Antiviral activity of berberine and related compounds against human cytomegalovirus

Hayashi, Kyoko; Minoda, Kazuki; Nagaoka, Yasuo; Hayashi, Toshimitsu; Uesato, Shinichi

doi:10.1016/j.bmcl.2006.12.085

Cited by 142 publications

(70 citation statements)

References 20 publications

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“…Moreover, the alkaloids detected can significantly inhibit the progression of diabetes (Tang et al, 2006), suppress inflammatory agents-induced cytokine production in lung cells , exert an antidepressant-like effect and inhibit the replication of human cytomegalovirus (Hayashi et al, 2007), and the steroidal saponins have the function of lowering the blood glucose level in alloxandiabetic mice (Nakashima et al, 1993), improving memory and dysfunction induced by cerebral ischemia , antagonizing vessel contraction (Wang et al, 2002), inhibiting platelet aggregation and generating stimulus-induced superoxide in human neutrophils (Kaname et al, 2000;Zhang et al, 1999a,b).…”

Section: Identification Of Compoundmentioning

confidence: 99%

Identification of major alkaloids and steroidal saponins in rat serum by HPLC‐diode array detection‐MS/MS following oral administration of Huangbai‐Zhimu herb‐pair Extract

Fan

Tang

et al. 2008

Biomedical Chromatography

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Huangbai-Zhimu herb-pair (HBZMHP) is a widely used Chinese traditional medicine formula in treating various diseases; however, its active components have remained unknown. In this paper, serum chemistry and combined high-performance liquid chromatography (HPLC), diode-array detection and mass-spectrometry (MS) techniques were used to study the constituents of HBZMHP extract absorbed into rat serum after oral administration. A total of nine characteristic HPLC peaks in the TIC chromatograms were identified as magnoflorine (1), menisperine (2), palmatine (3), berberine (4), timosaponin N or timosaponin E1 (5), timosaponin D (6), timosaponin BIII, anemarsaponin C or xilingsaponin B (7) timosaponin BII (8) and timosaponin AIII (9). All of the identified peaks were constituents of HBZMHP extract. The results narrow the range of active compounds to be found in HBZMHP extract, and pave the way for the follow-up action mechanism research.

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Section: Identification Of Compoundmentioning

confidence: 99%

Identification of major alkaloids and steroidal saponins in rat serum by HPLC‐diode array detection‐MS/MS following oral administration of Huangbai‐Zhimu herb‐pair Extract

Fan

Tang

et al. 2008

Biomedical Chromatography

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“…Its chemical structure is 5,8-dihydro-9,10-dimethoxy-6H-benzo(g)-1,3-benzodioxolo(5,6-a)quinolizine. Berberine exhibits a wide variety of bioactivities such as antidiarrheic (Sack and Froehlich, 1982;Taylor and Greenough, 1989), antimicrobial (Yan et al, 2008), hypolipidemic (Kong et al, 2004;Doggrell, 2005;Brusq et al, 2006;Cicero et al, 2007), hypoglycemic (Yin et al, 2002;Pan et al, 2003;Zhou et al, 2007;Turner et al, 2008;Yin et al, 2008), antiarrhythmic (Wang et al, 1994;Lau et al, 2001), anticancer (Inoue et al, 2005;Lanvers-Kaminsky et al, 2006;Lin et al, 2006Lin et al, , 2007Piyanuch et al, 2007;Serafim et al, 2008;Yu et al, 2007), anti-inflammatory (Kuo et al, 2004Lee et al, 2007), antiviral (Hayashi et al, 2007), antidepressant (Kulkarni and Dhir, 2007), and hepatoprotective (Zhang et al, 2008) effects. Its chloride salt has been used for several decades in clinical situations to treat gastroenteritis and secretory diarrhea in China.…”

Section: Introductionmentioning

confidence: 99%

Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans

Qiu

Zhu²,

Kang³

et al. 2008

Drug Metab Dispos

118

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ABSTRACT:The urinary metabolites of berberine, an isoquinoline alkaloid isolated from several Chinese herbal medicines, were investigated in rats and humans. Using macroporous adsorption resin chromatography, open octadecyl silane column chromatography and preparative high-performance liquid chromatography, we isolated seven metabolites (HM1-HM7) from human urine and five metabolites (RM1-RM5) from rat urine after oral administration. Berberine is an isoquinoline alkaloid isolated from several Chinese herbal medicines such as rhizoma coptidis, cortex phellodendri, and caulis mahoniae. Its chemical structure is 5,8-dihydro-9,10-dimethoxy-6H-benzo(g)-1,3-benzodioxolo(5,6-a)quinolizine. Berberine exhibits a wide variety of bioactivities such as antidiarrheic (Sack and Froehlich, 1982;Taylor and Greenough, 1989), antimicrobial (Yan et al., 2008), hypolipidemic (Kong et al., 2004;Doggrell, 2005;Brusq et al., 2006;Cicero et al., 2007), hypoglycemic (Yin et al., 2002;Pan et al., 2003;Zhou et al., 2007;Turner et al., 2008;Yin et al., 2008), antiarrhythmic (Wang et al., 1994;Lau et al., 2001), anticancer (Inoue et al., 2005;Lanvers-Kaminsky et al., 2006;Lin et al., 2006Lin et al., , 2007Piyanuch et al., 2007;Serafim et al., 2008;Yu et al., 2007), anti-inflammatory (Kuo et al., 2004Lee et al., 2007), antiviral (Hayashi et al., 2007), antidepressant (Kulkarni and Dhir, 2007), and hepatoprotective (Zhang et al., 2008) effects. Its chloride salt has been used for several decades in clinical situations to treat gastroenteritis and secretory diarrhea in China. In recent years, berberine has also shown significant effects in treatment of diabetes mellitus (Ni, 1988), hyperlipemia (Kong et al., 2004), arrhythmia, and heart failure (Zeng and Zeng, 1999;Lau et al., 2001;Zeng et al., 2003). However, pharmacokinetic studies have indicated that berberine has poor oral bioavailability (Shen et al., 1993;Yu et al., 2000;Zuo et al., 2006), and a few of the metabolites have been identified in rats (Zuo et al., 2006) and in humans (Pan et al., 2002). To obtain more information about its metabolism to improve its clinical applications, we examined the biotransformation of berberine in rats and humans. In the present article we describe the isolation and identification of urinary metabolites of berberine in these two species. Materials and Methods Materials.Berberine chloride (purity Ͼ 99.5%) was supplied by the Northeast General Pharmaceutical Factory (Shenyang, China). Methanol was HPLC grade and water was double-distilled in our laboratory. All other reagents were of analytical grade and were purchased from Shenyang Chemical Company (Shenyang, China). Normal-phase and reverse-phase preparatory thin-layer chromatography was performed using products from Merck (Darmstadt, Germany). Macroporous resin D101 was purchased from the Chemical Plant of Nankai University (Tianjin, China) and Diaion ion exchange resin HP20 from Mitsubishi Chemical Corporation (Tokyo, Japan). Sephadex LH-20 and ODS were obtained from Pfizer (Freiburg, Germany). Spot...

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“…Berberine exhibits inhibitory activity against some viruses, including influenza A virus (39) and human cytomegalovirus (40). Chin et al first reported that berberine from Coptidis rhizoma showed an anti-HSV effect (41).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Cellular c-Jun N-Terminal Protein Kinase and NF-κB Activation by Berberine May Result in Inhibition of Herpes Simplex Virus Replication

Song

Qiu

Chu

et al. 2014

Antimicrob Agents Chemother

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bBerberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Some reports show that berberine exhibits anti-inflammatory, antitumor, and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor B (NF-B), and mitogen-activated protein kinase. In the present study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current antiherpes medicines such as acyclovir can lessen the recurring activation when used early at infection but are unable to prevent or cure infections where treatment has selected for resistant mutants. In searching for new antiviral agents against herpesvirus infection, we found that berberine reduced viral RNA transcription, protein synthesis, and virus titers in a dose-dependent manner. To elucidate the mechanism of its antiviral activity, the effect of berberine on the individual steps of viral replication cycle of HSV was investigated via time-of-drug addition assay. We found that berberine acted at the early stage of HSV replication cycle, between viral attachment/entry and genomic DNA replication, probably at the immediate-early gene expression stage. We further demonstrated that berberine significantly reduced HSV-induced NF-B activation, as well as IB-␣ degradation and p65 nuclear translocation. Moreover, we found that berberine also depressed HSV-induced c-Jun N-terminal kinase (JNK) phosphorylation but had little effect on p38 phosphorylation. Our results suggest that the berberine inhibition of HSV infection may be mediated through modulating cellular JNK and NF-B pathways.

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Antiviral activity of berberine and related compounds against human cytomegalovirus

Cited by 142 publications

References 20 publications

Identification of major alkaloids and steroidal saponins in rat serum by HPLC‐diode array detection‐MS/MS following oral administration of Huangbai‐Zhimu herb‐pair Extract

Identification of major alkaloids and steroidal saponins in rat serum by HPLC‐diode array detection‐MS/MS following oral administration of Huangbai‐Zhimu herb‐pair Extract

Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans

Downregulation of Cellular c-Jun N-Terminal Protein Kinase and NF-κB Activation by Berberine May Result in Inhibition of Herpes Simplex Virus Replication

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