Evaluation of potential antidiabetic and antibacterial activities of Bolivian nutraceutical plants

Abstract: Type 2 diabetes mellitus is a health problem worldwide that requires the search for novel therapeutic strategies. Natural products are a source of potential therapies due to their acceptation and traditional use or consumption. This study aims to evaluate selected Bolivian traditionally consumed plants as potential antidiabetic products using animal models. Besides, focused on the urinary tract infection, as one common complication in diabetes, the antibacterial effect was evaluated in the uroepithelial in vitro infection. Initially, the screening of glycemia-reducing effect, performed in healthy Swiss albino mice, showed that the hydroethanolic extracts of Amaranthus caudatus, Chenopodium quinoa, Lupinus mutabilis, and Smallanthus sonchifolius reduced the postprandial glycemia and the glucose tolerance during the oral glucose tolerance test. Moreover, the in vitro insulin secretion in mice pancreatic islets was stimulated only by Amaranthus caudatus, Chenopodium quinoa and Lupinus mutabilis. Based on the results of the screening study, we continued evaluating the antidiabetic effect of Amaranthus caudatus and Lupinus mutabilis using the Goto-kakizaki (GK) type 2 diabetic rats and the respective healthy control the Wistar (W) rats. The oral administration of A. caudatus and L. mutabilis, separately, improved the glucose tolerance and augmented serum insulin levels in both GK and W rats, in a dose-dependent way. The daily oral administration of each extract (1000 mg/kg b.w.) during 21 days improved the glucose tolerance, increased the serum insulin and reduced the glycated hemoglobin. Additionally, the insulin secretion was stimulated in islets isolated from treated animals. Furthermore, both extracts stimulated the in vitro insulin secretion in a glucose-independent manner. In perifused islets, the insulin secretion was augmented in low glucose (3 mM), increased gradually in high glucose (16.7 mM), and was restored to basal levels when each extract was removed. The mechanism behind the stimulation of insulin secretion of A. caudatus mainly involved the protein kinases A and C activation, while the effect was partially dependent on the L-type calcium channel and the G protein-coupled exocytosis. L. mutabilis effect depended on L-type calcium channels, PKC and PKA systems, G protein-coupled exocytosis and K-ATP channels. The main constituents found in A. caudatus were amino acids, sugars, and polyphenols, while L. mutabilis extract has higher amounts of alkaloids. A caudatus is traditionally used to treat disorders in the urinary tract. L. mutabilis, on the other hand, is well known for its glycemic lowering effect. Since there is a globally increase of antibiotic resistance, we sought to investigate the possible role of these two medicinal plants in the treatment of urinary tract infections (UTI). We observed that the hydroethanolic extracts from A. caudatus and L. mutabilis prevented the uropathogenic E. coli (UPEC) in vitro infection. A. caudatus inhibited the first steps of infection, adhesion, and invasion of UPEC, including ESBL-producing E. coli and other uropathogenic bacteria, including multidrugresistant strains. The effect was attributed to the decrease of gene expression of uroplakin1a and caveolin-1. L. mutabilis inhibited UPEC adhesion and interfered in the adhesion process of other Gram-negative and positive uropathogenic bacteria, an effect observed in high glucose concentrations. This effect was explained by a downregulation of gene and protein expression of uroplakin-1a and an upregulation of the antimicrobial peptide RNase 7. Furthermore, the UPEC biofilm formation was inhibited only in low glucose conditions. In summary, this study provides information about the potential use of Amaranthus caudatus and Lupinus mutabilis, as a nutraceutical product, since they are part of the traditional Bolivian diet. The hydroethanolic extracts of Amaranthus caudatus and Lupinus mutabilis have pharmacological properties being promising candidates to treat type 2 diabetes mellitus and to prevent urinary tract infections.