The Natural Products Targeting on Allergic Rhinitis: From Traditional Medicine to Modern Drug Discovery

Abstract

More than 500 million people suffer from allergic rhinitis (AR) in the world. Current treatments include oral antihistamines and intranasal corticosteroids; however, they often cause side effects and are unsuitable for long-term exposure. Natural products could work as a feasible alternative, and this study aimed to review the efficacies and mechanisms of natural substances in AR therapies by examining previous literature. Fifty-seven studies were collected and classified into plants, fungi, and minerals decoction; clinical trials were organized separately. The majority of the natural products showed their efficacies by two mechanisms: anti-inflammation regulating diverse mediators and anti-oxidation controlling the activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway stimulated by reactive oxygen species (ROS). The main AR factors modified by natural products included interleukin (IL)-4, IL-5, IL-13, interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), cyclooxygenase 2 (COX-2), and phospho-ERK1/2 (p-ERK1/2). Although further studies are required to verify their efficacies and safeties, natural products can significantly contribute to the treatment of AR.

Keywords: allergic rhinitis; antioxidants; inflammation; interleukin; natural products; nuclear factor kappa-light-chain-enhancer of activated B cells.

Figure 1

The mechanism of allergic rhinitis (AR) symptoms triggered by APC. APC, antigen-presenting cell; IL, interleukin; Th, T helper; T-bet, T-box-expressed-in-T-cells; STAT, signal transducers and activators of transcription; TGF, transforming growth factor; RoRyt, retinoid-related orphan receptor; FoxP3, Forkhead box p3; IFN, interferon; Treg, regulatory T; DTH, delayed type hypersensitivity; Ig, immunoglobulin; NK-1, neurokinin-1 receptor.

Figure 2

Schematic diagram of plants and decoctions that ameliorated allergic rhinitis by triggering T helper cell differentiation; BCE, Bupleurum chinense water extract; RMFE, Rosae Multiflorae Fructus water extract; BGPP, Brazilian green propolis; EGCG, Epigallocatechin gallate; DC, Dryopteris crassirhizoma.

Figure 3

Histamine receptors. HDC, histidine decarboxylase; H1R, histamine H1 receptor; H₂R, histamine H2 receptor; H₃R, histamine H3 receptor; G, G protein; IP₃, inositol 3,4,5-triphosphate; DAG, diacylglycerol; PKC, protein kinase C; AC, adenylyl cyclase; cAMP, cycling AMP; PKA, protein kinase A; CREB, cAMP-responsive element binding protein; MAPK, mitogen-activated protein kinase; Pl3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; BGPP, Brazilian green propolis.

Figure 4

LO pathway, PGE₂ synthesis and signaling pathway. MAPK, mitogen-activated protein kinase; COX-2, cyclooxygenase-2; NFκB, nuclear factor-κB; ROS, reactive oxygen species; PGE₂, prostaglandin E2; DNP, dinitrophenyl; IgE, immunoglobulin E; FcεRI, high-affinity IgE receptor; Syk, spleen tyrosine kinase; PKC, protein kinase C; AA, arachidonic acid; 5-Lox, arachidonate 5-lipoxygenase; FLAP, 5-LO-activating protein; 5HPETE, 5-hydroperoxyeicosatetraenoic acid; LT, leukotriene; EC, endothelial cell; SMC, smooth muscle cell; CysLT1, cysteinyl leukotriene 1; EGCG, Epigallocatechin gallate.

Figure 5

Various pathways for immune response. PIP₂, phosphatidyl inositol 4, 5-trisphosphate; PIP₃, phosphatidylinositol 3, 4, 5-trisphosphate; P, phosphate; NF-κB, p65 nuclear factor kappa B; BCR, B cell receptor; Ig, immunoglobulin; Syk, spleen tyrosine kinase; BKT, Bruton’s tyrosine kinase; PLCγ2, phospholipase C gamma 2; IL, interleukin; IL-R, interleukin receptor; MAPK, mitogen-activated protein kinase; NF-AT, nuclear factor of activated T-cells.