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| Study on mechanism of action of Galangin cream against vitiligo based on network pharmacology and experimental verification |
| Zulipikaer Wusiman1 ZHANG Shushu1 YAN Ming2 LI Zhijian3▲ HUO Shixia3▲ |
1.School of Pharmacology, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China;
2.Uyghur Medicine Research Institute of Xinjiang Uygur Autonomous Region, Uygur Autonomous Region, Urumqi 830049, China;
3. Hospital of Xinjiang Traditional Uygur Medicine, Xinjiang Uygur Autonomous Region, Urumqi 830049, China |
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Abstract Objective To investigate the mechanism of action of Galangin (GA) cream against vitiligo by network pharmacology and animal experiments. Methods The active ingredients and targets of GA were screened through Swiss Target Prediction, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and vitiligo-related targets were screened in TTD, OMIM, and DrugBank databases. The drugs and disease targets were imported into the String platform to construct a protein-protein interaction (PPI) network to screen the core targets. Cytoscape 3.7.1 software was used to construct the network of traditional se medication-active ingredients-core target-key pathways, and enrichment analysis was performed. The molecular docking of GA with the core target protein was performed by Autodock Vina 1.2. Sixty SPF male C57BL/6 mice aged four weeks, weighing (21±3) g, were selected, of which ten mice were set as the normal control group, and the other 50 mice were evenly applied with 10%H2O2 on the back to establish the vitiligo model. After successful modeling, the mice were divided into model group, positive drug group (8-methoxyepsoralen, 4.25 mg/kg), and GA cream high (4%GA, 1g/ time), medium (2%GA, 1g/ time), low (1%GA, 1g/ time) dose groups, with ten rats in each group. After 30 days of continuous administration, the changes of mice skin tissues were observed by hematoxylin-eosin staining; the serum levels of interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), and endothelin-1 (ET-1) of mice were detected by enzyme-linked immunosorbent assay. The protein expression levels of TNF-α and ET-1 in the skin tissues of mice were detected by Western blot. The mRNA expression of ET-1, IL-18, and TNF-α in the skin tissues of mice was detected by real-time fluorescent quantitative PCR. Results A total of 17 GA targets, 459 vitiligo targets, and ten drug-disease targets were identified. PPI network showed that tyroinase, TNF, IL-1β, and IL-18 were the core targets of GA in the treatment of vitiligo. Enrichment analysis showed that GA may play an anti-vitiligo effect through nuclear factor-κB signaling pathway, NOD-like receptor signaling pathway, and HIF-1 pathway. Molecular docking results showed that GA had good binding ability with ET-1, TNF-α, and IL-18. The results of hematoxylin-eosin staining showed that there was no obvious abnormality in the normal control group. In the model group, the fold of the epidermal spinous layer became thicker, the hair follicle was damaged, and the stratum corneum was significantly proliferated. There were slight spinous folds in the epidermis of the GA cream groups, which were lighter than those of the model group. The serum levels of ET-1, IL-18, and TNF-α in the model group were higher than those in the normal control group, the protein expressions of ET-1 and TNF-α in the skin tissues were higher than those in the normal control group, and the mRNA expressions of ET-1, IL-18, and TNF-α in the skin tissues were higher than those in the normal control group (P＜0.05). The levels of serum ET-1, IL-18, and TNF-α in GA cream low, medium, high dose groups were lower than those in the model group, the expression of ET-1 protein in the skin tissues in the GA cream high dose group was lower than that in the model group, the expression of TNF-α protein and IL-18 mRNA in the skin tissues in the GA cream medium and high dose groups were lower than those in the model group, the mRNA expressions of ET-1 and TNF-α in the skin tissues of the GA cream low, medium, high dose groups were lower than those of the model group (P＜0.05). The expression of TNF-α protein and IL-18 mRNA in skin tissues of GA cream medium and high dose groups were lower than those of GA cream low dose group, and the expression of ET-1 protein in skin tissues of GA cream high dose group was lower than that of GA cream low dose group (P＜0.05). Conclusion GA cream may exert its anti-vitiligo effect by regulating various pathways and inhibiting ET-1, IL-18, and TNF-α.
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