Exogenous monosodium glutamate exacerbates lipopolysaccharide-induced neurobehavioral deficits, oxidative damage, neuroinflammation, and cholinergic dysfunction in rat brain.

Extensive experimental evidence points to neuroinflammation and oxidative stress as major pathogenic events that initiate and drive the neurodegenerative process. Monosodium glutamate (MSG) is a widely used food additive in processed foods known for its umami taste-enhancing properties. However, concerns about its potential adverse effects on the brain have been raised. Thus, the present study investigated the impact of MSG on lipopolysaccharide (LPS)-induced neurotoxicity in rat brains. Wistar rats weighing between 180 g and 200 g were randomly allocated into four groups: control (received distilled water), MSG (received 1.5 g/kg/day), LPS (received 250 µg/kg/day), and LPS + MSG (received LPS, 250 µg/kg, and MSG, 1.5 g/kg). LPS was administered intraperitoneally for 7 days while MSG was administered orally for 14 days. Our results showed that MSG exacerbated LPS-induced impairment in locomotor and exploratory activities in rats. Similarly, MSG exacerbated LPS-induced oxidative stress as evidenced by increased levels of malondialdehyde (MDA) with a concomitant decrease in levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione-s-transferase (GST) in the brain tissue. In addition, MSG potentiated LPS-induced neuroinflammation, as indicated by increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) as well as myeloperoxidase (MPO) and nitric oxide (NO) in the brain. Moreover, MSG aggravated LPS-induced cholinergic dysfunction, as demonstrated by increased activity of acetylcholinesterase (AChE) in the brain. Further, we found a large number of degenerative neurons widespread in hippocampal CA1, CA3 regions, cerebellum, and cortex according to H&E staining. Taken together, our findings suggest that MSG aggravates LPS-induced neurobehavioral deficits, oxidative stress, neuroinflammation, cholinergic dysfunction, and neurodegeneration in rat brains.

Beet leaf (beta vulgaris L.) extract attenuates iron-induced testicular toxicity: Experimental and computational approach.

The purpose of this study was to investigate the protective effect of Beta vulgaris leaf extract (BVLE) on Fe2+-induced oxidative testicular damage via experimental and computational models. Oxidative testicular damage was induced via incubation of testicular tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. Treatment was achieved by incubating the testicular tissues with BVLE under the same conditions. The catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels, acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K + ATPase), ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase), glucose-6-phosphatase (G6Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase) were all measured in the tissues. We identified the bioactive compounds present using high-performance liquid chromatography (HPLC). Molecular docking and dynamic simulations were done on all identified compounds using a computational approach. The induction of testicular damage (p < 0.05) decreased the activities of GSH, SOD, CAT, and ENTPDase. In contrast, induction of testicular damage also resulted in a significant increase in MDA and NO levels and an increase in ATPase, G6Pase, and F-1,6-BPase activities. BVLE treatment (p < 0.05) reduced these levels and activities compared to control levels. An HPLC investigation revealed fifteen compounds in BVLE, with quercetin being the most abundant. The molecular docking and MDS analysis of the present study suggest that schaftoside may be an effective allosteric inhibitor of fructose 1,6-bisphosphatase based on the interacting residues and the subsequent effect on the dynamic loop conformation. These findings indicate that B. vulgaris can protect against Fe2+-induced testicular injury by suppressing oxidative stress, acetylcholinesterase, and purinergic activities while regulating carbohydrate dysmetabolism.

Quercetin-3-O-ß-D-glucopyranoside-rich fraction demonstrated efficacy against infectious, secretory, and osmotic models of diarrhoeal rats.

BACKGROUND: The prevalence of diarrhoea remains high despite efforts by governments and NGOs to reverse trend. This study investigated the antidiarrhoeal activity and mechanism of Spondias mombin leaf fraction rich in quercetin-3-O-ß-D-glucopyranoside (Q3G-RF) because of the acclaimed therapeutic efficacy. Secretory, osmotic, and infectious diarrhoea models using castor oil, magnesium sulphate, and Shigella flexneri respectively were evaluated at the doses of 100, 200, and 400 mg/kg in Wistar rats. Enteropathy was induced with castor oil and magnesium sulphate, while gastrointestinal motility was determined with charcoal meal. RESULTS: Findings showed no mortality after 14 days of experimental period and no significant changes in behaviour, food, and water consumption. Relative to control, Q3G-RF inhibited the three models of diarrhoea, enteropathy, and gastrointestinal motility; bacterial colonies were reduced by Q3G-RF, while it improved the relative body weight of the animals. Q3G-RF also increased the intestinal concentration/activity of glucose, total protein, and Na+-K+ ATPase but reduced the concentration of TNF-α, PGE2, IL-1ß, nitric oxide, Na+, K+, and Cl- in the diarrhoeal models. The intestinal fluid level of K+, Na+, and Cl- was significantly decreased by Q3G-RF in the enteropathy model. Length of the small intestine in the motility model was also increased by Q3G-RF, while peristaltic index and inhibition of peristalsis were reduced. CONCLUSION: Overall, quercetin-3-O-ß-D-glucopyranoside from Spondias mombin leaves demonstrated efficacy against infectious, secretory, and osmotic form of diarrhoeal and further justified its traditional use in the treatment of diarrhoea due to its antimotility, antisecretory, and antimicrobial properties by mechanism related to enhanced Na+-K+ ATPase, repressed nitric oxide, and suppressed prostaglandins.

Nutritional benefits, ethnomedicinal uses, phytochemistry, pharmacological properties and toxicity of Spondias mombin Linn: a comprehensive review.

OBJECTIVES: Spondias mombin is traditionally used as an herbal medicine for several human diseases and ailments in the tropical regions across the globe including the African countries. This study aimed to provide comprehensive information on nutritional benefits, ethnomedicinal uses, phytochemical constituents, pharmacological properties and toxicology study of S. mombin. Information was gathered from documented literatures in scientific database. KEY FINDINGS: The study revealed that S. mombin has nutritional values; with the leaf, fruit, flower, seed, and stem bark possessing a wide range of ethnomedicinal uses across several regions, with documented pharmacological properties. S. mombin has a frequent rate of ethnomedicinal utility in cases of abortion, constipation, fever, gonorrhea, postpartum hemorrhage, digestive pain, diarrhoea, dysentery and wounds. Ethnopharmacological studies showed that crude extracts and chemical compounds from S. mombin manifested in vivo and in vitro biological and pharmacological activities. About 102 isolated compounds from the leaf, fruit, or stem bark of S. mombin have been reported. SUMMARY: Overall, S. mombin has several nutritive and ethnomedicinal benefits owing to its chemical constituents, which are linkable to the several pharmacological activities. There remains however, the need for dosage intake caution, upon the advice of medical professionals.

Fadogia agrestis (Schweinf. Ex Hiern) Stem Extract Restores Selected Biomolecules of Erectile Dysfunction in the Testicular and Penile Tissues of Paroxetine-Treated Wistar Rats.

Inadequate release of nitric oxide (NO) by the penile tissue impacts negatively on penile erection causing erectile dysfunction (ED). Fadogia agrestis has been implicated in the management of ED without information on key biomolecules associated with ED in male rats. Therefore, this study evaluated the influence of aqueous extract of Fadogia agrestis stem (AEFAS) on key biomolecules associated with ED in the penile and testicular tissues of male Wistar rats induced with ED by paroxetine. Thirty male rats were assigned into 6 groups (I, II, III, IV, V and VI) of 5. Group I (sham control, without ED) was administered distilled water orally. Paroxetine-induced ED rats in groups II (negative control), III (positive control), IV, V and VI received distilled water, sildenafil citrate (SC, 50 mg/kg body weight) and AEFAS at 18, 50 and 100 mg/kg body weight respectively. Paroxetine lowered/reduced (p < 0.05) the MF, IF, EF, NO, cGMP, catalase, SOD, T-SH, GSH and GST whilst it prolonged/increased ML, IL, EL, PEI, AChE, PDE5, arginase, ACE, TBARS and H2O2. Contrastingly, AEFAS like sildenafil citrate increased (p < 0.05) the penile and testicular NO, cGMP, catalase, SOD, T-SH, GSH and GST and reduced AChE, PDE5, arginase, ACE, TBARS and H2O2 to levels that compared favourably (p > 0.05) with those of sham control. The study concluded that AEFAS restored the NO/cGMP pathway and ED-associated key enzymes in the penile and testicular tissues of male rats via antioxidant means. The study recommended the use of aqueous extract of Fadogia agrestis stem in managing ED after clinical trials.

An assessment of the ameliorative role of hesperidin in Drosophila melanogaster model of cadmium chloride-induced toxicity.

Cadmium chloride (CdCl2) is an important heavy metal widely regarded as an environmental contaminant. Hesperidin, a flavanone glycoside found in citrus fruits, has an established properties against free radicals, apoptosis, and inflammation. The present study investigated the protective actions of hesperidin on CdCl2-induced oxidative damage and inflammation in Drosophila melanogaster. For 7 consecutive days via their diet regimen, the flies were exposed to CdCl2 alone (0.05 mM) or in combination with hesperidin (50 and 100 µM). Exposure to CdCl2 significantly (p < 0.05) increased mortality rate of flies, whereas the survived flies demonstrated significant oxidative toxicity from decreased activities of catalase and Glutathione S-transferase (GST) and Total Thiol (T-SH) and Non-Protein Thiols (NPSH) levels as well as accumulation of Nitric Oxide (NO (nitrite/nitrate)), protein carbonyl and Hydrogen Peroxide (H2O2). However, hesperidin-supplemented diet improved Acetylcholinesterase (AChE) activity, mitochondrial metabolic rate (cell viability), locomotor activity, and amelioration of oxidative damage and lipid peroxidation induced by CdCl2. The hesperidin diet supplement boosted the antioxidant milieu and ameliorated the oxidative damage in the treated flies. Overall, the findings revealed that hesperidin improved antioxidative protective capacity in Drosophila melanogaster model of CdCl2-induced toxicity. This suggests hesperidin as a potential therapeutic agent against oxidative stress disorders due to exposure to CdCl2 and or related toxicants.

Quercetin-3-O-ß-D-Glucopyranoside-Rich Fraction from Spondias mombin Leaves Halted Responses from Oxidative Stress, Neuroinflammation, Apoptosis, and Lipid Peroxidation in the Brain of Dichlorvos-Treated Wistar Rats.

Dichlorvos (2,3-dichlorovinyl dimethyl phosphate or DDVP), is a popular organophosphate (OP) with several domestic, industrial, and agricultural uses and applications in developing countries [...].