Norartocarpetin from a folk medicine Artocarpus communis plays a melanogenesis inhibitor without cytotoxicity in B16F10 cell and skin irritation in mice

Abstract

BackgroundMany natural products used in preventive medicine have also been developed as cosmeceutical ingredients in skin care products, such as Scutellaria baicalensis and Gardenia jasminoides. Norartocarpetin is one of the antioxidant and antityrosinase activity compound in Artocarpus communis; however, the cytotoxicity, skin irritation and antimelanogenesis mechanisms of norartocarpetin have not been investigated yet.MethodsIn the present study, cell viability in vitro and skin irritation in vivo are used to determine the safety of norartocarpetin. The melanogenesis inhibition of norartocarpetin was determined by cellular melanin content and tyrosinase in B16F10 melanoma cell. Moreover, we examined the related-melanogenesis protein by western blot analysis for elucidating the antimelanogenesis mechanism of norartocarpin.ResultsThe result of the present study demonstrated that norartocarpetin not only present non-cytotoxic in B16F10 and human fibroblast cells but also non-skin irritation in mice. Moreover, our result also first found that norartocarpetin downregulated phospho-cAMP response element-binding (phospho-CREB) and microphthalmia-associated transcription factor (MITF) expression, which in turn decreased both synthesis of tyrosinases (TRP-1 and TRP-2) and cellular melanin content. This process is dependent on norartocarpetin phosphorylation by mitogen-activated protein kinases such as phospho-JNK and phospho-p38, and it results in decreased melanogenesis.ConclusionThe present study suggests that norartocarpetin could be used as a whitening agent in medicine and/or cosmetic industry and need further clinical study.

Chemical Composition, Antioxidant and Anti‐melanogenic Activities of Essential Oils from Chrysanthemum boreale Makino at Different Harvesting Stages

“…On the other hand, activated p38 MAPK and Erk1/2 signaling stimulate microphthalmia‐associated transcription factor expression and tyrosinase transcription to lead to melanin synthesis, implying that the activation of p38 MAPK or Erk1/2 signaling may result in melanin accumulation by activation of tyrosinase. Therefore, p38MAPK and Erk1/2 activation can be involved in both positive and negative actions in anti‐melanogensis . In the present study, we showed that all CBMEOs inhibited melanogenesis in B16BL6 cell and elevated α ‐MSH‐decreased phosphorylation of p38 MAPK and Erk1/2.…”

“…Therefore, p38MAPK and Erk1/2 activation can be involved in both positive and negative actions in anti-melanogensis. [10][13] [14] In the present study, we showed that all CBMEOs inhibited melanogenesis in B16BL6 cell and elevated a-MSHdecreased phosphorylation of p38 MAPK and Erk1/2. Although there are conflicting reports about the role of p38 MAPK and Erk1/2 activation in melanogenesis, our results indicate that CBMEOs may inhibit B16BL6 cell melanogenesis at various levels through activation of both p38 MAPK and Erk1/2 signaling pathway.…”

“…Many skin‐whitening products contain tyrosinase inhibitors that can prevent or treat abnormal skin pigmentation . However, skin‐whitening products that contain chemical depigmenting agents have side effects such as dermatitis, erythema, genotoxicity or skin irritation . Hence, safer and more effective depigmenting agents for skin whitening products are needed.…”

“…[11 -13] However, skin-whitening products that contain chemical depigmenting agents have side effects such as dermatitis, erythema, genotoxicity or skin irritation. [14] [15] Hence, safer and more effective depigmenting agents for skin whitening products are needed.…”

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…Modulation of p38 phosphorylation prevented excessive melanin synthesis through the accelerated degradation of melanogenic enzymes . Norartocarpetin (C 15 H 10 O 6 ), a flavone, which can be found in plants such as A communis , Artocarpus heterophyllus, and Artocarpus dadah was proposed to downregulate MITF expression via JNK‐ and p38‐dependent pathway . ERK and JNK phosphorylation causes MITF ubiquitination and degradation, whereby downregulating melanin biosynthesis .…”