期刊论文详细信息
Virology Journal
Antiviral activity of carnosic acid against respiratory syncytial virus
Kyung-Soo Inn2  Dae Sik Jang2  Kyung-Tae Lee1  Jun Chang3  Hye-Eun Choi1  Hye-In Kim2  Na-Rae Lee2  Byeol Ryu2  Myung-Soo Choi2  Han-Bo Shin2 
[1] Department of Pharmaceutical Biochemistry and Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Korea;Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, College of Pharmacy, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Korea;College of Pharmacy, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, Korea
关键词: Anti-hRSV activity;    Carnosic acid;    Rosemarinus officinalis;    hRSV;   
Others  :  820584
DOI  :  10.1186/1743-422X-10-303
 received in 2013-06-25, accepted in 2013-10-02,  发布年份 2013
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【 摘 要 】

Background

Human respiratory syncytial virus (hRSV) is a leading cause of severe lower respiratory infection and a major public health threat worldwide. To date, no vaccine or effective therapeutic agent has been developed. In a screen for potential therapeutic agents against hRSV, we discovered that an extract of Rosmarinus officinalis exerted a strong inhibitory effect against hRSV infection. Subsequent studies identified carnosic acid as a bioactive constituent responsible for anti-hRSV activity. Carnosic acid has been shown to exhibit potent antioxidant and anti-cancer activities. Anti-RSV activity of carnosic acid was further investigated in this study.

Methods

Effects of extracts from various plants and subfractions from R. officinalis on hRSV replication were determined by microneutralization assay and plaque assay. Several constituents were isolated from ethyl acetate fraction of R. officinalis and their anti-RSV activities were assessed by plaque assay as well as reverse-transcription quantitative PCR to determine the synthesis of viral RNAs.

Results

Among the tested bioactive constituents of R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses. Carnosic acid efficiently suppressed the replication of hRSV in a concentration-dependent manner. Carnosic acid effectively suppressed viral gene expression without inducing type-I interferon production or affecting cell viability, suggesting that it may directly affect viral factors. A time course analysis showed that addition of carnosic acid 8 hours after infection still effectively blocked the expression of hRSV genes, further suggesting that carnosic acid directly inhibited the replication of hRSV.

Conclusions

The current study demonstrates that carnosic acid, a natural compound that has already been shown to be safe for human consumption, has anti-viral activity against hRSV, efficiently blocking the replication of this virus. Carnosic acid inhibited both A- and B- type hRSV, while it did not affect the replication of influenza A virus, suggesting that its antiviral activity is hRSV-specific. Collectively, this study suggests the need for further evaluation of carnosic acid as a potential treatment for hRSV.

【 授权许可】

   
2013 Shin et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D, et al.: The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009, 360:588-598.
  • [2]Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE: Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005, 352:1749-1759.
  • [3]Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O'Brien KL, Roca A, Wright PF, Bruce N, et al.: Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 2010, 375:1545-1555.
  • [4]American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis: Diagnosis and management of bronchiolitis. Pediatrics 2006, 118:1774-1793.
  • [5]Hall CB, McBride JT, Walsh EE, Bell DM, Gala CL, Hildreth S, Ten Eyck LG, Hall WJ: Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. A randomized double-blind study. N Engl J Med 1983, 308:1443-1447.
  • [6]Guerguerian AM, Gauthier M, Lebel MH, Farrell CA, Lacroix J: Ribavirin in ventilated respiratory syncytial virus bronchiolitis. A randomized, placebo-controlled trial. Am J Respir Crit Care Med 1999, 160:829-834.
  • [7]Law BJ, Wang EE, MacDonald N, McDonald J, Dobson S, Boucher F, Langley J, Robinson J, Mitchell I, Stephens D: Does ribavirin impact on the hospital course of children with respiratory syncytial virus (RSV) infection? An analysis using the pediatric investigators collaborative network on infections in Canada (PICNIC) RSV database. Pediatrics 1997, 99:E7.
  • [8]Moler FW, Steinhart CM, Ohmit SE, Stidham GL: Effectiveness of ribavirin in otherwise well infants with respiratory syncytial virus-associated respiratory failure. Pediatric Critical Study Group. J Pediatr 1996, 128:422-428.
  • [9]Ma SC, But PP, Ooi VE, He YH, Lee SH, Lee SF, Lin RC: Antiviral amentoflavone from Selaginella sinensis. Biol Pharm Bull 2001, 24:311-312.
  • [10]Ma SC, Du J, But PP, Deng XL, Zhang YW, Ooi VE, Xu HX, Lee SH, Lee SF: Antiviral Chinese medicinal herbs against respiratory syncytial virus. J Ethnopharmacol 2002, 79:205-211.
  • [11]Li Y, Jiang R, Ooi LS, But PP, Ooi VE: Antiviral triterpenoids from the medicinal plant Schefflera heptaphylla. Phytother Res 2007, 21:466-470.
  • [12]Wang KC, Chang JS, Lin LT, Chiang LC, Lin CC: Antiviral effect of cimicifugin from Cimicifuga foetida against human respiratory syncytial virus. Am J Chin Med 2012, 40:1033-1045.
  • [13]Tena MT, Valcarcel M, Hidalgo PJ, Ubera JL: Supercritical fluid extraction of natural antioxidants from rosemary: comparison with liquid solvent sonication. Anal Chem 1997, 69:521-526.
  • [14]al-Sereiti MR, Abu-Amer KM, Sen P: Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. Indian J Exp Biol 1999, 37:124-130.
  • [15]Bernardes WA, Lucarini R, Tozatti MG, Flauzino LG, Souza MG, Turatti IC, Silva ML A e, Martins CH, da Silva Filho AA, Cunha WR: Antibacterial activity of the essential oil from Rosmarinus officinalis and its major components against oral pathogens. Z Naturforsch C 2010, 65:588-593.
  • [16]Klancnik A, Guzej B, Kolar MH, Abramovic H, Mozina SS: In vitro antimicrobial and antioxidant activity of commercial rosemary extract formulations. J Food Prot 2009, 72:1744-1752.
  • [17]Zegura B, Dobnik D, Niderl MH, Filipic M: Antioxidant and antigenotoxic effects of rosemary (Rosmarinus officinalis L.) extracts in Salmonella typhimurium TA98 and HepG2 cells. Environ Toxicol Pharmacol 2011, 32:296-305.
  • [18]Schwarz K, Ternes W: Antioxidative constituents of Rosmarinus officinalis and Salvia officinalis. II. Isolation of carnosic acid and formation of other phenolic diterpenes. Z Lebensm Unters Forsch 1992, 195:99-103.
  • [19]Einbond LS, Wu HA, Kashiwazaki R, He K, Roller M, Su T, Wang X, Goldsberry S: Carnosic acid inhibits the growth of ER-negative human breast cancer cells and synergizes with curcumin. Fitoterapia 2012, 83:1160-1168.
  • [20]Tai J, Cheung S, Wu M, Hasman D: Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro. Phytomedicine 2012, 19:436-443.
  • [21]Kar S, Palit S, Ball WB, Das PK: Carnosic acid modulates Akt/IKK/NF-kappaB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis 2012, 17:735-747.
  • [22]Oluwatuyi M, Kaatz GW, Gibbons S: Antibacterial and resistance modifying activity of Rosmarinus officinalis. Phytochemistry 2004, 65:3249-3254.
  • [23]Peng CH, Su JD, Chyau CC, Sung TY, Ho SS, Peng CC, Peng RY: Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects. Biosci Biotechnol Biochem 2007, 71:2223-2232.
  • [24]Satoh T, Izumi M, Inukai Y, Tsutsumi Y, Nakayama N, Kosaka K, Shimojo Y, Kitajima C, Itoh K, Yokoi T, Shirasawa T: Carnosic acid protects neuronal HT22 Cells through activation of the antioxidant-responsive element in free carboxylic acid- and catechol hydroxyl moieties-dependent manners. Neurosci Lett 2008, 434:260-265.
  • [25]Paris A, Strukelj B, Renko M, Turk V, Pukl M, Umek A, Korant BD: Inhibitory effect of carnosic acid on HIV-1 protease in cell-free assays [corrected]. J Nat Prod 1993, 56:1426-1430.
  • [26]Goswami R, Majumdar T, Dhar J, Chattopadhyay S, Bandyopadhyay SK, Verbovetskaya V, Sen GC, Barik S: Viral degradasome hijacks mitochondria to suppress innate immunity. Cell Res 2013, 23:1025-1042.
  • [27]Swedan S, Andrews J, Majumdar T, Musiyenko A, Barik S: Multiple functional domains and complexes of the two nonstructural proteins of human respiratory syncytial virus contribute to interferon suppression and cellular location. J Virol 2011, 85:10090-10100.
  • [28]Ling Z, Tran KC, Teng MN: Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I. J Virol 2009, 83:3734-3742.
  • [29]Spann KM, Tran KC, Chi B, Rabin RL, Collins PL: Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages [corrected]. J Virol 2004, 78:4363-4369.
  • [30]Fearns R, Collins PL: Role of the M2-1 transcription antitermination protein of respiratory syncytial virus in sequential transcription. J Virol 1999, 73:5852-5864.
  • [31]Jang JE, Lee JB, Kim KH, Park SM, Shim BS, Cheon IS, Song MK, Chang J: Evaluation of protective efficacy of respiratory syncytial virus vaccine against A and B subgroup human isolates in Korea. PLoS One 2011, 6:e23797.
  • [32]McKimm-Breschkin JL: A simplified plaque assay for respiratory syncytial virus–direct visualization of plaques without immunostaining. J Virol Methods 2004, 120:113-117.
  • [33]Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, Garcia-Sastre A: Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 2009, 5:439-449.
  • [34]Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, Wang SC, Dormitzer M, O'Grady J, Koenig S, Tamura JK, et al.: Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis 1997, 176:1215-1224.
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