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

Abstract

Summary Human skin pigmentation is a result of constitutive and facultative pigmentation. Facultative pigmentation is frequently stimulated by UV radiation, pharmacologic drugs, and hormones whereby leads to the development of abnormal skin hyperpigmentation. To date, many state‐of‐art depigmenting compounds have been studied using in vitro model to treat hyperpigmentation problems for cosmetic dermatological applications; little attention has been made to compare the effectiveness of these depigmenting compounds and their mode of actions. In this present article, new and recent depigmenting compounds, their melanogenic pathway targets, and modes of action are reviewed. This article compares the effectiveness of these new depigmenting compounds to modulate several melanogenesis‐regulatory enzymes and proteins such as tyrosinase (TYR), TYR‐related protein‐1 (TRP1), TYR‐related protein‐2 (TRP2), microphthalmia‐associated transcription factor (MITF), extracellular signal—regulated kinase (ERK) and N‐terminal kinases (JNK) and mitogen‐activated protein kinase p38 (p38 MAPK). Other evidences from in vitro assays such as inhibition on melanosomal transfer, proteasomes, nitric oxide, and inflammation‐induced melanogenesis are also highlighted. This article also reviews analytical techniques in different assays performed using in vitro model as well as their advantages and limitations. This article also provides an insight on recent finding and re‐examination of some protocols as well as their effectiveness and reliability in the evaluation of depigmenting compounds. Evidence and support from related patents are also incorporated in this present article to give an overview on current patented technology, latest trends, and intellectual values of some depigmenting compounds and protocols, which are rarely highlighted in the literatures.

Liquiritin and Liquiritigenin Induce Melanogenesis via Enhancement of p38 and PKA Signaling Pathways

“…MITF expression and CREB phosphorylation are activated by p38 and ERK, which belong to the MAPK signaling pathway [8,11,12]. Before treatment, p38 and ERK were not phosphorylated, but LQ and LQG induced the phosphorylation of p38 and ERK after 5 min treatment in the same fashion as α-MSH.…”

“…At the transcription level, the expression of melanogenic enzymes is regulated by microphthalmia-associated transcription factor (MITF) via binding to the M-box motif in their promoter regions [8,10,11]. In melanocyte cells, the mitogen-activated protein kinase (MAPK) family, including p38 MAPK (p38) and extracellular signal-regulated kinase (ERK), is particularly involved in regulating MITF expression [8,11,12]. In addition, protein kinase A (PKA) signaling is also known to play crucial roles in melanogenesis.…”

Natural skin‑whitening compounds for the treatment of melanogenesis (Review)

“…In addition, investigation into the regulatory mechanism involved in melanogenesis should be performed. Finally, the in vivo activity of the prospective agents should be evaluated using non-invasive techniques such as UV light photography or spectrophotometry to obtain comparable results (12,142). It is expected that the aforementioned research methodology can provide better opportunities for the development of novel lightening agents that are effective and safe for use in the clinical and cosmetic industries.…”

“…Therefore, recent research by cosmetic companies and research institutions has been focusing on the development of novel whitening agents that selectively suppress the activity of tyrosinase (TYR) to reduce hyperpigmentation whilst avoiding cytotoxicity to normal, healthy melanocytes. As a result, natural skin whitening compounds are currently garnering significant attention in the cosmetic and medical industry (11,12).…”

Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae

“…In addition to cAMP/PKA axis activation by binding of α-melanocyte stimulating hormone (α-MSH) to its specific receptor, melanocortin 1 receptor (MC1R), mitogen-activated protein kinases (MAPKs) are particularly involved in regulating MITF expression [8]. In particular, data based on many depigmenting small-molecule compounds verified that extracellular signal-regulated kinase (ERK) downregulates melanogenesis through proteasomal degradation of MITF, thereby inhibiting melanogenesis; on the contrary, p38 MAPK and c-Jun N-terminal kinase (JNK) stimulates MITF-mediated tyrosinase activity, leading to hypermelanogenesis [10]. Even though some discrepancy has been found in the function of MAPKs during melanogenesis, MAPK regulation is a promising target for melanogenesis.…”