ABSTRACT
This study investigated the influence of betulinic acid on high-fructose diet-induced metabolic syndrome in rats. Oral administration of betulinic acid significantly reversed high-fructose diet-mediated increase in body mass index and blood glucose. Furthermore, betulinic acid restored high-fructose diet-mediated alterations in metabolic hormones (insulin, leptin and adiponectin). Betulinic acid-mediated upregulation of protein kinase B (Akt) and phosphoinositde-3 kinase (PI3K) anulled high-fructose diet mediated depletion. Also, elevated tumour necrosis factor-α, interleukin-6 and -8 were significantly lowered. Administration of betulinic acid restored high-fructose diet-mediated increase in the levels of lipid profile parameters and indices of atherosclerosis, cardiac and cardiovascular diseases. High-fructose diet-mediated decrease in activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase) and increase in oxidative stress biomarkers (reduced glutathione, lipid peroxidation products, protein oxidation and fragmented DNA) were significantly restored by the phenolic acids. Conclusively, betulinic acid improves insulin sensitivity, elevated blood glucose, inflammation and dyslipidaemia and oxidative stress in high-fructose diet-induced metabolic syndrome through the PI#Kand Akt pathways .
Subject(s)
Hyperglycemia/drug therapy , Hypoglycemic Agents/pharmacology , Metabolic Syndrome/drug therapy , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Triterpenes/pharmacology , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Catalase/genetics , Catalase/metabolism , Cholesterol/blood , Diet/adverse effects , Fructose/adverse effects , Gene Expression Regulation , Glutathione/genetics , Glutathione/metabolism , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Hyperglycemia/etiology , Hyperglycemia/genetics , Hyperglycemia/metabolism , Insulin/blood , Interleukin-6/genetics , Interleukin-6/metabolism , Male , Malondialdehyde/antagonists & inhibitors , Malondialdehyde/metabolism , Metabolic Syndrome/etiology , Metabolic Syndrome/genetics , Metabolic Syndrome/metabolism , Oxidative Stress/drug effects , Pentacyclic Triterpenes , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Wistar , Signal Transduction , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Triglycerides/blood , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Betulinic AcidABSTRACT
Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) leaves are widely used in the treatment of neurological disorders in Nigeria. We investigated the protective effect of aqueous leaf extract of Phyllanthus muellarianus on ciprofloxacin neurotoxicity in male rats. Control rats (Group A) received distilled water, Groups C-E According to the Animal grouping and treatment section, Group B did not receive P. muellarianus> rats were administered 100, 200, and 400 mg/kg body weight P. muellarianus, respectively, and Group F rats received 200 mg/kg body weight valproate orally for 7 days. In addition, groups B-F rats were orally administered ciprofloxacin for 7 days. Motor coordination and motor function were assessed using narrow beam and landing foot splay distance. The levels of neurotransmitter and oxidative stress biomarkers were also determined. Aqueous leaf extract of P. muellarianus significantly attenuated ciprofloxacin-mediated increases in narrow beam, landing foot splay distance, and gait scores. Ciprofloxacin-mediated depletion of acetylcholine and dopamine in the brains of rats was significantly annulled by P. muellarianus. Furthermore, the extract significantly reversed ciprofloxacin-mediated increases in acetylcholinesterase, monoamine oxidase A, and monoamine oxidase B by 73.13%, 71.52%, and 86.54%, respectively. The altered biomarkers of oxidative stress were significantly reversed by P. muellarianus. Overall, the results of this study show that P. muellarianus reversed ciprofloxacin-induced neurotoxicity by restoring ciprofloxacin-mediated alterations in acetylcholine, dopamine, acetylcholinesterase, monoaminergic enzymes, and oxidative stress biomarkers in the brains of rats.
Subject(s)
Neuroprotective Agents/pharmacology , Neurotoxicity Syndromes/drug therapy , Phyllanthus/chemistry , Plant Extracts/pharmacology , Animals , Biomarkers/metabolism , Brain/drug effects , Brain/metabolism , Ciprofloxacin , Disease Models, Animal , Male , Nigeria , Oxidative Stress/drug effects , Phytotherapy , Plant Leaves , RatsABSTRACT
We evaluated the inactivation of DNA gyrase on the oxidative stress response and sensitivity of A. baumannii to lophirones B and C. The sensitivity of parental and the mutant strains of A. baumannii to lophirones B and C was determined using minimum inhibitory concentration (MIC) and time-kill sensitivity. Inactivation of sodB, katG, recA enhanced the sensitivity of A. baumannii to lophirones B and C. Furthermore, this inactivation increased the accumulation of superoxide anion radical and hydrogen peroxide in lophirones B and C-treated A. baumannii, which was reversed in the presence of thiourea. Inactivation of gyrA stalled lophirones B and C-mediated ROS accumulation in A. baumannii. In addition, lophirones B and C raised the Fe2+ contents of A. baumannii. Dipyridyl (Fe chelator) reversed the sensitivity of A. baumannii to lophirones B and C. Lophirones significantly lowered the NAD+/NADH ratio of A. baumannii. The results of this study revealed that the impact of DNA gyrase in lophirones B and C-mediated ROS accumulation, Fe2+ release and cell death.
