Genistein (Synonyms: CI-75610, NSC 36586)

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.