Background: Diabetes Mellitus (DM) can appear due to the absence of insulin (DM1- type 1) or poor response of cells to insulin (DM2-type 2). Even though DM1 cannot be controlled using general treatments, DM2 can be easily controlled or prevented using pharmaceuticals, nutraceuticals, or dietary practices. Ceylon cinnamon (Cinnamomum zeylanicum) is one such natural remedy that has been consumed against elevated blood glucose levels in the past. Cinnamon and different types of cinnamon extracts have been scientifically tested for their activities on the inhibition of α-amylase and α-glucosidase enzymes that are responsible for carbohydrate metabolism and are effective in blood glucose regulation. However, the combined effect of aqueous and ethanol extracts of cinnamon bark on blood glucose regulation is still lacking. In this study, Water Extract of Cinnamon (CWE), Ethanol Extracts of Cinnamon (hot ethanol extract of cinnamon-CHEE, cold ethanol extract of cinnamon-CEE, and 50% ethanol extract of cinnamon- CEE-50) were studied for their sugar-controlling properties. Objectives: This study was performed to identify the efficacy of different cinnamon extracts on the inhibition of α-amylase and α-glucosidase enzymes, followed by animal studies to confirm the use of the extracts in nutraceutical formulations. Methods: Water and ethanol-based extraction method was used to prepare cinnamon extracts. These extracts have been scientifically tested for their activities on the inhibition of α-amylase and α-glucosidase enzymes. Molecular docking studies were used to identify the binding of the active molecules to the substrate binding sites of α-amylase and α-glucosidase. In-vivo time dependence postprandial blood glucose regulation studies have been performed with healthy Wistar male rats. Results: Yields of the CHEE, CEE, and CWE were 14±2%, 12±2%, and 8±1% respectively. According to the LCMS data, the major component in the CEE was cinnamaldehyde. Both CWE and CEE were subjected to the Total Polyphenol assay (TPC) and Total Flavonoids (TFC) assays. The TPC of CWE and CEE were 117±1 mg (Gal)/g and 170±10 mg (Gal)/g, while the TFC of CWE and CEE were 359±1 mg (Qc)/g and 254±4 mg (Qc)/g, respectively. In the α-amylase inhibition assay, Acarbose; a known α-amylase inhibitor, and CEE showed IC50 values of 65.4 ppm and 2.6 ppm, while CWE failed to show inhibition against α-amylase. In the α-glucosidase inhibition assay, Acarbose; a known α-amylase inhibitor, CEE, and CWE showed IC50 values of 312 ppm, 4.5 ppm, and 1.3 ppm, respectively. In-vivo time dependence postprandial blood glucose regulation studies that have been performed with healthy Wistar male rats showed a lowering of blood glucose concentrations by 22%, 11%, and 10% of glucose at 30 min, 60 min, and 90 min compared to the control group. Conclusion: The CEE contains polyphenols and flavonoids and is effective in inhibiting both α- amylase and α-glucosidase. The CWE also contains polyphenols and a comparatively higher level of flavonoids and is effective in inhibiting α-glucosidase while not affecting α-amylase inhibition. Overall, the IC50 data, TPC data, and TFC data proposed that the inhibition of carbohydrate hydrolyzing enzymes by polyphenols may depend on the polarity of particular polyphenols. Based on the rat trials, it can be concluded that the 1:1 combination of CWE and CEE may be useful in formulating postprandial blood glucose level-regulating nutraceuticals.
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