Exploring the Effect of Xiao-Chai-Hu Decoction on Treating Psoriasis Based on Network Pharmacology and Experiment Validation.

BACKGROUND: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. OBJECTIVE: To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, in vivo experiments were carried out further to validate the therapeutic effects of XCHD on psoriasis. RESULTS: 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. CONCLUSION: XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.

The Role of Nicotinamide Mononucleotide Supplementation in Psoriasis Treatment.

Psoriasis is one of several chronic inflammatory skin diseases with a high rate of recurrence, and its pathogenesis remains unclear. Nicotinamide mononucleotide (NMN), as an important precursor of nicotinamide adenine dinucleotide (NAD+), has been reported to be a promising agent in treating various diseases, its positive effects including those induced via its anti-inflammatory and antioxidant properties. For this reason, we have aimed to explore the possible role of NMN in the treatment of psoriasis. Psoriasis models were constructed with imiquimod (IMQ) stimulation for 5 days in vivo and with M5 treatment in keratinocyte cell lines in vitro. NMN treatment during the IMQ application period markedly attenuated excess epidermal proliferation, splenomegaly, and inflammatory responses. According to GEO databases, Sirtuin1 (SIRT1) levels significantly decreased in psoriasis patients' lesion tissues; this was also the case in the IMQ-treated mice, while NMN treatment reversed the SIRT1 decline in the mouse model. Moreover, NMN supplementation also improved the prognoses of the mice after IMQ stimulation, compared to the untreated group with elevated SIRT1 levels. In HEKa and HaCaT cells, the co-culturing of NMN and M5 significantly decreased the expression levels of proinflammation factors, the phosphorylation of NF-κB, stimulator of interferon genes (STING) levels, and reactive oxygen species levels. NMN treatment also recovered the decrease in mitochondrial membrane potential and respiration ability and reduced mtDNA in the cytoplasm, leading to the inhibition of autoimmune inflammation. The knockdown of SIRT1 in vitro eliminated the protective and therapeutic effects of NMN against M5. To conclude, our results indicate that NMN protects against IMQ-induced psoriatic inflammation, oxidative stress, and mitochondrial dysfunction by activating the SIRT1 pathway.

TAZ acting as a potential pathogenic biomarker to promote the development of lichen planus.

BACKGROUND: Lichen planus is a chronic inflammatory disorder. Transcriptional coactivator with PDZ-binding motif (TAZ/WWTR1) is an important downstream effector of the Hippo pathway which regulates organ size and tissue homeostasis. But little is known about the role of TAZ in lichen planus so far. OBJECTIVE: To explore the expression of TAZ in lichen planus and normal skin, and to discover the relationship between TAZ expression and the clinical characteristics of lichen planus patients. METHODS: The method of immunohistochemistry was performed to quantify the expression of TAZ in 262 patients with lichen planus and 90 control tissues. Western blot and quantitative real-time reverse transcriptase-PCR (qRT-PCR) analysis were performed to examine and compare TAZ expression in 4 cases of fresh lichen planus lesions and normal skin tissues. RESULTS: TAZ was weakly expressed in the basal layers of the epidermis in normal skin tissues with a positive rate of 52.22% (47/90). But in lichen planus, TAZ was strongly expressed in almost the entire epidermis with a positive rate of 81.30% (213/262), and the difference between the two groups was statistically significant (p<0.05). Additionally, TAZ expression was significantly related to the location of the lichen planus, clinical phenotype, smoking, and alcohol preference (p<0.05). Western blot and qRT-PCR showed that the expression of TAZ in protein and mRNA levels in four cases of lichen planus lesions was significantly higher than that in normal skin tissues. CONCLUSION: TAZ may play a regulatory role in the occurrence and development of lichen planus, which might provide a new perspective for studying pathogenesis and theoretical treatment targets.

Oral administration of punicalagin attenuates imiquimod-induced psoriasis by reducing ROS generation and inflammation via MAPK/ERK and NF-κB signaling pathways.

Psoriasis, an immune-mediated chronic inflammatory skin disease, imposes a huge mental and physical burden on patients and severely affects their quality of life. Punicalagin (PU), the most abundant ellagitannin in pomegranates, has become a research hotspot owing to its diverse biological activities. However, its effects on psoriasis remain unclear. We explored the impact and molecular mechanism of PU on M5-stimulated keratinocyte cell lines and imiquimod (IMQ)-induced psoriasis-like skin inflammation in BABL/c mice using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), hematoxylin and eosin (H&E) stain, immunohistochemistry, and immunofluorescent. Administration of PU-enriched pomegranate extract at dosages of 150 and 250 mg/kg/day markedly attenuated psoriatic severity, abrogated splenomegaly, and reduced IMQ-induced abnormal epidermal proliferation, CD4+ T-cell infiltration, and inflammatory factor expression. Moreover, PU could decrease expression levels of pro-inflammatory cytokines, such as IL-1ß, IL-1α, IL-6, IL-8, TNF-α, IL-17A, IL-22, IL-23A, and reactive oxygen species (ROS), followed by keratinocyte proliferation inhibition in the M5-stimulated cell line model of inflammation through inhibition of mitogen-activated protein kinases/extracellular regulated protein kinases (MAPK/ERK) and nuclear factor kappaB (NF-κB) signaling pathways. Our results indicate that PU may serve as a promising nutritional intervention for psoriasis by ameliorating cellular oxidative stress and inflammation.