## 1 Introduction
Activated Syk subsequently phosphorylates the linker for activation of T cells (LAT), initiating downstream signaling cascades involving phospholipase C (PLC)-\(\gamma 1\) and protein kinase C (PKC) [21; 22]. In addition, Fyn phosphorylates LAT and further facilitates signaling through the PI3K-Akt pathway [23; 24]. LAT phosphorylation ultimately activates PLC-\(\gamma 1\) and PKC-\(\delta\), which, through the mitogen-activated protein kinase (MAPK) pathway (ERK, JNK, p38), promote the release of histamine, cytokines, and leukotrienes, thereby driving mast cell degranulation and allergic responses [25; 26]. Currently, allergic disease treatments primarily involve medications such as antihistamines, corticosteroids, and leukotriene antagonists [27]. While these drugs effectively alleviate symptoms, they fail to address the underlying cause--mast cell activation. Moreover, they may cause side effects such as dry eyes, nausea, vomiting, nasal itching, headaches, anxiety, and drowsiness [28]. Given these limitations, there is growing interest in mast cell stabilizers that can inhibit mast cell activation, a key driver of allergic reactions. These stabilizers are classified based on their mechanisms of action, including anti-IgE agents (e.g., omalizumab, quilizumab), Ca\({}^{2+}\) influx inhibitors (e.g., cromolyn), Syk inhibitors that block intracellular signaling (e.g., piceatannol, curcumin), and PKC family inhibitors (e.g., calphostin C, sphingosine) [29]. As the demand for safer and more effective treatments increased, the development of therapies based on natural compounds has emerged as a promising focus. _Lonica caerulea_, belonging to the Caprifoliaaceae family, is widely distributed across Northern Europe, North America, and Northeast Asia. This fruit is oblong, with a deep blue-to-purple color [30]. _Lonica caerulea_ fruit is a rich source of anthocyanins, especially cyanidin-3-glucoside (C3G), which constitutes over 60% of its total phenolic content. Other significant polyphenols include chlorogenic acid, caffeoylquinic acid, quercetin, and catechin, though in smaller amounts [31; 32; 33]. Various studies have demonstrated the fruit's physiological benefits. In a paw edema model using 4-week-old male ICR mice (\(n=4\)) administered with LPS (1 mg/kg), oral administration of _Lonica caerulea_ fruit extract (300 mg/kg, p.o.) for four days, along with treatment of LPS-stimulated RAW 264.7 cells (300 mg/mL), significantly reduced inflammation and oxidative stress by inhibiting the MAPK/NF-\(\kappa\)B pathway and enhancing nuclear factor erythroid-2-related factor 2 (Nrf2) and manganese-dependent superoxide dismutase (MnSOD) expression [34]. In 6-week-old male Sprague-Dawley mice (\(n=6\)) fed a high-fat diet, eight weeks of oral administration of _Lonicera caerulea_ (250 mg/kg, p.o.) improved lipid profiles by activating the Nrf2-ARE pathway [35]. Additionally, 84 days of oral administration of _Lonicera caerulea_ (400 mg/kg, p.o.) in 6-week-old female ICR mice (\(n=6\)) on a high-Tructose diet improved obesity and liver health, influencing antioxidant systems (catalase, glutathione), the AMP-activated protein kinase (AMPK) pathway, and glucose metabolism (UCP2, adiponectin) was administered [36]. The primary constituent of _Lonicera caerulea_ fruit, C3G has been shown to exhibit various biological activities. Oral administration of C3G (0.2% wt/wt, p.o.) for six weeks suppressed atherosclerosis in diabetic male apoE\(-/-\)mice (6 weeks old, STZ-induced, \(n=5\)-6) by improving endothelial function via AMPK regulation and restoration of eNOS phosphorylation [37]. In an oxidative stress model using HT22 cells (glutamate, 5 mM, 18 h), treatment with C3G (0-100 \(\upmu\)M, 24 h) promoted neuronal survival by activating the ERK and Nrf pathways, upregulating anti-oxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) [38]. Oral administration of C3G (500 mg/kg, p.o.)