Simultaneous anti-diabetic and anti-vascular calcification activity of Nocardia sp. UTMC 751

Alpha-amylase can act as a significant player in causing hyperglycaemia, leading to protein glycation, which is the main complication in this condition, besides causing vascular calcification (VC), an important vascular failure caused due to this. In order to find a natural source of the biocompounds with inhibitory effects on α-amylase, 15 fermentation broth extracts of actinobacteria (FBEA) (200 μg ml^-1 ) have been screened. Finally, the effects of the most efficient FBE have been investigated on osteopontin (OPN, a VC marker) mRNA level in the vascular smooth muscle cells under the calcification conditions, and the chemical constituents of the most efficient FBE were analysed using gas chromatography and mass spectrometry (GC-MS) analysis. The tested FBEA showed anti-amylase (7·2-21%) and anti-denaturation (7·5-37%) activities. Among the tested FBEA, Nocardia sp. UTMC 751 FBE showed the highest anti-amylase activity (21%). This treatment group also displayed the minimum fructosamine and the maximum thiol groups content. In addition, this FBE reduced the mRNA level of the OPN (fourfold). The GC-MS analysis demonstrated the existence of three volatile and known antioxidants including pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)-, pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(phenylmethyl)- and methyl ester of 3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid in the FBE of Nocardia sp. UTMC 751. The results indicated that Nocardia sp. UTMC 751 is a considerable source of bioactive compounds that are effective against the direct and indirect pathological targets involved in diabetes. This study highlights the significant potential of rare Actinomycetes in producing pharmaceutically important biocompounds.

Actinobacteria are one of the best natural libraries for discovering drugs. Various commercial drugs have been developed against infectious and metabolic disorders from actinobacteria; however, there is no report on their simultaneous inhibitory effect against diabetes, a life-threatening disease, and its related pathological processes, like inflammation and vascular calcification (VC). In this research, after several screening, Nocardia sp. UTMC 751 was introduced as the first microbial source exhibiting a simultaneous inhibitory activity on the targets, including hyperglycaemia and protein glycation, and other involved pathological processes like inflammation and VC.