Syzygium zeylanicum (L.) DC. polyphenols exhibit anti-diabetic activity by modulation of ACC1, SGLT1, and GLP-1 genes and restoration of gut microbiota in overfeeding and high glucose exposure-induced diabetic zebrafish

[Display omitted] •Syzygium zeylanicum (L.) polyphenol extract reduced hyperglycemia in diabetes-induced zebrafish.•The increased expression of Glucagon-like peptide-1 was associated with decreased levels of Acetyl-CoA carboxylase 1 and Sodium–glucose cotransporters 1.•Remarkable anti-pathogenic and promoted probiotic bacteria in in vitro hyperglycemic conditions.•Restored the gut microbiome and metabolic pathways of diabetic zebrafish to those of normal. Syzygium zeylanicum (L.) DC. (SZL) has long been used as a traditional remedy for diabetes, but its underlying mechanisms of action remain unknown. This study aimed to investigate the antidiabetic activity of SZL polyphenols (SZL_EAF) via anti-hyperglycemic effect, regulation of gene expression related to lipid metabolism, glucose uptake and glucose utilization, and the gut microbiome modulation in diabetic zebrafish models. The results revealed that SZL_EAF exhibited a significant anti-hyperglycemic effect after five days of treatment. It also effectively regulated the expression of genes such as Acetyl-CoA carboxylase 1 (ACC1), Sodium–glucose cotransporters (SGLT1), and Glucagon-like peptide-1 (GLP-1) in diabetic zebrafish models. Additionally, SZL_EAF exhibited anti-pathogenic properties, promoted probiotics under hyperglycemic conditions, and restored the gut microbiome of diabetic zebrafish to normal levels. Overall, our finding indicated that SZL_EAF alleviates diabetes by reducing the blood glucose level, regulating the expression of diabetes-related genes, and restoring the gut microbiota.