Modulation of cytochrome P450 3A4 mediated quinine metabolism in healthy volunteers by two honey samples from different floral and geographical sources

Background: Honey is widely used both for its nutritional and medicinal benefits and reports exist to suggest it may alter the disposition of conventional drugs whose metabolism is mediated by CYP3A4. The study aimed at investigating the effect of multiple dose administration of honey sourced from two different geographical zones in Nigeria, on an antimalarial, quinine and its CYP3A4 mediated metabolism.Methods: In a randomized cross-over study, twenty healthy volunteers divided into two groups A and B [A used honey (HA) from Northern and B used honey (HB) from Eastern Nigeria; n=10 respectively] received single oral doses of 600 mg quinine sulphate tablet alone  and after 7 days administration of 10 ml of honey (HA or HB)  twice daily. Blood samples collected at the 16th hour following quinine administration were subjected to HPLC analysis.Results: Compared to baseline, 10 ml of honey HA significantly increased (0.86±0.22 versus 1.36±0.43) (p<0.05; Wilcoxon test); mean metabolic ratio of quinine (3-hydroxyquinine/quinine) in group A subjects. On the other hand, administration of honey HB resulted in a non-significant reduction (p>0.05) (0.84±0.19 versus. 0.69±0.34) of the metabolic ratio of quinine in group B volunteers. Also, the geometric mean [95% CI: 0.63(0.45, 0.91)] of quinine metabolic ratio in the presence of honey HA alone was significantly increased (p=0.02, t-test).Conclusions: Honey sample from Northern Nigeria significantly stimulated CYP3A4-mediated quinine metabolism as reflected by an increased metabolic ratio of quinine. In conclusion some honey samples may have the potential to significantly modulate CYP3A4 activity, thus honey effects cannot be generalized

Subchronic toxicity and behavioural effects of Glycine max (L.) oil emulsion in male rats

The oil of Glycine max commonly known as soybean oil has over the decades grown popularity for its low cholesterol hence its use within the household and commercially for food production has grossly increased. This study was aimed to determine the effects of long term consumption of soybean oil toxicologically and behaviourally.Male albino rats were administered with the vehicle, 5 and 10% oil emulsion for 30 days orally. The rats were subjected to behavioural tests such as novelty-induced behaviour (NIB), learning and memory tests and food intake measurement weekly. At the end of 30 days, rats were anesthetized and carefully dissected and blood sample was taken and analyzed haematogically and biochemically. The liver sample was also taken for biochemical analysis. Histopathological examinations were carried out on the brain, spleen, liver, kidney, lungs and testis samples.The results showed that oral administration of oil caused an increase in food intake, significant effect on NIB but had no effect on learning and memory. There was a significant (p<0.05) reduction in the level of both haemoglobin and PCV in the grouped administered with high dose. Biochemical analysis revealed a significant (p<0.05) increase in triglyceride, ALT, AST levels, with no effect on cholesterol. Histopathological analysis revealed no significant effects on the essential organs tested when compared with the vehicle treated rats.This study conclusively showed that soybean oil has central excitatory effects and there is need for caution when used for a long period since it has significant effects on biochemical parameters

Subchronic toxicity and behavioural effects of Glycine max (L.) oil emulsion in male rats

The oil of Glycine max commonly known as soybean oil has over the decades grown popularity for its low cholesterol hence its use within the household and commercially for food production has grossly increased. This study was aimed to determine the effects of long term consumption of soybean oil toxicologically and behaviourally.Male albino rats were administered with the vehicle, 5 and 10% oil emulsion for 30 days orally. The rats were subjected to behavioural tests such as novelty-induced behaviour (NIB), learning and memory tests and food intake measurement weekly. At the end of 30 days, rats were anesthetized and carefully dissected and blood sample was taken and analyzed haematogically and biochemically. The liver sample was also taken for biochemical analysis. Histopathological examinations were carried out on the brain, spleen, liver, kidney, lungs and testis samples.The results showed that oral administration of oil caused an increase in food intake, significant effect on NIB but had no effect on learning and memory. There was a significant (p<0.05) reduction in the level of both haemoglobin and PCV in the grouped administered with high dose. Biochemical analysis revealed a significant (p<0.05) increase in triglyceride, ALT, AST levels, with no effect on cholesterol. Histopathological analysis revealed no significant effects on the essential organs tested when compared with the vehicle treated rats.This study conclusively showed that soybean oil has central excitatory effects and there is need for caution when used for a long period since it has significant effects on biochemical parameters

Anxiolytic and Antistress Potentials of Ethanol Stem-Bark Extract of Milicia Excelsa (Moraceae) in Mice: Anxiolytic and Antistress Potentials of Milicia excelsa in mice

Milicia excelsa stem bark is applied in traditional medicine in some African societies, primarily as a tonic to rejuvenate the body after demanding episodes. However, there is a paucity of scientific evidence to support this usage. Therefore, this research aimed to evaluate the anxiolytic and anti-stress potentials of ethanol extract of the stem bark of Milicia excelsa (ESBME) in mice. The central nervous system inhibitory effect of the extract was determined using novelty-induced rearing, grooming, and locomotion behaviors while the anxiolytic effect was investigated by using a hole board and elevated plus maze (EPM) test models. The extract’s ability to alleviate the anxiety-like and depressive-like behaviors triggered by acute restraint stress was evaluated with the use of EPM and tail suspension test respectively. The ESBME significantly (p<0.05) decreased the novelty-induced rearing, grooming, and locomotion behaviors indicating a central nervous system inhibitory effect. At 37.5 mg/kg, ESBME significantly (p<0.05) increased the number of head poking in the hole board test designating anxiolytic potential. Subsequently, the ESBME significantly (p<0.05) increased the percentage of open-arm entries and percentage open-arm duration as well as reducing the anxiety index on elevated plus Maze consistent with the antianxiety effect. The extract also significantly (p<0.05) alleviated the anxiety-like and depressive-like behaviors triggered by acute restraint stress suggesting an anti-stress effect. In conclusion, ESBME possesses central nervous system inhibitory, anxiolytic, and anti-stress effects thereby providing scientific evidence to the ethnomedicinal claim of the plant as an anti-stress agent

Neuropharmacological Effects of Nigerian Honey in Mice

Honey is a natural sweet substance that bees produce by transforming flower nectar or other sweet secretions of plants. It has widespread use in traditional medicine in various parts of the world. It has been reported to assist in building the entire central nervous system. The beneficial effects of honey have been attributed to the possible polyphenolic contents and some other constituents. The geographical locations and the sources of plant nectars may contribute to the effects of honey samples. Thus, we evaluated the neuropharmacological effects of six samples of honey (10%, 20% and 40%V/v, p.o.) from three geographical locations of Nigeria using the following behavioral models: Novelty-induced behaviors (NIB), learning and memory, pentobarbital-induced hypnosis, anxiolytic, anticonvulsant, analgesic and antidepressant models in mice. The results showed that honey significantly (p< 0.05) decreased locomotion and rearing behaviors in NIB and amphetamine-induced locomotor activity when compared to the control group. Exploratory behavior was significantly increased in both holeboard and elevated plus maze but had no significant effect on spatial working memory. Honey sample from Umudike has significant hypnotic and anticonvulsant effects. The antinociceptive models (hot plate and tail flick tests) showed that the honey samples significantly increased the pain reaction time and naloxone blocked these central antinociceptive effects. The force swimming test showed that only the Idanre (ID) honey sample had antidepressant effect. In conclusion, some of these honey samples have central inhibitory property, anxiolytic, antinociceptive, anticonvulsant and antidepressant effects, thus may be used as nutraceutic. It can also be inferred that some of these effects are probably mediated through dopaminergic and opioidergic systems

An improved method for toxicological profiling of chemical substances

Toxicity profiling is an integral part of the drug discovery pipeline. The 3Rs principle—Replacement, Reduction, and Refinement, is considered a golden rule in determining the most appropriate approach for toxicity studies. The acute toxicity study with proper estimate of median lethal dose (LD50) is usually an initial procedure for the determination of most suitable test doses for preclinical toxicological and pharmacological profiling. Several methods, which have been devised to determine the LD50, are faced with the challenge of using a large number of animals and time constraints. Despite the inherent advantage of the newer OECD Test Guidelines, the increasing concerns among toxicologists, the regulatory authorities and the general public, on the need to adhere to 3Rs principle, necessitated the need for an improved approach. Such an approach should not only minimize the time and number of animals required, but also take into cognizance animal welfare, and give accurate, comparable, and reproducible results across laboratories. While taking advantage of the inherent merits of the existing methods, here is presented the mathematical basis and evaluation of an improved method for toxicity profiling of test substances and estimation of LD50. The method makes use of the generated Table of values for the selection of appropriate test doses. Our proposed method has capacities to optimize the time and number of animal use, ensure more reliable and reproducible results across laboratories, allow for easy selection of doses for subsequent toxicity profiling, and be adaptable to other biological screening beyond toxicity studies.</p