Doaa A. Ghareeb

Vanadium improves brain acetylcholinesterase activity on early stage alloxan-diabetic rats.

The present study is designed to screen the possible effects of sodium orthovanadate therapy on the kinetic parameters of brain membrane-bound and soluble acetylcholinesterase (AChE) forms in alloxan-induced diabetic rats. The diabetic rats were treated with 300 mg/kg sodium orthovanadate orally for 45 days. While diabetes significantly decreased the brain specific activity (V(max)) of AChE soluble form by 42%, it caused a fivefold increase of the K(m) of the membrane-bound form. Furthermore, the activity of brain glutathione-S-transferase (GST) was significantly decreased and this was associated with a remarkable increase in brain lipid peroxidative parameter, thiobarbituric acid reactive substances (TBARS), as compared to sham control. The alterations of both AChE forms observed in diabetic state could be attributed to hyperglycemia and lipid peroxidation that triggered brain dysfunction by disturbing the neurotransmitter acetylcholine level. Administration of sodium orthovanadate reversed the diabetic conditions by lowering the blood glucose level and normalized the blood Hb(A1C) level. It also normalized the levels of brain AChE, GST and TBARS as compared to diabetic state and control. Therefore, vanadate administration could protect against direct action of lipid peroxidation on brain AChE and in this way, it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes.

Ameliorated effects of garlic (Allium sativum) on biomarkers of subchronic acrylamide hepatotoxicity and brain toxicity in rats

Acrylamide (ACR) exerts its toxicity through stimulation of the oxidative stress; yet, its effect on neurotransmitter catabolic enzymes has not been elucidated. We investigated the effects of ACR exposure on brain and hepatic tissues antioxidant enzymes activities and different markers such as, acetylcholinesterase (AChE), nitric oxide (NO), monoamine oxidase (MAO), and lipid profile, and to evaluate the protective effects of garlic against ACR toxicity. Male Sprague-Dawley rats were exposed to ACR (1 mg kg−1 body weight) with or without diet containing 1.5% of garlic powder for 40 days. ACR administration showed a decrease in AChE activity associated with an increase in MAO activity in both brain and hepatic tissues. In addition, ACR administration increased the lipid peroxidation and NO levels of both tissues while decreased the activities of glutathione (GSH), superoxide dismutase, and glutathione-S-transferase (GST). On the other hand, the activities of glutathione peroxidase (GPx) and catalase activities increased as a consequence of GSH depletion after ACR exposure. Finally, ACR exposure increased the brain and liver lipid profile of cholesterol, triglycerides and total lipid, while phospholipids level was decreased. Coadministration of garlic powder with ACR significantly attenuated oxidative stress, MAO activity, and inflammation in brain and hepatic tissues but did not ameliorate AChE activity. In conclusion, our results emphasized the role of garlic as a potential adjuvant therapy to prevent ACR neurotoxicity and hepatotoxicity.

Toxic effects of lead exposure on the brain of rats: Involvement of oxidative stress, inflammation, acetylcholinesterase, and the beneficial role of flaxseed extract

The current study was carried out to investigate the effects of low level lead (Pb) exposure on brain tissue antioxidant enzymes activities and acetylcholinesterase (AChE), inflammatory markers (nitrites (NO) and TNF-α), and lipid profile. Furthermore, the possible effects of flaxseed extract to reverse PB-induced toxicity were examined. Female Sprague-Dawley rats were exposed to Pb (200 mg L−1 in drinking water) for three weeks followed by 21 days of orally administrated flaxseed extract (300 mg kg−1). AChE activity increased by 64% and a significant decrease in glutathione (GSH) levels, total antioxidants capacity, glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities after Pb exposure. Moreover, NO and α-TNF were increased by 166.5% and 400%, respectively. Finally, Pb exposure increased the brain cholesterol and triglycerides levels. Chronic treatment with flaxseed significantly attenuated cholinergic dysfunction, oxidative stress, and inflammation in the brain after a three week treatment period. Data showed the involvement of factors such as oxidative stress, inflammation, and high expression of AChE activity in Pb-induced neurotoxicity, and showed that flaxseed prevented these adverse effects.

Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling.

Role of Oxidative Stress in Male Fertility and Idiopathic Infertility: Causes and Treatment

Role of Oxidative Stress in Male Fertility and Idiopathic Infertility: Causes and Treatment Epidemiological studies regarding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammation of the genitourinary tract, which often occurs without any symptoms. The exact mechanism for unexplained male infertility and its correlation to oxidative stress incidence and/ or the inflammatory reactions within the male genital tract is still controversially unclear till know. Previous studies have shown the presence of cytokines such as tumor necrosis factor-α (TNF-α), a key player in the inflammation process, in the semen of infertile men. However, the mechanism of their effect on human sperm functions is still in need for further under investigations. We expect that, seminal inflammatory cytokine (TNF-α) and its expression regulator, testicular ADAM 17, will be varied, when seminal OS is established, that in turn, will vary cellular integrity and energy status. As conventional treatment of male infertility such as mineral and vitamins supplementation has poor success rates and leaves a lot to be desired, natural antioxidant ingredients are greatly suggested, nowadays, to ameliorate oxidative stress and the inflammatory detrimental effects accompanied to idiopathic male infertility. Thus, the empirical investigations of naturally occurring antioxidant modulators with prospective curative effect may support their administration as safe potent natural remedies against IMI. The role of antioxidants in the treatment of unexplained male infertility correlation to ROS and/or the inflammatory cytokines are discussed in this review.

Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (AβPP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40 (Aβ 40) and increased beta-amyloid42 (Aβ 42) in the hippocampal region. Daily administration of berberine (50 mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer's-like disease in rats

Heavy metals are reported as neurodegenerative disorders progenitor. They play a role in the precipitation of abnormal β-amyloid protein and hyper-phosphorylated tau, the main hallmarks of Alzheimers disease (AD). The present study aimed to validate the heavy metals-induced Alzheimers-like disease in rats as an experimental model of AD and explore the therapeutic effect of berberine via tracking its effect on the oxidative stress-inflammatory pathway. Alzheimers-like disease was induced in rats orally by a mixture of aluminium, cadmium and fluoride for three months, followed by berberine treatment for another one month. Berberine significantly improved the cognitive behaviors in Morris water maze test and offered a protective effect against heavy metals-induced memory impairment. Docking results showed that berberine inhibited AChE, COX-2 and TACE. Matching with in silico study, berberine downregulated the AChE expression and inhibited its activity in the brain tissues. Also, it normalized the production of TNF- α, IL-12, IL-6 and IL-1β. Moreover, it evoked the production of antioxidant Aβ40 and inhibited the formation of Aβ42, responsible for the aggregations of amyloid-β plaques. Histopathological examination confirmed the neuroprotective effect of berberine. The present data advocate the possible beneficial effect of berberine as therapeutic modality for Alzheimers disease via its antiinflammatory/antioxidant mechanism.

In vitro screening for anti-acetylcholiesterase, anti-oxidant, anti-glucosidase, anti-inflammatory and anti-bacterial effect of three traditional medicinal plants

In this study we investigated the phytoconstituents Calluna vulgaris, Ferula hermonis and Tribulus terrestris, and then assessed their possible biological activities by using standard methods. A preliminary phytochemical investigation of the three extracts revealed the presence of alkaloids, flavonoids, proteins, lipids, phenolic compounds, saponins, sterols and amino acids. Three extracts showed anti-oxidant effect as they inhibited the 1,1-diphenyl-2-picryl hydrazyl (DPPH) oxidation and production of thiobarbituric acid reactive substances (TBARS). Moreover, three extracts showed anti-acetylcholiesterase (AChE) and this effect was concentration dependent. C. vulgaris was the most potent inhibitor of AChE. Furthermore, the three plant extracts had an inhibitory effect toward α-glucosidase. The inhibitory effect was concentration dependent and the most potent inhibitor for α-glucosidase was the extract from T. terrestris. Calluna vulgaris showed anti-inflammatory effect at tested concentrations while the other two extracts exhibited this effect only at concentration of 25 μg/mL. Finally, C. vulgaris had a significant effect against pathogenic bacteria (Agrobacterium tumefaciens, Erwinia sp., Klebsiella pneumonia and Pseudomonas aeruginosa) in comparison to other extracts from Ferula sp., or Tribulus sp. In conclusion, all tested extracts could be promising sources for the treatment of diabetes, Alzheimers disease, infectious diseases and oxidative stress related disorders because they are rich in phenols and flavonoids that give anti-oxidant molecules and produce an inhibitory effect against the tested enzymes.

The Ameliorating Effect of Berberine-Rich Fraction against Gossypol-Induced Testicular Inflammation and Oxidative Stress

This study was aimed at evaluating the efficacy of berberine-rich fraction (BF) as a protective and/or a therapeutic agent against inflammation and oxidative stress during male infertility. Sexually mature Sprague-Dawley male rats were divided into five groups treated with either corn oil, BF (100 mg/kg BW, orally, daily for 30 days), gossypol acetate (5 mg/kg BW, i.p.) eight times for 16 days, BF alone for 14 days then coadministered with gossypol acetate for the next 16 days (protected group), or gossypol acetate for 16 days then treated with BF for 30 days (treated group). All animals completed the experimental period (46 days) without obtaining any treatments in the gap period. Sperm parameters, oxidative index, and inflammatory markers were measured. Gossypol injection significantly decreased the semen quality and testosterone level that resulted from the elevation of testicular reactive oxygen and nitrogen species (TBARS and NO), TNF-α, TNF-α-converting enzyme, and interleukins (IL-1β, IL-6, and IL-18) by 230, 180, 12.5, 97.9, and 300%, respectively, while interleukin-12 and tissue inhibitors of metalloproteinases-3 were significantly decreased by 59 and 66%, respectively. BF (protected and treated groups) significantly improved the semen quality, oxidative stress, and inflammation associated with male infertility. It is suitable to use more advanced studies to validate these findings.

Synthesis and evaluation of new phenolic derivatives as antimicrobial and antioxidant agents

New phenolic derivatives bearing hydrazine and 1,3,4-oxadiazole moieties were synthesized and evaluated for their in vitro antimicrobial and antioxidant activities. Most of the compounds revealed pronounced activity against Pseudomonas aeruginosa as well as promising antioxidant activities. N1-(2,5-Dihydroxybenzoyl)-N2-(4-methylphenylsulfonyl)hydrazine displayed promising activity against Escherichia coli and P. aeruginosa. N1-(2,5-Dihydroxybenzoyl)-N2-(2-naphthalenylmethylene)hydrazine was almost equipotent to the standard antioxidant vitamin C having scavenging activities of 84 and 93%, respectively. In vitro cytotoxicity study revealed that N1-(2,5-dihydroxybenzoyl)-N2-(2,3,4-trimethoxyphenylmethylene)hydrazine, N1-(2,5-dihydroxybenzoyl)-N2-(3,4,5-trimethoxyphenylmethylene)hydrazine, and N1-(2,5-dihydroxybenzoyl)-N2-(4-methylphenylsulfonyl)hydrazine are more safe than reference 5-fluorouracil. In silico drug relevant properties proposed that all compounds have high to moderate drug-likeness scores. Accordingly, these derivatives can be potential leads for development of potent antimicrobial and antioxidant agents.Graphical abstract