Rosacea is a chronic inflammatory skin disorder that affects approximately 5.5 % of the adult population worldwide(Dirr et al., 2024). It is characterised by facial erythema, telangiectasia, oedema, papules, pustules, and recurrent flushing(Chen et al., 2024). Rosacea was originally classified according to a subtype approach, with four predominant subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. It not only affects facial appearance but is also associated with various systemic conditions, including inflammatory bowel disease, gastroesophageal reflux disease, and mental health disorders, such as anxiety and depression, thereby significantly affecting patients’ quality of life(Choi et al., 2021; Meng et al., 2024; Rainer et al., 2015).

The pathogenesis of rosacea is complex and involves genetic and environmental factors. Immune dysfunction, chronic inflammation, microbial imbalance, and vascular and neurological dysfunction all contribute to the development of the disease(Yang et al., 2024). Therefore, the treatment of rosacea is challenging.

Current treatment options for rosacea include topical creams, oral medications, and laser therapy(Dirr et al., 2024). FDA-approved drugs, such as metronidazole, ivermectin, azelaic acid, and sub-antimicrobial doses of oral doxycycline, are commonly used(Thiboutot et al., 2020). However, side effects and risks such as photosensitivity, microbial imbalance, and skin barrier impairment can exacerbate this condition. As a result, existing treatments are limited, and patients may struggle to adhere to them. Many natural compounds, including flavanols, saponins, flavones, flavanones, and volatile oils, can be used to manage rosacea. Owing to their anti-inflammatory, antioxidant, and vasoprotective functions, natural compounds are used to treat rosacea or as part of combination therapy with medications(Semenescu et al., 2024).

Nonetheless, exploring its pathogenesis and developing targeted therapies remain key research directions for treating rosacea. Among the various cell types involved, mast cells play a central role in rosacea(Chen et al., 2024). Mas-related G protein-coupled receptor X2 (MRGPRX2; mouse counterpart MrgprB2), which is mainly expressed in mast cells, is primarily involved in pseudo-allergic reactions induced by pharmaceuticals, host defence peptides, neuropeptides, and other agents. Activation of mast cells via MRGPRX2 leads to the release of tryptase (TPS), histamine, and serotonin, as well as the activation of itch-sensory neurones, which promotes inflammation(Ali, 2017; Meixiong et al., 2019). MRGPRX2 is involved in various inflammatory skin diseases, including chronic spontaneous urticaria, psoriasis, atopic dermatitis (AD) and rosacea(Fuentes-Duculan et al., 2017; Fujisawa et al., 2014; Hao et al., 2020; Jia et al., 2024; Kumar et al., 2025). Cathelicidin LL-37-MRGPRX2 is a key pathway in the pathogenesis of rosacea, and a rosacea mouse model constructed by the intradermal injection of LL-37 is recognised(Yang et al., 2024). Thus, MRGPRX2 is a promising target for the therapeutic management of rosacea.

Stellera chamaejasme L. (family Thymelaeaceae) has been traditionally used in Mongolian medicine to treat various diseases, including chronic tracheitis, tuberculosis, and psoriasis. Stellera chamaejasme L. exhibits antioxidant and anti-inflammatory activities and can be applied as a new and innovative natural formulation for the treatment of chronic inflammatory diseases(Selenge et al., 2023). The active compounds in Stellera chamaejasme L. improve symptoms in 2,4-dinitrochlorobenzene (DNCB)-treated AD mice and attenuate DNCB-induced increases in IL-4 expression and serum IgE levels(Jo et al., 2018). Neochamaejasmin B (NCB) is the most abundant component of the dried roots of Stellera chamaejasme L. and exhibits pharmacological activities(Pan et al., 2015). NCB may be suitable for the prevention and treatment of allergic asthma, as it attenuates the recruitment of inflammatory cells and reduces the levels of interleukin-5 (IL-5), interleukin-6 (IL-6), interleukin-13 (IL-13) and immunoglobulin E (IgE) in a murine model(Lee et al., 2021). However, the pharmacological mechanism of NCB remains unclear. Whether NCB improves skin inflammatory responses under various dermatological conditions, such as rosacea, remains unclear.

We used mouse models and mast cell lines to explore whether NCB could reduce rosacea-associated inflammation by inhibiting mast cell activation via MRGPRX2 and the underlying molecular mechanisms. This study aimed to expand the treatment options for rosacea and explore and validate potential therapeutic targets.