Urticaria is an immune-mediated inflammatory disease characterized by spontaneous or inducible urticaria, angioedema or both (Gimenez-Arnau et al., 2015). Patients often have pale to bright wheals, erythema, and itching on the skin (Schaefer, 2017). Sometimes, this condition is often accompanied for the whole life and detrimental to the quality of life of patients (Maurer et al., 2011). There are many pathogenic factors for the onset of urticaria, including food, drugs, acute or chronic infection, physical stimulation, chemical stimulation, certain diseases, genetics, and so on. Three-quarters of patients with urticaria have difficulty in identifying the causative factor, especially those with chronic urticaria (Vestergaard and Deleuran, 2015). Immunoglobulin E (IgE) which mediates the accumulation and degranulation of mast cells plays a central role in the pathogenesis of urticaria, which results in the release of histamine and other inflammatory mediators (Peng et al., 2022; Church et al., 2018). Furthermore, the abnormal immune response caused by the imbalance of human immune cells, especially CD4+ helper T cells (Th), plays an important role in the pathogenesis of urticaria. Antihistamines or monoclonal antibodies are often used to treat urticaria. However, in addition to adverse side effects such as drowsiness and headache, these drugs still cannot fundamentally relieve the suffering of patients with urticaria (Maurer et al., 2013; Bernstein et al., 2014). Therefore, safe, effective therapeutic drugs remain an unmet clinical need.

Jingfang Granule (JFG) is a modern formulation of Jingfang Baidu Powder recorded in She-Sheng-Zhong-Miao-Fang, a Traditional Chinese Medicine (TCM) book of the Ming Dynasty in China. Jingfang Baidu Powder or JFG is suitable for the “beginning of the plague”, and it is often used clinically for the treatment of epidemic and infectious diseases, such as acute viral upper respiratory tract infection, dengue fever, influenza A (H1N1), chickenpox, and mumps (Zhao et al., 2020). A biological information technology study indicated that JFG treated corona virus infectious diseases through the compatibility of multiple TCM. Its resistance to corona virus infection maybe through the β-sitosterol, cerevisterol, isorhamnetin and luteolin acting on the VEGFA, IL-6, TNF, PPARγ, APP and other targets, and then affected the pathways in cancer, MAPK signaling pathway, PI3K-AKT signaling pathway, TNF signaling pathway (Chen et al., 2020). It has also been reported that JFG has a significant effect of inhibiting thrombosis. In the mice tail thrombosis model induced by carrageenan, Zhou et al. found that JFG can inhibit the activation of ERK1/2 and p38 MAPK signaling pathways, thereby reducing the length of mouse tail thrombosis (Zhou et al., 2022). Anti-inflammation and inhibition of oxidative stress are another important function of JFG. Using aristolochic acid induced renal injury model, Cao et al. found that JFG could alleviate acute kidney injury by regulating oxidative stress and inflammation, and its mechanism may be related to regulting Akt/MDm2/p53 pathway and inhibiting apoptosis (Cao et al., 2022). Li et al. used LPS-induced mastitis model and confirmed that JFG could inhibit inflammation, improve the integrity of the blood-milk barrier and inhibit apoptosis, which also indicates the potential application of JFG for the prevention and treatment of mastitis (Li et al., 2022).

Meanwhile, JFG has a remarkable curative effect on various skin sores and ulcers caused by toxin accumulation in the muscle surface. Modern physicians have also confirmed in clinical practice that JFG has therapeutic effects on various skin diseases, such as drug-related skin diseases (Xu et al., 2018), acne (Xu and Duan, 2016) and urticaria (Feng Q et al., 2022). However, the underlying mechanisms by which JFG treats skin diseases are still largely unknown. The present study aimed to examine the effects of JFG on OVA/aluminum hydroxide induced urticaria mice, and the effects of JFG on inflammation and Th subsets imbalance in model mice were also investigated. Further, we discussed the modern pharmacological mechanism of JFG in the treatment of urticaria by proteomics and central carbon metabolomics techniques.