Decryption of Active Constituents and Action Mechanism of the Traditional Uighur Prescription (BXXTR) Alleviating IMQ-Induced Psoriasis-Like Skin Inflammation in BALB/c Mice

Abstract

Bai Xuan Xia Ta Re Pian (BXXTR) is a traditional Uighur medicine ancient prescription in China widely used in the treatment of psoriasis, presenting a high curative rate and few side effects. Given that the active constituents and action mechanism still remain unclear, the aim of this study is to explore the potential active constituents and mechanism of antipsoriasis of BXXTR. Psoriasis-like lesions model in BALB/c mice was induced by Imiquimod (IMQ), including five treatment groups: control group, IMQ-treated group, IMQ-ACITRETIN group (Positive control group), IMQ-BXXTR low dose group, IMQ-BXXTR medium dose group and IMQ-BXXTR high dose group. The Psoriasis Area and Severity Index (PASI) score, skin and ear thickness, and histologic section were collected. The differentially expressed genes were determined by using RNAseq technology and the relevant pathways were analyzed by KEGG database. The ELISA kit and western blot assays were used to detect the related protein expression levels. In addition, the chemical constituents of BXXTR were determined by UPLC-TOF-MS analysis and the potential active constituents were predicted by SEA DOCK and Gene Ontology (GO). The data demonstrated that BXXTR significantly alleviated IMQ-induced psoriasis. RNA-seq analysis showed that BXXTR induced the expression levels of 31 genes; the KEGG analysis suggested that BXXTR could significantly change IL-17-related inflammatory pathways. The ELISA kit confirmed that the expression level of IL-17A protein was significantly reduced. 75 compounds of BXXTR were determined by UPLC-TOF-MS analysis, 11 of 75 compounds were identified as potential active compounds by similarity ensemble approach docking (SEA DOCK) and Gene Ontology (GO). BXXTR reduced the severity of skin lesions by inhibiting IL-17-related inflammatory pathways. The results indicated that BXXTR could suppress psoriasis inflammation by multiple-constituents-regulated multiple targets synergistically. Collectively, this study could provide important guidance for the elucidation of the active constituents and action mechanism of BXXTR for the treatment of psoriasis.

Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking

“…6, hsa04657 (IL-17 signaling pathway), hsa04933 (AGE-RAGE signaling pathway in diabetic complications), and hsa0406 (cytokine-cytokine receptor interaction pathway) enriched the highest number of genes, indicating that these pathways may play an important role in the mechanism of action of DYY in the treatment of COVID-19. The IL-17 signaling pathway is involved in the body's immune response [25,26] and inflammatory response [27]. The AGE-RAGE signaling pathway has important protective effects on bones and the heart and participates in oxidative stress response [25] and fibrosis transduction [22].…”

Fluorescent Light Incites a Conserved Immune and Inflammatory Genetic Response within Vertebrate Organs (Danio rerio, Oryzias latipes and Mus musculus)

“…As bioinformatics analyses showed that inflammation and immune related genes dominate the genetic response incited by FL, we hypothesized that gene expression pattern change after FL exposure should be similar to that after known treatments that lead to inflammation and infection. We compared the FL-incited DEGs to literature-reported organism and organ-matched transcriptomic data associated with an inflammatory condition, immune response, and acute phase response [38,39,40]. Mouse skin FL-incited DEGs were compared to DEGs modulated by Imiquimod (IMQ), a compound that is used to induce psoriasis-like skin inflammation [41,42]; mouse liver FL-incited DEGs were compared to DEGs modulated by Lipopolysaccharide (LPS) challenge; and zebrafish liver FL-incited DEGs were compared to DEGs modulated by Edwardsiella tarda vaccination.…”

Chemical profiling and anti-psoriatic activity of marine sponge (Dysidea avara) in induced imiquimod-psoriasis-skin model

“…Buffalo, NY, USA). The samples were stained with hematoxylin and eosin, and photographs were prepared [ 22 ].…”

“…The samples in the RIPA lysis buffer were suspended and homogenized by the probe type sonicator for 10 s. The lysed skin back tissue was centrifuged for 10 minutes at 12,000 RPM, and the supernatant was collected and the cytokine concentration was quantified using the manufacturing protocol for ELISA kit (LEGEND MAX, San Diego, CA, USA). The experiment was carried out in triplicates, calculating the means and standard deviations [ 22 ].…”