Comparative study of the effect of oleuropein and hydroxytyrosol rich extracts on the reproductive toxicity induced by bisphenol A in male rats: biochemical, histopathological, and molecular analyses.

Bisphenol A, or BPA, goes into the composition of a large number of products including sunglasses, infant's feeding bottles, receipts, or food packaging. Nowadays, there is a growing evidence that BPA may be at the origin of several physiological malignancies. Oleuropein and hydroxytyrosol extracted from olive leaves are highly investigated for numerous health benefits. The present work investigates the potential protective proprieties of olive leaf extracts against BPA-induced testicular damage in Wistar rats. Thirty-two animals were randomly divided into 4 groups: control, BPA-treated (10 mg/kg), BPA and oleuropein rich extract (16 mg/kg) treatment, and the last group treated with BPA and hydroxytyrosol rich extract (16 mg/kg). Biochemical parameters and histological and molecular analyses were evaluated. Our data demonstrated that BPA treatment caused significant alteration in biochemical parameters, disorganization of germinal epithelium, an up-regulation of p53 and Bax, and a reduction of Bcl-2 protein levels. The ingestion of oleuropein- and hydroxytyrosol-rich extracts attenuated BPA-induced biochemical and histological changes. In fact, olive leaf extracts enhanced the enzymatic antioxidant system and the level of Bcl-2, and reduced the expression of p53 and Bax. Fairly, our findings propose that olive leaf extracts may compete with BPA-induced reprotoxicity in vivo.

Olive Leaves Extract and Oleuropein Improve Insulin Sensitivity in 3T3-L1 Cells and in High-Fat Diet-Treated Rats via PI3K/AkT Signaling Pathway.

Olive leaves extracts are known to exert potential pharmacological activities especially, antidiabetic and antiobesity. This study explores the anti-insulin resistant effect of olive leaves extracts and oleuropein in 3 T3-L1 cells and in high-fat diet fed rats. Our results showed that ethanol extract (EE) suppressed significantly (P < 0.01) triacylglycerol accumulation. In preadipocytes cells, EE 1/100 decreased cell viability and induced apoptosis. Real-time PCR analysis showed that EE reduced the mRNA levels of adipogenesis (CEBP-α, PPARγ, SREBP-1c, and FAS) and proinflammatory (TNF-α and IL-6) genes. Moreover, the cotreatment of EE 1/1000 or oleuropein with insulin increased considerably the expression of p-IRS, p85-pI3K, and p-AKT. In vivo model, the oral administration of oleuropein at 50 mg/kg in rats fed with high fat diet for 8 weeks reduced inflammation in liver and adipose tissues (WAT), improved glucose intolerance, and decreased hyperinsulinemia. Furthermore, the immunohistochemistry revealed that the expression level of p-Akt, IRS1, and Glut-4 were significantly enhanced in liver and WAT tissues after oleuropein supplementation comparing with that in HFD group. Additionally, the expression of IRS1 was markedly ameliorated in pancreas. Our obtained results can be adopted as an approach to used olive leaves as complement to prevent insulin-resistance disease.

A jojoba (Simmondsia chinensis) seed cake extracts express hepatoprotective activity against paracetamol-induced toxicity in rats.

This study aimed to investigate the hepatoprotective activity of jojoba seed cake extracts against an acute paracetamol (PC) intoxication. Two aqueous extracts from jojoba (Simmondsia chinensis) seed cake, a simmondsin-rich extract (WE), and a simmondsin-hydrolyzed extract (NE) using Viscozyme L enzyme have been prepared and characterized. After enzyme treatment, simmondsin content decreased from 33.0 % to 3.0 % and glucose content increased from 16.2 % to 27.3 % reflecting simmondsin hydrolysis. Both extracts were administered to different rat groups via gavage (0.6 g/kg b.w.) before PC treatment (2 g/kg b.w.) three times a week for 3 weeks. The PC intoxication altered the serum biomarkers, the oxidative status, and the Tumor necrosis factor alpha (TNF-α), Bax and Bcl-2 protein expressions of tested animals. In addition, the histological analysis of liver tissues proved significant injury and hepatocellular necrosis. WE and NE extract showed a relatively high in vitro radical scavenging (ORAC) and averting activities (HORAC) with a polyphenol content of 3.6 % and 2.9 %, respectively. Both extracts showed a powerful in vivo hepatoprotective activity against PC-induced toxicity by improving the hepatocellular antioxidant status and blocking proteins expression (TNF-α, Bax and Bcl-2), involved in inflammation and liver damage. However, the enzymatic treatment improved the hepatoprotective activity of NE despite its lower simmondsin content and lower in vitro antioxidant capacity. This enhancement could be linked to the synergetic effect between the antioxidant components and the new hydrolytic products as glucose, uronic acids, arabinose and simmondsin-aglycons. These results suggest that jojoba waste could be potentially valorized in developing hepatoprotective drugs.

Wound healing potential of quercetin-3-O-rhamnoside and myricetin-3-O-rhamnoside isolated from Pistacia lentiscus distilled leaves in rats model.

The development of bioproducts able to accelerate wound healing is an important topic in biomedicine. In the current study, Pistacia lentiscus distilled leaves (PDL) extract and its two isolated glycosylated flavonoids, myricetin-3-O-rhamnoside (MM) and quercetin-3-O-rhamnoside (QM), were evaluated for their wound healing activity, including evaluation of wound closure, revascularization, wound re-epithelialization, fibroblast proliferation, and collagen deposition on rat skin samples. Moreover, hydroxyproline content, C-reactive protein (CRP) level, and immunohistochemistry study were evaluated on blood and tissues collected from rats on day 14 post-wounding. Results showed that the topical application of PDL (at a concentration of 20 mg/ml) (PDL 20), MM, and QM increased wound healing and decreased inflammatory cells infiltration compared to the negative control group. Moreover, the cutaneous wound tissues treated with PDL 20, MM, and QM exhibited significantly higher hydroxyproline content than the negative control group, which means a high collagen biosynthesis in wound tissues. Indeed, the level of the inflammatory protein CRP is significantly lower in groups treated with MM and QM than in the negative control group. Also, the expression of the pro-inflammatory factor TNF-α and the angiogenesis marker CD-31 in PDL 20, MM, and QM treated groups is lower than in the negative control group. Moreover, MM, and QM induced a good elastase inhibition at 100 µg/ml compared to the standard epigallocatechin gallate. Therefore, PDL 20, MM, and QM could be used as effective cutaneous wound healing agents.

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.

Contribution of Major Polyphenols to the Antioxidant Profile and Cytotoxic Activity of Olive Leaves.

AIMS: This study was designed to investigate the phytochemical profile and the cytotoxic activities of the eco-friendly extracts of olive leaves from Chemlali cultivar. MATERIALS AND METHODS: The Phenolic composition of olive leaves extracts, the antioxidant activity and the cytotoxic effects against MCF-7 and HepG2 cells were determined. RESULTS: Olive leaves extracts showed relevant total polyphenols contents. Oleuropein was the major detected phenolic compound reaching a concentration of 16.9 mg/ml. The antioxidant potential of the studied extracts varied from 23.7 to 46.5mM Trolox equivalents as revealed by DPPH and ABTS assays. Cytotoxicity experiments showed similar trends for both HepG2 and MCF-7 cells with the infusion extract being the most active. CONCLUSION: This study denotes that olive leaves may have great potential as endless bioresource of valuable bioactive compounds which may have a wide application.

Oleuropein and hydroxytyrosol rich extracts from olive leaves attenuate liver injury and lipid metabolism disturbance in bisphenol A-treated rats.

In the present study, we investigated the protective effects of oleuropein- and hydroxytyrosol-rich extracts obtained from olive leaves against bisphenol A (BPA)-induced hyperlipidemia and liver injury in male rats. For this purpose, four groups of male rats (8 per group) were used: control group (Control), rats treated with BPA, rats treated with both BPA and oleuropein (OLE-BPA), and rats treated with both BPA and hydroxytyrosol (HYT-BPA). After 60 days of treatment, the results obtained using the DXA technique showed that treatment with BPA (10 mg per kg b.w.) increased the body weight and adipose tissue mass in male rats. Moreover, plasma levels of triglycerides, total cholesterol, LDL-cholesterol, AST, ALT, LDH, and TNF-α increased. The immunohistochemical analysis revealed a significant increase in the expression of COX-2 and p53 and a decrease in the expression of Bcl-2 related to liver inflammation. Oral administration of oleuropein and hydroxytyrosol-rich extracts obtained from olive leaves at 16 mg kg-1 reduced both the body weight and adipose tissue mass. These extracts were able to ameliorate liver damage and improve the elevated levels of TG and liver enzymes of BPA-treated rats possibly through enhancing CAT and SOD activities. Western blot results revealed that administration of the abovementioned extracts decreased the protein expression of NF-κB and TNF-α through the p38 signaling pathway. Overall, the findings suggest that the olive leaf extracts possess hypolipidemic and hepatoprotective effects against BPA-induced metabolic disorders through enhancing the antioxidative defense system and regulating the important signaling pathway activities.

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.

Oleuropein and hydroxytyrosol protect from bisphenol A effects in livers and kidneys of lactating mother rats and their pups'.

Bisphenol A (BPA) is a chemical found in hard plastics and the coatings of food and drinks cans which can behave in a similar way to estrogen and other hormones in the human body. This study aimed to evaluate the significance of the treatment with oleuropein and hydroxytyrosol olive leaves rich extracts in reducing functional perturbations and oxidative stress arising from BPA treatment in livers and kidneys of lactating mother rats and their pups'. For this, four groups of lactating mothers were used: controls (group A), treated with bisphenol A (group B), treated with bisphenol A and oleuropein (group C) and with bisphenol A and hydroxytyrosol (group D). As results, we had found, in BPA treated group, either in mothers or in their pups', a significant decrease in morphological parameters, in catalase activity and in total antioxidant capacity associated to an increase in malondialdehyde levels in livers and kidneys. For these rats, the histological aspect showed, also, deep changes. Indeed, we had observed, in livers, hepatocellular necrosis associated to leucocytes infiltration and in kidneys tubular and glomerular necrosis. The co-treatments with BPA and oleuropein (group C) or with BPA and hydroxytyrosol (group D) ameliorate all morphological, biochemical and histological parameters as compared to BPA treated group B. The analysis of BPA and its derivatives with LC-MS/MS showed changes in their localizations between serum, livers or kidneys in all studied groups. In conclusion, the present study demonstrates the hepato-protective and reno-protective effects of oleuropein and hydroxytyrosol olive leaves extracts from BPA and its derivates toxicity.