Skip to main content

Advertisement

SpringerLink
Log in

Pratensein glycoside attenuates respiratory syncytial virus infection-induced oxidative and inflammatory injury via TGF-β signaling pathway

  • Original Article
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

Respiratory syncytial virus (RSV)-induced oxidative stress and inflammation are the leading causes of many severe diseases, especially in infants and children. Although many studies focused on the mechanism during RSV infection, an effective therapy is still urgently needed.

Objectives

In our study, we examined the function of pratensein glycoside (PG) in the progression of RSV-induced infection in vitro.

Results

PG treatment significantly inhibited RSV-induced oxidative stress and inflammation in a dose-dependent manner. We found that 40 μM of PG had no significant cytotoxicity and exerted an anti-viral effect. RSV infection led to the activation of the TGF-β signaling pathway, which in turn promoted RSV infection. We hyperactivated the TGF-β signaling pathway by TGF-β and found that PG treatment can repress the pro-inflammation effect of TGF-β, suggesting that PG inhibits RSV infection through inhibiting TGF-β signaling pathway.

Conclusions

PG attenuated RSV infection-induced oxidative stress and inflammation through inhibiting the TGF-β signaling pathway. This study provides evidence for the application of traditional Chinese herbal medicine in the treatment of viral infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  • Abu-Harb M, Bell F, Finn A, Rao WH, Nixon L, Shale D, Everard ML (1999) IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis. Eur Respir J 14:139–143

    Article  CAS  Google Scholar 

  • Bakre A, Wu W, Hiscox J, Spann K, Teng MN, Tripp RA (2015) Human respiratory syncytial virus non-structural protein NS1 modifies miR-24 expression via transforming growth factor-β. J Gen Virol 96:3179–3191

    Article  CAS  Google Scholar 

  • Behbahani M (2017) Anti-human immunodeficiency virus-1 activities of pratensein and pratensein glycoside from Alhaji maurorum and its parasite Cuscuta kotchiana. Chin J Integr Med. https://doi.org/10.1007/s11655-017-2820-2

    Article  PubMed  Google Scholar 

  • Boukhvalova MS, Yim KC, Blanco J (2018) Cotton rat model for testing vaccines and antivirals against respiratory syncytial virus. Antivir Chem Chemother 26:2040206618770518

    Article  CAS  Google Scholar 

  • Chen HQ, Wang XJ, Jin ZY, Xu XM, Zhao JW, Xie ZJ (2008) Protective effect of isoflavones from Trifolium pratense on dopaminergic neurons. Neurosci Res 62:123–130

    Article  CAS  Google Scholar 

  • Chen HY, Ho YJ, Chou HC, Liao EC, Tsai YT, Wei YS, Lin LH, Lin MW, Wang YS, Ko ML, Chan HL (2020) TGF-β1 signaling protects retinal ganglion cells from oxidative stress via modulation of the HO-1/Nrf2 pathway. Chem Biol Interact 331:109249

    Article  CAS  Google Scholar 

  • De Weerd W, Twilhaar WN, Kimpen JL (1998) T cell subset analysis in peripheral blood of children with RSV bronchiolitis. Scand J Infect Dis 30:77–80

    Article  Google Scholar 

  • Dinarello CA (2000) Proinflammatory cytokines. Chest 118:503–508

    Article  CAS  Google Scholar 

  • Emboriadou M, Hatzistilianou M, Magnisali C, Sakelaropoulou A, Exintari M, Conti P, Aivazis V (2007) Human neutrophil elastase in RSV bronchiolitis. Ann Clin Lab Sci 37:79–84

    CAS  PubMed  Google Scholar 

  • Everard ML, Swarbrick A, Wrightham M, McIntyre J, Dunkley C, James PD, Sewell HF, Milner AD (1994) Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection. Arch Dis Child 71:428–432

    Article  CAS  Google Scholar 

  • Gibbs JD, Ornoff DM, Igo HA, Zeng JY, Imani F (2009) Cell cycle arrest by transforming growth factor beta1 enhances replication of respiratory syncytial virus in lung epithelial cells. J Virol 83:12424–12431

    Article  CAS  Google Scholar 

  • Gill MA, Palucka AK, Barton T, Ghaffar F, Jafri H, Banchereau J, Ramilo O (2005) Mobilization of plasmacytoid and myeloid dendritic cells to mucosal sites in children with respiratory syncytial virus and other viral respiratory infections. J Infect Dis 191:1105–1115

    Article  Google Scholar 

  • Gill MA, Long K, Kwon T, Muniz L, Mejias A, Connolly J, Roy L, Banchereau J, Ramilo O (2008) Differential recruitment of dendritic cells and monocytes to respiratory mucosal sites in children with influenza virus or respiratory syncytial virus infection. J Infect Dis 198:1667–1676

    Article  Google Scholar 

  • Halfhide CP, Flanagan BF, Brearey SP, Hunt JA, Fonceca AM, McNamara PS, Howarth D, Edwards S, Smyth RL (2011) Respiratory syncytial virus binds and undergoes transcription in neutrophils from the blood and airways of infants with severe bronchiolitis. J Infect Dis 204:451–458

    Article  CAS  Google Scholar 

  • Heidema J, Lukens MV, van Maren WW, van Dijk ME, Otten HG, van Vught AJ, van der Werff DB, van Gestel SJ, Semple MG, Smyth RL, Kimpen JL, van Bleek GM (2007) CD8+ T cell responses in bronchoalveolar lavage fluid and peripheral blood mononuclear cells of infants with severe primary respiratory syncytial virus infections. J Immunol 179:8410–8417

    Article  CAS  Google Scholar 

  • Hosakote YM, Jantzi PD, Esham DL, Spratt H, Kurosky A, Casola A, Garofalo RP (2011) Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med 183:1550–1560

    Article  CAS  Google Scholar 

  • Hou S, Xu X, Wang Y, Yang Y (2020) Ephedrannin B exerts anti-viral and anti-inflammatory properties in BEAS-2B cells infected with respiratory syncytial virus. J Biosci 45:46

    Article  Google Scholar 

  • Hu M, Bogoyevitch MA, Jans DA (2020) Impact of respiratory syncytial virus infection on host functions: implications for antiviral strategies. Physiol Rev 100:1527–1594

    Article  Google Scholar 

  • Ji F, Fu SJ, Shen SL, Zhang LJ, Cao QH, Li SQ, Peng BG, Liang LJ, Hua YP (2015) The prognostic value of combined TGF-β1 and ELF in hepatocellular carcinoma. BMC Cancer 15:116

    Article  Google Scholar 

  • Khan NA, Singla M, Samal S, Lodha R, Medigeshi GR (2020) Respiratory syncytial virus-induced oxidative stress leads to an increase in labile zinc pools in lung epithelial cells. mSphere. https://doi.org/10.1128/mSphere.00447-20

    Article  PubMed  PubMed Central  Google Scholar 

  • Larrañaga CL, Ampuero SL, Luchsinger VF, Carrión FA, Aguilar NV, Morales PR, Palomino MA, Tapia LF, Avendaño LF (2009) Impaired immune response in severe human lower tract respiratory infection by respiratory syncytial virus. Pediatr Infect Dis J 28:867–873

    Article  Google Scholar 

  • McCann KL, Imani F (2007) Transforming growth factor beta enhances respiratory syncytial virus replication and tumor necrosis factor alpha induction in human epithelial cells. J Virol 81:2880–2886

    Article  CAS  Google Scholar 

  • Medigeshi GR, Kumar R, Dhamija E, Agrawal T, Kar M (2016) N-desmethylclozapine, fluoxetine, and salmeterol inhibit postentry stages of the dengue virus life cycle. Antimicrob Agents Chemother 60:6709–6718

    Article  CAS  Google Scholar 

  • Mgbemena V, Segovia J, Chang T, Bose S (2011) Krüppel-like factor 6 regulates transforming growth factor-β gene expression during human respiratory syncytial virus infection. Virol J 8:409

    Article  CAS  Google Scholar 

  • Midulla F, Villani A, Panuska JR, Dab I, Kolls JK, Merolla R, Ronchetti R (1993) Respiratory syncytial virus lung infection in infants: immunoregulatory role of infected alveolar macrophages. J Infect Dis 168:1515–1519

    Article  CAS  Google Scholar 

  • Openshaw PJ, Tregoning JS (2005) Immune responses and disease enhancement during respiratory syncytial virus infection. Clin Microbiol Rev 18:541–555

    Article  CAS  Google Scholar 

  • Panuska JR, Hertz MI, Taraf H, Villani A, Cirino NM (1992) Respiratory syncytial virus infection of alveolar macrophages in adult transplant patients. Am Rev Respir Dis 145:934–939

    Article  CAS  Google Scholar 

  • Raes M, Peeters V, Alliet P, Gillis P, Kortleven J, Magerman K, Rummens JL (1997) Peripheral blood T and B lymphocyte subpopulations in infants with acute respiratory syncytial virus brochiolitis. Pediatr Allergy Immunol 8:97–102

    Article  CAS  Google Scholar 

  • Reed JL, Welliver TP, Sims GP, McKinney L, Velozo L, Avendano L, Hintz K, Luma J, Coyle AJ, Welliver RC Sr (2009) Innate immune signals modulate antiviral and polyreactive antibody responses during severe respiratory syncytial virus infection. J Infect Dis 199:1128–1138

    Article  CAS  Google Scholar 

  • Russell CD, Unger SA, Walton M, Schwarze J (2017) The human immune response to respiratory syncytial virus infection. Clin Microbiol Rev 30:481–502

    Article  CAS  Google Scholar 

  • Schmidt ME, Varga SM (2017) Modulation of the host immune response by respiratory syncytial virus proteins. J Microbiol (seoul) 55:161–171

    Article  CAS  Google Scholar 

  • Spielmann S, Kerner T, Ahlers O, Keh D, Gerlach M, Gerlach H (2001) Early detection of increased tumour necrosis factor alpha (TNFalpha) and soluble TNF receptor protein plasma levels after trauma reveals associations with the clinical course. Acta Anaesthesiol Scand 45:364–370

    Article  CAS  Google Scholar 

  • Sun Y, López CB (2016) Preparation of Respiratory Syncytial Virus with High or Low Content of Defective Viral Particles and Their Purification from Viral Stocks. Bio-Protoc 6:e1820

    PubMed  Google Scholar 

  • Wang SZ, Smith PK, Lovejoy M, Bowden JJ, Alpers JH, Forsyth KD (1998a) The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis. Clin Exp Immunol 114:49–54

    Article  CAS  Google Scholar 

  • Wang SZ, Smith PK, Lovejoy M, Bowden JJ, Alpers JH, Forsyth KD (1998b) Shedding of L-selectin and PECAM-1 and upregulation of Mac-1 and ICAM-1 on neutrophils in RSV bronchiolitis. Am J Physiol 275:L983–L989

    CAS  PubMed  Google Scholar 

  • Wang J, Xu C, Wong YK, Li Y, Liao F, Jiang T, Tu Y (2019) Artemisinin, the magic drug discovered from traditional Chinese medicine. Engineering 5:32–39

    Article  CAS  Google Scholar 

  • Yang Y, Jiang W, Wang L, Zhang ZB, Si SY, Hong B (2009) Characterization of the isoflavone pratensein as a novel transcriptional up-regulator of scavenger receptor class B type I in HepG2 cells. Biol Pharm Bull 32:1289–1294

    Article  CAS  Google Scholar 

  • Yoshino H, Seki N, Itesako T, Chiyomaru T, Nakagawa M, Enokida H (2013) Aberrant expression of microRNAs in bladder cancer. Nat Rev Urol 10:396–404

    Article  CAS  Google Scholar 

  • Yui I, Hoshi A, Shigeta Y, Takami T, Nakayama T (2003) Detection of human respiratory syncytial virus sequences in peripheral blood mononuclear cells. J Med Virol 70:481–489

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

No funding.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Xihu District, Hangzhou, 310012, Zhejiang, China

    Qiong Zhang, Si Li & Qiong Huang

Authors
  1. Qiong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Si Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiong Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QZ and QH made the majority contribution to the conception of this study, carried out all the experiments, and prepared the first draft of this manuscript. QH agreed with the final design of this work and revised this manuscript critically. SL performed cell culture and Western blot. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Qiong Huang.

Ethics declarations

Conflict of interest

Qiong Zhang declares that she has no conflict of interest. Si Li declares that he has no conflict of interest. Qiong Huang declares that she has no conflict of interest.

Human and animal rights

The article does not contain any studies with human and animal and this study was performed following institutional and national guidelines.

Ethical approval

Ethical approval of this study was obtained from the Ethics Committee of Tongde Hospital of Zhejiang Province.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

13273_2021_200_MOESM1_ESM.tif

Supplementary fig 1 Effects of PG and TGF-β on markers of inflammation and oxidative stress in BEAS-2B cells. BEAS-2B cells were treated with 40 μM PG for 48 h. (a) ROS level, (b) SOD activity, (c) IL-6, and (d) TNF-α were detected with corresponding commercial kits. **p<0.01 and ***p<0.001 (TIF 362 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Q., Li, S. & Huang, Q. Pratensein glycoside attenuates respiratory syncytial virus infection-induced oxidative and inflammatory injury via TGF-β signaling pathway. Mol. Cell. Toxicol. 18, 329–337 (2022). https://doi.org/10.1007/s13273-021-00200-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-021-00200-2

Keywords

Search

Navigation