Cedrol from Platycladus orientalis (L.) Franco regulates M1/M2 polarization of macrophages and promotes hair regeneration

Ethnopharmacological relevance: Platycladus orientalis (L.) Franco is traditionally used to promote hair growth. Cedrol (CE) is the main active ingredient in Platycladus orientalis (PO), promoting hair growth. However, the anti-alopecia areata (AA) effect and mechanism of action of CE in the imiquimod-induced AA model have not been reported.

Aim of the study: The macrophage polarization imbalance is a key pathological driving factor for AA. This study aims to elucidate the potential mechanism by which CE ameliorates AA by regulating macrophage polarization homeostasis.

Materials and methods: The effect of CE (30 mg/kg) on the polarization of macrophages was studied using an AA model induced by imiquimod (62.5 mg/kg), and HaCaT and THP-1 macrophages induced with LPS/TNF-α/IFN-γ (M3; 100 ng/mL+10 ng/mL+10 ng/mL).

Results: CE exerted a good promoting effect on in vitro mouse hair follicle and AA mouse hair growth. Transcriptomics reveals that CE ameliorated alopecia by inhibiting inflammatory responses mediated by IFN-γ and rebuilding the immune microenvironment. Mechanistic studies showed that CE inhibited the release of M1-type inflammatory factors, macrophage numbers, and related chemokines. When combined with IL-4, their expression was reversed, and they have an intervention effect on immune microenvironment disorders (CD4, CD8, etc). This indicates that CE has a good regulatory effect on M1/M2 polarization imbalance, possibly through the STATs and MAPK signaling pathways. The combination with the pathway inhibitor enhanced the inhibition of M1 polarization.

Conclusion: The inhibition of macrophage-mediated inflammatory infiltration by CE showed a strong germinal effect, providing new insights into CE's effect on AA.

Alopecia areata; Cedrol; Immunosuppression; Macrophage polarization; Platycladus orientalis.