Inhibition studies of some natural antioxidant substances on HMG-COA reductase and α-glucosidase enzymes to reduce cholesterol and glucose levels

Antioxidants play an important role in reducing the harmful effects of free radicals in the body. These compounds, which are obtained from natural sources, have received increasing attention in the health and food industries. Medicinal and aromatic plants, in particular, represent a rich source of antioxidants. These molecules neutralize or stabilize free radicals by reacting with them. In this study, four different antioxidant capacity assays—ABTS, DPPH, CUPRAC, and FRAP—were employed. Angolensin and Nimbidiol were used as natural antioxidant compounds in the thesis work. Additionally, the enzyme HMG-CoA reductase was investigated. This enzyme catalyzes the conversion of HMG-CoA (hydroxymethylglutaryl-CoA), one of the major intermediates required for cholesterol synthesis, into mevalonate. HMG-CoA reductase inhibitors constitute a class of drugs used to reduce cholesterol levels. These agents help control cholesterol and glucose levels and reduce the risk of cardiovascular disease. Among the inhibitors of HMG-CoA reductase and α-glucosidases, statins are known as the main representatives. Statins are a class of drugs used to lower cholesterol levels, acting by inhibiting this enzyme and thereby reducing cholesterol production in the liver. The obtained results demonstrated that, particularly on the α-glucosidase enzyme, Angolensin exhibited an IC₅₀ value of 0.3837 nM, while Nimbidiol showed an IC₅₀ value of 0.5651 nM. This finding indicates that Angolensin inhibits this enzyme, which plays a role in carbohydrate hydrolysis and glucose regulation, more effectively. Similarly, strong inhibition was also observed on the HMG-CoA reductase enzyme, which catalyzes the rate-limiting step of cholesterol biosynthesis. Angolensin demonstrated an IC₅₀ value of 2.2873 nM, whereas Nimbidiol exhibited an IC₅₀ value of 3.5831 nM, suggesting that these compounds may possess a statin-like mechanism of action. Furthermore, molecular docking analyses performed to determine interactions at the molecular level revealed that both Angolensin and Nimbidiol bind to the active sites of α-glucosidase and HMG-CoA reductase with high affinity. In conclusion, this study strongly demonstrates that Angolensin and Nimbidiol can be evaluated as new-generation, natural-source inhibitors and antioxidants with potential applications in the management of metabolic diseases.