Background/purpose: Tocopherol from raw pumpkin seeds has been reported to be effective in
the alleviation of diabetes through its antioxidant activities. This study evaluates the antidiabetic
activities of the tocopherol fraction of raw seeds of Cucurbita pepo L. (CPSE) in a diabetic
rat model. In addition, the putative action mechanisms of its botanicals were
computationally investigated.
Methods: Seed water activity (Aw) was assessed. Tocopherol was extracted and quantified
from raw seed oil. The effect of CPSE was studied in poloxamer-407 (PX-407)-induced type 2
diabetic Wistar rats. Glycemic, insulinemic, and lipid profiles, as well as lipid peroxidation status,
were evaluated. Glucagon like peptide-1 (GLP-1) content in the cecum was evaluated and histopathological analysis of the pancreas was performed. Further, HYBRID and FRED docking
were performed for 10 documented CPSE botanicals, for putative action mechanisms concerning
three proteins [protein-tyrosine phosphatase 1B (PTP-1B), peroxisome proliferatoractivated
receptor gamma (PPAR-g), and dipeptidyl peptidase IV (DPP-IV)] known to have diabetic
therapeutic potential.
Results: The Aw of raw seeds was found to be 0.544 0.002. Using tocopherol standards, HPLC
determination of CPSE revealed the presence of tocopherol isomers (a, b, g, and d). The
tocopherol content was found to be 107.4 2.9 mg/100 g of CPSE. When compared to diabetic
control (DC) rats, the CPSE-treated diabetic rats presented a significant amelioration of glycemia,
insulinemia, and lipid dysmetabolism. A remarkable reduction in oxidative markers and
improved cecal and pancreatic characteristics were also observed. Tocopherol isomers have
shown a considerable interaction potential with the aforesaid proteins in docking.
Conclusion: The results provide pharmacological evidence of CPSE as an antihyperglycemic
mediated by the interaction of various botanicals with multiple targets operating in diabetes
mellitus (DM).