Study on Baicalein and Genistein to Inhibit Human Cytomegalovirus Infection in Human Astrocyte

Author(s): Xiangmin YU, Jingguo XU, Ling LI, Yan WEI, Bin WANG, Dongmeng QIAN, Ming HU, Lingling DING, Linlin YUE

There are no specific ways to prevent and cure human cytomegalovirus (HCMV) infection to date. We investigate the effect and mechanism of baicalein (BAI) and genistein (GEN) used as a drug to inhibit HCMV infection in human astrocyte(AS). RT-qPCR was used to detect the expression changes of viral IE1,IE2 genes. Chromatin immunoprecipitation assay (ChIP) was used to detect the expression change of major immediate early promoter (MIEP). RT-qPCR results showed that compared with HCMV group, 20 μmol/L BAI+HCMV,HCMV+BAI group, and 10 μmol/L GEN+HCMV,HCMV+GEN group can down-regulate the IE1,IE2 genes expressions. ChIP results showed that compared with HCMV group, 20 μmol/L BAI+HCMV,HCMV+BAI group, and 10 μmol/L GEN+HCMV and HCMV+GEN group can reduce histone acetylation of MIEP. A certain concentration of BAI or GEN can inhibit the human astrocyte’s IE1 and IE2 to some extent. The inhibiting mechanism may be that BAI and GEN can decrease the expression of IE1,IE2 genes and also inhibit histone acetylation of MIEP, thus decrease the expression of IE1,IE2 genes, which makes BAI and GEN inhibit viral proliferation.

Human Cytomegalovirus, Human Astrocyte, Baicalein, Genistein, ChIP

1. Britt W. Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease. Current topics in microbiology and immunology. 2008;325:417-70.
2. Griffiths P, Baraniak I, Reeves M. The pathogenesis of human cytomegalovirus. The Journal of pathology. 2015;235:288-97.
3. Huang Y, Tsang SY, Yao X, Chen ZY. Biological properties of baicalein in cardiovascular system. Current drug targets Cardiovascular & haematological disorders. 2005;5:177-84.
4. Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer treatment reviews. 2009;35:57-68.
5. Xu G, Dou J, Zhang L, Guo Q, Zhou C. Inhibitory effects of baicalein on the influenza virus in vivo is determined by baicalin in the serum. Biological & pharmaceutical bulletin. 2010;33:238-43.
6. Moghaddam E, Teoh BT, Sam SS, Lani R, Hassandarvish P, Chik Z, et al. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Scientific reports. 2014;4:5452.
7. Yu X, He G, Du G. [Neuroprotective effect of baicalein in patients with Parkinson's disease]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 2012;37:421-5.
8. de Oliveira MR, Nabavi SF, Habtemariam S, Erdogan Orhan I, Daglia M, Nabavi SM. The effects of baicalein and baicalin on mitochondrial function and dynamics: A review. Pharmacological research. 2015;100:296-308.
9. Ganai AA, Farooqi H. Bioactivity of genistein: A review of in vitro and in vivo studies. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2015;76:30-8.
10. Tarkowski M, Kokocinska M, Latocha M. [Genistein in chemoprevention and treatment]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2013;34:54-7.
11. Stinski MF, Meier JL. Immediate-early viral gene regulation and function. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, et al., editors. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge2007.
12. Spagnuolo C, Russo GL, Orhan IE, Habtemariam S, Daglia M, Sureda A, et al. Genistein and cancer: current status, challenges, and future directions. Advances in nutrition (Bethesda, Md). 2015;6:408-19.
13. Andres A, Donovan SM, Kuhlenschmidt MS. Soy isoflavones and virus infections. The Journal of nutritional biochemistry. 2009;20:563-9.
14. Argenta DF, de Mattos CB, Misturini FD, Koester LS, Bassani VL, Simoes CM, et al. Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein. International journal of nanomedicine. 2014;9:4737-47.
15. Sauter D, Schwarz S, Wang K, Zhang R, Sun B, Schwarz W. Genistein as antiviral drug against HIV ion channel. Planta medica. 2014;80:682-7.
16. Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic beta-cell function. Food & function. 2013;4:200-12.
17. Behloul N, Wu G. Genistein: a promising therapeutic agent for obesity and diabetes treatment. European journal of pharmacology. 2013;698:31-8.