Elsevier

Journal of Functional Foods

Volume 13, March 2015, Pages 100-107
Journal of Functional Foods

Anti-allergenic activity of polymethoxyflavones from Kaempferia parviflora

https://doi.org/10.1016/j.jff.2014.12.029Get rights and content

Highlights

  • The 13 polymethoxyflavones from Kaempferia parviflora suppressed antigen-induced degranulation of RBL-2H3 cells.

  • 5-hydroxy-3,7,4′,-trimethoxyflavone and 5,3′-dihydroxy-3,7,4′-trimethoxyflavone had potent inhibitory effects.

  • These flavones suppressed degranulation due to Ca2+ influx, phosphorylation of PLCγ1, and translocation of FcεRI.

Abstract

The inhibitory effects of 13 polymethoxyflavones (PMFs) obtained from Kaempferia parviflora extracts were evaluated on RBL-2H3 cell degranulation. These flavones suppressed antigen-induced degranulation in RBL-2H3 cells. 5-Hydroxy-3,7,4′,-trimethoxyflavone (KP02) and 5,3′-dihydroxy-3,7,4′,-trimethoxyflavone (KP10) showed potent inhibitory activities. KP10 significantly suppressed calcium ionophores, such as A23187 and 2,5-ditert-butylhydroquinone, which promoted calcium influx from the outside of cells and from the endoplasmic reticulum, respectively. However, these activities did not fully explain the PMFs' effects. Immunoblot analysis of KP02 and KP10 showed that the inhibitory effects were attributable to the downregulation of PLCγ1 kinase phosphorylation in the signaling pathways involved in degranulation. The phosphorylation levels of Syk were also suppressed by the addition of KP10. KP02 and KP10 treatment to the cells did not affect the high affinity IgE receptor (FcεRI) levels inside RBL-2H3 cells, but they suppressed the FcεRI levels in the plasma membrane. Therefore, K. parviflora PMFs have multiple degranulation mechanisms to suppress RBL-2H3 cells and would be beneficial for alleviating type I allergy symptoms.

Introduction

The incidence of allergic disorders has increased dramatically in developed countries (Yamada, Saito, & Fujieda, 2014). In particular, allergic rhinitis represents a global health care problem that greatly affects daily activity, work productivity, learning, sleep, and quality of life in persons of all ages (Yamada et al., 2014). Allergic reactions represent a dysregulated immune response to a multitude of allergens normally present either in the environment, such as dust and pollen, or in food, such as milk, eggs, and wheat (Campbell, Hill, & Kemp, 1998). A chronic use of drugs for allergic therapy is sometimes associated with adverse effects (Coureau, Bussières, & Tremblay, 2008). Ideally, an anti-allergic therapy should be beneficial against different allergic disorders i.e. atopic dermatitis, food allergies, and ultimately be safe on long-term administration. Recent scientific evidence from pre-clinical studies and human clinical trials has highlighted that daily polyphenol intake can improve allergic symptoms (Singh et al., 2011).

Allergy is mainly classified into four types. Among them, the type I allergy is the most common allergic reaction associated with asthma, hives, hay fever, and allergic dermatitis. During the initiation of type I allergic reaction, the allergen binds to IgE molecules, which then bind to high affinity IgE receptors (FcεRI) on the surfaces of mast cells and basophils. The cross-linking of the cell-bound IgE–FcεRI complex with a specific antigen causes the aggregation of FcεRI, which induces a variety of cellular responses, including the release of chemical mediators such as histamine, arachidonic acid metabolites, and cytokines (Kalesnikoff & Galli, 2008). The prevention of allergic diseases using food ingredients has been intensively studied and there is evidence of the preventive effect of dietary polyphenols against allergic diseases (Singh et al., 2011).

Kaempferia parviflora Wall ex. Baker belongs to the family Zingiberaceae. In Thailand, the rhizomes of K. parviflora have been used to treat allergies, gastrointestinal disorders, and peptic ulcers (Yenjai, Prasanphen, Daodee, Wongpanich, & Kittakoop, 2004). Tewtrakul, Subhadhirasakul, and Kummee (2008) reported the antiallergic effects of the 7 species of methoxyflavones from K. parviflora using RBL-2H3 cells, although detailed mechanism of the action remains unknown. Recently, we isolated and elucidated the structures of 14 polymethoxyflavones (PMFs) and 3 new phenolic glycosides from various K. parviflora extracts (Azuma et al, 2011, Azuma et al, 2008).

In recent studies, many PMFs have been shown to have a broad spectrum of biological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic properties (Chinapongtitiwat et al, 2013, Lee et al, 2013, Li et al, 2009). PMFs exclusively exist in the citrus genus which has been used as Chinese herbal medicine for thousands of years. Because nobiletin and tangeretin are the most abundant PMFs in citrus fruits, they have been the focus of primary research owing to their bioactivity (Lee et al, 2013, Li et al, 2014). Although PMFs have poor aqueous solubility, they have high intestinal permeability and bioavailability, thereby gaining importance in clinical studies for the benefit of humans in disease prevention and treatment (Lee et al., 2013).

In the present study, we investigated the detailed mechanism of action using isolated PMFs in the degranulation of RBL-2H3 cells.

Section snippets

Chemicals and reagents

Murine anti-dinitrophenyl IgE (anti-DNP IgE) and DNP-labeled human serum albumin were purchased from Sigma (St. Louis, MO, USA). FcεRI, Na+/K+-ATPase, PLCγ1, p-PLCγ1, PLCγ2, p-PLCγ2 Syk, and p-Syk antibodies were obtained from Cell Signaling Technology (MA, USA). All other chemicals were of reagent grade.

Cell culture

RBL-2H3 cells (Cell Bank, RIKEN BioResource Center, Tsukuba, Japan) were cultured in Dulbecco's modified Eagle's medium supplemented with 10% heat-inactivated fetal bovine serum, 100 U/mL

Effects of K. parviflora extracts on the antigen-mediated degranulation of RBL-2H3 cells

We examined the effects of K. parviflora extracts on the antigen-mediated degranulation of RBL-2H3 cells. Table 1 shows that the CH2Cl2 extract and EtOAc soluble fraction had potent inhibitory effects.

Effects of K. parviflora flavones on the antigen-mediated degranulation of RBL-2H3 cells

Next, we studied the effects of the flavones isolated from the CH2Cl2 extract and EtOAc soluble fraction. Previously, we reported the identification of PMFs isolated from a CH2Cl2 extract of K. parviflora and an EtOAc-soluble fraction (Azuma et al., 2011). The chemical structures are shown in

Conclusions

PMFs isolated from K. parviflora were found to be capable of inhibiting antigen-stimulated degranulation in RBL-2H3 cells. The inhibitory effects of KP02 and KP10 on antigen-stimulated degranulation in RBL-2H3 cells were demonstrated and these effects were related to the suppression of degranulation due to Ca2+ influx, phosphorylation of Syk and PLCγ1, and translocation of FcεRI to the cell surface (Fig. 4). K. parviflora and PMFs may be beneficial for ameliorating the symptoms of type I

Acknowledgements

This work was supported by Council for Science, Technology and Innovation (CSTI), Cross-ministerial Strategic Innovation Promotion Program (SIP), “Technologies for creating next-generation agriculture, forestry and fisheries”

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