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BMC Complementary Medicine and Therapies

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Open Access 01-12-2017 | Research article

Inhibition of influenza virus via a sesquiterpene fraction isolated from Laggera pterodonta by targeting the NF-κB and p38 pathways

Authors: YuTao Wang, Beixian Zhou, Jingguang Lu, QiaoLian Chen, Huihui Ti, WanYi Huang, Jing Li, ZiFeng Yang, Zhihong Jiang, XinHua Wang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Abstract

Background

Influenza virus poses serious threats to human health, especially human infection with avian influenza virus. Laggera pterodonta (DC.) Benth is a medicinal plant that is widely used in Traditional Chinese Medicine, especially in Yunnan province, and has been used to treat influenza, pharyngolaryngitis, and bronchitis. However, the compound(s) responsible for the activity and their mechanisms of action against the influenza virus remain to be elucidated.

Methods

L. pterodonta extract was fractionated, and the active fraction was identified as Fraction 14 (Fr 14). Fr 14 was further analysed and characterized by ultra-high-performance liquid chromatography hyphenated with quadrupole-time of flight mass spectrometry (UHPLC/Q-TOF-MS). The inhibitory effect against influenza virus was evaluated using a cytotoxicity assay. Then, cytokines and chemokines were detected by qRT-PCR and a bio-plex assay. Signalling pathways that inhibited the influenza virus were identified using a western blotting assay.

Results

The active fr 14 showed a wide spectrum of anti-influenza virus activity. The pharmacological mechanisms showed that Fr 14 acts on the early stage of virus replication (0–6 h). It inhibited the p38/MAPK pathway and then inhibited the NF-κB pathway and COX-2. Fr 14 also prevented the increased expression of cytokines and chemokines.

Conclusion

This study demonstrated the preliminary mechanisms of fr 14 against the influenza virus. Fr 14 possessed antiviral and anti-inflammatory effects. L. pterodonta can be used to develop innovative antiviral drugs, and further studies will be performed to illustrate the detailed mechanisms.

Palese P, Shaw ML. Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM, editors. Fields virology. Philadelphia: Lippincott Williams &Wilkins; 2007. p. 1450.

Dunning J, Baillie JK, Cao B, Hayden FG. International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Antiviral combinations for severe influenza. Lancet Infect Dis. 2014;14(12):1259–70.CrossRefPubMed

Yang ZF, Li RF, Zhang TY. Evolution of Influenza A H7N9 Virus with an Emphasis on Gene Constellation. J Genet Genomics. 2014;41:3–6.CrossRef

Moss RB, Davey RT, Steigbigel RT, Fang F. Targeting pandemic influenza: a primer on influenza antivirals and drug resistance. J Antimicrob Chemother. 2010;65(6):1086–93.CrossRefPubMed

Wu Y, Zhou C, Li X, Song L, Wu X, Lin W, Chen H, Bai H, Zhao J, Zhang R, Sun H, Zhao Y. Evaluation of Antiinflammatory Activity of the Total Flavonoids of Laggera pterodonta on Acute and Chronic Inflammation Models. Phytother Res. 2006;20(7):585–90.CrossRefPubMed

Cao C, Liu B, Zeng C, Lu Y, Chen S, Yang L, Li B, Li Y, Li Y. Polymethoxyflavone from Laggera pterodonta induces apoptosis in imatinib-resistant K562R cells via activation of the intrinsic apoptosis pathway. Cancer Cell Int. 2014;14(1):137.CrossRefPubMedPubMedCentral

Shi S, Huang K, Zhang Y, Zhao Y, Du Q. Purification and identification of antiviral components from Laggera pterodonta by high-speed counter-current chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;859(1):119–24.CrossRefPubMed

Yang ZF, Bai LP, Huang WB, Li XZ, Zhao SS, Zhong NS, Jiang ZH. Comparison of in vitro antiviral activity of tea polyphenols against influenza A and B viruses and structure–activity relationship analysis. Fitoterapia. 2014;93:47–53.CrossRefPubMed

Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Epidemiol. 1938;27:493–7.

10.

Wu W, Li R, Li X, He J, Jiang S, Liu S, Yang J. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses. 2016;8(1).

11.

Mok CK, Kang SS, Chan RW, Yue PY, Mak NK, Poon LL, Wong RN, Peiris JS, Chan MC. Anti-inflammatory and antiviral effects of indirubin derivatives in influenza A (H5N1) virus infected primary human peripheral blood-derived macrophages and alveolar epithelial cells. Antiviral Res. 2014;106:95–104.CrossRefPubMed

12.

Zhao Y, Yue JM, Lin ZW, Ding JK, Sun HD. Eudesmane sesquiterpenes from Laggera pterodonta. Phytochemistry. 1997;44(3):459–64.CrossRef

13.

Ardanaz CE, Tonn CE, Donadel OJ, Guerreiro E, Kurina MB. Mass spectral studies of a sesquiterpene: 1(10),2,11(13)-eremophylatrien-12-oic acid. Rapid Commun Mass Spectrom. 2004;18:1407–10.CrossRefPubMed

14.

Barik S. New treatments for influenza. BMC Med. 2012;10:104.CrossRefPubMedPubMedCentral

15.

Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH, Lu SH, Yang YD, Fang Q, Shen YZ, Xi XM, Gu Q, Zhou XM, Qu HP, Yan Z, Li FM, Zhao W, Gao ZC, Wang GF, Ruan LX, Wang WH, Ye J, Cao HF, Li XW, Zhang WH, Fang XC, He J, Liang WF, Xie J, Zeng M, Wu XZ, Li J, Xia Q, Jin ZC, Chen Q, Tang C, Zhang ZY, Hou BM, Feng ZX, Sheng JF, Zhong NS, Li LJ. Clinical findings in 111 cases of influenza A H7N9) virus infection. N Engl J Med. 2013;368(24):2277–85.CrossRefPubMed

16.

Wang X, Jia W, Zhao A, Wang X. Anti-influenza agents from plants and traditional Chinese medicine. Phytother Res. 2006;20(5):335–41.CrossRefPubMed

17.

König R, Stertz S, Zhou Y, Inoue A, Hoffmann HH, Bhattacharyya S, Alamares JG, Tscherne DM, Ortigoza MB, Liang Y, Gao Q, Andrews SE, Bandyopadhyay S, De Jesus P, Tu BP, Pache L, Shih C, Orth A, Bonamy G, Miraglia L, Ideker T, García-Sastre A, Young JA, Palese P, Shaw ML, Chanda SK. Human Host Factors Required for Influenza Virus Replication. Nature. 2010;463(7282):813–7.CrossRefPubMedPubMedCentral

18.

Whitmarsh AJ. Regulation of gene transcription by mitogen-activated protein kinase signaling pathways. Biochim Biophys Acta. 2007;1773(8):1285–98.CrossRefPubMed

19.

Pleschka S, Wolff T, Ehrhardt C, Hobom G, Planz O, Rapp UR, Ludwig S. Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade. Nat Cell Biol. 2001;3(3):301–5.CrossRefPubMed

20.

Vitiello M, Galdiero M, Finamore E, Galdiero S, Galdiero M. NF-kB as a potential therapeutic target in microbial diseases. Mol Biosyst. 2012;8(4):1108–20.CrossRefPubMed

21.

Ehrhardt C, Rückle A, Hrincius ER, Haasbach E, Anhlan D, Ahmann K, Banning C, Reiling SJ, Kühn J, Strobl S, Vitt D, Leban J, Planz O, Ludwig S. The NF-kB inhibitor SC75741 efficiently blocks influenza virus propagation and confers a high barrier for development of viral resistance. Cell Microbiol. 2013;15(7):1198–211.CrossRefPubMed

22.

Geiler J, Michaelis M, Sithisarn P, Cinatl Jr J. Comparison of pro-inflammatory cytokine expression and cellular signal transduction in human macrophages infected with different influenza A viruses. Med Microbiol Immunol. 2011;200(1):53–60.CrossRefPubMed

23.

Pan W, Yu H, Huang S, Zhu P. Resveratrol Protects against TNF-α-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK. PLoS One. 2016;11(1):e0147034.CrossRefPubMedPubMedCentral

24.

Sanders CJ, Doherty PC, Thomas PG. Respiratory epithelial cells in innate immunity to influenza virus infection. Cell Tissue Res. 2011;343(1):13–21.CrossRefPubMed

25.

Paquette SG, Banner D, Zhao Z, Fang Y, Huang SS, Leόn AJ, Ng DC, Almansa R, Martin-Loeches I, Ramirez P, Socias L, Loza A, Blanco J, Sansonetti P, Rello J, Andaluz D, Shum B, Rubino S, de Lejarazu RO, Tran D, Delogu G, Fadda G, Krajden S, Rubin BB, Bermejo-Martin JF, Kelvin AA, Kelvin DJ. Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection. PLoS One. 2012;7(6):e38214.CrossRefPubMedPubMedCentral

26.

Liu YB, Jia W, Yao Z, Pan Q, Takaishi Y, Duan HQ. Two eudesmane sesquiterpenes from Laggera pterodonta. J Asian Nat Prod Res. 2007;9(3):233–7.CrossRefPubMed

27.

Zhao AH, Wei JX. Studies on the Constituent of decoctum of Laggera Pterodonta(DC) Benth II. Acta Chimica Sinica. 1994;52(5):517–20.

28.

Li SL, Ding JK. Four new sesquiterpenoids from Laggera pterodonta. Acta Botanica Yunnanica. 1996;18(3):349–52.

29.

Zhang ZJ, He J, Li Y, Wu XD, Gao X, Peng LY, Cheng X, Li RT, Zhao QS. Three New Sesquiterpenes from Laggera pterodonta. Helv Chim Acta. 2013;96(4):732–7.CrossRef

Title: Inhibition of influenza virus via a sesquiterpene fraction isolated from Laggera pterodonta by targeting the NF-κB and p38 pathways
Authors: YuTao Wang
Beixian Zhou
Jingguang Lu
QiaoLian Chen
Huihui Ti
WanYi Huang
Jing Li
ZiFeng Yang
Zhihong Jiang
XinHua Wang
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-016-1528-8

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Inhibition of influenza virus via a sesquiterpene fraction isolated from Laggera pterodonta by targeting the NF-κB and p38 pathways

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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