Background: The development of therapeutic agents against Alzheimer’s disease (AD) has stalled recently. Drug candidates targeting amyloid-β (Aβ) deposition have often failed clinical trials at different stages, prompting the search for novel targets for AD therapy. The NLRP3 inflammasome is an integral part of innate immunity, contributing to neuroinflammation and AD pathophysiology. Thus, it has become a promising new target for AD therapy. Objective: The study sought to study the potential of bioactive compounds derived from Azadirachta indica to inhibit the NLRP3 protein implicated in the pathophysiology of AD. Methods: Structural bioinformatics via molecular docking and density functional theory (DFT) analysis was utilized for the identification of novel NLRP3 inhibitors from A. indica bioactive compounds. The compounds were further subjected to pharmacokinetic and drug-likeness analysis. Results obtained from the compounds were compared against that of oridonin, a known NLRP3 inhibitor. Results: The studied compounds optimally saturated the binding site of the NLRP3 NACHT domain, forming principal interactions with the different amino acids at its binding site. The studied compounds also demonstrated better bioactivity and chemical reactivity as ascertained by DFT analysis and all the compounds except 7-desacetyl-7-benzoylazadiradione, which had two violations, conformed to Lipinski’s rule of five. Conclusion: In silico studies show that A. indica derived compounds have better inhibitory potential against NLRP3 and better pharmacokinetic profiles when compared with the reference ligand (oridonin). These compounds are thus proposed as novel NLRP3 inhibitors for the treatment of AD. Further wetlab studies are needed to confirm the potency of the studied compounds.

Cane rat (Thryonomys swinderianus) is an herbivorous animal which feeds on plant materials, including cassavas that are known to contain cyanogenic glycosides. Cyanide or cyanogenic glycosides are known to be toxic for animal consumption. Therefore, Cane rat must have an inherent mechanism for detoxifying cyanide to be able to survive on its food. Previous works on 3MST have been done on several tissues of cane rats other than the intestine. In this work, we characterized and explored a partially purified 3MST (cyanide detoxifying enzyme) from the intestine of a cane rat for a possible therapeutic source against cyanide poisoning in other mammals that are susceptible to the toxin. 3MST from the intestine of T. swinderianus had a yield of 10.3% with specific activity of 0.21Umg-. The Km and Vmax values of the 3-MST were determined to be 40 mm and 0.20µmol/ml/min respectively for KCN (Potassium Cyanide); also 33.3 mm and 0.15 µmol/ml/min for mercaptoethanol. 3-MST presents in the intestine of T. swinderianus plays a significant role in detoxification of cyanogenic compounds, which makes it an effective target for cyanide poisoning therapy.

Background: To date, only a few studies have attempted to monitor the changes in antioxidant enzyme levels by using massage devices. The aim of this study was to determine the effects of massage on superoxide dismutase (SOD) and catalase (antioxidant) in undergraduate students of Olabisi Onabanjo University. Methods: Ten (10) Subjects from Physiology department, Olabisi Onabanjo University were recruited for the study via personal contact. The participants received vibratory massage on the back for 10 days. Data from 10 participants were used for analysis. All subjects were apparently healthy as confirmed by their medical history and were not taking any medications. Results: There was a significant decrease (p<0.05) in the antioxidant enzyme SOD level while a non-significant decrease (p>0.05) in Catalase level in the subjects under experiment when results at the end of experiment was compared to baseline result. Conclusion: The result of this present study showed that vibratory massage hammer may be an effective strategy for reducing oxidative stress and free radicals are eliminated and also useful in the prevention and treatment of diseases associated with oxidation: stress, pain, injury.