Skip to main content
SpringerLink
Log in

Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Rosmarinic acid (RA), a polyphenol from edible-medical Lamiaceae herbs, is known to possess a variety of pharmacological activity, like anti-inflammatory, hepatoprotective and immunoregulation activities.

Methods and results

Hereon, we investigated the anti-allergic activity of RA on immunoglobulin E (IgE)-mediated anaphylaxis responses in rat basophilic leukemia (RBL)-2H3 mast cell. RA hindered the morphological changes of IgE-induced degranulated RBL-2H3 cells. The release of two key biomarkers (β-hexosaminidase (β-HEX) and histamine) of IgE-induced degranulated mast cells was also remarkably down-regulated by RA intervention in a dose dependent manner. Moreover, RA inhibited IgE-induced ROS overproduction and flux of intracellular Ca2+ in IgE-mediated degranulated mast cells. The q-PCR analysis showed that the expressions of genes (COX 2, PGD 2, LTC 4, HDC, Nrf2, HO-1 and NQO1) involved in MAPK and oxidative stress signaling pathways were significantly regulated by RA intervention. Moreover, the degranulation inhibitory effect of rosmarinic acid was investigated on the anti-DNP IgE/DNP-HSA induced passive cutaneous anaphylaxis (PCA) mice model in vivo. It showed that RA significantly inhibited the PCA reaction and allergic edema of ears in anti-DNP IgE/DNP-HSA stimulated mice.

Conclusion

These findings suggest that RA has the potential to be used as a therapeutic candidate for allergic diseases by inhibiting mast cell degranulation. This indicates a possible role for RA in managing allergic reactions and related conditions.

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

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

References

  1. Bessa C, Francisco T, Dias R, Mateus N, Freitas Vd, Pérez-Gregorio R (2021) Use of polyphenols as modulators of food allergies. From chemistry to biological implications. Front Sustain Food Syst 5:623611

    Article  Google Scholar 

  2. Braegelmann C, Niebel D, Ferring-Schmitt S, Fetter T, Landsberg J, Hölzel M, Effern M, Glodde N, Steinbuch S, Bieber T et al (2022) Epigallocatechin-3-gallate exhibits anti-inflammatory effects in a human interface dermatitis model-implications for therapy. J Eur Acad Dermatol Venereol 36:144–153

    Article  CAS  PubMed  Google Scholar 

  3. Civelek M, Bilotta S, Lorentz A (2022) Resveratrol attenuates mast cell mediated allergic reactions: potentia l for use as a nutraceutical in allergic diseases? Mol Nutr Food Res 66:e2200170

    Article  PubMed  Google Scholar 

  4. Desheva Y, Mamontov A, Petkova N, Karev V, Nazarov P (2020) Mast cell degranulation and histamine release during A/H5N1 influenza infection in influenza-sensitized mice. Life Sci 258:118230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fei X, Je I-G, Shin T-Y, Kim S-H, Seo S-Y (2017) Synthesis of gallic acid analogs as histamine and pro-inflammatory cyt okine inhibitors for treatment of mast cell-mediated allergic inflammation. Molecules 22:898

    Article  PubMed  PubMed Central  Google Scholar 

  6. Frieri M (2018) Mast cell activation syndrome. Clin Rev Allergy Immunol 54:353–365

    Article  CAS  PubMed  Google Scholar 

  7. Fu S, Ni S, Wang D, Fu M, Hong T (2019) Berberine suppresses mast cell-mediated allergic responses via regulating FcɛRI-mediated and MAPK signaling. Int Immunopharmacol 71:1–6

    Article  CAS  PubMed  Google Scholar 

  8. Guan H, Luo W, Bao B, Cao Y, Cheng F, Yu S, Fan Q, Zhang L, Wu Q, Shan M (2022) A comprehensive review of rosmarinic acid: from phytochemistry to pharmacology and its new insight. Molecules 27:3292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hiemori-Kondo M, Morikawa E, Fujikura M, Nagayasu A, Maekawa Y (2021) Inhibitory effects of cyanidin-3-O-glucoside in black soybean hull extract on RBL-2H3 cells degranulation and passive cutaneous anaphylaxis reaction in mice. Int Immunopharmacol 94:107394

    Article  CAS  PubMed  Google Scholar 

  10. Hitl M, Kladar N, Gavarić N, Božin B (2020) Rosmarinic acid–human pharmacokinetics and health benefits. Planta Med 87:273–282

    PubMed  Google Scholar 

  11. Hitl M, Kladar N, Gavarić N, Božin B (2021) Rosmarinic acid-human pharmacokinetics and health benefits. Planta Med 87:273–282

    Article  CAS  PubMed  Google Scholar 

  12. Kawauchi H, Yanai K, Wang D-Y, Itahashi K, Okubo K (2019) Antihistamines for allergic rhinitis treatment from the viewpoint of nonsedative properties. Int J Mol Sci 20:213

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kim Y-Y, Je I-G, Kim MJ, Kang B-C, Choi Y-A, Baek M-C, Lee B, Choi JK, Park HR, Shin T-Y et al (2017) 2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway. Acta Pharmacol Sin 38:90–99

    Article  CAS  PubMed  Google Scholar 

  14. Kim DE, Min K-j, Kim M-J, Kim S-H, Kwon TK (2019) Hispidulin inhibits mast cell-mediated allergic inflammation through down-regulation of histamine release and inflammatory cytokines. Molecules 24:2131

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kubo M (2018) Mast cells and basophils in allergic inflammation. Curr Opin Immunol 54:74–79

    Article  CAS  PubMed  Google Scholar 

  16. Li L, Liu R, Peng C, Chen X, Li J (2022) Pharmacogenomics for the efficacy and side effects of antihistamines. Exp Dermatol 31:993–1004

    Article  CAS  PubMed  Google Scholar 

  17. Luo C, Zou L, Sun H, Peng J, Gao C, Bao L, Ji R, Jin Y, Sun S (2020) A review of the anti-inflammatory effects of rosmarinic acid on inflammatory diseases. Front Pharmacol 11:153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ma J, Tong P, Chen Y, Wang Y, Ren H, Gao Z, Yue T, Long F (2022) The inhibition of pectin oligosaccharides on degranulation of RBL-2H3 cells from apple pectin with high hydrostatic pressure assisted enzyme treatment. Food Chem 371:131097

    Article  CAS  PubMed  Google Scholar 

  19. Maintz L, Novak N (2007) Histamine and histamine intolerance. Am J Clin Nutr 85:1185–1196

    Article  CAS  PubMed  Google Scholar 

  20. Nishikawa H, Wakano K, Kitani S (2007) Inhibition of NADPH oxidase subunits translocation by tea catechin EGCG in mast cell. Biochem Biophys Res Commun 362:504–509

    Article  CAS  PubMed  Google Scholar 

  21. Niu L, Wei J, Li X, Jin Y, Shi X (2021) Inhibitory activity of narirutin on RBL-2H3 cells degranulation. Immunopharmacol Immunotoxicol 43:68–76

    Article  CAS  PubMed  Google Scholar 

  22. Noor S, Mohammad T, Rub MA, Raza A, Azum N, Yadav DK, Hassan MI, Asiri AM (2022) Biomedical features and therapeutic potential of rosmarinic acid. Arch Pharm Res 45:205–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ohtsu H (2012) Pathophysiologic role of histamine: evidence clarified by histidine decarboxylase gene knockout mice. Int Arch Allergy Immunol 158(Suppl 1):2–6

    Article  CAS  PubMed  Google Scholar 

  24. Passante E, Frankish N (2009) The RBL-2H3 cell line: its provenance and suitability as a model for the mast cell. Inflamm Res 58:737–745

    Article  CAS  PubMed  Google Scholar 

  25. Simonsen E, Komenda P, Lerner B, Askin N, Bohm C, Shaw J, Tangri N, Rigatto C (2017) Treatment of uremic pruritus: a systematic review. Am J Kidney Dis 70:638–655

    Article  CAS  PubMed  Google Scholar 

  26. Stone KD, Prussin C, Metcalfe DD (2010) IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 125:S73-80

    Article  PubMed  PubMed Central  Google Scholar 

  27. Suzuki Y, Yoshimaru T, Inoue T, Niide O, Ra C (2005) Role of oxidants in mast cell activation. Chem Immunol Allergy 87:32–42

    Article  CAS  PubMed  Google Scholar 

  28. Swindle EJ, Metcalfe DD (2007) The role of reactive oxygen species and nitric oxide in mast cell-depe ndent inflammatory processes. Immunol Rev 217:186–205

    Article  CAS  PubMed  Google Scholar 

  29. Wang K, Pramod SN, Pavase TR, Ahmed I, Lin H, Liu L, Tian S, Lin H, Li Z (2020) An overview on marine anti-allergic active substances for alleviating food-induced allergy. Crit Rev Food Sci Nutr 60:2549–2563

    Article  CAS  PubMed  Google Scholar 

  30. Yamanishi Y, Karasuyama H (2016) Basophils and mast cells in immunity and inflammation. Semin Immunopathol 38:535–537

    Article  PubMed  Google Scholar 

  31. Yang H, Qu Y, Gao Y, Sun S, Ding R, Cang W, Wu R, Wu J (2022) Role of the dietary components in food allergy: a comprehensive review. Food Chem 386:132762

    Article  CAS  PubMed  Google Scholar 

  32. Yao Y, Li R, Liu D, Long L, He N (2022) Rosmarinic acid alleviates acetaminophen-induced hepatotoxicity by targeting Nrf2 and NEK7-NLRP3 signaling pathway. Ecotoxicol Environ Saf 241:113773

    Article  CAS  PubMed  Google Scholar 

  33. Yu Y, Li Y, Qi K, Xu W, Wei Y (2022) Rosmarinic acid relieves LPS-induced sickness and depressive-like behaviors in mice by activating the BDNF/Nrf2 signaling and autophagy pathway. Behav Brain Res 433:114006

    Article  CAS  PubMed  Google Scholar 

  34. Zhang W, Cheng C, Sha Z, Chen C, Yu C, Lv N, Ji P, Wu X, Ma T, Cheng H et al (2021) Rosmarinic acid prevents refractory bacterial Pneumonia through regulating Keap1/Nrf2-mediated autophagic pathway and mitochondrial oxidative stress. Free Radic Biol Med 168:247–257

    Article  CAS  PubMed  Google Scholar 

  35. Zhao Y, Li X, Chu J, Shao Y, Sun Y, Zhang Y, Liu Z (2021) Inhibitory effect of paeoniflorin on IgE-dependent and IgE-independent mast cell degranulation in vitro and vivo. Food Funct 12:7448–7468

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was founded by Open Research Fund Program of Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, China (No: NJZ2022009).

Author information

Authors and Affiliations

  1. Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Wuhan Polytechnic University, Wuhan, 430023, China

    Binmei Jia, Jieli Shang, Xuanpei Wang, Lin Xu, Min Fang & Qing Yang

  2. Food Safety Research Center, Key Research Institute of Humanities and Social of Hubei Province, Wuhan, 430023, China

    Binmei Jia, Jieli Shang, Xuanpei Wang, Lin Xu, Min Fang & Qing Yang

  3. Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hao-Long Zeng

  4. Wuhan BioCSi Tech Laboratory Co., LTD, Wuhan, 430000, China

    Fengbo Zeng

Authors
  1. Binmei Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao-Long Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jieli Shang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuanpei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Min Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fengbo Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QY and H-LZ: wrote the main manuscript text. BJ, JS and XW: exerted the data curation. LX: was responsible for the methodology. MF: analyzed the data. FZ: written the project administration. QY: was responsible for the funding acquisition. All authors reviewed the manuscript.

Corresponding author

Correspondence to Qing Yang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

All the experiments were approved by the Animal Care and Use Committee of Wuhan polytechnic university.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jia, B., Zeng, HL., Shang, J. et al. Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo. Mol Biol Rep 51, 194 (2024). https://doi.org/10.1007/s11033-023-09164-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11033-023-09164-z

Keywords

Search

Navigation