Euryale ferox Salisb. (prickly water lily) is the only extent of the genus Euryale that has been widely distributed in China, India, Korea, and Japan. The seeds of E. ferox (EFS) have been categorized as superior food for 2000 years in China, based on their abundant nutrients including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids. These constituents exert multiple pharmacological effects, such as antioxidant, hypoglycemic, cardioprotective, antibacterial, anticancer, antidepression, and hepatoprotective properties. There are very few summarized reports on E. ferox, albeit with its high nutritional value and beneficial activities. Therefore, we collected the reported literature (since 1980), medical classics, database, and pharmacopeia of E. ferox, and summarized the botanical classification, traditional uses, phytochemicals, and pharmacological effects of E. ferox, which will provide new insights for further research and development of EFS-derived functional products.

Background: Mounting evidences indicate that oxidative stress, neuroinflammation, and dysregulation of gut microbiota 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 regarding its in vivo effects, whereas zebrafish (Danio rerio) could be used as a convenient in vivo model of toxicology and central nervous system (CNS) diseases. Methods: Here, we employed in vivo and in silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established a cognitive deficit model in zebrafish by intraperitoneal (i.p.) injection of aluminum trichloride (AlCl₃) (21 μg) and assessed their behaviors in the T-maze test. The proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) as well as acetylcholinesterase (AChE) activity or glutathione (GSH) levels were assayed 24 h after AlCl₃ injection. The intestinal flora variation of the zebrafish was investigated by 16S rDNA high-throughput analysis. The marine fungal metabolite, butyrolactone I (BTL-I), was used to modulate zebrafish cognitive deficits evoked by AlCl₃ and evaluated about its effects on the above inflammatory, cholinergic, oxidative stress, and gut floral indicators. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by the in silico tool ADMETlab. Results: BTL-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 brains of zebrafish, these effects, except GSH reduction, were reversed by 25–100 mg/kg BTL-I administration. Besides, 16S rDNA high-throughput sequencing of the intestinal flora of zebrafish showed that AlCl₃ decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacteria, while BTL-I contributed to maintaining the predominance of beneficial Gram-positive bacteria. Moreover, the in silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles. Conclusions: The present findings suggest that BTL-I is a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance.

The inhibition of dipeptidyl peptidase-IV (DPP-IV) is a promising approach for regulating the blood glucose levels in patients with type 2 diabetes (T2D). Oysters, rich in functional peptides, contain peptides capable of inhibiting DPP-IV activity. This study aims to identify the hypoglycemic peptides from oysters and investigate their potential anti-T2D targets and mechanisms. This research utilized virtual screening for the peptide selection, followed by in vitro DPP-IV activity assays to validate the chosen peptide. Network pharmacology was employed to identify the potential targets, GO terms, and KEGG pathways. Molecular docking and molecular dynamics simulations were used to provide virtual confirmation. The virtual screening identified LRGFGNPPT as the most promising peptide among the screened oyster peptides. The in vitro studies confirmed its inhibitory effect on DPP-IV activity. Network pharmacology revealed that LRGFGNPPT exerts an anti-T2D effect through multiple targets and signaling pathways. The key hub targets are AKT1, ACE, and REN. Additionally, the molecular docking results showed that LRGFGNPPT exhibited a strong binding affinity with targets like AKT1, ACE, and REN, which was further confirmed by the molecular dynamics simulations showcasing a stable peptide–target interaction. This study highlights the potential of LRGFGNPPT as a natural anti-T2D peptide, providing valuable insights for potential future pharmaceutical or dietary interventions in T2D management.