Genistein

Genistein is an isoflavone belonging to the flavonoid group of compounds and is found in a number of plants. It's a tyrosine kinase inhibitor.

Results revealed that Genistein markedly induced cell growth and osteoblast differentiation depending upon dose. Antioxidant ability of GS, which reduced the H2O2- induced intracellular oxidative stress in osteoblasts. GS treatment upregulated the expression of osteoblastic genes of Runt-related transcription factor 2 (Runx2), bone morphogenetic proteins 2 (BMP2), and osteocalcin^[7]. Pre-treatment with genistein did not affect insulin-induced tyrosine kinase activity of the insulin receptor or activation of protein kinase B. On the other hand, genistein acted as a direct inhibitor of insulin-induced glucose uptake in 3T3-L1 adipocytes with an IC(50) of 20 microM^[4]. Migration of inflammatory cells is also inhibited by genistein through diminishing adherence of leukocytes to endothelial cells^[5].Genistein decreases NF-kappa B DNA binding and abrogates NF-kappa B activation by DNA-damaging agents, H2O2 and tumor necrosis factor-alpha, in prostate cancer cells regardless of androgen sensitivity. Genistein reduces phosphorylation of the inhibitory protein I kappa B alpha and blocks the nuclear translocation of NF-kappa B, prohibiting DNA binding and preventing NF-kappa B activation^[6]. Genistein decreases NF-kappa B DNA binding and abrogates NF-kappa B activation by DNA-damaging agents, H2O2 and tumor necrosis factor-alpha, in prostate cancer cells regardless of androgen sensitivity. Genistein reduces phosphorylation of the inhibitory protein I kappa B alpha and blocks the nuclear translocation of NF-kappa B, prohibiting DNA binding and preventing NF-kappa B activation ^[1].

No difference of body weight gain, total energy intake, liver weight/body weight or body fat percentage in both STD- and HFD-fed sub-groups was observed after treatment with BPA, genistein, or BPA plus genistein. Genistein alleviated lipid metabolism disorder and decreased the mRNA and protein expression of PPARγ, and increased the protein expression of LC3II in liver of HFD-fed rats^[2]. Cultivation of the tiny clusters of cells scattered throughout the pancreas, also known as pancreatic islets, were isolated from three to five day-old animals (rats) with genistein, resulting in a rapid and more enhanced insulin exudation in a dose-dependent manner, genistein substantially increased insulin secretion in pancreatic islets of adult mice as well^[3].

References:
[1]: Peterson G, Barnes S. Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ. 1996 Oct;7(10):1345-51. PMID: 8891338
[2]: Ding S, Zuo X, et,al. Environmentally Relevant Dose of Bisphenol A Does Not Affect Lipid Metabolism and Has No Synergetic or Antagonistic Effects on Genistein's Beneficial Roles on Lipid Metabolism. PLoS One. 2016 May 12;11(5):e0155352. doi: 10.1371/journal.pone.0155352. PMID: 27171397; PMCID: PMC4865196.
[3]: Jonas JC, Plant TD, et,al. Multiple effects and stimulation of insulin secretion by the tyrosine kinase inhibitor genistein in normal mouse islets. Br J Pharmacol. 1995 Feb;114(4):872-80. doi: 10.1111/j.1476-5381.1995.tb13285.x. PMID: 7773549; PMCID: PMC1510214.
[4]: Bazuine M, van den Broek PJ, et,al. Genistein directly inhibits GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2005 Jan 14;326(2):511-4. doi: 10.1016/j.bbrc.2004.11.055. PMID: 15582607.
[5]: MacGregor CA, Canney PA, et,al. A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. Eur J Cancer. 2005 Mar;41(5):708-14. doi: 10.1016/j.ejca.2005.01.005. PMID: 15763646.
[6]: Davis JN, Kucuk O, et,al. Genistein inhibits NF-kappa B activation in prostate cancer cells. Nutr Cancer. 1999;35(2):167-74. doi: 10.1207/S15327914NC352_11. PMID: 10693171.
[7]: Siddiqui S, Mahdi AA, et,al. Genistein contributes to cell cycle progression and regulates oxidative stress in primary culture of osteoblasts along with osteoclasts attenuation. BMC Complement Med Ther. 2020 Sep 11;20(1):277. doi: 10.1186/s12906-020-03065-5. PMID: 32917180; PMCID: PMC7488498.

染料木黄酮是一种异黄酮,属于类黄酮化合物,存在于多种植物中。 It'；是一种酪氨酸激酶抑制剂。

结果表明,Genistein 显着诱导细胞生长和成骨细胞分化,具体取决于剂量。 GS 的抗氧化能力,可降低 H2O2 诱导的成骨细胞细胞内氧化应激。 GS 处理上调了 Runt 相关转录因子 2 (Runx2)、骨形态发生蛋白 2 (BMP2) 和骨钙素^[7] 的成骨细胞基因的表达。用染料木黄酮预处理不影响胰岛素诱导的胰岛素受体酪氨酸激酶活性或蛋白激酶 B 的激活。另一方面,染料木黄酮作为具有 IC 的 3T3-L1 脂肪细胞中胰岛素诱导的葡萄糖摄取的直接抑制剂(50) 20 microM^[4]。染料木黄酮还通过减少白细胞与内皮细胞的粘附来抑制炎症细胞的迁移^[5]。染料木黄酮降低 NF-kappa B DNA 结合并消除 DNA 损伤剂 H2O2 对 NF-kappa B 的激活和肿瘤坏死因子-α,在前列腺癌细胞中,无论雄激素敏感性如何。 Genistein 可降低抑制蛋白 I kappa B α 的磷酸化并阻断 NF-kappa B 的核转位,从而抑制 DNA 结合并阻止 NF-kappa B 激活^[6]。无论雄激素敏感性如何,Genistein 都会降低 NF-kappa B DNA 结合并消除 DNA 损伤剂、H2O2 和肿瘤坏死因子-α 对 NF-kappa B 的激活。 Genistein 降低抑制蛋白 I kappa B α 的磷酸化并阻断 NF-kappa B 的核转位,从而抑制 DNA 结合并阻止 NF-kappa B 激活^[1]。

在用 BPA、染料木黄酮或 BPA 加染料木黄酮治疗后,在 STD 和 HFD 喂养的亚组中,体重增加、总能量摄入、肝脏重量/体重或体脂百分比没有差异。 Genistein减轻脂代谢紊乱,降低PPARγ的mRNA和蛋白表达,并增加HFD喂养大鼠肝脏中LC3II的蛋白表达^[2]。散布在胰腺各处的微小细胞簇（也称为胰岛）的培养是从三到五天大的动物（大鼠）中分离出来的染料木黄酮,导致以剂量依赖的方式快速和增强胰岛素渗出,染料木素显着增加成年小鼠胰岛的胰岛素分泌^[3]。