Abstract
The present study investigated the neuroprotective and nephroprotective effects of the sponge Ircinia sp. ethyl acetate extract (ISPE) against persistent aromatic pollutants in vitro and in vivo. Different exponential experimental assays were applied to this study. An in vitro study to investigate the potential therapeutic effect of ISPE using antioxidants (for example, ABTS and DPPH) and anti-Alzheimer assays (inhibition of acetylcholinesterase); the in-vivo study was designed to evaluate the protective effect of ISPE as neuroprotective and nephroprotective against the destructive effect of PAH. Several assays included oxidative assays (LPO), antioxidant biomarkers (GSH, GST), and inflammatory and neurodegenerative biomarkers (PTK,SAA). Additionally, the results were confirmed using histopathological examination. The in silico screening study improved the in vitro and in vivo findings through interaction between the aryl hydrocarbon receptor (AHR) and the polyphenolic content of ISPE extract, which was determined using LCMSM. The results and discussion showed that ISPE exhibited a promising antioxidant and anti-acetylcholinesterase activity as evidenced by IC50 values of 49.74, 28.25, and 0.18 µg/mL in DPPH, ABTS, and acetylcholinesterase inhibition assays, respectively. In vivo, the study showed that animals receiving ISPE before poly aromatic hydrocarbons administration PAHs (Prot, ISPE) showed significant amelioration in kidney functions manifested by the reduction of serum urea, uric acid, and creatinine by 40.6%, 66.4%, and 134.8%, respectively, concerning PAH-injected mice (HAA). Prot, ISPE revealed a decline in malondialdehyde (MDA) and total proteins (TP) in kidney and brain tissues by 73.63% and 50.21%, respectively, for MDA and 59.82% and 80.41%, respectively, for TP with respect to HAA. Prot, ISPE showed significant elevation in reduced glutathione (GSH) and glutathione transferase (GST) in kidney and brain tissues and reduction in the inflammatory and pre-cancerous biomarkers, namely, serum protein tyrosine kinases (PTKs) and serum amyloid A (SAA). These findings were further supported by histopathological examination of kidney and brain tissues, which revealed normal structure approaching normal control. Metabolic profiling of ISPE using LC-MS-MS showed the presence of fourteen polyphenolic compounds belonging mainly to phenolic acids and flavonoids. In silico study revealed that all the tested compounds exerted certain binding with the aryl hydrocarbon receptor, where rutin showed the best fitting (ΔG = - 7.6 kcal/mol-1) with considerable pharmacokinetic and pharmacodynamic properties revealed from in silico ADME (Absorption, Distribution, Metabolism, and Excretion) study. Hence, it can be concluded that the Ircinia sponge showed a promising protective effect versus kidney and brain toxicity triggered by PAHs.