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 (EC₅₀ 85.58 and 105.50 μg/mL), α-glucosidase (EC₅₀ of 92.56 and 106.20 μg/mL), and α-amylase (EC₅₀ 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.