Liraglutide and Naringenin relieve depressive symptoms in mice by enhancing Neurogenesis and reducing inflammation.

Depression is a debilitating mental disease that negatively impacts individuals' lives and society. Novel hypotheses have been recently proposed to improve our understanding of depression pathogenesis. Impaired neuroplasticity and upregulated neuro-inflammation add-on to the disturbance in monoamine neurotransmitters and therefore require novel anti-depressants to target them simultaneously. Recent reports demonstrate the antidepressant effect of the anti-diabetic drug liraglutide. Similarly, the natural flavonoid naringenin has shown both anti-diabetic and anti-depressant effects. However, the neuro-pharmacological mechanisms underlying their actions remain understudied. The study aims to evaluate the antidepressant effects and neuroprotective mechanisms of liraglutide, naringenin or a combination of both. Depression was induced in mice by administering dexamethasone (32 mcg/kg) for seven consecutive days. Liraglutide (200 mcg/kg), naringenin (50 mg/kg) and a combination of both were administered either simultaneously or after induction of depression for twenty-eight days. Behavioral and molecular assays were used to assess the progression of depressive symptoms and biomarkers. Liraglutide and naringenin alone or in combination alleviated the depressive behavior in mice, manifested by decrease in anxiety, anhedonia, and despair. Mechanistically, liraglutide and naringenin improved neurogenesis, decreased neuroinflammation and comparably restored the monoamines levels to that of the reference drug escitalopram. The drugs protected mice from developing depression when given simultaneously with dexamethasone. Collectively, the results highlight the usability of liraglutide and naringenin in the treatment of depression in mice and emphasize the different pathways that contribute to the pathogenesis of depression.

Cardioprotective effect of 6-shogaol against hyperglycemia-induced toxicity in H9c2 cardiomyocytes via suppressing of NF-κB pathway.

Diabetic cardiomyopathy (DC) is a serious complication of diabetes. Apoptosis, inflammatory and ROS production are among the factors that are involved in the progression of diabetic cardiomyopathy. 6-shogaol is reported to inhibit apoptosis and reduce inflammatory and ROS production. This study aimed to study the effect of 6-shogaol (6S) on the progression of diabetic cardiomyopathy in vitro. To develop DC model, H9c2 cell line was exposed to high glucose (HG) level (33 M glucose) for 24 h and used as a model for diabetic cardiomyopathy. Another set of H9c2 cell lines were 1 h pretreated with different conc. of 6-shogaol (5-20 µM). Cell viability, apoptosis, ROS production, IL-6, TNF-alpha and NF-κB were estimated in these cell lines treated with HG level or pretreated with 6-shgoal before HG. Exposing cardiomyocytes H9c2 cells to HG produced dramatic changes in cell biology and chemistry. There is a significant reduction in cell viability and enhancement in cell apoptosis as compared with control. In addition, ROS production, IL-6, TNF-α levels were increased in H9c2 line treated with HG. Also, there is overexpression of NF-κB in cells treated with HG levels alone. On the other hand, pretreatment of cardiomyocytes H9c2 cells with 6-shogaol (5-20µM) significantly improved cell viability and reduced apoptosis, in addition, 6S at a dose of 10 µM abrogated the deleterious effects of HG on oxidative stress and inflammatory parameters via modulation of NF-κB pathway. Therefore, 6S has a potential protective effect against hyperglycemia-induced DC in vitro.

Induction of heme oxygenase-1 attenuates chemotherapy-induced pulmonary toxicity in rats: A possible link between heme oxygenase-1 and NF-κB.

A critical restriction in the use of bleomycin (BLM) is development of pulmonary fibrosis via oxidative and inflammatory mechanisms. Drugs that induce heme oxygenase-1 (HO-1) like hemin (HEM), have anti-inflammatory, antioxidant, and immunomodulatory effects. Accordingly, it is worth to test HEM against BLM-induced lung Injury. Four groups of rats were used: control group; HEM group (50 mg/kg, i.p.); BLM group (5 mg/kg, intratracheal single injection) and HEM+BLM group (HEM administered 1 day before BLM injection and continued for 14 days). At the end of experiment, lactate dehydrogenase (LDH) and NO levels were estimated in bronchoalveolar lavage fluid (BALF). Hydroxyproline (HP), myeloperoxidase (MPO), IL-6, GSH, MDA levels and SOD activity were determined in lung tissues. In addition, expression of HO-1 and NF-κB protein in lung tissues was determined using both western blot and immunohistochemical techniques. Also lung tissues were investigated histopathologically. BLM produced lung damage as indicated from the elevation in LDH and NO, perturbation in lung oxidative stress indicators, increased HP, MPO, IL-6 contents and NF-κB expression. On the other side, HEM, reduced BLM harmful effects as noticed from amelioration of biochemical markers and histopathological lesions, which is concomitant with over-expression of HO-1. Therefore, induction of HO-1 in lung by HEM may alleviate the lung damaging effects of BLM.

Protective effect of quercetin against gentamicin-induced nephrotoxicity in rats.

Gentamicin (GM) is an antibiotic widely used in treating severe gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Several lines of evidence indicate that free radicals are important mediators of gentamicin nephrotoxicity. Therefore, the aim of this work was to investigate the possible protective effect of the flavonoid quercetin, an antioxidant, on gentamicin-induced nephrotoxicity. For this purpose, rats were divided into four groups. First group served as a control and injected with the normal saline, second group was injected with quercetin (50 mg/kg/d, per os) for 7 d, third group was injected with gentamicin (80 mg/kg/d, intraperitoneally) for 7 d and the fourth group of animals was injected with quercetin plus gentamicin simultaneously for 7 d. Total protein levels were estimated in 24-h urine samples to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, glutathione (GSH), lipid peroxide (TBARS) levels, superoxide dismutase (SOD) and catalase (CAT) activities were determined in renal tissues. GM-treated rats showed early kidney dysfunction as urinary total protein, BUN and serum creatinine levels were significantly increased. The significant decrease in GSH levels, SOD, CAT activities and increase in TBARS levels, indicated that GM-induced nephrotoxicity was mediated through oxidative stress reactions. Histopathological examination of GM-treated rats revealed degenerative changes in glomeruli and tubules. On the other hand, simultaneous administration of quercetin plus gentamicin protected kidney tissues against nephrotoxic effects of gentamicin as evidenced from amelioration of histopathological changes and normalization of kidney biochemical parameters.