Pinocembrin Reduces Keratinocyte Activation and Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis in BALB/c Mice through the Heme Oxygenase-1/Signal Transducer and Activator of Transcription 3 Pathway

Abstract

Psoriasis is an autoimmune disease characterized by chronic skin inflammation and excessive keratinocyte proliferation. The itchy, scaly, and erythematous lesions present on psoriatic skin negatively affect patients’ quality of life. Pinocembrin is a flavonoid present in propolis, fruits, and vegetables. It exerts neuroprotective effects and was used for treating ischemic stroke in a human clinical trial. However, the effects of pinocembrin on psoriasis have never been examined. In this study, we evaluated the effects of pinocembrin on human HaCaT keratinocytes and BALB/c mice with imiquimod- (IMQ-) induced psoriatic dermatitis. In interferon-γ- (IFN-γ-) activated HaCaT cells, pinocembrin reduced the expression of inflammatory cytokines, namely, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and keratinocyte proliferation markers, namely, keratin (K)16, K17, and Ki-67. The mechanism underlying these inhibitory effects involved the regulation of the heme oxygenase- (HO-) 1/signal transducer and activator of transcription (STAT) 3 pathway. In the IMQ-induced psoriatic dermatitis mouse model, the topical application of pinocembrin significantly ameliorated the Skin Psoriasis Area and Severity Index score, epidermal thickness, inflammation, hyperplasia, hyperkeratosis, and cluster of differentiation (CD) 4+ T-cell infiltration. Expression of the inflammatory cytokines and keratinocyte proliferation markers in dorsal skin was significantly decreased in the pinocembrin-treated group. Meanwhile, in lesional skin, the expression of HO-1 was upregulated, but that of phospho-STAT3 (pSTAT3) was downregulated. Collectively, our results indicated the therapeutic potential of pinocembrin. Additional studies are warranted to evaluate its clinical benefits in patients with psoriasis.

Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation

“…RMSD refers to the occurrence of deviations that were noticed during the evolution of the simulation ( Peng et al, 2012 ; Ghildiyal et al, 2020 ; Huang et al, 2022 ). Furthermore, the RMSD defines the stability of the structural as the smaller the RMSD, the greater the stability ( Huang et al, 2022 ).…”

“…RMSD refers to the occurrence of deviations that were noticed during the evolution of the simulation ( Peng et al, 2012 ; Ghildiyal et al, 2020 ; Huang et al, 2022 ). Furthermore, the RMSD defines the stability of the structural as the smaller the RMSD, the greater the stability ( Huang et al, 2022 ). RMSD calculations for protein backbones, ligands, and complexes during a100 ns MD simulation of each protein-ligand complex were used to get an insight into conformational changes during protein-ligand interactions, as shown in Figure 7 .…”

“…Pinocembrin demonstrated potent antifungal action in a dose-dependent manner against Penicillium italicum ( Peng et al, 2012 ). Pinocembrin exhibits anti-viral activity against the reproduction of the Zika virus ( Ghildiyal et al, 2020 ; Huang et al, 2022 ). Pinocembrin inhibits the Zika virus replication cycle’s post-entry process, and also, it also prevents the formation of viral envelope protein and RNA ( Guang and Du, 2006 ).…”

Anti-proliferative Effects of Pinocembrin Isolated From Anomianthus dulcis on Hepatocellular Carcinoma Cells

“…It is also a potential and promising protein for HCC-targeted therapy. 14 , 15 Previous studies showed that pinocembrin can inhibit the phosphorylation of STAT3 at Ser727 in keratinocytes 31 and at Tyr705 in microglial 32 and non-small cell lung cancer cells. 23 In the present study, we showed that pinocembrin can inhibit the phosphorylation at both tyrosine and serine residues.…”

Pre-treatment with galectin-1 attenuates lipopolysaccharide-induced myocarditis by regulating the Nrf2 pathway

“… 28 HO-1 exhibits a potentially beneficial role in numerous cardiovascular diseases. 29 In the inactive state, Nrf2 stays in the cytoplasm by binding with Keap1. Some pharmacological as well as pathophysiological stimulation can deactivate Keap1, resulting in Nrf2 dissociating from Keap1 and translocating into nuclei.…”