Calycosin

Calycosin (CA, 7, 3-dihydroxy-4-methoxy isoflavone, C16H12O5) is one of the flavonoids extracted from astragalus root, also known as the typical phytoestrogens[1,2]. Calycosin is widely used in the pharmaceutical and food fields, and likely to be taken at low or high doses in daily life[3].

Treatment with Calycosin lower doses (6.25 or 12.5 μM) promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner[4]. Calycosin induced apoptosis of osteosarcoma cells (143B) via increasing caspase-3 protein levels, reducing intracellular Bcl-2B-cell lymphoma 2 (Bcl-2) protein expression and up-regulating apoptotic protease activating factor-1 (Apaf-1) in tumors[5]. Moreover, Calycosin induced apoptosis of osteosarcoma cells through the dose-dependent reducing proliferating cell nuclear antigen and the expression of Bcl-2, and increasing the cleavage of Poly (ADP-ribose) polymerase (PARP)[7]. Calycosin also has antioxidant properties (SC50 = 42.53±1.77 μg/mL)[9].

In estrogen receptor (ER)-positive MG-63 human osteosarcoma cells and MG-63 tumor-bearing nude mice, Calycosin induced apoptosis of osteosarcoma cells by increasing the expression of the phosphorylated-phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway proteins[6]. Calycosin can play an anti-inflammatory role by binding with IL-6. Calycosin inhibited kidney inflammation caused by diabetes by inhibiting the phosphorylation of IκBα and nuclear factor κB (NF-κB)/p65 in vitro and in vivo[8].

References:
[1]. Deng M, Chen H,et,al. Calycosin: a Review of its Pharmacological Effects and Application Prospects. Expert Rev Anti Infect Ther. 2021 Jul;19(7):911-925. doi: 10.1080/14787210.2021.1863145. Epub 2020 Dec 21. PMID: 33346681.
[2]. Wang, Yl., Liang, Yz., et,al. Simultaneous separation and determination of four main isoflavonoids in Astragali Radix by an isocratic LC/ESI-MS method. J. Cent. South Univ. 23, 303-309 (2016). https://doi.org/10.1007/s11771-016-3074-4
[3]. Zhang LJ, Liu HK, et,al. New isoflavonoid glycosides and related constituents from astragali radix ( Astragalus membranaceus ) and their inhibitory activity on nitric oxide production. J Agric Food Chem. 2011 Feb 23;59(4):1131-7. doi: 10.1021/jf103610j. Epub 2011 Jan 31. PMID: 21280630.
[4]. Li S, Wang Y, et,al. Calycosin Inhibits the Migration and Invasion of Human Breast Cancer Cells by Down-Regulation of Foxp3 Expression. Cell Physiol Biochem. 2017;44(5):1775-1784. doi: 10.1159/000485784. Epub 2017 Dec 6. PMID: 29241196.
[5]. Qiu R, Ma G, et,al.Antineoplastic effect of calycosin on osteosarcoma through inducing apoptosis showing in vitro and in vivo investigations. Exp Mol Pathol. 2014 Aug;97(1):17-22. doi: 10.1016/j.yexmp.2014.04.014. Epub 2014 May 4. PMID: 24797937.
[6]. Sun H, Yin M, et,al. Calycosin, a Phytoestrogen Isoflavone, Induces Apoptosis of Estrogen Receptor-Positive MG-63 Osteosarcoma Cells via the Phosphatidylinositol 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway. Med Sci Monit. 2018 Sep 5;24:6178-6186. doi: 10.12659/MSM.910201. PMID: 30182951; PMCID: PMC6134888.
[7]. Qiu R, Ma G, et,al.Clinical case report of patients with osteosarcoma and anticancer benefit of calycosin against human osteosarcoma cells. J Cell Biochem. 2019 Jun;120(6):10697-10706. doi: 10.1002/jcb.28360. Epub 2019 Jan 16. PMID: 30652346.
[8]. Elsherbiny NM, Said E, et,al. Renoprotective effect of calycosin in high fat diet-fed/STZ injected rats: Effect on IL-33/ST2 signaling, oxidative stress and fibrosis suppression. Chem Biol Interact. 2020 Jan 5;315:108897. doi: 10.1016/j.cbi.2019.108897. Epub 2019 Nov 11. PMID: 31726037.
[9].Toukam, Paul Djouonzo, et al. "Novel saponin and benzofuran isoflavonoid with in vitro anti-inflammatory and free radical scavenging activities from the stem bark of Pterocarpus erinaceus (Poir)." Phytochemistry Letters (2018): n. pag.