RESUMO
Earthworms are used to cure wounds in Chinese villages for thousands of years. Recently, scientists realized their extracts could promote wound healing and they have anti-inflammatory, antioxidant, anti-apoptosis, and anti-microbial properties, but its mechanism of promoting wound healing remains unclear. In the presented study, electronic literature databases and LC-MS/MS were used to determine earthworms' ingredients and differential metabolites. Swiss Target Prediction database was used for ingredients' target prediction and wound disease-relevant genes were found from GeneCards, OMIM, and DrugBank databases. Network pharmacology was conducted to demonstrate filtering hub targets, biological functions, and the signaling pathways of earthworms extract against wounds. Molecular docking and metabolism analysis were used to look for core target genes and key bioactive molecules from earthworms. Finally, the investigation shows 5 most important signal pathways, 5 core genes, and 6 bioactive ingredients-related cell-cell adhesion, cell proliferation, and cell migration processes could be affected by earthworms' extract. On 3rd day, the extract could regulate HIF1A and EGFR targets to make the differences of quantities of 4-pyridoxate, tetradecanoic acid, and L-kynurenine. While on 7th day, the regulation refers 6 earthworms' bioactive ingredients, 4 core genes (CTNNB1, EGFR, SRC, and CASP3), and 4 differential metabolites (4-hydoxy-2-quinolinecarboxylic acid, urocanate, deoxyinosine, creatine, and sn-glycerol-3-phosphocholine). on 14th day, 2 core genes (EGFR, SRC) are influenced in the biological processes. Briefly, we found that 6 ingredients from earthworms have most bioactive and 5 core genes play an important role in promoting wound-healing processes. These discovers indicates earthworms could against wound via AGE-RAGE, PI3K-Akt, HIF1A, MAPK, and Axon guidance pathways.
RESUMO
Background: In recent years, many studies have found that vitamin K is beneficial to wound healing. However, some research results seem to be in conflict. The purpose of this study was to evaluate the effect of vitamin K on wound healing. Methods: We systematically and comprehensively searched the PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang eletronic databases. We applied revman5.3 software to calculate the weighted mean difference (WMD) of 95% confidence interval (CI) of animal and cell groups to evaluate the effect of vitamin K on wound healing. Two researchers independently selected studies and used the Cochrane Collaboration tool to assess the risk of bias in the included studies. The overall quality of evidence was assessed using the Recommendation, Assessment, Development and Evaluation (GRADE) working group approch. Results: Among the 1081 articles searched, 6 articles (16 studies in total) met the inclusion criteria. The results of quantitative analysis showed that vitamin K was beneficial to increase the wound healing rate in animal models [rat model: WMD = 27.45 (95% CI: 13.46, 41.44); p = 0.0001], but the opposite result was obtained in cell experiments [WMD = -33.84 (95% CI: -56.90, -10.79); p = 0.004]. Conclusion: This meta-analysis hits that vitamin K could affect the process of wound healing, especially in animal models. While we could not know the clear role at present, which requires larger scale research. In addition, the concentration and safe dose of vitamin K also deserve further study.