Natural products from plants targeting key enzymes for the future development of antidiabetic agents

Covering: 2000 to January 2023Diabetes is a metabolic disease of serious concern nowadays, with a negative economic impact. In 2021, the International Diabetes Federation estimated that more than 537 million adults live with diabetes, causing over 6.7 million deaths in that year. Intensive scientific research on medicinal plants in the last 100 years reveals that herbal drugs have been an essential source of products for developing antidiabetic agents acting on different physiological targets. This review summarizes recent research from 2000 to 2022 on plant natural compounds affecting selected crucial enzymes (dipeptidyl peptidase IV, diacylglycerol acyltransferase, fructose 1,6-biphosphatase, glucokinase, and fructokinase) involved in glucose homeostasis. Enzyme-aimed treatments usually induce reversible inhibition, irreversible by covalent changes of the objective enzymes, or bind non-covalently but so tightly that their inhibition is irreversible. Depending on the binding site, these inhibitors could be orthosteric or allosteric; in any case, the desired pharmacological action is achieved. One crucial advantage of targeting enzymes in drug discovery is that the required assays are usually simple, using biochemical experiments capable of analyzing enzyme activity.