Implications of Cannabis sativa on serotonin receptors 1B (HTR1B) and 7 (HTR7) genes in modulation of aggression and depression

The use of Cannabis sativa L. is rampant in the young generation and it induces diverse psychological disturbances, hence the correlation between cannabinoids and expression of serotonin receptors in modulation of depression tendencies. Alterations in the expression of serotonin receptors 1B (HTR1B) and 7 (HTR7) genes in the brain of Wistar rats after oral administration of graded doses of C. sativa extract was investigated for different durations of daily administration to establish a correlation between dose, duration of exposure and modulation of aggression/depression. C. sativa was extracted using petroleum ether as the solvent and constituents analyzed through gas chromatography. We orally administered doses of cannabis extract (12.5, 25, and 50 mg/kg) daily for 4, 8, and 12 weeks to male Wistar rats divided into 12 groups of six animals. Reverse transcriptase polymerase chain reaction (RT-PCR) technique was used to quantify the expressions of genes. Expression of HTR1B was upregulated after 4 and 8-weeks’ exposure to 50 mg/kg dose with relative expressions of 0.68 and 0.91 as compared to 0.48 and 0.52 of the control group, resulting in 41.7% and 75% upregulation. However, results got at 12 weeks revealed a downregulation in the lower doses group by 76% and 71% while the 50 mg/kg dose produced a downregulation of the gene. This suggests a reversal of effect because of prolonged exposure. The extract successfully upregulated HTR7 only after 12 weeks of exposure to 25 and 50 mg/kg doses by 22% and over 100% respectively. Cannabis sativa alters the expression of HTR1B and HTR7 and accounts for the mechanism through which users exhibit depression/aggression attributes, as well as modulation of cognitive ability

Antihypertensive activity of roasted cashew nut in mixed petroleum fractions-induced hypertension: An in vivo and in silico approaches

Consumption of water polluted by crude oil is a major environmental problem typical in exploration areas. Numerous health complications such as high blood pressure, myocardial infarction, and other heart complications are prevalent and ravaging. These have gradually become age-defiling disease conditions that are usually maintained with lifestyle changes and diet control. The effect of dietary supplementation with 10% and 20% roasted cashew nuts (RCN) on systolic blood pressure and angiotensin converting enzyme I (ACE I) activities in mixed petroleum fraction (MPF) induced toxicity was studied in male Wistar rats through the modulation of the renin-angiotensin system. The phytochemicals in RCN were quantified using the high performance liquid chromatography (HPLC) technique. To predict likely binding affinity and stability, computational methods such as molecular docking, ADME, and molecular dynamic simulation were used. Out of the seven phytochemicals identified, rutin, gallic acid, and quercetin had the greatest quantities. Similarly, rutin had the highest binding affinities with ACE I, -10.7 kcal/mol, followed by quercetin, at -9.1 kcal/mol. During the molecular dynamics simulation, all of the identified phytochemicals demonstrated good pharmacokinetic capabilities and remained stable at their respective binding sites. Subsequent in vivo validation studies revealed that RCN was able to attenuate the effect of MPF by significantly (p < 0.05) lowering the systolic blood pressure and ACE I activity in comparison to the reference medication, atenolol. We recommend that cashew nuts be explored as dietary snacks as well as a low-cost, easily available component of supplements for the treatment of high blood pressure

Computer aided and experimental study of cinnamic acid analog for oxidative stress treatment: The therapeutic validations

Objectives: The purpose of this study was to investigate the therapeutic activity of the cinnamic acid derivative KAD-3 (ethyl 3-(4-methoxyphenyl) acrylate) on Fe2+-induced oxidative hepatic damage via experimental and computer aided studies. Methods: Oxidative hepatic damage was induced via incubation of tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C ex vivo with different concentration of KAD-3. Molecular docking, ADMET profiling, and density functional theory were conducted on the candidate to filter the properties of the drug candidate for drug design. Key findings: GSH, CAT, and ENTPDase activities were reduced when hepatic damage was induced (p < 0.05). In contrast, a significant increase in MDA levels and an increase in ATPase activity were observed. When compared to control levels, KAD-3 treatment reduced these levels and activities (p < 0.05). KAD-3 demonstrated good bond formation (−5.8 kcal/mol, −5.6 kcal/mol), drug-likeness (no rule violation), and electronic properties (chemically reactive) as compared to the standard (quercetin). Molecular docking, ADMET profiling, and density functional theory predict the functional attributes of the drug candidate against ATPase and ENTPDase targets. Conclusion: The findings from our study indicated that KAD-3 can protect against Fe2+-induced hepatic damage by suppressing oxidative stress and purinergic activities