Therapuetic Effection Of Glycyrrhizin On Herpes Simplex Encephalitis

Backgrounds and objective: The outbreak of SARS within the scope of world last year, particularly in our country, brought about a great disaster to mankind. The widespreading of West nile virus encephalitis occurring in north America in 2002 and outbreak of lethal encephalitis caused by Nipah virus in Malaysia in 1998 made thousands of people dead and 1 million infectious pigs slaughted. These cases suggested that studies of epidemics , underlying mechanisms,diagnosis and clinic treatment of viral infectious diseases should be strengthened so as to protect and control outbreak of these diseases, enhancing social ability to cope with public hygiene affairs occurring suddenly. Herpes simplex encephalitis(HSE) is the commonest non-epidemic viral encephalitis among adults. According to the statistic data, the incidence of HSE is 2～3／100 thousands yearly. Without treatment, mortality of HSE is 60%～80%. although through effective antiviral treatment, its mortality is also as high as 20% or so. survivors often present with sequela of different degrees, only 2.5% of HSE patients can achieve complete recovery from this illness, giving rise to heavy burden for family and society. with the fast development of modern molecular biology technique and image technique, detecting DNA of HSV-1 with PCR(polymerase chain reaction) has become gold standard of diagnosis of HSE.MRI(magnetic resonace imaging) can show inflammatory change of temporal lobe in HSE at its early stage,which makes clinically fast and accurate diagnosis of HSE possible. All of these bring forward demanding for valid cure of HSE urgently. Recently, HSE patients are mainly treated with nucleoside-like drugs inhibiting DNA polymerase of HSV,such as acyclovir .These drugs have some deficiency demonstrated by clinic practices,such as drug resistance and side effects,et al.Of course, the urgent thing must been done is to search for effective anti-HSV drugs with low side effects. Recently,it has been reported that glycyrrhizin inhibits replication of some viruses,such as vaccinia virus,varicella-zoster virus,Newcastle disease virus,influenza virus,vesicular stomatitis,Japanese encephalitis virus,human immunodeficiency virus 1,et al. We conduct this study in order to investigate whether glycyrrhizin is effective in herpes simplex encephalitis.Methods:Experiment is divided into two parts of in vitro and in vivo .(1)experiment in vitro: establish HSV-1 infectious cell model to observe inhibitive effect of glycyrrhizin on HSV in cell with plaque forming units means and determine which steps of virus infection be affected. The concentration of glycyrrhizin at which the plaques were inhibited in 50% cultures in contrast to virus controls was designated as 50% inhibitory concentration(IC50).(2)experiment in vivo: Establishing the HSE model of Balb/c mouse intracranially to identify effection of glycyrrhizin on mortality of mice with HSE, the replication of HSV-1and expression of iNOS mRNA due to secondary antoimmune-mediated tissue damage.Results:(1)50% inhibitory concentration of glycyrrhizin was 0.56mM by means of plaque forming units.(2)Glycyrrhizin greatly inhibited the forming of plaque units.(3)The mortality of groups treated with glycyrrhizin was 25%,and the untreated was 60%.(4)The HSV-1 DNA copies of treated groups with mean value 2131 was much lower than those of untreated groups 5496. The mean value of iNOS/GAPD of treated groups was 0.6387 while the untreated was 0.8610.Conclusion: (1)Glycyrrhizin inhibits the replication of HSV-1 effectively in vivo and its 50% inhibitory concentration is 0.56mM. furthermore, glycyrrhizin shows no cytotoxicity.(2)Glycyrrhizin decreases the mortality of HSE from 60% to 25%,and inhibits the replication of HSV-1 obviously in Balb/c mice brains suffering from HSE.(3)Glycyrrhizin lowers the expression level of iNOS mRNA and to alleviate secondary damage mediated by autoimmune reaction due to HSV-1 infection.