Abstract: To investigate the effect of co-fermentation on Astragalus membranaceus and Pueraria lobata blends (AP), in terms of their chemical components and bioactivities, an appropriate starter was selected and the fermentation process was optimized. This study compared the differences in physicochemical properties and bioactive components before and after fermentation and evaluated the enhancing effect of fermentation on the antioxidant capacity of AP blends and their efficacy in ameliorating insulin resistance. The results showed that fermentation with lactic acid bacteria significantly altered the bioactive composition of AP blends and enhanced their ability to improve insulin resistance. Lactiplantibacillus plantarum NX-11 was identified as the optimal starter strain for fermenting AP blends, and the optimal process parameters were determined as follows: temperature 37 ℃, inoculum size 5.3%, fermentation time 64 h, material dosage 2.4%, and A. membranaceus/P. lobata ratio 2:1. After fermentation, the contents of total phenols and total flavonoids increased significantly (P < 0.01), whereas the contents of polysaccharides and total saponins decreased significantly (P < 0.01). The scavenging rates against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl free radicals also significantly rose. Non-targeted metabolomics analysis revealed that the contents of eight potential hypoglycemic components including 4-hydroxyphenyllactic acid, L-(–)-3-phenyllactic acid, kaempferol, soyasaponin βg, coumestrol, quercetin, biochanin A-7-O-(6”-malonyl) glucoside, and luteolin-7-O-glucoside significantly increased after fermentation. Cell experiments showed that compared with the unfermented AP blend, the high-dose fermented AP blend increased the glycogen content by 36.55% and glucose uptake by 44.05%, decreased glucose-6-phosphatase (G-6-Pase) activity by 39.69%, and elevated high-density lipoprotein cholesterol (HDL-C) levels by 62.29%. In conclusion, fermentation with L. plantarum NX-11 can effectively enhance the efficacy of AP blends in ameliorating hepatic insulin resistance and glucose-lipid metabolic disorders. This finding opens up a new avenue for the development of a new generation of functional foods.

Key words: Astragalus membranaceus; Pueraria lobata; lactic acid bacteria; fermentation technology; non-targeted metabolomics; hypoglycemia