The protective effect of proanthocyanidins on the psoriasis-like cell models via PI3K/AKT and HO-1

Background: Inflammation and oxidative stress (OS) are important contributors to psoriasis pathogenesis. Proanthocyanidins (PCs) have anti-inflammatory and anti-oxidative activities. Previously, we discovered that PCs alleviated psoriasis-like mice symptoms, likely via mitigating inflammation and OS damage.

Objective: To elucidate the protective mechanism underlying PCs against the damage of TNF-ɑ-induced psoriasis-like cell models.

Methods: Psoriasis-like cell models were established with 7.5 ng/mL TNF-ɑ and then subjected to different-concentrations PCs treatment. Finally, inflammatory and oxidative parameters were determined. Besides, LY294002 (PI3K Inhibitor) and ZnPP (HO-1 inhibitor) were employed to investigate the roles of PI3K/Akt and HO-1 in PCs against psoriasis-like cell models.

Results: After TNF-α treatment, cells organized tightly and proliferated greatly (P<0.01); HO-1 expression dropped obviously, along with the increased OS/inflammatory indicators and the decreased antioxidants (P<0.05); consequently, psoriasis-like cell models were well established. In the presence of PCs, nevertheless, the proliferation rate and number of psoriasis-like cells evidently decreased (P<0.01), accompanied with enhanced HO-1 and antioxidants, and lowered OS/inflammatory indicators as well as phosphorylated JAK2/STAT3/PI3/Akt (P<0.01). Similar changes appeared after LY294002 pretreatment, regardless of PCs or not. But after ZnPP pretreatment with or without PCs, the opposite occurred.

Conclusion: The study reveals that PCs can suppress psoriasis-like cell proliferation and reduce inflammatory/OS damage through PI3K/Akt inhibition and HO-1 activation, thus promising a candidate for PCs in treating psoriasis.

AKT; HO-1; PI3K; Psoriasis; cell model; inflammation; oxidative stress (OS); proanthocyanidins.