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- Diabetes mellitus (DM) is a metabolic condition characterized by chronic hyperglycemia caused by insulin secretion and action deficiencies. Type 2 DM results from impaired insulin secretion by β cells of the pancreas and unresponsive signals between insulin-target tissues and insulin. Most drugs used in treating DM have one or more negative side effects and are primarily focused on lowering blood glucose levels rather than addressing the underlying mechanisms that cause DM. Therefore, developing new drugs to address these underlying causes is a priority. This study seeks to explore the antidiabetic roles of phytochemicals from Chrysobalanus orbicularis Hook. f. (Chrysobalanaceae) using in silico techniques to identify a novel regimen for DM. High-performance liquid chromatography (HPLC) analysis of C. orbicularis identified four bioactive compounds (sapogenin, delphinidin, cyanidin, and petunidin). To screen and find acceptable potential hit compound(s), these compounds were subjected to molecular docking to decipher their interactions with some proteins identified in the literature as being involved in the pathophysiology of DM (dipeptidyl peptidase IV, alpha-amylase, glucagon-like peptide−1 receptor, alpha-glucosidase, poly[ADP-ribose] polymerase 1, and G-protein coupled bile acid receptor 1). Petunidin had the best interaction with most of the proteins based on the precision docking score and MM-PBSA analysis. More importantly, parameters for discovering drugs for biotherapeutic candidates, viz., distribution, absorption, metabolism, toxicity, and excretion, were calculated for petunidin. Our findings suggest that petunidin could be a promising new therapeutic target for treating DM.
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- Chrysobalanus orbicularis is a medicinal plant present in West Africa in the Itsekiri speaking part of Nigeria. It is used conventionally in diabetes mellitus management. This research investigates the ameliorative activity of the aqueous leaf extract of C. orbicularis in a streptozotocin-induced diabetic rat model. Freshly prepared streptozotocin (40 mg/kg body weight [BW]) was administered intraperitoneally to induce diabetes. Three diabetic groups were placed on aqueous leaf extract of C. orbicularis at 11.076, 22.134, and 44.268 mg/kg BW respectively; a group was placed on metformin (44.28 mg/kg BW), and the other two groups were the diabetic control and normal control. The experiment lasted for 28 days, thereafter, fasting blood glucose levels and body weight variations were recorded. Also, glycogen level, antioxidant enzyme, hexokinase and glucose-6-phosphatase activities, malonaldehyde (MDA) as well as glucose transporters 2 and 4 levels were analyzed using standard procedures. Diabetic rats administered aqueous extract of C. orbicularis leaf significantly (p < 0.05) decreased the fasting blood glucose and MDA levels, and glucose-6-phosphatase activity. In addition, administration of aqueous extract of C. orbicularis leaf to diabetic rats demonstrated a momentous increase in liver glycogen level, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, glutathione transferase, and hexokinase activities as well as GLUT-2 and GLUT-4 levels. The data from this study suggest that the aqueous extract of C. orbicularis leaf may be beneficial in the management of diabetic mellitus and its secondary effects.
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