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1.
J Ethnopharmacol ; 274: 114041, 2021 Jun 28.
Article in English | MEDLINE | ID: mdl-33757812

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease mediated by immunity. Our pre-clinical studies have proved that QZLX mixture can improve patients' clinical symptoms with psoriasis without noticeable adverse reactions. In a psoriasis-like mouse model induced by imiquimod, QZLX mixture has been shown to alleviate epidermal inflammation and inhibit the hyperproliferation of keratinocytes. However, its related molecular mechanism remains to be elucidated. AIM OF THE STUDY: To assess the mechanism of QZLX mixture against psoriasis. MATERIALS AND METHODS: This study combines network pharmacology and experiments to study the mechanism of QZLX against psoriasis. First, construct the active compound-target network and PPI network. Secondly, determine possible drug targets through Molecular docking and KEGG. Thirdly, high-performance liquid chromatography (HPLC) was used for the quality control of QZLX. Finally, use a mouse model of psoriasis to further confirm the role of QZLX. RESULTS: (1) Network pharmacology analysis shows that QZLX alleviates psoriasis's epidermal inflammation, and neovascularization may be achieved by inhibiting the IL6/STAT3 signaling pathway. (2) QZLX improves the pathological characteristics of IMQ-induced skin damage in psoriasis-like mice. (3) QZLX inhibits the IL6/STAT3 signaling pathway and reduces the expression of IL-17, IL-23, and TNF-α related to inflammation in peripheral blood, as well as the expression of S100A7 in the lesion area. QZLX is better than MTX in inhibiting neovascularization by down-regulating the expression of HIF-1 and CD31 in the lesion area. Finally, inhibition of Ki67 alleviates the excessive proliferation of keratinocytes. CONCLUSION: In sum, this study clarifies the mechanism of QZLX against psoriasis and provides evidence to support its clinical use.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Psoriasis/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Proliferation/drug effects , Cytokines/genetics , Cytokines/immunology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Hypoxia-Inducible Factor 1, alpha Subunit/immunology , Imiquimod , Keratinocytes/drug effects , Male , Mice, Inbred C57BL , Molecular Docking Simulation , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Protein Interaction Maps , Psoriasis/chemically induced , Psoriasis/immunology , Psoriasis/pathology , STAT3 Transcription Factor/immunology , Skin/drug effects , Skin/immunology , Skin/pathology
2.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1406-1417, 2020 Mar.
Article in Chinese | MEDLINE | ID: mdl-32281355

ABSTRACT

This study was designed to investigate the effect of Gegen Qinlian(GGQL) Decoction and its different compatibility groups on gut microbiota in rats with acute enteritis, and to explore the efficacy of GGQL Decoction in improving acute enteritis and gut microbiota. Male SD rats were randomly divided into control group, model group, positive control group(SASP), GGQL decoction group, Glycyrrhizae-free group(QGC), Puerariae-free group(QGG), Qinlian-free group(QQL), and Qinlian group(QL). The pathological sections and detection indexes of the rats were observed before and after modeling and administration. After 7 days of administration, fecal samples from 24 rats were collected and Illumina Miseq platform was used for high-throughput sequencing. From the anti-inflammatory and pharmacodynamic indicators, the effect was the most obvious in GGQL Decoction group, QGC group, QGG group and QL group(P<0.05). The alpha diversity and beta diversity showed that there were significant differences in the composition of intestinal flora in each group. As compared with the model group, the increased abundance and diversity of the flora caused by acute inflammation could be down-regulated in all groups except QQL group(P<0.05). The differential bacteria were explored by using LEfSe analysis, and the results showed that Bifidobacterium and other beneficial bacteria only appeared in the normal group. As compared with the normal group, Lactobacillus was significantly reduced(P<0.01), and Bacteroides, Flavonifractor and Clostridium_sensu_stricto_1 were up-regulated in model group(P<0.05, P<0.01). As compared with the model group, the number of Akkermansia was significantly increased(P<0.05), and the number of Clostridium_sensu_stricto_1 associated with intestinal inflammatory diseases was decreased in the GGQL Decoction group, QGC group and QL group. QGC group and QQL group caused the up-regulation of Ruminococcaceae and induced enrichment of Desulfovibrio which could lead to colon cell toxicity; QGG group caused the up-regulation of Proteobacteria and Burkhonderiales. The study suggests that the GGQL Decoction may play a role in the treatment of acute enteritis partially through improving the intestinal barrier, regulating the immune response and the structure of gut microbiota.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Enteritis/drug therapy , Gastrointestinal Microbiome/drug effects , Animals , Bacteria/classification , Feces , High-Throughput Nucleotide Sequencing , Male , Random Allocation , Rats , Rats, Sprague-Dawley
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