Red ginger confers antioxidant activity, inhibits lipid and sugar metabolic enzymes, and downregulates miR-21/132 expression

Ginger is a spice and medicinal plant with several varieties. This study aimed to understand the antioxidant, antidiabetic, and antiobesity properties of red ginger (RG) ( Zingiber officinale var. rubrum ), through pharmacoinformatics coupled with in vitro studies. Additionally, the suppression of miR-21/132 expression by RG was studied. Two RG extracts were sequentially produced using hexane (RGH) and ethanol (RGE) and characterized using UHPLC-Q-Orbitrap HRMS-based untargeted metabolomics analysis. Seven compounds identified in RGE and six in RGH were subjected to molecular docking tests on iNOS, lipase, α-glucosidase, α-amylase, and FTO protein receptors. Overall, 5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8-bis(3,4,5-trihydroxyoxan-2-yl)-4H-chromen-4-one and pheophorbide A from RGE, and nictoflorin and rutin from RGH showed superior binding to most receptors. In vitro studies confirmed the ability of both RGE and RGH extracts to scavenge DPPH and ABTS radicals; inhibit activities of three metabolic enzymes, lipase (EC 50 85.58 and 105.50 μg/mL), α-glucosidase (EC 50 of 92.56 and 106.20 μg/mL), and α-amylase (EC 50 of 96.60 and 111.80 μg/mL). Ex vivo RGE and RGH considerably suppressed protein expression associated with obesity, diabetes, and oxidative stress, including miR-21/132. This presents new insights into the molecular mechanism of RG in combating metabolic syndrome; however, further in vivo and clinical trials are needed to validate these findings. • Red ginger extract shows potent antioxidant activity, comparable to Trolox. • Both hexane and ethanol extracts inhibit enzymes linked to obesity. • Red ginger suppresses miR-21/132, reducing metabolic syndrome risk. • Molecular docking reveals strong receptor binding of key ginger compounds. • This study reveals the potential of red ginger in combating diabetes through enzyme inhibtion.