Diabetes-Related Mechanisms of Action Involved in the Therapeutic Effect of Croton Species: A Systematic Review

Over the years, ethnopharmacological and phytochemical investigations have been conducted to understand the potential effects of the Croton genus on several diseases. It has been revealed that these terpenoid-rich species traditionally used to treat gastrointestinal diseases, heal wounds, and relieve pain have a wide range of therapeutic effects; however, those used to treat diabetes, as well as their action mechanisms, have not been reviewed so far. Therefore, the main objective of this review was to compile all Croton species that have shown pharmacological effects against diabetes and describe their action mechanisms. Through a search of the literature, 17 species with hypoglycemic, antihyperglycemic, antilipidemic, antihypertensive, antioxidant, and anti-inflammatory effects were found. Among the mechanisms by which they exerted these effects were the inhibition of α-glucosidases, the promotion of insulin secretion, and the increase in glucose uptake. Interestingly, it was found that some of them may have antihyperglycemic properties, although there were no ethnopharmacological reports that support their traditional use. Moreover, others only presented studies on their hypoglycemic effect in fasting, so further works are encouraged to describe the mechanisms involved in lowering fasting blood glucose levels, such as hepatic glucose production, especially for C. cajucara, C. cuneatus, C. gratissimus var. gratissimus, C. guatemalensis, and C. membranaceus. It is expected that this review contributes to the plant science knowledge of the genus, and it can be used in future references on the identification and development of new molecules/phytomedicines that help in the treatment of diabetes.