Protocatechuic acid protects against menadione-induced liver damage by up-regulating nuclear erythroid-related factor 2.

Menadione (Vitamin K3) is an over-the-counter (OTC) drug used in the treatment of abdominal cramps, colitis, diarrhea, hay fever, hemorrahage, hypoprothrombinemia, and joint pains. In this study, we evaluated the protective influence of protocatechuic acid on menadione-induced hepatotoxicity in rats. Rats were randomized into five groups (A-E) of five rats each. Control rats orally received 1% dimethyl sulfoxide (DMSO) in distilled water (the vehicle for protocatechuic administration) for 7 days. In addition, control rats intraperioneally received olive oil (vehicle for menadione administration) on the 7th day. Groups B, D, and E received single dose of 100 mg/kg body weight menadione on day 7. Furthermore, groups C-E were pretreated with protocatechuic acid for 7 days. Pretreatment of rats with protocatechuic acid significantly halted menadione mediated-alterations in serum alkaline phosphatase, alanine and aspartate aminotransferases, albumin, and total bilirubin. Furthermore, menadione-mediated increase in superoxide ion and hydrogen peroxide with concomitant decrease in the activities of superoxide dismutase and catalase were significantly reversed by protocatechuic acid. Protocatechuic acid annulled menadione-mediated decrease in glutathione S-transferase and NADH: quinone oxidoreductase-1 through nuclear erythroid related factor-2 (Nrf-2). In addition, the decreased glutathione and increased glutathione disulfide, caspase-3, fragmented DNA, malondialdehyde and protein carbonyl were reversed. Results of this study show that protocatechuic acid protects against menadione-induced oxidative stress in rats by enhancing the antioxidant and phase II enzymes through Nrf-2.

Betulinic acid improves insulin sensitivity, hyperglycemia, inflammation and oxidative stress in metabolic syndrome rats via PI3K/Akt pathways.

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 .

Protective Influence of Phyllanthus Muellarianus on Ciprofloxacin-Induced Neurotoxicity in Male Rats.

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.

Caffeic acid abrogates 1,3-dichloro-2-propanol-induced hepatotoxicity by upregulating nuclear erythroid-related factor 2 and downregulating nuclear factor-kappa B.

1,3-dichloro-2-propanol is a food-borne contaminant reported to cause liver injury. In this study, we evaluated the protective influence of caffeic acid on 1,3-dichloro-2-propanol-induced hepatotoxicity in rats. Rats were randomized into five groups (A-E). Rats received distilled water or caffeic acid (10 or 20 mg/kg body weight) for 7 days. In addition, rats were challenged with 1,3-dichloro-2-propanol on day 7. Caffeic acid prevented 1,3-dichloro-2-propanol-mediated alterations in alkaline phosphatase, alanine and aspartate aminotransferases, albumin and total bilirubin in the serum of rats. Furthermore, caffeic acid lowered superoxide ion, hydrogen peroxide and cytochrome P2E1 while increasing the activities of superoxide dismutase, catalase and glutathione S-transferase in the liver of 1,3-dichloro-2-propanol-treated rats. Caffeic acid raised the levels of nuclear erythroid-related factor 2 (Nrf-2), protein kinase A and phosphoinositide 3-kinase. Caffeic acid pretreatment annulled 1,3-dichloro-2-propanol-mediated alterations in the oxidative stress biomarkers; caspase-3, glutathione, malondialdehyde, protein carbonyl and fragmented DNA, in the liver of rats. Contrastingly, caffeic acid lowered 1,3-dichloro-2-propanol-mediated increase in the levels of nuclear factor-kappa B (NF-κB), tumour necrosis factor-α, interleukin-1ß (IL-1ß) and IL-6. In addition, caffeic acid preserved the morphological features of 1,3-dichloro-2-propanol-treated rats. Results from this study revealed that caffeic acid protects against 1,3-dichloro-2-propanol-induced hepatotoxicity by enhancing the cytoprotective enzymes through Nrf-2 while lowering inflammation through NF-κB.

Lophirones B and C induce oxidative cellular death pathway in Acinetobacter baumannii by inhibiting DNA gyrase.

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.

Contributions of reactive oxygen species, oxidative DNA damage and glutathione depletion to the sensitivity of Acinetobacter baumannii to 2-(2-nitrovinyl) furan.

2-(2-nitrovinyl) furan is a broad-spectrum antibacterial agent with activity against Gram-positive and Gram-negative bacteria. In this study, the contributions of reactive oxygen species, oxidative DNA damage and glutathione depletion to its activity against Acinetobacter baumannii was investigated. Inactivation of sodB, katG and recA lowered the minimum inhibitory concentration of 2-(2-nitrovinyl) furan. Furthermore, the inactivation increased the superoxide anion radical and hydrogen peroxide contents of 2-(2-nitrovinyl) furan-treated A. baumannii. Antioxidant (thiourea) reversed the elevated levels of superoxide anion radical and hydrogen peroxide. In addition, thiourea lowered the susceptibility of A. baumannii to 2-(2-nitrovinyl) furan. 2-(2-nitrovinyl) furan depleted reduced glutathione (GSH) contents of parental, sodB, katG and recA strains of A. baumannii. NAD+/NADH ratio parental, sodB, katG and recA strains of A. baumannii exposed to 2-(2-nitrovinyl) furan increased significantly. Inactivation of type-I NADH dehydrogenase lowered the reactive oxygen species generation in 2-(2-nitrovinyl) furan-treated A. baumannii. It is evident from this study that 2-(2-nitrovinyl) furan stimulates respiratory chain activity of A. baumannii leading to enhanced ROS generation, which depletes GSH and reacts with Fe2+ to produce hydroxyl radical that damage DNA.

Ferulic acid potentiates the antibacterial activity of quinolone-based antibiotics against Acinetobacter baumannii.

Ferulic acid is a cinnamic derivative of phenolic acid and its pharmacophore (catechol) is responsible for antioxidant, prooxidant and antibacterial activities. In this study, we evaluated the influence of ferulic acid on the antibacterial activity of quinolone-based antibiotics against Acinetobacter baumannii. The minimum inhibitory concentration of ferulic acid against Acinetobacter baumannii AB5075 were considerably lowered for ΔsodB and ΔkatG mutants. Checkerboard assay shows synergistic interactions between ferulic acid and quinolones. In a murine sepsis model, ferulic acid potentiated the antibacterial activities of quinolones. Ferulic acid amplified quinolones-induced redox imbalance by increasing superoxide ion generation, NAD+/NADH ratio and ADP/ATP ratio. Conversely, the level of reduced glutathione was significantly lowered. We conclude that ferulic acid potentiates the antibacterial activity of quinolone-based antibiotics against A. baumannii by increasing ROS generation, energy metabolism and electron transport chain activity with a concomitant decrease in glutathione.

Impact of zinc uptake regulator Zur on the susceptibility and oxidative stress response of Acinetobacter baumannii to antibiotics.

Zinc is a highly coveted redox-inactive micronutrient required for the growth and virulence of Acinetobacter baumannii. In this study, the role of the zinc uptake regulator Zur in the susceptibility and oxidative stress response of A. baumannii to antibiotics was evaluated. Inactivation of zur increased the susceptibility of A. baumannii AB5075 to colistin, gentamicin, rifampicin and tigecycline. Furthermore, activities of superoxide dismutase and catalase decreased significantly in the Δzur mutant compared with the parental strain. Colistin, gentamicin, rifampicin and tigecycline raised the superoxide anion radical (·O2-) and hydrogen peroxide (H2O2) contents of the Δzur mutant compared with the parental strain. In addition, the antibiotics lowered glutathione and concomitantly raised glutathione disulphide levels in the Δzur mutant. All of the antibiotics, except tigecycline, significantly raised the NAD+/NADH and ADP/ATP ratios in A. baumannii. We conclude that decreased capability of the Δzur mutant to detoxify reactive oxygen species increased its susceptibility to antibiotics.

(+)-Catechin potentiates the oxidative response of Acinetobacter baumannii to quinolone-based antibiotics.

(+)-Catechin is a versatile compound with its pharmacophore (catechol and resorcinol) responsible for prooxidant and antibacterial activities. In this study, we present that demonstrating the synergistic interaction between (+)-catechin and quinolone-based antibiotics, ciprofloxacin and gemifloxacin is related to reactive oxygen species generation. The minimum inhibitory concentration of (+)-catechin against Acinetobacter baumannii AB5075 were considerably lowered for ΔsodB and ΔkatG mutants. Checkerboard assay shows synergistic interactions between (+)-catechin and quinolones. (+)-Catechin amplified quinolones-induced redox imbalance by increasing superoxide ion generation, NAD+/NADH ratio and ADP/ATP ratio. Conversely, the level of reduced glutathione was significantly lowered. We conclude that (+)-catechin potentiates quinolone-based antibiotics-induced oxidative stress in A. baumannii by increasing ROS generation, energy metabolism and electron transport chain activity with a concomitant decrease in glutathione.

Colistin sulphate induced neurotoxicity: Studies on cholinergic, monoaminergic, purinergic and oxidative stress biomarkers.

This study evaluated the influence of colistin sulphate on cholinergic, monoaminergic, purinergic and oxidative stress biomarkers in the brain of male rats. Rats were randomized into four (4) groups (A-D) of five rats each. Group A rats received the vehicle of administration for 7 days. Rats in groups B, C and D received 5-, 7.5- and 15-mg/kg body weight colistin sulphate intravenously for 7 days. Colistin sulphate administration significantly raised the narrow beam, landing foot spread distance and gait scores. Administration of colistin sulphate dose dependently increased the activities of acetylcholinesterase, butyrylcholinesterase, monoamine oxidases A and B, ecto-nucleoside triphosphate diphosphohydrolase and ecto-5' nucleotidase. Furthermore, the activities of superoxide dismutase, catalase and glutathione S-tranferase activities in the brain of rats treated with colistin sulphate decreased significantly. Similarly, colistin sulphate lowered the level of reduced glutathione. Caspase-3, malondialdehyde and fragmented DNA in the brain of rats were significantly raised. Colistin sulphate induced gross nuclear condensation and depletion, in addition to cytoplasmic degenerative changes and dilated blood vessels in the brain of rats. Available data from this study show that alterations in the cholinergic, monoaminergic, purinergic and oxidative stress biomarkers are associated with colistin sulphate-mediated neurotoxicity.

Contributions of ferric uptake regulator Fur to the sensitivity and oxidative response of Acinetobacter baumannii to antibiotics.

Ferric uptake regulator (Fur) is important in the regulation of bacterial iron metabolism and uptake of Fe from the environment. We evaluated the contribution of fur to the sensitivity and oxidative response of A. baumannii to antibiotics. Deletion of fur increased the sensitivity of A. baumannii AB5075 to colistin, gentamicin, rifampicin and tigecycline. Furthermore, activities of superoxide dismutase and catalase in Δfur mutant decreased significantly compared to the parental strain. Conversely, •O2- and H2O2 accumulate in colistin, gentamicin, rifampicin or tigecycline-treated Δfur mutant compared to the parental strain. Ferrous ion (Fe2+) content of Δfur mutant increased compared to the parental strain. Fe chelator 2,2'-bipyridyl lowered the sensitivity of A. baumannii to the antibiotics. The antibiotics, except tigecycline, raised the NAD+/NADH and ADP/ATP ratio of Δfur mutant compared to the WT. Glutathione content of Δfur mutant was significantly depleted compared to parental strain following exposure to the antibiotics. We conclude that decreased capability of Δfur mutant to detoxify reactive oxygen species raised its susceptibility to antibiotics through Fenton chemistry.

2-(2-Nitrovinyl) furan exacerbates oxidative stress response of Escherichia coli to bacteriostatic and bactericidal antibiotics.

The influence of 2-(2-nitrovinyl) furan on the activities of selected bacteriostatic and bactericidal antibiotics was investigated. Minimum inhibitory concentration and fractional inhibitory concentration index were determined to evaluate the interaction between 2-(2-nitrovinyl) furan and the antibiotics. 2-(2-nitrovinyl) furan exhibited additive interactions with chloramphenicol, erythromycin, lincomycin and gemifloxacin. However, synergistic interaction was observed with amoxicillin, ampicillin and ciprofloxacin. Superoxide anion content of Escherichia coli exposed to antibiotics with/without 2-(2-nitrovinyl) furan increased significantly (p < .05). Furthermore, reduced glutathione decreased significantly with a corresponding increase in glutathione disulphide. In addition, malondialdehyde, a product of lipid peroxidation, increased significantly in E. coli exposed to antibiotics and 2-(2-nitrovinyl) furan. It can be deduced from this study that 2-(2-nitrovinyl) furan enhanced bacteriostatic and bactericidal antibiotics-mediated bacterial death possibly by potentiating reactive oxygen species generation and oxidative stress.

Antidyslipidemic, Anti-Inflammatory, and Antioxidant Activities of Aqueous Leaf Extract of Dioscoreophyllum cumminsii (Stapf) Diels in High-Fat Diet-Fed Rats.

Dioscoreophyllum cumminsii (Stapf) Diels leaves are widely used in the treatment of diabetes, obesity, and cardiovascular related complications in Nigeria. This study investigates the anti-inflammatory and antiobesity effect of aqueous extract of Dioscoreophyllum cumminsii leaves in high-fat diet- (HFD-) induced obese rats. HFD-fed rats were given 100, 200, and 400 mgkg-1 body weight of aqueous extract of Dioscoreophyllum cumminsii leaves for 4 weeks starting from 9th week of HFD treatment. D. cumminsii leaves aqueous extract reversed HFD-mediated decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase. Moreover, HFD-mediated elevation in the levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl, and DNA fragmentation in rats liver was lowered. HFD-mediated alterations in serum total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were significantly reversed by the extract. The treatment of HFD-fed rats reduced the levels of insulin, leptin, protein carbonyl, fragmented DNA, and tumour necrosis factor-α and interleukin- (IL-) 6 and IL- 8 and increased the adiponectin level. This study showed that aqueous extract of Dioscoreophyllum cumminsii leaves has potential antiobesity and anti-inflammatory effects through modulation of obesity-induced inflammation, oxidative stress, and obesity-related disorder in HFD-induced obese rats.

Influence of oxidative stress on the antibacterial activity of betulin, betulinic acid and ursolic acid.

Contribution of reactive oxygen species and oxidative stress in the antibacterial activities of betulin, betulinic acid and ursolic acid against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was investigated. The minimum inhibitory concentrations of betulin, betulinic acid and ursolic acid against E. coli, P. aeruginosa and S. aureus are 1024-, 256- and 1024-µg/mL; 512-, 256- and 256 µg/mL; 256-, 256- and 64 µg/mL respectively. Cell viability of betulin-, betulinic acid- and ursolic acid-treated bacteria decrease in time dependent manner. Treatment of bacteria in the presence of 2,2'-bipyrydyl increased cell viability. Superoxide anion radical production increased significantly (p < 0.05) in bacterial cells-treated with betulin, betulinic acid and ursolic acid. Furthermore, NAD+/NADH ratio increased significantly (p < 0.05) in betulin-, betulinic acid- and ursolic acid-treated bacteria. Similarly, level of reduced glutathione in E. coli, P. aeruginosa and S. aureus decreased significantly with corresponding increase in glutathione disulphide, malondialdehyde and fragmented DNA following betulin, betulinic acid and ursolic acid treatments. It is evident from the above findings that betulin, betulinic acid and ursolic acid enhanced electron transport chain activity in E. coli, P. aeruginosa and S. aureus leading to increased ROS generation, Fenton reaction, lipid peroxidation, fragmented DNA and consequentially bacterial death.

Aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (Apocynaceae) palliates hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hunteria umbellata is used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous seed extract of Hunteria umbellata on insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome MATERIALS AND METHODS: Rats were randomized into seven groups (A-G). Control (group A) and group C rats received control diet for nine weeks while rats in groups B, D - G were placed on high-fructose diet for 9 weeks. In addition to the diets, groups C - F rats orally received 400, 100, 200 and 400mg/kg body weight aqueous seed extract of Hunteria umbellata for 3 weeks starting from 6th - 9th week. RESULTS: High-fructose diet (when compared to control rats) mediated a significant (p<0.05) increase in body weight, body mass index and abdominal circumference. Similarly, levels of blood glucose, insulin, leptin, adiponectin and insulin resistance were increased. It also caused a significant increase in the levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index while high-density lipoprotein cholesterol was decreased significantly. Levels of proinflammatory factor, tumour necrosis factor-α, interleukin-6 and 8 were also increased by the high fructose diet. Moreover, it mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and level of glutathione reduced. Conversely, levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were elevated. Aqueous seed extract of Hunteria umbellata significantly ameliorated the high fructose diet-mediated alterations. CONCLUSIONS: From this study, it is concluded that aqueous seed extract of Hunteria umbellata possesses hypoglycemic, hypolipidemic and antioxidants abilities as evident from its capability to extenuate insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats.

Contribution of reactive oxygen species to (+)-catechin-mediated bacterial lethality.

The contribution of reactive oxygen species to (+)-catechin-mediated bacterial lethality was investigated. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) of (+)-catechin against E. coli, P. aeruginosa and S. aureus were investigated using 96-well microtitre plate. MIC and MBC of (+)-catechin against E. coli, P. aeruginosa and S. aureus are 600 and 700; 600 and 800; 600 and 800 µg/mL respectively. The optical densities and colony forming units of (+)-catechin-treated bacteria decreased. (+)-Catechin (4× MIC) significantly increased the superoxide anion content of E. coli, P. aeruginosa and S. aureus compared to DMSO. Superoxide dismutase and catalase in (+)-catechin treated E. coli, P. aeruginosa and S. aureus increased significantly. Conversely, level of reduced glutathione in (+)-catechin-treated E. coli, P. aeruginosa and S. aureus decreased significantly while glutathione disulfide increased significantly. Furthermore, malondialdehyde and fragmented DNA increased significantly following exposure to (+)-catechin. From the above findings, (+)-catechin enhanced the generation of reactive oxygen species (superoxide anion radical and hydroxyl radical) in E. coli, P. aeruginosa and S. aureus, possibly by autoxidation, Fenton chemistry and inhibiting electron transport chain resulting into lipid peroxidation and DNA fragmentation and consequentially bacterial cell death.

Redox and respiratory chain related alterations in the lophirones B and C-mediated bacterial lethality.

The influence of chalcone dimers, lophirones B and C on redox status and respiratory chain activity of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa was investigated. Minimum inhibitory concentrations (MIC) of lophirones B and C against E. coli, P. aeruginosa and S. aureus are 200-; 100-; 200- and 150-µg/mL respectively. Similarly, the minimum bactericidal concentrations (MBC) of lophirones B and C are 250; 200; 300 and 200-µg/mL respectively. The optical densities and colony forming units of lophirones B and C-treated bacteria decreased in time-dependent manner. Superoxide anion content of E. coli, P. aeruginosa and S. aureus exposed to lophirones B and C (4× MIC) increased significantly. Superoxide dismutase and catalase in the chalcone dimers-treated bacteria increased significantly. Conversely, reduced glutathione in lophirones B and C-treated bacteria decrease significantly with corresponding increase in glutathione disulfide. Furthermore, malondialdehyde and fragmented DNA increased significantly following exposure to the chalcone dimers. The respiratory complex I and II decreased significantly in the chalcone dimers-treated bacteria. From the findings, lophirones B and C altered intracellular redox status via enhanced oxidant generation possibly by autoxidation, Fenton chemistry and inhibiting electron transport chain resulting to lipid peroxidation and DNA fragmentation and consequentially bacterial cell death.

Dioscoreophyllum cumminsii (Stapf) Diels leaves halt high-fructose induced metabolic syndrome: Hyperglycemia, insulin resistance, inflammation and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscoreophyllum cumminsii is widely used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous leaf extract of D. cumminsii on high-fructose diet-induced metabolic syndrome. METHODS: Seventy male rats were randomized into seven groups. All rats were fed with high-fructose diet for 9 weeks except groups A and C rats, which received control diet. In addition to the diet treatment, groups A and B rats received distilled water for 3 weeks starting from the seventh week of the experimental period. Rats in groups C-F orally received 400, 100, 200 and 400mg/kg body weight of aqueous leaf extract of D. cumminsii respectively, while group G received 300mg/kg bodyweight of metformin for 3 weeks starting from the seventh week. RESULTS: There was significant (p<0.05) reduction in high-fructose diet-mediated increase in body weight, body mass index, abdominal circumference, blood glucose, insulin, leptin and insulin resistance by aqueous leaf extract of D. cumminsii. Conversely, high-fructose diet-mediated decrease in adiponectin was reversed by the extract. Increased levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index were significantly lowered by the extract, while high-fructose diet mediated decrease in high-density lipoprotein cholesterol was increased by the extract. Tumour necrosis factor-α, interleukin-6 and interleukin-8 levels increased significantly in high-fructose diet-fed rats, which were significantly reversed by the extract. High-fructose mediated-decrease in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and glutathione reduced were significantly reversed by aqueous leaf extract of D. cumminsii. Conversely, elevated levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were significantly lowered by the extract. CONCLUSION: Data generated in this study further laid credence to the hypoglycemic activity of aqueous leaf extract of D. cumminsii as evident from the reversal of hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats.

Antibacterial activity of Syzygium aromaticum seed: Studies on oxidative stress biomarkers and membrane permeability.

Oxidative stress and membrane permeability as mode of antibacterial activity of aqueous extract of Syzygium aromaticum seeds against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was investigated. The concentration of phytochemical constituents of Syzygium aromaticum was determined using gas chromatography. Syzygium aromaticum seeds contain eugenol acetate > ß-carophyllene > eugenin > eugenol > methyl salicylate > ß-humulene > rhamnatin > fernesol > α-copeane > ß-ylangene > kaempferol > cinnamic acid > oleanolic acid > benzaldehyde > α-humulene > vanillin > α-cubebene > carvicol > benzoic acid. Syzygium aromaticum showed antimicrobial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as 0.06 and 0.10 mg/mL respectively. Time kill susceptibility by Syzygium aromaticum at MBC values showed significant decrease in the optical density and colony-forming unit (CFU) of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Superoxide anion radical content of the bacterial cells increased significantly following exposure to the extract. In a similar vein, superoxide dismutase and catalase activities increased significantly, while the level of reduced glutathione reduced, malondialdehyde increased significantly in bacterial cells exposed to the extract. The extract at MBC also enhanced the leakage of 260 nm absorbing materials and outer membrane permeability. It is evident from the data generated from this study that aqueous extract of Syzygium aromaticum seeds enhanced membrane permeability and oxidative stress in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.

Involvement of oxidative stress in bactericidal activity of 2-(2-nitrovinyl) furan against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.

The involvement of reactive oxygen species and oxidative stress in 2-(2-nitrovinyl) furan mediated bacterial cell death was investigated in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Time kill assay resulted in significant decrease in the optical density and colony-forming unit (CFU) of E. coli, P. aeruginosa and S. aureus. The level of superoxide anion radical and nitric oxide increased significantly in concentration dependent when compared with dimethyl sulfoxide (DMSO) treated bacteria. Similar concentration dependent increase in the activity of superoxide dismutase and catalase were recorded. The non-enzymatic antioxidant glutathione decreased significantly with a concomitant increase in glutathione disulfide. The level of malondialdehyde and fragmented DNA increased significantly in the bacterial cells treated with 2-(2-nitrovinyl) furan when compared with DMSO treated cells. The CFU of E. coli, P. aeruginosa and S. aureus following exposure to 2-(2-nitrovinyl) furan increased significantly (p < 0.05) in the presence of 2,2' bipyridyl, an Fe chelator, significantly when compared with only 2-(2-nitrovinyl) furan suggesting the involvement of hydroxyl radical in the cell death. The available data from this study showed that 2-(2-nitrovinyl) furan induced oxidative stress in E. coli, P. aeruginosa and S. aureus as evident from elevated levels of superoxide anion radical nitric oxides and antioxidant enzymes.