Abstract

Although Myrciaria dubia (camu-camu) has been shown to exert anti-oxidant and anti-inflammatory effects in both in vitro and in vivo studies, its use in allergic responses has not been elucidated. In the present study, the anti-allergic effect of 70% ethanol camu-camu fruit extract was tested on calcium ionophore (A23187)-induced allergies in RBL-2H3 cells. The RBL-2H3 cells were induced with 100 nM A23187 for 6 h, followed by a 1 h camu-camu fruit extract treatment. A23187 sanitization exacerbated mast cell degranulation; however, camu-camu fruit extract decreased the release of histamine and β-hexosaminidase, which are considered as key biomarkers in cell degranulation. Camu-camu fruit extract inhibited cell exocytosis by regulating the calcium/nuclear factor of activated T cell (NFAT) signaling. By downregulating the activation of mitogen-activated protein kinase (MAPK) signaling, camu-camu fruit extract hindered the activation of both histamine H1 and H4 receptors and inhibited histidine decarboxylase (HDC) expression by mediating its transcription factors KLF4/SP1 and GATA2/MITF. In A23187-induced ROS overproduction, camu-camu fruit extract activated nuclear factor erythroid-2-related factor 2 (Nrf2) to protect mast cells against A23187-induced oxidative stress. These findings indicate that camu-camu fruit extract can be developed to act as a mast cell stabilizer and an anti-histamine. This work also “opens the door” to new investigations using natural products to achieve breakthroughs in allergic disorder treatment.

Highlights

  • Allergic diseases are global concerns that roughly account for 25% of healthcare spending in developed countries

  • The present study demonstrated the potential anti-allergic effect of camu-camu fruit extract in A23187-induced RBL-2H3 cells by inhibiting mast cell degranulation and targeting histamine receptors (HRs) and histidine decarboxylase (HDC) expression, presenting novel therapeutic strategies on allergic treatment

  • These results suggest that camu-camu fruit extract suppresses exocytosis of mast cell granules by regulating the calcium/nuclear factor of activated T cell (NFAT) signaling pathway to reduce the release of histamine and β-hexosaminidase (Figure 11)

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Summary

Introduction

Allergic diseases are global concerns that roughly account for 25% of healthcare spending in developed countries. Exposure to allergens causes hypersensitivity of the immune system to release immunoglobulin E (IgE), which binds to a high-affinity IgE receptor (FcεRI) on mast cells and basophils [1]. Histamine has a key pathological function in many allergic diseases, including atopic dermatitis, allergic rhinitis, and urticaria due to activation of its distinct receptors [3]. New therapeutic approaches have been developed to fight histamine-mediated allergies through inhibition of the activation of Antioxidants 2022, 11, 104.

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