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BackgroundMounting evidences indicate that oxidative stress and neuroinflammation are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in-vitro neuroprotectant and inflammation inhibitor. However, little is known about its in-vivo effects. Zebrafish (Danio rerio) could be used as a convenient model in evaluation of toxicology and central nervous system (CNS) diseases. MethodsHere, we employ the in-vivo and in-silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established cognitive deficits model in zebrafish by intraperitoneal (i.p.) injection of AlCl3 (21 μg), and assessed their behaviors in the T-maze test. Proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well as acetylcholinesterase (AChE) activity, glutathione (GSH) levels were assayed 24 h after the AlCl3 injection. The intestinal flora of the zebrafish were investigated by 16 S rDNA high-throughput analysis. A marine fungal metabolite, butyrolactone I (BTL-I) was used to modulate zebrafish cognitive deficits evoked by AlCl3. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by in-silico tool of ADMETlab.ResultsBTL-I dose-dependently ameliorated AlCl3-induced cognitive deficits in zebrafish. While, AlCl3 treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brain of zebrafish, these effects except GSH reducing were reversed by 25–100 mg/kg BTL-I administration. 16S rDNA high-throughput sequencing of intestinal flora of zebrafish showed that AlCl3 decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacterial while BTL-I contributed to maintain the predominance of beneficial Gram-positive bacteria. The in-silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles.ConclusionsThe present findings suggest BTL-I as a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance. |
