Background@#
Acitretin and
matrine have been used in the
treatment of
psoriasis in
China. This study was designed to investigate the
role and related mechanisms of
matrine alone and in combination with
acitretin in the
treatment of
psoriasis in vitro and in vivo.@*
Methods@#
HaCaT cells were treated with
matrine at different concentrations of 0 (blank control), 0.2, 0.4, 0.8, and 1.6 mg/mL for 24, 48, 72 h, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
cell viability assay was used to assess the
growth and proliferation of
HaCaT cells.
Cell cycle and
apoptosis were detected by
flow cytometry. Expression of
protein was detected by
Western blotting.
Autophagy was observed by
transmission electron microscopy. Then
HaCaT cells were assigned to
normal saline (NS)
control group,
matrine (0.4 mg/mL) group,
acitretin (10 μmol/L) group, and
matrine plus
acitretin group, and the above
methods were repeated. In
animal experiments, the cumulative score (
erythema, scaling, thickening) as a
measure of the severity of
inflammation was used to
measure the
skin performance of
mice after treated with
matrine 50 mg/kg,
acitretin 4.5 mg/kg or combination of the two
drugs on the
psoriasis-like
mouse models, respectively. Pathological findings of the lesions were observed, and the
protein expressions in the lesions were detected by
immunohistochemistry.@*Results@#
Cell proliferation inhibition was seen in
HaCaT cells with
treatment of
matrine in a
dose- and
time-dependent manner (P < 0.01, respectively).
Cell cycle G0/
G1 phase arrest was observed in a
dose-dependent way (P < 0.01). The expression of p21 (P < 0.05), LC3II/I (P < 0.01), and
Beclin 1 (P < 0.01) increased and the expression of
cyclin D1 (P < 0.05) decreased with increasing doses of
matrine. Compared with the blank control, more
autophagosomes were seen in
HaCaT cells treated with
matrine at 0.4 mg/mL by
transmission electron microscopy (2.667 ± 1.202 vs. 21.33 ± 1.453, t = 9.899, P < 0.01).
Cell proliferation inhibition and degree of the G0/
G1 phase arrest was significantly higher in
matrine plus
acitretin group than those in
matrine,
acitretin, or the NS
control group (P < 0.01, respectively). Compared with
matrine or
acitretin group, the expression of p21 (P < 0.05, P < 0.05) and LC3II/I (P < 0.01, P < 0.05) in
matrine plus
acitretin group increased significantly and the expression of
cyclin D1 (P < 0.01, P < 0.05) and p62 (P < 0.05, P < 0.05) was reduced significantly. Compared with
matrine or
acitretin,
matrine plus
acitretin significantly down-regulated the
phosphorylation of
phosphoinositide 3-
kinase (PI3K)/
protein kinase B (Akt)/
mammalian target of rapamycin (mTOR) pathway (P < 0.05) and its
downstream p-
p70S6K (P < 0.05). In addition, the cumulative score of
mice in the
matrine plus
acitretin group was significantly better than that in the
matrine or
acitretin group (1.480 ± 0.230 vs. 2.370 ± 0.241, P < 0.01; 1.480 ± 0.230 vs. 2.888 ± 0.341, P < 0.01). The expression of LC3
protein in the
matrine plus
acitretin group was also higher than that in the
matrine,
acitretin, or the NS
control group (P < 0.05, respectively).@*Conclusions@#
Matrine has
therapeutic potentials for
psoriasis.
Matrine and
acitretin show synergistic effect via
cell cycle arrest and
autophagy induction by PI3K/Akt/mTOR pathway.