Dichloromethane fraction ofCimicifuga heracleifoliadecreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells

Abstract

Cimicifuga rhizoma has long been used in traditional Korean medicine. In particular, a Cimicifuga heracleifolia extract (CHE) was reported to inhibit the formation of glutamate and the glutamate dehydrogenase activity in cultured rat islet. Glutamate activates melanogenesis by activating tyrosinase. Accordingly, it was hypothesized that a CHE might inhibit the melanogenesis-related signal pathways including the inhibition of microphthalmia-associated transcription factor (MITF)-tyrosinase signaling and/or the activation of extracellular signal-regulated kinase (ERK)-Akt signaling. The results showed that CHE inhibits the cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including MITF, tyrosinase and tyrosinase-related protein (TRP)s in alpha-melanocyte-stimulating hormone-stimulated B16 cells. Moreover, CHE phosphorylates MEK, ERK1/2 and Akt, which are melanogenesis inhibitory proteins. The data suggest that CHE inhibits melanogenesis signaling by both inhibiting the tyrosinase directly and activating the MEK-ERK or Akt signal pathways-mediated suppression of MITF and its downstream signal pathway, including tyrosinase and TRPs. Therefore, C. heracleifolia would be a useful therapeutic agent for treating hyperpigmentation and an effective component in whitening and/or lightening cosmetics.

[6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

“…As shown in Figure 5A, suppression of melanin synthesis by [6]-shogaol was greatly attenuated by the pretreatment with PD98059 (55% inhibition in DMSO-treated cells vs 21% inhibition in PD98059-treated cells). We also found that the basal level of melanin was increased by the PD98059 treatment, which is consistent with previously published results [27] . In addition, [6]-shogaol-induced ERK phosphorylation was also inhibited by the PD98059 treatment ( Figure 5B).…”

“…[6]-Shogaol decreases expression of tyrosinase and MITF in B16 cells Several studies have shown that intracellular tyrosinase activity can be controlled by various mechanisms including the regulation of tyrosinase expression [26,27] . Therefore, we examined the effect of [6]-shogaol on the expression of both tyrosinase and MITF, the latter being a major transcription factor for tyrosinase [5] .…”

“…So far, many natural and synthetic agents have been found to inhibit melanogenesis in B16F10 cells through activation of the ERK and/or the Akt pathways. For example, baicalein, cimicifuga heracleifolia, and KHG22394 (a synthesized chemical) were found to decrease melanin synthesis by activating ERK or Akt [18,26,27] . Therefore, we are interested in the effects of [6]-shogaol on ERK and Akt activities.…”

Suppression of α-MSH and IBMX-induced melanogenesis by cordycepin via inhibition of CREB and MITF, and activation of PI3K/Akt and ERK-dependent mechanisms

“…In addition, the activation of Akt signaling also plays a key role in inhibiting melanogenesis. These observations support the suggestion that the inhibitory effect of natural compounds on melanogenesis may be dependent on control of the upstream signaling pathways related to the activation and expression of tyrosinase (14).…”

“…MAPKs play essential roles in melanogenesis (10,11). Moreover, investigations suggest that the p38 MAPK pathway activation has been reported to be related to increased melanin synthesis (12,13), and the activation of ERK signaling down-regulates melanogenesis by inhibiting the tyrosinase activity (14). In addition, the activation of Akt signaling also plays a key role in inhibiting melanogenesis.…”