In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.

The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.

GC-MS analysis of aqueous extract of Nymphaea lotus and ameliorative potential of its biosynthesized gold nanoparticles against cadmium-induced kidney damage in rats.

Plants possess compounds serving as reducing agents for green synthesis of gold nanoparticles (AuNPs), which is currently considered for biomedical application. Exposure to cadmium (Cd) can affect the functional integrity of the several organs such as kidney and liver. Nymphaea lotus (NL) is known for its several medicinal properties, including its protective role against tissue damages. This study investigated the bioactive compounds in NL using gas chromatography-mass spectroscopy (GC-MS) and ameliorative potential of its biosynthesized AuNPs (NL-AuNPs) against Cd-induced nephrotoxicity in rats. The presence of bioactive compounds in N. lotus was investigated by GC-MS in aqueous extract of NL. Gold nanoparticles were synthesized using aqueous extract of NL. Thirty rats were grouped into six (n = 5). Group 1 served as control, while group 2, 3, 4 and 5 received CdCl2 (10 mg/kg) orally for five days. Thereafter, groups 3, 4, and 5, respectively, received silymarin (75 mg/kg), 5 and 10 mg/kg NL-AuNPs, orally for 14 days, while group 6 received 10 mg/kg NL-AuNPs only. Rats were sacrificed after treatment, and biochemical parameters and kidney histopathology were evaluated. Bioactive compounds of pharmacological importance identified include pyrogallol, oxacyclohexadecan-2-one, 22-Desoxycarpesterol, 7,22-Ergostadienol, ß-sitosterol and Dihydro-ß-agarofuran. Cadmium caused nephrotoxicity in rats, as evidenced by significant (p < 0.05) increase in the levels of kidney function markers (serum urea and creatinine) and inflammatory markers (Interleukin-6 (IL-6) and Nuclear Factor-κB (NF-κB)) when compared with control. These changes were significantly (p < 0.05) ameliorated by the spherically-synthesized NL-AuNPs (25-30 nm) with the 5 mg/kg NL-AuNPs more potent against kidney damage induced by Cd in rats but high doses of NL-AuNPs (≥10 mg/kg) could be suggested toxic. NL possess phytochemicals capable of reducing gold salts to nanoparticle form, and doses up to 5 mg/kg could be considered safe for the treatment of renal damage occasioned by cadmium.