Amentoflavone is an orally active phenolic compound with anti-inflammatory, anti-oxidation, anti-microbial, and anti-cancer activities [1]. Amentoflavone exerts anti-SARS-CoV-2 effect via binding to the main protease (Mpro/3CLpro), spike protein receptor binding domain (RBD), and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 [2]. Amentoflavone has been widely used to inhibit the growth of malignant tumors, induce apoptosis of tumor cells, and suppress angiogenesis[3].
In vitro, Amentoflavone treatment for 48 hours significantly inhibited the proliferation of HepG2, T24, and A549 cells, with IC50 values of 9.13, 10.67, and 8.36µM, respectively[4]. Treatment with 5µM Amentoflavone for 24 hours significantly induced cell cycle arrest and autophagy in BV-2 cells, and increased the expression of CDK2, p27Kip1, and p53/p-p53[5]. Treatment with 60µM Amentoflavone for 1 hour significantly inhibited the nuclear translocation of p65 and the activation of NF-κB in RAW 264.7 cells induced by lipopolysaccharide (LPS), and reduced NO production[6].
In vivo, Amentoflavone treatment via oral administration at a dose of 25mg/kg daily for 3 days prevented pilocarpine-induced epilepsy in mice, inhibited the activation and expression of NF-κB, and suppressed the hyperexcitability of hippocampal neurons [7]. Oral administration of Amentoflavone at a dose of 100mg/kg weekly for 2 weeks significantly inhibited tumor growth and prolonged the survival of CT26 xenograft tumor-bearing mice[8].
References:
[1] Yu S, Yan H, Zhang L, et al. A review on the phytochemistry, pharmacology, and pharmacokinetics of amentoflavone, a naturally-occurring biflavonoid[J]. Molecules, 2017, 22(2): 299.
[2] Xiong X, Tang N, Lai X, et al. Insights into amentoflavone: A natural multifunctional biflavonoid[J]. Frontiers in Pharmacology, 2021, 12: 768708.
[3] Tuli H S, Joshi H, Vashishth K, et al. Chemopreventive mechanisms of amentoflavone: recent trends and advancements[J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2023, 396(5): 865-876.
[4] Wang C G, Yao W N, Zhang B, et al. Lung cancer and matrix metalloproteinases inhibitors of polyphenols from Selaginella tamariscina with suppression activity of migration[J]. Bioorganic & medicinal chemistry letters, 2018, 28(14): 2413-2417.
[5] Liu Z, Wang F, Ma H, et al. Amentoflavone induces cell cycle arrest, apoptosis, and autophagy in BV-2 cells[J]. Frontiers in Bioscience-Landmark, 2020, 25(5): 798-816.
[6] Woo E R, Lee J Y, Cho I J, et al. Amentoflavone inhibits the induction of nitric oxide synthase by inhibiting NF-κB activation in macrophages[J]. Pharmacological Research, 2005, 51(6): 539-546.
[7] Zhang Z, Sun T, Niu J, et al. Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects[J]. Neural regeneration research, 2015, 10(7): 1125-1133.
[8] Fang Y J, Chen C H, Ku H J, et al. Amentoflavone inhibits colorectal tumor growth, stemness, and metastasis, prolonging survival through GLI-1/IL6/STAT3 axis targeting[J]. Biomedicine & Pharmacotherapy, 2025, 191: 118435.