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.