Gingerenone A is an orally active Nrf2-Gpx4 activator with an EC50 value of 24μM[1]. Nrf2-Gpx4 pathway is a key signaling pathway in cellular antioxidant defense[2]. Gingerenone A is commonly used for research on anti-inflammation, anti-diabetes, anti-tumor, and aging-related mechanisms[3].
In vitro, treatment of 3T3-L1 cells or L6 myotubes with Gingerenone A(2.5–40μM) for 5h induced phosphatidylinositide-3 kinase (PI3K) feedback activation and increased insulin receptor tyrosine phosphorylation in L6 myotubes and IRS-1 binding to the PI3K[4]. Treatmen of MCF7 and MDA-MB-231 cells with 80µM Gingerenone A increased ROS levels and induced G2/M phase delay and senescence[5].
In vivo, oral administration of high-fat diet (HFD)-induced obese mice with Gingerenone A (50mg/kg/day) for 15weeks significantly reduced fat mass increase and inhibited obesity and adipose tissue inflammation in mice by decreasing adipocyte size[6]. Oral treatment of dextran sodium sulfate (DSS)-induced secondary liver injury (SLI) mice with Gingerenone A(5, 20mg/kg, p.o., once a day for 7days) alleviated DSS-induced hepatic pathological damage, liver parameters, and cytokine levels, increased the antioxidant enzyme activities, attenuated ferroptosis in DSS-induced liver injury and upregulated Gpx4 expression[7].
References:
[1] Changtam, C., de Koning, H. P., Ibrahim, H., Sajid, M. S., Gould, M. K., & Suksamrarn, A. (2010). Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species. European journal of medicinal chemistry, 45(3), 941–956.
[2] Zhang, S., Sun, Z., Jiang, X., Lu, Z., Ding, L., Li, C., Tian, X., & Wang, Q. (2022). Ferroptosis increases obesity: Crosstalk between adipocytes and the neuroimmune system. Frontiers in immunology, 13, 1049936.
[3] Moaddel, R., Rossi, M., Rodriguez, S., Munk, R., Khadeer, M., Abdelmohsen, K., Gorospe, M., & Ferrucci, L. (2022). Identification of gingerenone A as a novel senolytic compound. PloS one, 17(3), e0266135.
[4] Chen, J., Sun, J., Prinz, R. A., Li, Y., & Xu, X. (2018). Gingerenone A Sensitizes the Insulin Receptor and Increases Glucose Uptake by Inhibiting the Activity of p70 S6 Kinase. Molecular nutrition & food research, 62(23), e1800709.
[5] Yu, T. J., Tang, J. Y., Shiau, J. P., Hou, M. F., Yen, C. H., Ou-Yang, F., Chen, C. Y., & Chang, H. W. (2022). Gingerenone A Induces Antiproliferation and Senescence of Breast Cancer Cells. Antioxidants (Basel, Switzerland), 11(3), 587.
[6] Suk, S., Kwon, G. T., Lee, E., Jang, W. J., Yang, H., Kim, J. H., Thimmegowda, N. R., Chung, M. Y., Kwon, J. Y., Yang, S., Kim, J. K., Park, J. H. Y., & Lee, K. W. (2017). Gingerenone A, a polyphenol present in ginger, suppresses obesity and adipose tissue inflammation in high-fat diet-fed mice. Molecular nutrition & food research, 61(10), 10.1002/mnfr.201700139.
[7] Chen, Y., Zhu, S., Chen, Z., Liu, Y., Pei, C., Huang, H., Hou, S., Ning, W., & Liang, J. (2022). Gingerenone A Alleviates Ferroptosis in Secondary Liver Injury in Colitis Mice via Activating Nrf2-Gpx4 Signaling Pathway. Journal of agricultural and food chemistry, 70(39), 12525–12534.