Hepatoprotective Effect of Oleuropein-Rich Extract from Olive Leaves against Cadmium-Induced Toxicity in Mice.

Cadmium (Cd) is a harmful pollutant which mainly affects the liver and kidney. In this work, we investigated the hepatoprotective effects of olive leaf extract based on oleuropein against hepatic cadmium toxicity in mice. Three groups of animals were used: the first one served as the control (C); the second one received intraperitoneal injection of cadmium 2 mg/kg b.w. (CD), administered five times during two weeks; and the third group received the same doses of Cd and simultaneously 16 mg/kg b.w. of oleuropein. Results showed that Cd induced a significant increase in liver injury biomarkers coupled with enhanced lipid peroxidation (MDA) and significant depletion of antioxidants (CAT and SOD). Histological and immunohistochemical analysis confirmed these findings. In fact, we observed a severe central lobular apoptosis and inflammation around central veins. Cotreatment with oleuropein significantly reduced the oxidative damage induced by cadmium. Our findings suggest that oleuropein could be used in the prevention of Cd hepatotoxicity.

Comparative Study on Beneficial Effects of Hydroxytyrosol- and Oleuropein-Rich Olive Leaf Extracts on High-Fat Diet-Induced Lipid Metabolism Disturbance and Liver Injury in Rats.

Oleuropein and hydroxytyrosol, as major compounds of olive leaves, have been reported to exert numerous pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory activities. The purpose of this study is to evaluate and compare the protective effect of oleuropein- and hydroxytyrosol-rich extracts, derived from olive leaves, on high-fat diet-induced lipid metabolism disturbance and liver injury in rats. In this respect, four groups of male rats (8 per group) were used: control group (Control), group treated with high-fat diet (HFD), group treated with HFD and oleuropein (HFD + OLE), and group treated with HFD and hydroxytyrosol (HFD + HYD). The current research showed that the treatment with the HFD increased the body weight and adipose tissue mass in male rats. Moreover, the plasma levels of triglycerides, total cholesterol, LDL-cholesterol, AST, ALT, LDH, and TNF-α were also raised. The hepatic immunohistochemical analysis revealed a significant increase in the expression of inflammatory genes (COX-2, NF-κB, and TNF-α). Equally, it showed a rise of the apoptotic markers (a decrease in the expression of the Bcl-2 and an increase of the P53). In addition, the oral administration of oleuropein- and hydroxytyrosol-rich olive leaf extracts at 16 mg/kg similarly reduced the body weight and adipose tissue mass and improved the lipid profile. Moreover, these extracts, mainly the hydroxytyrosol-rich extract, reduced the elevated liver enzymes, enhanced the antioxidant status, and attenuated the liver inflammation and apoptosis. These findings suggest that the oleuropein- and hydroxytyrosol-rich olive leaf extracts possessed hypolipidemic and hepatoprotective effects against the HFD-induced metabolic disorders by enhancing the antioxidative defense system and blocking the expression of the proteins involved in inflammation and liver damage.

Olive phenolic compounds attenuate deltamethrin-induced liver and kidney toxicity through regulating oxidative stress, inflammation and apoptosis.

The purpose of this study was to evaluate the protective effect of ethanolic olive fruit extract (OFE) and its phenolic compound, oleuropein (OLE), against hepato-renal toxicity induced by deltamethrin (DEM), a synthetic pyrethroid, in Wistar rats. The kidney and liver tissues were collected after 30 days of treatment for subsequent investigation. Rats that were given DEM had a highly significant elevation in the serum biomarkers as well as hepatic and renal levels of lipid peroxidation (MDA). Additionally, a significant reduction in the total antioxidant capacity (ABTS+), superoxide dismutase (SOD) and catalase (CAT) activities was noted. This toxic effect was confirmed by histological studies and the expression levels of inflammatory (cox-2) and apoptotic genes (bcl-2 and p53). The findings for the OFE and OLEtreated groups highlighted the efficacy of olive fruit phenolic compounds as hepatic and renal-protectant in DEM-induced hepato-renal toxicity through improving the oxidative status as well as suppressing inflammation and apoptosis. Therefore, they may be used as protective natural compounds against DEM-induced hepato-renal toxicity.

Hypolipidimic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves.

Oleuropein-rich extracts from olive leaves and their enzymatic and acid hydrolysates, respectively rich in oleuropein aglycone and hydroxytyrosol, were prepared under optimal conditions. The antioxidant activities of these extracts were examined by a series of models in vitro. In this study the lipid-lowering and the antioxidative activities of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts in rats fed a cholesterol-rich diet were tested. Wistar rats fed a standard laboratory diet or cholesterol-rich diets for 16 weeks were used. The serum lipid levels, the thiobarbituric acid reactive substances (TBARS) level, as indicator of lipid peroxidation, and the activities of liver antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) were examined. The cholesterol-rich diet induced hyperlipidemia resulting in the elevation of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). Administration of polyphenol-rich olive leaf extracts significantly lowered the serum levels of TC, TG and LDL-C and increased the serum level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the content of TBARS in liver, heart, kidneys and aorta decreased significantly after oral administration of polyphenol-rich olive leaf extracts compared with those of rats fed a cholesterol-rich diet. In addition, these extracts increased the serum antioxidant potential and the hepatic CAT and SOD activities. These results suggested that the hypocholesterolemic effect of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts might be due to their abilities to lower serum TC, TG and LDL-C levels as well as slowing the lipid peroxidation process and enhancing antioxidant enzyme activity.

Lipid-lowering and antioxidant effects of hydroxytyrosol and its triacetylated derivative recovered from olive tree leaves in cholesterol-fed rats.

This study was designed to test the lipid-lowering and antioxidative activities of triacetylated hydroxytyrosol compared with its native compound, hydroxytyrosol, purified from olive tree leaves. Wistar rats fed a standard laboratory diet or a cholesterol-rich diet for 16 weeks were used. The serum lipid levels, the thiobarbituric acid-reactive substances (TBARS) level, as an indicator of lipid peroxidation, and the activity of superoxide dismutase (SOD) as well as that of catalase (CAT) were examined. The cholesterol-rich diet induced hypercholesterolemia that was manifested in the elevation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Administration of hydroxytyrosol and triacetylated hydroxytyrosol (3 mg/kg of body weight) decreased the serum levels of TC, TG, and LDL-C significantly and increased the serum level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the content of TBARS in liver, heart, kidney, and aorta decreased significantly when hydroxytyrosol and its triacetylated derivatives were orally administered to rats compared with those fed a cholesterol-rich diet. In addition, triacetylated hydroxytyrosol and hydroxytyrosol increased CAT and SOD activities in the liver. These results suggested that the hypolipidemic effect of triacetylated hydroxytyrosol and hydroxytyrosol might be due to their abilities to lower serum TC, TG, and LDL-C levels as well as to their antioxidant activities preventing the lipid peroxidation process.

Hypocholesterolemic effects of phenolic extracts and purified hydroxytyrosol recovered from olive mill wastewater in rats fed a cholesterol-rich diet.

In our previous studies, a phenolic-rich extract of olive mill wastewaters (OMW) was prepared under optimal conditions, using a continuous countercurrent extraction unit, and hydroxytyrosol was purified from the obtained OMW extract. The antioxidant activity of OMW extract and hydroxytyrosol was determined by a series of models in vitro. In this study, the hypocholesterolemic effects of hydroxytyrosol and OMW extract in rats fed a cholesterol-rich diet were tested. Wistar rats, fed a standard laboratory diet or a cholesterol-rich diet for 16 weeks, were used. Serum lipid levels, as well as thiobarbituric acid reactive substances (TBARS) and superoxide dismutase and catalase activities in liver were examined. Cholesterol-rich diet-induced hypercholesterolemia was manifested in the elevation of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Administration of a low-dose (2.5 mg/kg of body weight) of hydroxytyrosol and a high-dose (10 mg/kg of body weight) of OMW extract significantly lowered the serum levels of TC and LDL-C while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Furthermore, the TBARS contents in liver, heart, kidney, and aorta decreased significantly after oral administration of hydroxytyrosol and OMW extract as compared with those of rats fed a cholesterol-rich diet. In addition, OMW phenolics increased CAT and SOD activities in liver. These results suggested that the hypocholesterolemic effect of hydroxytyrosol and OMW extract might be due to their abilities to lower serum TC and LDL-C levels as well as slowing the lipid peroxidation process and enhancing antioxidant enzyme activity.

Hypocholesterolemic effects of phenolic-rich extracts of Chemlali olive cultivar in rats fed a cholesterol-rich diet.

This study was designed to test the lipid-lowering and the antioxidative activities of green and black olive phenolic extracts. Wistar rats fed a standard laboratory diet or a cholesterol-rich diet for 16 weeks were used. The serum lipid levels, the malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) as well as that of catalase (CAT) were examined. The cholesterol-rich diet induced hypercholesterolemia that was manifested in the elevation of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). Administration of aqueous methanol and ethyl acetate extracts of green olives and ethyl acetate extract of black olives significantly lowered the serum levels of TC and LDL-C, while increasing the serum level of high density lipoprotein cholesterol (HDL-C). Furthermore, the content of MDA in liver, heart and kidney decreased significantly after oral administration of green and black olive extracts compared with those of rats fed a cholesterol-rich diet. In addition, olive extracts increased CAT and SOD activities in liver. These results suggested that the hypocholesterolemic effect of green and black olive extracts might be due to their abilities to lower serum cholesterol level as well as to slow down the lipid peroxidation process and to enhance the antioxidant enzyme activity.

Toward a high yield recovery of antioxidants and purified hydroxytyrosol from olive mill wastewaters.

We investigated to develop effective procedures to recover the potentially high-added-value phenolic compounds contained in the discontinuous three-phase olive processing wastewaters (OMW). Particular emphasis was made to extract and purify hydroxytyrosol, one of the major compounds occurring in OMW. Batch optimization experiments showed that ethyl acetate is the most efficient solvent for the recovery of phenolic monomers from OMW. The latter was used with an optimal pH equal to 2. Furthermore, the percentage of each monomer, and particularly hydroxytyrosol, in the extract was maximum for a solvent ratio and a theoretical extraction stage number equal to 2 and 3, respectively. High yield (85.46%) recovery of hydroxytyrosol was achieved from OMW using a three-staged continuous counter-current liquid-liquid extraction unit. Hydroxytyrosol (1.225 g) were extracted per liter of OMW. One gram of hydroxytyrosol per liter of OMW was then purified by means of a chromatographic system which could be adapted to a large scale production process.