Beyond a spice: harnessing the anti-inflammatory potential of Indonesian ginger ̶ insights into gingerenones and isogingerenone

Indonesian ginger varieties, including sunti/red ginger (Zingiber officinale var. rubrum; ZOR) and emprit ginger (Zingiber officinale var. amarum; ZOA), are rich in bioactive compounds with anti-inflammatory properties. This study aimed to evaluate the anti-inflammatory potential of specific ginger compounds and compare the efficacy of two Indonesian ginger variants ZOR and ZOA. A computational approach was used to identify active compounds based on drug likeness and probable activity. Molecular docking simulations were performed to assess their interaction with key inflammatory proteins JAK2, STAT3, PI3K and AKT-1. Additionally, in vitro experiments were conducted to evaluate the anti-oxidant and anti-inflammatory effects of ZOR and ZOA. The identified 4 compounds from ginger—Isogingerenone B, Gingerenone B, Gingerenone A and Gingerenone C ginger demonstrated significant potential for modulating inflammation pathways, showing probable activity exceeding 0.5. Molecular docking confirmed their binding to the active sites of JAK2, STAT3, PI3K and AKT-1. ZOR exhibited greater efficacy in free radical scavenging and suppressing NO, iNOS, TNF-α and NF-κB in LPS-treated RAW 264.7 macrophages compared to ZOA. This study highlights the anti-inflammatory potential of Isogingerenone B, Gingerenone B, Gingerenone A and Gingerenone C from ginger. Further research is needed to identify and characterize the specific compounds in ZOR that contribute to its enhanced biological activity, providing deeper insights into its therapeutic potential.