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.
Highlights
Vitiligo is a long-term skin disease characterized by the loss of pigment in the skin
All compounds in Vernonia anthelmintica (L.) collecting and sorting Forty-eight compounds were collected from Vernonia anthelmintica (L.) (Additional file 1: Table S1)
Effects of Isorhamnetin and Kaempferide on the melanogenic pathway in B16F10 cells As Isorhamnetin and Kaempferide increased melanin synthesis, we further explored whether Isorhamnetin and Kaempferide affected tyrosinase activity, the expression of melanin-biosynthetic genes (MC1R, microphthalmia-associated transcription factor (MITF), TYR, Tyrosinase-related protein 1 (TYRP1) and L-dopachrome tautomerase (DCT)) and the protein level of MITF
Summary
Vitiligo is a long-term skin disease characterized by the loss of pigment in the skin. 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). Some populations have rates as high as 2–3% [3] Many theories, such as autoimmunity, neural and genetic theories, impaired melanocyte migration and/or proliferation, and oxidative stress, have been proposed to explain the mechanism of pigmentation loss [4]. Several treatment options aim to restore pigmentation, including excimer laser, vitamin D analogs and steroid therapy [6]. These treatments are not widely employed because they induce long-term side effects [7]. Increasing research has focused on the identification of novel therapeutic medicine and the assessment of multi-targets to explain the complex network of the therapeutic mechanism of vitiligo
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