Cianidanol suppresses M1 macrophage polarization via JAK2/STAT1 to ameliorate DNCB-induced atopic dermatitis

Cianidanol (Cian), also known as (+)-catechin, is a naturally occurring flavonoid found in medicinal plants including Camellia sinensis and Violae herba. Its role in inflammatory skin disease has not been well defined. Human single-cell RNA sequencing data showed an increased proportion of M1-like macrophages in atopic dermatitis (AD).

We therefore evaluated Cian in a 2,4-dinitrochlorobenzene-induced AD-like dermatitis mouse model and in RAW264.7 and THP-1 macrophage models. Cian alleviated skin lesions, reduced epidermal thickening, suppressed pro-inflammatory cytokine production, and restored anti-inflammatory responses. It also reduced CD86 expression without promoting a marked M2-like phenotypic shift.

Mechanistically, Cian decreased the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1). Molecular docking, molecular dynamics simulation, and cellular thermal shift assay supported a potential interaction between Cian and JAK2 in cell lysates. These findings indicate that Cian attenuates experimental AD-like inflammation in association with reduced M1-like macrophage activation and JAK2/STAT1 signaling, while its safety and pharmacokinetic profile require further investigation.