be due to its antioxidant and membrane stabilizing properties.

Protective effects of the apigenin-O/C-diglucoside saponarin from Gypsophila trichotoma on carbone tetrachloride-induced hepatotoxicity in vitro/in vivo in rats.

This study investigated the hepatoprotective activity of saponarin, isolated from Gypsophila trichotoma Wend., using in vitro/in vivo hepatotoxicity model based on carbone tetrachloride (CCl4)-induced liver damage in male Wistar rats. The effect of saponarin was compared with those of silymarin. In vitro experiments were carried out in primary isolated rat hepatocytes. Cell incubation with CCl4 (86 µmol l⁻¹) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH and elevation in MDA quantity. Cell pre-incubation with saponarin (60-0.006 µg/ml) significantly ameliorated CCl4-induced hepatic damage in a concentration-dependent manner. These results were supported by the following in vivo study. Along with decreased MDA quantity and increased level of cell protector GSH, seven day pre-treatment of rats with saponarin (80 mg/kg bw; p.o.) also prevented CCl4 (10%, p.o.)-caused oxidative damage by increasing antioxidant enzyme activities (CAT, SOD, GST, GPx, GR). Biotransformation phase I enzymes were also assessed. Administered alone, saponarin decreased EMND and AH activities but not at the same extent as CCl4 did. However, pre-treatment with saponarin significantly increased enzyme activities in comparison to CCl4 only group. The observed biochemical changes were consistent with histopathological observations where the hepatoprotective effect of saponarin was comparative to the effects of the known hepatoprotecor silymarin. Our results suggest that saponarin, isolated from Gypsophila trichotoma Wend., showed in vitro and in vivo hepatoprotective and antioxidant activity against CCl4-induced liver damage.

Alcesefoliside protects against oxidative brain injury in rats

ABSTRACT This study investigated the possible antioxidant and neuroprotective effects of alcesefoliside, isolated from Astragalus monspessulanus L., Fabaceae, against carbon tetrachloride (CCl4)-induced brain injury in Wistar rats. Iron sulphate/ascorbic acid lipid peroxidation was induced in rat brain microsomes and pre-incubated with alcesefoliside and silybin. Male rats were treated in vivo with alcesefoliside and with silymarin alone; animals challenged with CCl4; and pre-treated with alcesefoliside or silymarin in respective doses for 7 days, challenged with CCl4, followed by curative treatment (additional 14 days). The activity of acetylcholine esterase and the antioxidant enzymes: superoxide-dismutase, catalase, glutathione-peroxidase, glutathione reductase and glutathione-S-transferase as well as the biomarkers of oxidative stress malondialdehyde and reduced glutathione were measured. The alcesefoliside pre-treatment and consecutive curative treatment normalizes the activity of the antioxidant enzymes as well as levels of malondialdehyde and reduced glutathione. The observed effects on tissue level correlate with the histopathological observations of the brain. They were comparable to the effects of silymarin, used as a positive control. The results showed that alcesefoliside has a neuroprotective effect against CCl4-induced brain toxicity in rats.

Hepatoprotective and antioxidant effects of saponarin, isolated from Gypsophila trichotoma Wend. on paracetamol-induced liver damage in rats.

The hepatoprotective potential of saponarin, isolated from Gypsophila trichotoma, was evaluated in vitro/in vivo using a hepatotoxicity model of paracetamol-induced liver injury. In freshly isolated rat hepatocytes, paracetamol (100 µ mol) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH, and elevated MDA quantity. Saponarin (60-0.006 µ g/mL) preincubation, however, significantly ameliorated paracetamol-induced hepatotoxicity in a concentration-dependent manner. The beneficial effect of saponarin was also observed in vivo. Rats were challenged with paracetamol alone (600 mg/kg, i.p.) and after 7-day pretreatment with saponarin (80 mg/kg, oral gavage). Paracetamol toxicity was evidenced by increase in MDA quantity and decrease in cell GSH levels and antioxidant defence system. No changes in phase I enzyme activities of AH and EMND and cytochrome P 450 quantity were detected. Saponarin pretreatment resulted in significant increase in cell antioxidant defence system and GSH levels and decrease in lipid peroxidation. The biochemical changes are in good correlation with the histopathological data. Protective activity of saponarin was similar to the activity of positive control silymarin. On the basis of these results, it can be concluded that saponarin exerts antioxidant and hepatoprotective activity against paracetamol liver injury in vitro/in vivo.