Computational Evaluation of Azadirachta indica-Derived Bioactive Compounds as Potential Inhibitors of NLRP3 in the Treatment of Alzheimer's Disease.

BACKGROUND: The development of therapeutic agents against Alzheimer's disease (AD) has stalled recently. Drug candidates targeting amyloid-ß (Aß) 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 investigate 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 wet-lab studies are needed to confirm the potency of the studied compounds.

Known data on the therapeutic use of Azadiracta indica (neem) for type 2 diabetes mellitus.

There has been growing interest for the therapeutic use of traditional herbs in the management of diabetes mellitus (DM) and its complications. Data shows the hypoglycemic activity of Azadiracta indica in diabetes. Therefore, it is of interest to document known data on the therapeutic use of Azadiracta indica (neem) for type 2 diabetes mellitus (T2DM).

Synthesis and evaluation of anti-plasmodial and cytotoxic activities of epoxyazadiradione derivatives.

Epoxyazadiradione (1), a major compound derived from Neem oil, showed modest anti-plasmodial activity against CQ-resistant and CQ-sensitive strains of the most virulent human malaria parasite P. falciparum. A series of analogues were synthesized by modification of the key structural moieties of this high yield natural product. Out of the library of all compounds tested, compounds 3c and 3g have showed modest anti-plasmodial activity against CQ-sensitive (IC50 2.8 ± 0.29 µM and 1.5 ± 0.01 µM) and CQ-resistant strains (IC50 1.3 ± 1.08 µM and 1.2 ± 0.14), while compounds 3k, 3l and 3m showed modest activity against CQ-sensitive strain of P. falciparum with IC50 values of 2.3 ± 0.4 µM, 2.9 ± 0.1 µM and 1.7 ± 0.06 µM, respectively. Additionally, cytotoxic properties of these derivatives against SIHA, PANC 1, MDA-MB-231, and IMR-3 cancer cell lines were also studied and the results indicated that low cytotoxic potentials of all the derivatives which indicating the high selectivity index of the compounds.

Atividade anti-fúngica do neem e jurema-preta sobre cepas de Candida spp isolados de vacas com mastite subclínica no Estado de Pernambuco / Anti-fungal activity of neem and jurema-preta on samples of isolated Candida spp of cows with subclinical mastitis in the State of Pernambuco

O objetivo deste estudo foi avaliar a atividade anti-fungica (in vitro) do neem (Azadiracta indica A. Juss.) e de jurema preta (Mimosa tenuiflora (Wild) Poir.) sobre cepas de Candida spp. isoladas de casos de mastite subclínica em vacas no Estado de Pernambuco. As folhas do neem foram coletadas em árvores de fazendas do município de Patos-PB e a casca da jurema-preta foi coletada na UFCG, Campus de Patos e preparados extratos etanólicos. As amostras de Candida spp. foram coletadas de leite de vacas com mastite subclínica e semeadas em placas de Petri contendo ágar-base acrescido de 5 por cento de sangue desfibrinado de ovino Sabouraud. As placas foram incubadas em estufa bacteriológica a 37 ºC e a leitura foi realizada com 24 e 48 h. Os ensaios foram realizados em duplicata e o resultado final foi determinado pela média aritmética dos halos de inibição. A avaliação microbiológica destes ensaios demonstrou que o extrato da casca da jurema-preta apresentou atividade antifúngica bastante satisfatória sobre a levedura de C. albicans, proporcionando resultado superior aos obtidos com o extrato do neem e fluconazol.

The leaves of neem were collected on farms of the city of Patos-PB, and the bark of jurema-preta was collected in the UFCG - Campus of Patos-PB, and the extracts were prepared from the ethanol. The samples of Candida spp. were collected in milk of cows with subclinical mastitis and sown in plates of Petri containing agar-base 5 percent increased of de-fiber blood of sheep Sabouraud. The plates were incubated in bacteriological greenhouse 37 ºC and the reading was carried through with 24 and 48 h. The assays were carried through in duplicate and the final result was determined by the arithmetic mean of inhibition halos. The microbiological evaluation of these assays demonstrated that the extract from the bark of jurema-preta showed antifungal activity quite satisfactory on the yeast C. albicans, providing superior results to those obtained with the extract of neem and fluconazol.

Toxicity of Neem Seed Oil against the Larvae of Boophilus decoloratus, A One-Host Tick In Cattle.

The in vitro toxicity of neem seed oil (Azadirachta indica A. Juss, family: Meliaceae, Dogon yaro in Hausa language in Nigeria) was tested against the larvae of a one-host tick, Boophilus decoloratus (family: Ixodidae or hard tick, commonly known as blue tick) parasitic mainly to cattle generally found in savannas of tropical equatorial Africa. The 20, 40, 60, 80 and 100% concentrations of neem seed oil were found to kill all (100% mortality) the larvae after 27, 27, 27, 27 and 24 h respectively.

Eficácia do extrato aquoso de Azadiracta indica no controle de Boophilus microplus em bovino / Effectiveness of Azadiracta indica watery extract on the control of bovine ticks Boophilus microplus

This study was carried out with two groups of bovines naturally infected with Boophilus microplus. One group was treated every week during a month with Neem's watery extract and the other group was treated only once (at the test onset) with amabectin pour-on. The results of the Kruskal-Wallis test showed no significant difference (P<0.0001) between both groups (Neem and amabectin) throughout the experiment. However, time of collection [(day0 = day15) Õ day30] and age brackets (cows