Eugenol modulates insulin sensitivity by upregulating insulin receptor substrate-2 in non-alcoholic fatty liver disease in rats.

OBJECTIVES: The purpose of this study was to estimate the possible modulatory effect of Eugenol (EUG) on insulin resistance (IR) and liver fibrosis in high-fat diet (HFD)-induced experimental non-alcoholic fatty liver disease (NAFLD) in rats. It has been shown that EUG, a natural phenolic compound, has anti-hyperglycaemic, antioxidant and anti-inflammatory actions. METHODS: For 8 consecutive weeks, standard rat chow diet (control group, EUG only treated group) or HFD (HFD group and HFD+EUG-treated group) were fed to rats daily. HFD+EUG-treated group and EUG only treated group were administered EUG (10 mg/kg) orally three times per week. Various indices of hepatotoxicity, oxidative stress, indicators of inflammation and liver fibrosis were investigated. KEY FINDINGS: HFD-induced liver transaminases and triglycerides (TGs) were significantly decreased and histopathological lesions were improved with EUG treatment. EUG significantly improved IR evoked by HFD, as demonstrated by Homeostasis model assessment for insulin resistance (HOMA-IR) and increased insulin receptor substrate-2 (IRS-2) sensitivity. In addition, EUG improved oxidative stress damage elicited by HFD as shown by the restoration of reduced glutathione (GSH) level and nuclear factor erythroid-2-related factor 2 (Nrf-2) expression and plummeting lipid peroxidation. Further, EUG lessened pro-inflammatory cytokines surge [tumour necrosis factor-α (TNF-α) and IL-6] via inhibiting nuclear factor-κB (NF-κB) stimulation. As markers of fibrosis, EUG reduced collagen accumulation and smooth muscle alpha actin (SMaA) and TGF-ß expression. CONCLUSIONS: EUG may have protective effect against progression of fibrosis in NAFLD. The antifibrotic effect of EUG is probably due to EUG's antioxidant, anti-inflammatory and anti-hyperglycaemic.

Iron chelation by deferasirox confers protection against concanavalin A-induced liver fibrosis: A mechanistic approach.

Hepatic iron overload is one of the causative factors for chronic liver injury and fibrosis. The present study aimed to investigate the potential antifibrotic effect of the iron chelator; deferasirox (DFX) in experimentally-induced liver fibrosis in rats. Male Sprague-Dawley rats were administered concanavalin A (Con A) and/or DFX for 6 consecutive weeks. Con A injection induced significant hepatotoxicity as was evident by the elevated transaminases activity, and decreased albumin level. Also, it disturbed the iron homeostasis through increasing C/EBP homologous protein (CHOP), decreasing phosphorylated cAMP responsive element binding protein(P-CREB) and hepcidin levels leading to significant serum and hepatic iron overload. In addition, it induced an imbalance in the oxidative status of the liver via upregulating NADPH oxidase 4 (NOX4), together with a marked decrease in anti-oxidant enzymes' activities. As a consequence, upregulation of nuclear factor-kappa b (NF-κB) and the downstream inflammatory mediators was observed. Those events all together precipitated in initiation of liver fibrosis as confirmed by the elevation of alpha-smooth muscle actin (α-SMA) and liver collagen content. Co-treatment with DFX protected against experimentally-induced liver fibrosis in rats via its iron chelating, anti-oxidant, and anti-inflammatory properties. These findings imply that DFX can attenuate the progression of liver fibrosis.

Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine.

This study was designed to investigate if the impairment of learning and memory induced by acute administration of scopolamine (1.4 mg/kg ip) in rats is associated with altered brain oxidative stress status. The passive avoidance paradigm was used to assess retrieval memory of rats after scopolamine treatment. Following retrieval testing, biochemical assessments of malondialdehyde (MDA), glutathione peroxidase (GSHPx), glutathione (GSH), and superoxide dismutase (SOD) levels/activities as oxidative stress indices were performed. This study also investigated the effect of acute administration of Hypericum perforatum extract (4.0, 8.0, 12.0, and 25.0 mg/kg ip), containing flavonoids with documented antioxidant activity, on brain oxidative status of nai;ve rats treated with amnestic dose of scopolamine. Results showed that administration of 1.4 mg/kg of scopolamine impaired retrieval memory of rats and that such amnesia was associated with elevated MDA and reduced GSH brain levels. In nai;ve rats, which have not been exposed to conditioned fear, scopolamine administration also increased MDA and reduced GSH levels, although with an increase in brain GSHPx activity. Pretreatment of the animals with Hypericum extract (4, 8, and 12 mg/kg) resulted in an antioxidant effect through altering brain MDA, GSHPx, and/or GSH level/activity. Since oxidative stress is implicated in the pathophysiology of dementia, the findings of this study may substantiate the value of scopolamine-induced amnesia in rats as a valid animal model to screen for drugs with potential therapeutic benefit in dementia. Exposure of animals to conditioned fear may be suggested to impair the balance between the rate of lipid peroxidation and the activation of GSHPx as a compensatory antioxidant protective mechanism. It is also concluded that low doses of Hypericum extract, demonstrating antioxidant activity, may be of value for demented patients exhibiting elevated brain oxidative status. Since depression commonly coexists with dementia, Hypericum extract as a drug with documented antidepressant action may also be a better alternative than several other antidepressant medications that have not been evaluated to test their effect on brain oxidative status during amnesia.