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.

毛蕊花素（CA, 7, 3-dihydroxy-4-methoxy isflavone, C16H12O5）是从黄芪中提取的黄酮类化合物之一，也被称为典型的植物雌激素[1,2]。毛蕊花素广泛应用于制药和食品领域，日常生活中可能会以低剂量或高剂量服用[3]。

用较低剂量（6.25 或 12.5 μM）的 Calycosin 治疗可促进乳腺癌细胞的增殖，但较高剂量会显着降低 MCF-7 和 T47D 细胞的活力。此外，发现较高剂量的毛蕊花素以剂量依赖性方式抑制两种细胞系的迁移和侵袭[4]。毛蕊花素通过增加 caspase-3 蛋白水平、降低细胞内 Bcl-2B 细胞淋巴瘤 2 (Bcl-2) 蛋白表达和上调肿瘤中凋亡蛋白酶激活因子-1 (Apaf-1) 诱导骨肉瘤细胞凋亡 (143B) [5].此外，毛蕊花素通过剂量依赖性降低增殖细胞核抗原和 Bcl-2 的表达，并增加聚（ADP-核糖）聚合酶（PARP）的裂解，诱导骨肉瘤细胞凋亡[7]。毛蕊花素还具有抗氧化特性 (SC50 = 42.53±1.77 μg/mL)[9]。

在雌激素受体 (ER) 阳性 MG-63 人骨肉瘤细胞和 MG-63 荷瘤裸鼠中，毛蕊花素通过增加磷酸化磷脂酰肌醇 3-激酶 (PI3K)/Akt 的表达诱导骨肉瘤细胞凋亡/mTOR 通路蛋白[6]。 Calycosin可通过与IL-6结合发挥抗炎作用。毛蕊花素在体内外通过抑制IκBα和核因子κB（NF-κB）/p65的磷酸化来抑制糖尿病引起的肾脏炎症[8]。