**1. Introduction**

Food allergy is a potentially life-threatening allergic reaction that a ffects a substantial proportion of the population, being defined as a breakdown of immunological tolerance and clinical symptoms generated in response to ingested food [1]. It is estimated that approximately 8% of children and 5% of adults su ffer from food allergies around the world, and the prevalence has also been rising over the past two decades [2]. Food allergy is more common in children than in adults, and it often begins in childhood with the influence of genetic predisposition.

Eggs are indispensable nutrients in children's diet pagodas. However, the prevalence of egg allergy in children ranges from 1.2% to 2.0%. The majority allergens within eggs have been found in egg white, with ovalbumin (OVA) being the most abundant form (at 58%, although it is not the major allergen), which is claimed to frequently elicit allergic reactions [3,4]. Thus, the OVA-induced mice allergy model is often used to evaluate the anti-allergic activity of various materials [5,6].

Food allergy is characterized by a type I hypersensitivity reaction mediated by immunoglobulinE (IgE), and is often accompanied by adverse reactions, including diarrhea, intestinal injury, and hypothermia [7]. Moreover, it is also accompanied by increased intestinal permeability, which is positively correlated with symptom severity, which persists even in a diet without allergens [8]. Food particles and allergens can cross the epithelial barrier and cause allergic reactions induced by IgE production and mast cell (MC) recruitment [9]. In addition, the development of food allergy involves a variety of immune cells, which play di fferent roles in the process. B lymphocytes are mainly responsible for releasing antibodies (e.g., IgE), which are associated with basophil and MC activation [10]. Cellular immunity is primarily characterized by T lymphocytes, including T helper cells (Th) 1 and 2, and regulatory T cells (Tregs). CD4 + Foxp3 + Tregs can secrete transforming growth factor or interleukin (IL)-10, suppress MC activation, and modulate T and B cells, thereby promoting immunosuppression and relieving anaphylaxis [11,12].

As crucial and rapid immune e ffector cells, MCs play the key role in IgE-mediated allergic responses [13]. Several reports have indicated that targeting MCs may represent a promising strategy for the treatment of food allergies [14]. MCs are activated when IgE binds with high a ffinity to the IgE receptor (FcεRI) on the surface of MCs [15]. When re-exposed to specific allergens, MCs were activated with a cascade of tyrosine phosphorylation, and then released a series of allergic mediators [16,17]. During the process of MC activation and degranulation, Ca2+ is an essential co-factor that regulates the release of various mediators and granule-plasma membrane fusion [18]. It has been reported that glycyrrhizic acid can perform a function as an "MC stabilizer" and inhibit MC degranulation by suppressing Ca2+ influx [19]. Therefore, obtaining a stabilizer that can regulate Ca2+ influx may be important for inhibiting MC activation and degranulation.

Novel natural compounds from marine resources have attracted increased attention in recent years due to their potential medicinal value [20]. Due to their unique habitat, deep-sea fungi readily produce various secondary metabolites, which have novel structure and distinctive biological properties. Most fully researched secondary metabolites of deep-sea fungi have mainly been from a limited number of genera, including *Penicillium*, *Aspergillus*, *Fusarium*, and *Cladosporium* [21]. Within the facultative marine fungi, species of *Penicillium* and *Talaromyces* are particularly well known for their ability to produce important bioactive compounds [22]. *Penicillium*, an important genus of the phylum Ascomycota, is widely distributed and has a large impact on human life [23]. Moreover, as one of the most studied fungi, *Penicillium* was considered to be a primary source of drug discovery, which produces a wide range of highly active metabolites, including griseofulvin and the blockbuster drug penicillin [24,25]. After the discovery of penicillin, isolating secondary metabolites of *Penicillium* species has received a remarkable amount of interest from researchers due to the interesting structures and possible pharmaceutical applications of the compounds. It has been shown that *Penicillium* metabolites possess a wide range of biological properties such as antibacterial activities, antioxidant properties, and cytotoxic activities against cancer lines [22]. Thus, as the second most common genus of marine fungi, it is of good importance to investigate the properties and metabolites of *Penicillium* [22]. It has been reported that cyclopiane-type diterpenes from the deep sea-derived fungus *Penicillium* possess antimicrobial activity [26]. However, few systematic studies have investigated the anti-food allergy properties of *Penicillium* secondary metabolites, especially for deep-sea *Penicillium*.

In previous studies, the rat basophil leukemia (RBL)-2H3 cell model was established to explore the anti-allergic potential metabolite from deep-sea fungi including *Penicillium*, *Aspergillus*, *Actinomycete*, and so on [27,28]. The metabolites of deep-sea-derived *Aspergillus* and *Actinomycete* relieved allergy by regulating MC function and accelerating MC apoptosis, respectively. Additionally, nine compounds isolated from deep-sea fungus *Penicillium griseofulvum* were tested for their anti-allergic bioactivity using the RBL-2H3 cell model [29]. A further study on the fungus led to the isolation of another potent anti-allergic compound, viridicatol. As reported, viridicatol effectively inhibited the protein activities and expressions of Matrix matalloproteinases (MMP)-2 and -9 against cancer and tumor [30]. However, the investigation of the biological activity of viridicatol is limited at present. This study was aimed at seeking to further validate and explore the associated mechanism of viridicatol using mouse model, flow cytometry, and an RBL-2H3 cell model. The findings of this study are expected to provide a foundation for the development of new marine anti-allergic drugs.
