Network pharmacological mechanisms of Vernonia anthelmintica (L.) in the treatment of vitiligo: Isorhamnetin induction of melanogenesis via up-regulation of melanin-biosynthetic genes

Abstract

BackgroundVitiligo is a long-term skin disease characterized by the loss of pigment in the skin. The current therapeutic approaches are limited. Although the anti-vitiligo mechanisms of Vernonia anthelmintica (L.) remain ambiguous, the herb has been broadly used in Uyghur hospitals to treat vitiligo. The overall objective of the present study aims to identify the potential lead compounds from Vernonia anthelmintica (L.) in the treatment of vitiligo via an oral route as well as the melanogenic mechanisms in the systematic approaches in silico of admetSAR and substructure-drug-target network-based inference (SDTNBI).ResultsThe results showed that the top 5 active compounds with a relatively higher bioavailability that interacted with 23 therapeutic targets were identified in Vernonia anthelmintica (L.) using admetSAR and SDTNBI methods. Among these compounds, Isorhamnetin and Kaempferide, which are methyl-flavonoids, performed 1st and 2nd. Isorhamnetin and Kaempferide significantly increased the expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT) and the tyrosinase activity in B16F10 cells. Isorhamnetin and Kaempferide significantly increased the mRNA-expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT), the protein level of MITF and the tyrosinase activity. Based on the SDTNBI method and experimental verification, Isorhamnetin and Kaempferide effectively increased melanogenesis by targeting the MC1R-MITF signaling pathway, MAPK signaling pathway, PPAR signaling pathway (PPARA, PPARD, PPARG), arachidonic acid metabolism pathway (ALOX12, ALOX15, CBR1) and serotonergic synapses (ALOX12, ALOX15) in the treatment of vitiligo from a network perspective.ConclusionWe identified the melanogenic activity of the methyl-flavonoids Isorhamnetin and Kaempferide, which were successfully predicted in a network pharmacological analysis of Vernonia anthelmintica (L.) by admetSAR and SDTNBI methods.Electronic supplementary materialThe online version of this article (10.1186/s12918-017-0486-1) contains supplementary material, which is available to authorized users.

Kaempferide improves glycolipid metabolism disorder by activating PPARγ in high-fat-diet-fed mice

“…It was consistent with our hypothesis. The key target that Ka ameliorated glycolipid metabolism disorder was to activate PPARγ, which was consistent with the prediction of Wang JY et al [13] . In that study, researchers used computer simulation to predict that Ka might act on multiple sites and PPARs may be an important target.…”

Network Pharmacology‐Based Investigation of the System‐Level Molecular Mechanisms of the Hematopoietic Activity of Samul‐Tang, a Traditional Korean Herbal Formula

“…All networks were visualized using Cytoscape software (version 3.7.1) [88]. e target location network was generated based on the analysis of gene expression data of various hematopoietic tissues and organs obtained from e Human Protein Atlas [89] and BioGPS databases [90]; this network was generated by linking the target to the corresponding tissues and organs where it was analyzed to be specifically expressed using previously described procedures [91][92][93][94][95][96][97][98]. e protein-protein interaction (PPI) network was constructed using the STRING database (version 11.0) [99] and interactions with highest confidence scores (≥0.9) were selected for further analysis.…”

“…To understand the therapeutic effects of SMT at the tissue-and organ-level, we generated a target location network based on the gene expression data for individual myelosuppression-associated SMT targets across various tissues and organs, which were identified from e Human Protein Atlas [88] and BioGPS databases [90] and analyzed as previously described [91][92][93][94][95][96][97][98] (Figure 5; see Materials and Methods). Consequently, we found that the targets were expressed in various hematopoietic tissues and organs [129,130], including the liver (degree = 144), bone marrow (degree = 137), spleen (degree = 116), lymph nodes (degree = 113), and blood (degree = 100) ( Figure 5), which suggests the systematic mechanism of action responsible for the pharmacological effects of SMT.…”

System Prediction and Validation of TCM for Chronic Myeloid Leukemia Treatment from the Perspective of Low‐Toxicity Chemotherapy: A Stilbene α‐Viniferin Has a Proapoptotic Effect on K562 Cells via the Mitochondrial Pathway

“…Equation (1) adds together the results and overall predictive accuracy (Q) of each compound, with five major CYP isoforms (index k). e overall predictive accuracies (Q) of five major CYP isoforms (CYP450 1A2, CYP450 2C9, CYP450 2C19, CYP450 2D6, and CYP450 3A4) were 0.8147, 0.8018, 0.8551, 0.8054, and 0.6450, respectively [19]. Evidence-Based Complementary and Alternative Medicine…”