A Network Pharmacology Approach to Uncover the Molecular Mechanisms of Herbal Formula Kang-Bai-Ling for Treatment of Vitiligo.

BACKGROUND: Kang-bai-ling (KBL), a Chinese patent medicine, has been demonstrated as an effective therapy for vitiligo in China. However, the pharmacological mechanisms of KBL have not been completely elucidated. METHODS: In this study, the potential multicomponent, multitarget, and multipathway mechanism of KBL against vitiligo was clarified by using network pharmacology-based strategy. In brief, potential targets of KBL were collected based on TCMSP databases, followed by network establishment concerning the interactions of potential targets of KBL with well-known therapeutic targets of vitiligo by using protein-protein interaction (PPI) data. As a result, key nodes with higher level of seven topological parameters, including "degree centrality (DC)," "betweenness centrality (BC)," "closeness centrality (CC)," "eigenvector centrality (EC)," "network centrality (NC)," and "local average connectivity (LAC)" were identified as the main targets in the network, followed by subsequent incorporation into the ClueGO for GO and KEGG signaling pathway enrichment analysis. RESULTS: In accordance with the topological importance, a total of 23 potential targets of KBL on vitiligo were identified as main hubs. Additionally, enrichment analysis suggested that targets of KBL on vitiligo were mainly clustered into multiple biological processes (associated with DNA translation, lymphocyte differentiation and activation, steroid biosynthesis, autoimmune and systemic inflammatory reaction, neuron apoptosis, and vitamin deficiency) and related pathways (TNF, JAK-STAT, ILs, TLRs, prolactin, and NF-κB), indicating the underlying mechanisms of KBL on vitiligo. CONCLUSION: In this work, we successfully illuminated the "multicompounds, multitargets" therapeutic action of KBL on vitiligo by using network pharmacology. Moreover, our present outcomes might shed light on the further clinical application of KBL on vitiligo treatment.

[Glycyrrhizin inhibits IFN-γ-induced CXCL10 by suppressing the JAK/STAT1 signal pathway in HaCaT cells].

Objective To detect the effect of glycyrrhizin (GL) on the expression of CXCL10 induced by IFN-γ in HaCaT cells. Methods HaCaT cells were cultured in vitro. IFN-γ at the dosage of 10 ng/mL was used to establish the model group. GL (0.5 mmol/L), JAK1/2 inhibitor CYT387 (15 nmol/L), and combined therapy of GL and CYT387 were administrated in IFN-γ-treated HaCaT cells, respectively. Cell viability was detected by MTT assay. The expression of CXCL10 was assessed via real-time quantitative PCR and ELISA. Protein phosphorylation of the JAK1/2 and STAT1 was determined using western blot analysis. Results GL decreased IFN-γ-induced keratinocyte disruption. Moreover, GL had no significant effect on cell viability. Both GL and JAK1/2 inhibitor CYT387 down-regulated the expression of CXCL10 in HaCaT cells induced by IFN-γ. Its expression of CXCL10 mRNA was markedly lower in GL and CYT387 combined with GL group than that in CYT387 group. The phosphorylation of JAK1/2 and STAT1 declined by GL. Conclusion GL inhibits the activation of IFN-γ- mediated JAK/STAT1 signaling, thereby reducing CXCL10 level in HaCaT cells.

Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro.

Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, 102 nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, 102 and 103 nM significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to 102 nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at 102 nM. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression.

Effects of aqueous extracts of Ecliptae herba, Polygoni multiflori radix praeparata and Rehmanniae radix praeparata on melanogenesis and the migration of human melanocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni multiflori radix praeparata (PMRP), Ecliptae herba (EH) and Rehmanniae radix praeparata (RRP) are the most frequently-used herbs by Traditional Chinese Medicine practitioners for the treatment of vitiligo. Their abilities to stimulate melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression were evaluated in this study. MATERIALS AND METHODS: The effects of aqueous extracts of PMRP, EH and RRP on human melanocytes in vitro were examined by MTT assay, tyrosinase activity, melanin synthesis, migration assay and Western blot. RESULTS: Treatment with EH (at 100µg/ml and 400µg/ml) significantly increased intracellular tyrosinase activity in accordance with the elevation of melanin content at the same concentrations. Treatment with RRP (at 100µg/ml and 400µg/ml) promoted melanin production but had no stimulatory effect on tyrosinase activity. Treatment with PMRP and EH (at 100µg/ml) promoted the migration of human melanocytes in a type IV collagen-coated transwell migration assay. Western blot analysis showed MITF protein expression was elevated by PMRP, EH and RRP (at 100µg/ml). CONCLUSION: An aqueous extract of EH has a synergistic effect on melanocytes by up-regulating tyrosinase activity, enhancing melanin synthesis and promoting melanocyte migration as well as elevating MITF protein expression. RRP exhibits a significant stimulating effect on melanogenesis and MITF protein expression. These results suggest that EH and RRP contain substances with direct enhancing effects on melanogenesis and migration, possibly via their effects on MITF protein expression.

Spectrum of dermoscopic patterns in lichen planus: a case series from China.

BACKGROUND: Dermoscopy has been shown to be a promising method to facilitate the diagnosis of lichen planus (LP) outside of China. OBJECTIVE: To investigate the spectrum of dermoscopic patterns in Chinese LP patients. METHODS: The clinical data and dermoscopic patterns of nine LP cases with a total of 43 lesions were evaluated. RESULTS: To the naked eye, 20.97% of the lesions exhibited graying Wickham striae (WS); however, 37.5% presented with white streaks of annular, reticular, or leaf venation patterns under dermoscopy. Blue-white veils were occasionally observed in the center. Pigment patterns varied from dots, globules, and peppered pigment to pigmented lines, which were unrelated to the pigment network of the skin. At the periphery of the WS, red fine lines ran parallel to the delicate white streaming lines. CONCLUSIONS: WS exhibits five morphological patterns (leaf venation, reticular, white dots, circular and radial streaming) and three color patterns (homogeneous crystalline white, blue-white veil and yellowish-white). The pigment patterns consisted of dots/globules, peppered pigments and pigment. streaming lines.

Blaschkoid pityriasis versicolor.

A 31-year-old male patient complained of having follicular and brownish red maculopapules along the Blaschko's lines on the right chest for 2 days. On examination, follicular brownish maculopapules were present on the chest with a uniform size of about 3 mm in diameter. The lesions were isolated without a tendency to merge, giving several S-shaped, band-like appearances. Direct mycological examination of the skin flakes revealed many pseudomycelial hyphae and yeast cells with typical spaghetti and meatball appearance. Wood's light examination of the lesion revealed a golden yellow fluorescence. A diagnosis of blaschkoid pityriasis versicolor was suggested because of blaschkoid distribution of the lesions in this new variant of PV.