Fermented red pepper paste (kochujang) modulates glucose metabolism and gut microbiota in parasympathetic suppression: Network pharmacology and In vivo study

Abstract

We aimed to explore the relationship between Korean fermented red pepper paste, kochujang compounds, and the genes associated with type 2 diabetes (T2DM) and parasympathetic nervous system (PNS) dysfunction by network pharmacology. The study aimed to validate the kochujang efficacy on glucose metabolism in PNS-suppressed rats. Male Sprague-Dawley rats were intraperitoneally injected with scopolamine at 2 mg/kg body weight daily for 8 weeks. They were divided into four groups according to kochujang types: 1% traditionally-made kochujang (TMK) in 43% fat diets based on the capsaicin content and factory-made kochujang (FMK). The control and normal-C groups received a 43% fat diet. In the network pharmacology analysis, kochujang contained 26 chemical compounds: carotenoids, isoflavonoids, capsaicin-related compounds, and phytosterols. It highlighted critical genes, including AKT1, B-cell lymphoma-2(BLC2), catenin beta-1(CTNNB1), and caspase-3(CASP3) as the primary targets for treating T2DM and PNS suppression. Functional enrichment analysis indicated the involvement of kochujang compounds in endopeptidase activity and G-protein-coupled receptor activity relevant to diabetes and neuropathy. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed associations with cancer, infection and inflammation, lipid metabolism, and diabetic complication-related pathways. FMK and TMK consumption improved glucose homeostasis and lipid profiles by modulating serum insulin and glucagon-like peptide-1 concentration and insulin resistance in scopolamine-induced rats. Oral glucose tolerance tests showed reduced glucose intolerance in kochujang-treated groups, especially high capsaicin-containing TMK. Kochujang mitigated liver damage and inflammation and modulated the gut microbiota composition to prevent the inhibition of insulin and neurotransmitter secretion through potentiating cAMP and calcium signaling pathways. In conclusion, high capsaicin-containing kochujang exhibited promising therapeutic effects against T2DM induced by PNS suppression through gut microbiota modulation.