Polyphenols of Zingiber roseum Leaf as a Potential Source of α-Glucosidase Inhibitors for Type-2 Diabetes Management: LC–MS/MS, Pharmacological and Computational Analysis

Zingiber roseum Roscoe, a plant belonging to the Zingiberaceae family, has been extensively utilized in traditional medicine for its efficacy in treating diabetes, inflammation, and cancer. Earlier studies focused on the rhizomes of Z. roseum, which are rich in secondary plant metabolites such as phenolic acids, flavonoids, terpenoids, gingerols, and shogaols. However, fresh research suggests that the leaves may have similar or perhaps greater pharmacological potential. Therefore, the objective of this study was to identify and characterize the bioactive polyphenolic compounds responsible for antidiabetic action as well as to assess the antidiabetic properties of the methanolic extract of Z. roseum leaves (ZrlME). First, 16 phenolic compounds were identified and quantified in ZrlME by LC–MS/MS analysis. In addition, the in vitro results demonstrated that ZrlME had substantial α-glucosidase inhibitory activity, as evidenced by the low IC50 value of 570 μg/mL which was more pronounced than the IC50 value of acarbose (585 μg/mL). Furthermore, for the 20 day treatment period, both the 400 and 200 mg/kg BW dosages of ZrlME exhibited a substantial (P < 0.001) decrease in blood glucose levels in diabetic mice. Among the polyphenols, miquelianin, nicotiflorin, astragalin, kaempferol, and acacetin demonstrated higher binding affinity (−7.5 to −6.8 kcal/mol) to α-glucosidase enzyme (PDB ID: 5NN8) than the reference standard, acarbose (−6.6 kcal/mol) and a significant number of hydrogen bonds in the enzyme’s active site under molecular docking studies. Molecular dynamics simulations (MDS) also affirmed the stability of binding of miquelianin and nicotiflorin against α-glucosidase. Moreover, the pharmacokinetic parameters prediction, bioactivity and toxicity assessment ensured the safety and efficacy of those key compounds, suggesting the potential of Z. roseum leaves as a valuable natural source for the development of antidiabetic drugs.