Antiviral activity and possible mode of action of ellagic acid identified in Lagerstroemia speciosa leaves toward human rhinoviruses

BMC Complementary and Alternative Medicine

Young-Joon Ahn³  Hwa-Jung Choi¹  Ji Young Yoo³  Min Jung Kwon³  Sang Wook Park² 

[1] Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan 570-749, Jeollabuk-do, Republic of Korea;Interdisciplinary Program in Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea;Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea

关键词: RNA replication;    Selectivity;    Cytotoxicity;    Tannin;    Ellagic acid;    Lagerstroemia speciosa;    Natural antiviral agent;    Human rhinovirus;   

Others  :  1220137
DOI  :  10.1186/1472-6882-14-171

 received in 2014-02-10, accepted in 2014-05-21,  发布年份 2014

【 摘 要 】

Background

Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4.

Methods

The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin.

Results

As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 μg/mL), HRV-3 (31 μg/mL), and HRV-4 (29 μg/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 μg/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 μg/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 μg/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules.

Conclusions

Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the prevention or treatment of HRV infection.

【 授权许可】

   
2014 Park et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Heikkinen T, Jarvinen A: The common cold. Lancet 2003, 361:51-59.
• [2]Jacobs SE, Lamson DM, St George K, Walsh TJ: Human rhinoviruses. Clin Microbiol Rev 2013, 26:135-162.
• [3]Pitkaranta A, Virolainen A, Jero J, Arruda E, Hayden FG: Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 1998, 102:291-295.
• [4]Pitkaranta A, Arruda E, Malmberg H, Hayden FG: Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J Clin Microbiol 1997, 35:1791-1793.
• [5]Abzug MJ, Beam AC, Gyorkos EA, Levin MJ: Viral pneumonia in the first month of life. Pediatr Infect Dis J 1990, 9:881-885.
• [6]Duff AL, Pomeranz ES, Gelber LE, Price GW, Farris H, Hayden FG, Platts-Mills TA, Heymann PW: Risk factors for acute wheezing in infants and children: viruses, passive smoke, and IgE antibodies to inhalant allergens. Pediatrics 1993, 92:535-540.
• [7]Nicholson KG, Kent J, Ireland DC: Respiratory viruses and exacerbations of asthma in adults. British Med J 1993, 307:982-986.
• [8]Rotbart HA: Treatment of picornavirus infections. Antiviral Res 2002, 53:83-98.
• [9]Waterer G, Wunderink R: Respiratory infections: a current and future threat. Respirology 2009, 14:651-655.
• [10]Turner RB: The treatment of rhinovirus infections: progress and potential. Antiviral Res 2001, 49:1-14.
• [11]Vlietinck AJ, Vanden Berghe DA: Can ethnopharmacology contribute to the development of antiviral drugs? J Ethnopharmacol 1991, 32:141-153.
• [12]Cowan MM: Plant products as antimicrobial agents. Clin Microbiol Rev 1999, 12:564-582.
• [13]Williams JE: Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado. Altern Med Rev 2001, 6:567-579.
• [14]Jassim SA, Naji MA: Novel antiviral agents: a medicinal plant perspective. J Appl Microbiol 2003, 95:412-427.
• [15]Miura T, Takagi S, Ishida T: Management of diabetes and its complications with banaba (Lagerstroemia speciosa L.) and corosolic acid. Evid Based Complement Alternat Med 2012. doi:10.1155/2012/871495
• [16]Suzuki Y, Unno T, Ushitani M, Hayasi K, Kakuda T: Manti obesity activity of extracts from Lagerstroemia speciosa L. leaves on female kk-Ay mice. J Nutr Sci Vitaminol 1999, 45:791-795.
• [17]Unno T, Sakane I, Masumizu T, Kohno M, Kakuda T: Antioxidative activity of water extracts of Lagerstroemia speciosa leaves. Biosci Biotechnol Biochem 1997, 61:1772-1774.
• [18]Unno T, Sugimoto A, Kakuda T: Xanthine oxidase inhibitors from leaves of Lagerstroemia speciosa (L.) Pers. J Ethnopharmacol 2004, 93:391-395.
• [19]Priya TT: Free radical scavenging and anti-inflammatory properties of Lagerstroemia speciosa. Inflammopharmacology 2008, 16:182-187.
• [20]Ambujakdhi HR: Antibacterial activity of leaves of Lagerstroemia speciosa. J Pharm Res 2009, 2:1028.
• [21]Graci JD, Cameron CE: Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol 2006, 16:37-48.
• [22]Vichai V, Kirtikara K: Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 2006, 1:1112-1116.
• [23]Choi HJ, Kim JH, Lee CH, Ahn YJ, Song JH, Baek SH, Kwon DH: Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus. Antiviral Res 2009, 81:77-81.
• [24]Nawwar MAM, Souleman AMA: 3,4,8,9,10-Pentahydroxy-dibenzo[b, d]pyran-6-one from Tamarix nilotica. Phytochemistry 1984, 23:2966-2967.
• [25]Chiang LC, Chiang W, Lin CC: In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. J Antimicrob Chemother 2003, 52:194-198.
• [26]Murakami C, Myoga K, Kasai R, Ohtani K, Kurokawa T, Ishibashi S, Dayrit F, Padolina WG, Yamasaki K: Screening of plant constituents for effect on glucose transport activity in Ehrlich ascites tumur cells. Chem Pharm Bull 1993, 41:2129-2131.
• [27]Ragasa CY, Ngo HT, Rideout JA: Terpenoids and sterols from Lagerstroemia speciosa. J Asian Natural Prod Res 2005, 7:71-72.
• [28]Quisumbing E: Medicinal Plants of the Phillippines. Quezon, the Phillippines: Katha Publishing; 1978.
• [29]Judy WV, Hari SP, Stogsdill WW, Judy JS, Naguib YMA, Passwater R: Antidiabetic activity of a standardized extract (Glucosol™) from Lagerstroemia speciosa leaves in type II diabetics: a dose-dependence study. J Ethnopharmacol 2003, 87:115-117.
• [30]Liu AL, Du GH: Antiviral properties of phytochemicals. In Dietary Phytochemical and Microbes. Edited by Patra AK. New York: Springer; 2012:93-126.
• [31]Rollinger JM, Schuster D, Danzl B, Schwaiger S, Markt P, Schmidtke M, Gertsch J, Raduner S, Wolber G, Langer T, Stuppner H: In silico target fishing for rationalized ligand discovery exemplified on constituents of Ruta graveolens L. Planta Med 2009, 75:195-204.
• [32]Spasova M, Philipov S, Nikolaeva-Glomb L, Galabov AS, Milkova T: Cinnamoyl- and hydroxycinnamoyl amides of glaucine and their antioxidative and antiviral activities. Bioorg Med Chem 2008, 16:7457-7461.
• [33]Rollinger JM, Steindl TM, Schuster D, Kirchmair J, Anrain K, Ellmerer EP, Langer T, Stuppner H, Wutzler P, Schmidtke M: Structure-based virtual screening for the discovery of natural inhibitors for human rhinovirus coat protein. J Med Chem 2008, 51:842-851.
• [34]Ishitsuka H, Ohsawa C, Ohiwa T, Umeda I, Suhara Y: Antipicornavirus flavone Ro 09–0179. Antimicrob Agents Chemother 1982, 22:611-616.
• [35]Van Hoof L, Vanden Berghe DA, Hatfield GM, Vlietinck AJ: Plant antiviral agents V. 3-Methoxyflavones as potent inhibitors of viral-induced block of cell synthesis. Planta Med 1984, 50:513-517.
• [36]Tsuchiya Y, Shimizu M, Hiyama Y, Itoh K, Hashimoto Y, Nakayama M, Horie T, Morita N: Antiviral activity of natural occurring flavonoids in vitro. Chem Pharm Bull 1985, 33:3881-3886.
• [37]Semple SJ, Nobbs SF, Pyke SM, Reynolds GD, Flower RL: Antiviral flavonoid from Pterocaulon sphacelatum, an Australian Aboriginal medicine. J Ethnopharmacol 1999, 68:283-288.
• [38]De Tommasi N, De Simone F, Pizza C, Mahmood N, Moore PS, Conti C, Orsi N, Stein ML: Constituents of Eriobotrya japonica: a study of their antiviral properties. J Nat Prod 1992, 55:1067-1073.
• [39]Choi HJ, Bae EY, Song JH, Baek SH, Kwon DH: Inhibitory effects of orobol 7-O-D-glucoside from banaba (Lagerstroemia speciosa L.) on human rhinovirus replication. Lett Appl Microbiol 2010, 51:1-5.
• [40]Choi HJ, Lim CH, Song JH, Baek SH, Kwon DH: Antiviral activity of raoulic acid from Raoulia australis against Picornaviruses. Phytomedicine 2009, 16:35-39.
• [41]Choi HJ, Song JH, Bhatt LR, Baek SH: Anti-human rhinovirus activity of gallic acid possessing antioxidant capacity. Phytother Res 2010, 24:1292-1296.
• [42]Weber ND, Anderson DO, North JA, Murray BK, Lawson LD, Hughes BG: In vitro virucidal activity of Allium sativum (garlic) extract and compounds. Planta Med 1992, 58:417-423.
• [43]Andries K, Dewindt B, Snoeks J, Wouters L, Moereels H, Lewi PJ, Janssen AJ: Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity. J Virol 1990, 64:1117-1123.
• [44]Nutan MM, Goel T, Das T, Malik S, Suri S, Rawat AKS, Srivastava SK, Tuli R, Malhotra S, Gupta SK: Ellagic acid & gallic acid from Lagerstroemia speciosa L. inhibit HIV-1 infection through inhibition of HIV-1 protease & reverse transcriptase activity. Indian J Med Res 2013, 137:540-548.
• [45]Rollinger JM, Schmidtke M: The human rhinovirus: human pathological impact, mechanisms of antirhinoviral agents, and strategies for their discovery. Med Res Rev 2010, 31:42-92.
• [46]Kitazato K, Wang Y, Kobayashi N: Viral infectious disease and natural products with antiviral activity. Drug Discov Ther 2007, 1:14-22.
• [47]Doyle B, Griffiths LA: The metabolism of ellagic acid in the rat. Xenobiotica 1980, 10:247-256.