8-Prenylnaringenin is an orally active prenyl flavonoid for metabolic and cancer research

**Background**

Metabolic disorders, such as obesity and muscle atrophy, as well as various malignancies, remain significant challenges in global healthcare. The regulation of energy homeostasis and cellular proliferation often involves the activation of key signaling pathways, including the PI3K/Akt and AMPK pathways, as well as the modulation of Sirt1 and mitochondrial oxidative phosphorylation (OXPHOS). Targeting these pathways provides a strategic approach to treating muscle wasting, obesity, and tumor growth. In this context, we will introduce a potent prenyl flavonoid derived from the hop spike Humulus lupulus – 8-Prenylnaringenin.

**Definition**

8-Prenylnaringenin is an orally active prenyl flavonoid that acts as a SIRT1 activator and exhibits significant 8-Prenylnaringenin Biological Activity across various physiological systems. It is characterized by the 8-Prenylnaringenin Formula C20H20O5 and a molecular weight of 340.37.

**In Vitro and In Vivo Studies**

The 8-Prenylnaringenin Description highlights its multi-target efficacy. In 8-Prenylnaringenin In Vitro studies, the compound demonstrated strong antiproliferative effects against human colon cancer HCT-116 cells with an IC50 value of 23.83 μg/mL. In human glioblastoma U-118 MG cells, it showed cytotoxicity with an IC50 of approximately 138 μM, which was higher than that observed in normal BJ fibroblasts (IC50 = 172 μM). Furthermore, 8-Prenylnaringenin (0.001-20 μM; 48 h) reduced ROS production and SOD activity in MCF-7 breast cancer cells, while upregulating Sirt1 and OXPHOS complexes II, III, and V. It also inhibited BME cell invasion (IC50: 3-10 μM) and dose-dependently inhibited angiogenesis induced by bFGF and VEGF.

In 8-Prenylnaringenin In Vivo experiments, the compound showed significant therapeutic potential. In C57/BL6 mice, oral administration (0.00005-0.0005% wt/wt in diet) promoted recovery from immobilization-induced disuse muscle atrophy by activating the Akt phosphorylation pathway. In C57BL/6J male mice fed a high-fat diet, 8-Prenylnaringenin (0.0005%-0.005% wt/wt; 8 weeks) prevented obesity and fat accumulation in white adipose tissue by promoting adiponectin secretion and activating the AMPK pathway, which subsequently regulated SREBP-1 and PGC-1α expression. Additionally, in ovariectomized Sprague-Dawley rats, it suppressed serum LH/FSH levels and stimulated uterine weight. Regarding 8-Prenylnaringenin Cancer research, its ability to inhibit tumor cell proliferation and angiogenesis makes it a valuable tool for oncology studies. In conclusion, 8-Prenylnaringenin is a versatile prenyl flavonoid with potent activities in metabolic regulation and anticancer research.

Keywords

8-​Prenylnaringenin, 53846-50-7, PI3K, Akt, AMPK, Sirtuin, Reactive Oxygen Species (ROS), SOD, Phosphoinositide 3-kinase, PKB, Protein kinase B, AMP-activated protein kinase, Superoxide Dismutase, Inhibitor, inhibitor, inhibit

References

[1] Koosha S, et al. Antiproliferative and apoptotic activities of 8-prenylnaringenin against human colon cancer cells. Life Sci. 2019 Jul 3:116633.
[2] Mukai R, et al. 8-Prenylnaringenin promotes recovery from immobilization-induced disuse muscle atrophy through activation of the Akt phosphorylation pathway in mice. Am J Physiol Regul Integr Comp Physiol. 2016 Dec 1;311(6):R1022-R1031.
[3] Stompor M, et al. In Vitro Effect of 8-Prenylnaringenin and Naringenin on Fibroblasts and Glioblastoma Cells-Cellular Accumulation and Cytotoxicity. Molecules. 2017 Jun 30;22(7).
[4] Blanquer-Rosselló MM, et al. Effect of xanthohumol and 8-prenylnaringenin on MCF-7 breast cancer cells oxidative stress and mitochondrial complexes expression. J Cell Biochem. 2013 Dec;114(12):2785-94.
[5] Pepper MS, et al. 8-prenylnaringenin, a novel phytoestrogen, inhibits angiogenesis in vitro and in vivo. J Cell Physiol. 2004 Apr;199(1):98-107.
[6] Okada F, et al. 8-Prenylnaringenin suppresses obesity in high-fat diet-fed C57BL/6J mice via adiponectin secretion. J Clin Biochem Nutr. 2025 Jul;77(1):64-73.
[7] Christoffel J, et al. Effects of 8-prenylnaringenin on the hypothalamo-pituitary-uterine axis in rats after 3-month treatment. J Endocrinol. 2006 Mar;188(3):397-405.
[8] Hoffmann DB, et al. Effects of 8-Prenylnaringenin and Whole-Body Vibration Therapy on a Rat Model of Osteopenia. J Nutr Metab. 2016;2016:6893137.