Abstract
Trigonelline, one of the active compounds from Leonurus japonicus Houtt., has been proven to have pharmacological value in diabetes, the central nervous system and cardiovascular diseases. Recent studies have shown that it may also be beneficial in controlling inflammation. However, the mechanism of the antiallergic effects of trigonelline has not been well studied. As the key effector cells participating in the development of allergies, mast cells have been linked to the pathogenesis of asthma for ages. In this study, we demonstrated the inhibitory effect of trigonelline on activated bone marrow-derived mast cells (BMMCs) and verified its anti-inflammatory properties using an ovalbumin (OVA)-induced asthma model. Trigonelline suppressed BMMC degranulation and decreased the production of the cytokines, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) in a dose-dependent manner. The potent mechanism is mainly through the suppression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Trigonelline can alleviate pathological damage in lung tissue and reduce the levels of serum immunoglobulin E (IgE) and T helper 2 (Th2) cytokines. RNA-seq results revealed the HIF-1α to be a potential target for the allergic reaction. Taken together, our study demonstrated that trigonelline can inhibit allergic inflammation in vitro and in vivo, which may provide a basis for novel anti-inflammatory drug development.
Highlights
Allergic asthma is a worldwide disease characterized by local airway inflammation and hyperresponsiveness, followed by the activation of the immune system and the release of multiple cytokines (Mims, 2015)
bone marrow-derived mast cells (BMMCs) were treated with various concentrations of trigonelline hydrochloride (TH), and we found no significant cell toxicity at 1 mM (Figure 1B)
The results showed that TH suppressed the secretion of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and IL-6
Summary
Allergic asthma is a worldwide disease characterized by local airway inflammation and hyperresponsiveness, followed by the activation of the immune system and the release of multiple cytokines (Mims, 2015). The lack of treatment options is a serious challenge for allergic asthma. Mast cells play a prominent role in promoting various chronic inflammatory disorders such as asthma, allergic rhinitis, anaphylaxis and rheumatic disease (Méndez-Enríquez and Hallgren, 2019). Mast cells can be stimulated through many kinds of surface receptors, including the high-affinity receptor for IgE (FcεRI), receptor for stem cell factor (c-Kit), cytokine receptors, releasing three main classes of mediators: preformed granule-associated mediators histamine, serotonin and tryptase); newly generated lipid mediators (PGD2, LTC4); and various cytokines and chemokines such as TNF-α, IL-1β, IL6, IL-13, CCL5 and CCL8 (Moon et al, 2014). Mast cells seem to be a critical target in allergy-related diseases
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