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.

Background/Objectives: Ethnopharmacological studies indicates that plant-based infusions are usually consumed by some people in advanced stages of diabetes, that is, when poor pancreatic dysfunction coexists with insulin resistance (IR). Current treatments aim to prevent β-cell deterioration by promoting improved insulin function and/or enhancing pancreatic function to avoid the development of hyperglycemia. Therefore, Croton guatemalensis (Cg) and Eryngium cymosum (Ec), two medicinal plants with potential insulin-sensitizing effects described in previous studies, were assessed on parameters related to IR and on the architecture of pancreatic islets in rats exposed to a syrup containing 8.8% glucose and 5.2% fructose in drinking water. Methods: After an 8-week exposure to syrup, plant extracts were orally administered for four weeks at traditional doses (Cg: 30 mg/kg body weight; Ec: 470 mg/kg body weight). Body weight, food intake, and drinking water consumption were monitored. At the end of the study, IR surrogate indices were calculated, metabolic assays were performed, and white adipose tissues, liver, gastrocnemius muscle, and pancreas were extracted in fasting and postprandial state for lipid quantification (liver), measurement of Akt phosphorylation status by western blot (liver and muscle), and determination of insulin content by immunohistochemistry (pancreatic islets). Results: Both species decreased hepatic lipid content without promoting significant changes in visceral adiposity. Although they did not improve surrogate markers of fasting IR, both ameliorated insulin function, glucose tolerance, and restored the glucose-stimulated insulin secretory response in metabolic tests. Cg restored the insulin signaling response in liver and muscle, whereas Ec only did so in muscle. Moreover, both appeared to enhance insulin pancreatic content or restore pancreatic islet population. Conclusions: Cg and Ec can reverse the IR phenotype in a tissue-specific manner and improve pancreatic function.