Vitiligo 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). The 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. We 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.

Non-small-cell lung cancer (NSCLC), the most common type of lung cancers, is resistant to initial chemotherapy intrinsically. The expressions of xenobiotic metabolism genes, antioxidants, and drug efflux proteins are increased in NSCLC. In addition, a redox-sensitive transcription factor named Nrf2 regulates the drug resistance via the expression of electrophile, oxidants detoxification enzymes and efflux mechanism. As was detected by real-time PCR, inhibiting Nrf2 expression through the transfection of shRNA plasmids in A549 cells significantly inhibits the expressions of glutathione pathway genes, antioxidants and multidrug resistance proteins. Using biochemical assays and free radical medical experiments in vitro, it was identified that the RNAi-mediated reduction of Nrf2 expression in lung cancer cells induces the generation of reactive oxygen species, decreases the level of reduced glutathione and results in an increase in the A549 cell proliferation inhibition rate. Thus, targeting Nrf2 activity in NSCLC could be a practical way to inhibit tumor growth and eliminate chemoresistance.

Melanoma represents a formidable challenge in dermatological oncology due to its resistance to conventional treatments. The Celandine Alkali Injection Formula (CAIF) offers benefits on clinical internal medicine treatments, within which chelidonine and tetrandrine are recognized as potential quality markers. However, their synergistic mechanisms facilitating their anti-melanoma action remain unveiled. This study embarked on an exploration of CAIF’s therapeutic potential through a multifaceted research design, integrating system pharmacological predictions with empirical molecular biological evaluations. The dual application of chelidonine and tetrandrine within CAIF exhibited a pronounced inhibitory effect on the proliferation of B16F10 cells, surpassing the effectiveness of individual compound administration. Computational predictions identified the top 50 targets, involved in key signaling pathways including cell cycle regulation, and melanogenesis. RNA sequencing further elucidated that the combinatory treatment modulated a broader spectrum of differentially expressed genes, implicating crucial biological processes including cell differentiation, and tyrosinase metabolism. The combination markedly enhanced melanogenesis and apoptotic indices, arrested cell cycle progression, and fostered cellular differentiation. Notably, chelidonine additionally curtailed the migratory capacity of B16F10 cells. Our findings underscore the therapeutic potential of chelidonine and tetrandrine, key components of CAIF, in effectively combating melanoma by targeting cell proliferation, migration, differentiation, and melanogenesis.