蒲洁莹;何莉;吴思宇;张萍;黄曦;

• 1:中山大学中山医学院免疫学教研室

摘要(Abstract)：

甘草为豆科甘草属植物,是我国重要的传统中草药,三萜类化合物是其主要活性成分之一。近年来,多种甘草属植物中的三萜类化合物被证明具有显著而广谱的抗病毒活性,成为抗病毒免疫研究的热点,并有望作为新型广谱抗病毒药物而被广泛应用于临床治疗中。本文综述了近年来国内外关于甘草酸、甘草甜素、甘草次酸及其衍生物等甘草属三萜类化合物的抗病毒作用研究进展,主要对该类化合物抗疱疹病毒、人类免疫缺陷病毒(human immunodeficiency virus,HIV)、肝炎病毒、严重急性呼吸综合征(severe acute respiratory syndrome,SARS)冠状病毒、流感病毒等的作用进行简要综述。

关键词(KeyWords)： 甘草;三萜类化合物;甘草酸;甘草甜素;甘草次酸;抗病毒作用

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(30972763,81261160323);; 国家重大传染病防治专项基金(2013ZX10003001);; 广东省高等学校珠江学者岗位计划资助项目(No.2009);; 高等学校博士学科点专项科研基金(20100171110047);; 广东省引进创新科研团队专项基金(2009010058);; 广东省自然科学基金(10251008901000013)

作者(Authors): 蒲洁莹;何莉;吴思宇;张萍;黄曦;

DOI: 10.13242/j.cnki.bingduxuebao.002420

参考文献(References)：

• [1]钱信忠.中华人民共和国药典[M].北京:人民卫生出版社,1990:71-72.
• [2]Fiore C,Eisenhut M,Krausse R,et al.Antiviral effects of glycyrrhiza species[J].Phytother Res,2008,22(2):141-148.
• [3]Pompei R,Laconi S,Ingianni A.Antiviral properties of glycyrrhizic acid and its semisynthetic derivative[J].Mini Rev Med Chem,2009,9(8):996-1001.
• [4]Dargan D J,Subak-Sharpe J H.The antiviral activity against herpes simplex virus of the triterpenoid compounds carbenoxolone sodium and cicloxolone sodium[J].J Antimicrob Chemother,1986,18:185-200.
• [5]Dargan D J,Galt C B,Subak-Sharpe J H.The effect of cicloxolone sodium on the replication in cultured cells of adenovirus type 5,reovirus type 3,poliovirus type 1,two bunyaviruses and Semliki Forest virus[J].J Gen Virol,1992,73(Pt2):407-411.
• [6]Wang Renmin,Lin Chan,Liu Jingliang,et al.Pressured Microwave-assisted Hydrolysis of Crude Glycyrrhizic Acid for Preparation of Glycyrrhetinic Acid[J].Chin J Chem Eng,2012,20(1):152-157.
• [7]Kim D H,Lee S W,Han M J,et al.Biotransformation of glycyrrhizin to 18-beta-glycyrrhetinic acid-3-O-beta-Dglucuronide by Streptococcus LJ-22,a human intestinal bacterium[J].Biol Pharm Bull,1999,22(3):320-322.
• [8]Pompei R,Flore O,Marccialis M A,et al.Glycyrrhizic acid inhibits virus growth and inactivates virus particles[J].Nature,1979,281(5733):689-690.
• [9]Cinatl J,Morgenstern B,Bauer G,et al.Glycyrrhizin,an active component of liquorice roots,and replication of SARS-associated coronavirus[J].Lancet,2003,361(9374):2045-2046.
• [10]Jeong H G,Kim J Y.Induction of inducible nitric oxide synthase expression by 18β-glycyrrhetinic acid in macrophages[J].FEBS Lett,2002,513(2-3):208-212.
• [11]董时军.人疱疹病毒流行现状[J].传染病信息,2006,19(2):60-61.
• [12]Lin J C.Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro[J].Antiviral Res,2003,59(1):41-47.
• [13]Lampi G,Deidda D,Pinza M,et al.Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins[J].Antivir Chem Chemother,2001,12(2):125-131.
• [14]Huang W,Chen X,Li Q,et al.Inhibition of intercellular adhesion in herpex simplex virus infection by glycyrrhizin[J].Cell Biochem Biophys,2012,62(1):137-140.
• [15]Curreli F,Friedman-Kien A E,Flore O.Glycyrrhizic acid alters Kaposi sarcoma-associated herpesvirus latency,triggering p53-mediated apoptosis in transformed B lymphocytes[J].J Clin Invest,2005,115(3):642-652.
• [16]Klass C M,Offermann M K.Targeting human herpesvirus-8for treatment of Kaposi's sacroma and primary effusion lymphoma[J].Curr Opin Oncol,2005,17(5):447-455.
• [17]Nakashima H,Matsui T,Yoshida O,et al.A new anti-human immunodeficiency virus substance,glycyrrhizin sulfate;endowment of glycyrrhizin with reverse transcriptase-inhibitory activity by chemical modification[J].Jpn J Cancer Res,1987,78(8):767-771.
• [18]Ito M,Sato A,Hirabayashi K,et al.Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus(HIV)[J].Antiviral Res,1988,10(6):289-298.
• [19]Hattori T,Ikematsu S,Koito A,et al.Preliminary evidence for inhibitory effect of glycyrrhizin on HIV replication in patients with AIDS[J].Antiviral Res,1989,11(5-6):255-261.
• [20]Sasaki H,Takei M,Kobayashi M,et al.Effect of glycyrrhizin,an active component of licorice roots,on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients[J].Pathobiology,2002,70(4):229-236.
• [21]Harada S.The broad anti-viral agent glycyrrhizin directly modulates the fluidity of plasma membrane and HIV-1envelope[J].Bio J,2005,392(Pt 1):191-199.
• [22]Takei M,Kobayashi M,Li X D,et al.Glycyrrhizin inhibits R5 HIV replication in peripheral blood monocytes treated with 1-methyladenosine[J].Pathobiology,2005,72(3):117-123.
• [23]Yoshida T,Kobayashi M,Li X D,et al.Inhibitory effect of glycyrrhizin on the neutrophil-dependent increase of R5 HIV replication in cultures of macrophages[J].Immunol Cell Biol,2009,87(7):554-558.
• [24]庄辉.病毒性肝炎流行病学研究进展[J].中国继续医学教育,2010,2(3):1-5.
• [25]Romero M R,Efferth T,Serrano M A,et al.Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an“in vitro”replicative system[J].Antiviral Res,2005,68(2):75-83.
• [26]白木公康.甘草甜素抗乙型肝炎病毒作用的阐释[J].和汉医学杂志,1995,12(1):24.
• [27]Sato H,Goto W,Yamamura J,et al.Therapeutic basis of glycyrrhizin on chronic hepatitis B[J].Antiviral Res,1996,30(2-3):171-177.
• [28]Fujisawa K,Tandon B N.Therapeutic approach to the chronic active liver disease:Summary of a satellite symposium[J].Viral Hepatitis and Liver Disease,Tokyo:Springer,1994:662-665.
• [29]Matsuo K,Takenaka K,Shimomura H,et al.Lamivudine and glycyrrhizin for treatment of chemotherapyinduced hepatitis B virus(HBV)hepatitis in a chronic HBV carrier with non-Hodgkin lymphoma[J].Leuk Lymphoma,2001,41(1-2):191-195.
• [30]Eisenburg J.Treatment of chronic hepatitis B.part 2:effect of glycyrrhizic acid on the course of illness[J].Fortschr Med,1992,110(21):395-398.
• [31]沈巧凤.不同甘草酸类药物治疗慢性乙型病毒性肝炎的疗效比较[J].海峡药学,2012,24(7):101-103.
• [32]Ashfaq U A,Masoud M S,Nawaz Z J,et al.Glycyrrhizin as antiviral agent against hepatitis C virus[J].J Transl Med,2011,9:112-113.
• [33]Korenaga M,Hidaka I,Nishina S,et al.A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice[J].Liver International,2011,31(4):552-560.
• [34]易波,曹明华.SARS流行病学及预防控制研究进展[J].海峡预防医学杂志,2008,14(1):30-32.
• [35]Chen F,Chan K H,Jiang Y,et al.In vitro susceptibility of 10clinical isolates of SARS coronavirus to selected antiviral compounds[J].J Clin Virol,2004,31(1):69-75.
• [36]Hoever G,Baltina L,Michaelis M,et al.Antiviral activity of glycyrrhizic acid derivatives against SARScoronavirus[J].J Med Chem,2005,48(4):1256-1259.
• [37]Pompei R,Paghi L,Ingianni A,et al.Glycyrrhizic acid inhibits influenza virus growth in embryonated eggs[J].Microbiologica,1983,6(3):247-250.
• [38]Utsunomiya T,Kobayashi M,Pollard R B,et al.Glycyrrhizin,an active component of licorice roots,reduces morbidity and mortality of mice infected with lethal doses of influenza virus[J].Antimicrob Agents Chemother,1997,41(3):551-556.
• [39]Smirnov V S,Zarubaev V V,Anfimov P M,et al.Effect of a combination of glutamyl-tryptophan and glycyrrhizic acid on the course of acute infection caused by influenza(H3H2)virus in mice[J].Vopr Virusol,2012,57(3):23-27.
• [40]Moisy D,Avilov S V,Jacob Y,et al.HMGB1protein binds to influenza virus nucleoprotein and promotes viral replication[J].J Virol,2012,86(17):9122-9133.
• [41]Hardy M E,Hendricks J M,Paulson J M,et al.18beta-glycyrrhetinic acid inhibits rotavirus replication in culture[J].Virol J,2012,9(1):96-97.
• [42]Crance J M,Scaramozzino N,Jouan A,et al.Interferon,ribavirin,6-azauridine and glycyrrhizin:antiviral compounds active against pathogenic flaviviruses[J].Antiviral Res,2003,58(1):73-79.