Desmethylglycitein, a metabolite of daidzein, is a potent tyrosinase inhibitor with an IC50 value of 9.2μM for mushroom tyrosinase [1]. Desmethylglycitein inhibits the development of Aedes aegypti larvae by strongly suppressing the activity of glutathione S-transferase Noppera-bo, with an IC50 value of 0.287μM[2]. Desmethylglycitein simultaneously reduces Pin1 isomerase activity and the downstream activation targets of Pin1 to suppress esophageal cancer growth [3]. Desmethylglycitein has been widely used to inhibit neuronal cell death and alleviate oxidative stress[4].
In vitro, Desmethylglycitein treatment for 72 hours significantly inhibited the proliferation of MCF10CA1a cells, with an IC50 value of 12.4μM [5]. Treatment with 80μM Desmethylglycitein for 8 days significantly inhibited adipogenesis in 3T3-L1 preadipocytes and reduced the expression of PPAR-γ and C/EBP-α[6].
In vivo, Desmethylglycitein treatment via a single oral dose of 5mg/kg improved the cognitive impairment caused by scopolamine in mice within one hour, and enhanced the learning and memory abilities in the Y-maze test[7]. Intraperitoneal injection of 25mg/kg dose of Desmethylglycitein was administered every other day for 20 days, which significantly inhibited the growth of HCT-116 xenograft tumors in mice and reduced the activities of CDK1 and CDK2 within the tumors[8].
References:
[1] Chang T S, Ding H Y, Lin H C. Identifying 6, 7, 4′-trihydroxyisoflavone as a potent tyrosinase inhibitor[J]. Bioscience, biotechnology, and biochemistry, 2005, 69(10): 1999-2001.
[2] Inaba K, Ebihara K, Senda M, et al. Molecular action of larvicidal flavonoids on ecdysteroidogenic glutathione S-transferase Noppera-bo in Aedes aegypti[J]. BMC biology, 2022, 20(1): 43.
[3] Lim T G, Lee S Y, Duan Z, et al. The prolyl isomerase Pin1 is a novel target of 6, 7, 4′-trihydroxyisoflavone for suppressing esophageal cancer growth[J]. Cancer Prevention Research, 2017, 10(5): 308-318.
[4] Ko Y H, Kwon S H, Kim S K, et al. Protective effects of 6, 7, 4′-trihydroxyisoflavone, a major metabolite of daidzein, on 6-hydroxydopamine-induced neuronal cell death in SH-SY5Y human neuroblastoma cells[J]. Archives of Pharmacal Research, 2019, 42(12): 1081.
[5] Lee J H, Lee H J. A daidzein metabolite, 6, 7, 4′-trihydroxyisoflavone inhibits cellular proliferation through cell cycle arrest and apoptosis induction in MCF10CA1a human breast cancer cells[J]. Journal of the Korean Society for Applied Biological Chemistry, 2013, 56(6): 695-700.
[6] Seo S G, Yang H, Shin S H, et al. A metabolite of daidzein, 6, 7, 4′‐trihydroxyisoflavone, suppresses adipogenesis in 3 T 3‐L 1 preadipocytes via ATP‐competitive inhibition of PI 3 K[J]. Molecular nutrition & food research, 2013, 57(8): 1446-1455.
[7] Ko Y H, Kim S Y, Lee S Y, et al. 6, 7, 4′-Trihydroxyisoflavone, a major metabolite of daidzein, improves learning and memory via the cholinergic system and the p-CREB/BDNF signaling pathway in mice[J]. European Journal of Pharmacology, 2018, 826: 140-147.
[8] Lee D E, Lee K W, Jung S K, et al. 6, 7, 4′-trihydroxyisoflavone inhibits HCT-116 human colon cancer cell proliferation by targeting CDK1 and CDK2[J]. Carcinogenesis, 2011, 32(4): 629-635.