Lupenone from Erica multiflora Leaf Extract Stimulates Melanogenesis in B16 Murine Melanoma Cells through the Inhibition of ERK1/2 Activation

Abstract

Hypopigmentation diseases are usually managed using UVB light which increases the patients' risk for skin cancer. Here, we evaluated the melanogenesis stimulatory effects of leaf extracts of Erica multiflora, a medicinal plant from the Mediterranean region, and its active component, lup-20(29)-en-3-one, as possible therapeutic agents to address hypopigmentation disorders. B16 murine melanoma cells were treated with E. multiflora extracts or its active component lupenone to evaluate their effects on melanin biosynthesis. The mechanism underlying the observed effects was also determined. Bioactivity-guided fractionation of fifteen ethyl acetate fractions identified fraction 2 to have melanogenesis stimulatory effects due to its ability to decrease mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 activation. Preparative TLC of ethyl acetate fraction 2 revealed the presence of lup-20(29)-en-3-one as the major bioactive component. B16 cells treated with lup-20(29)-en-3-one increased melanin content without cytotoxicity. To determine the mechanism for the observed effects of lup-20(29)-en-3-one, the tyrosinase enzyme activity, the tyrosinase protein expression, and the activation of phosphorylated extracellular signal-regulated kinases 1 and 2 were determined. In addition, the expression of the tyrosinase mRNA was quantified using real-time PCR. Results showed that lup-20(29)-en-3-one has no effect on the tyrosinase enzyme activity but can increase tyrosinase expression at both the transcriptional and translational levels. The increase in the tyrosinase mRNA expression was most likely due to the inhibited mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 activation. We report for the first time that E. multiflora ethyl acetate extract and its active compound lup-20(29)-en-3-one stimulate melanogenesis by increasing the tyrosinase enzyme expression via mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 phosphorylation inhibition, making it a possible treatment for hypopigmentation diseases.

Melia azedarach extract stimulates melanogenesis through increase of tyrosinase-related protein 1 expression in B16F10 mouse melanoma cells

“…It has been shown that human placental lipid (25), sesamin (26), quercetin (27), and extracts from Erica multiflora (28) and Pyrostegia venusta (29) can increase melanogenesis in vitro. Thus, these compounds and extracts can be considered as candidates for developing tanning cosmetics and medicines for vitiligo.…”

RP-HPLC Characterization of Lupenone and β-Sitosterol in Rhizoma Musae and Evaluation of the Anti-Diabetic Activity of Lupenone in Diabetic Sprague-Dawley Rats

“…Ba-jiao is a perennial herb, and when we measured the largest part of fresh Rhizoma Musae using a standard ruler, the obtained size (diameter) was used to represent the growth stage. The different growth stages (5,7,10,13,15, and 20 cm) of Rhizoma Musae collected at the same harvest time and origin displayed a range of lupenone and β-sitosterol levels. When the diameter of Rhizoma Musae was approximately 7-13 cm, lupenone content was higher.…”

“…Current studies have shown that lupenone and β-sitosterol possess multiple pharmacological activities. For example, in vitro studies have found that lupenone stimulates melanogenesis in B 16 murine melanoma cells [10], as well as inhibits α-glucosidase (α-Glu) and protein tyrosine phosphatase 1B (PTP1B) activities [11,12], Furthermore, lupenone inhibits adipogenic differentiation via downregulation of peroxisome proliferator-activated receptor PPARγ expression in 3T3-L1 cells [13]. Additionally, previous studies have reported that β-sitosterol inhibits the growth of HT-29 human colon cancer cells and induces apoptosis of LNCaP human prostate cancer cells in vitro [14,15].…”

Cytotoxic effect ofErythroxylum daphnitesextract is associated with G1cell cycle arrest and apoptosis in oral squamous cell carcinoma

“…As we can see, EDH demonstrated moderate cytotoxicity in SCC-9 cells in a dose response manner. The concentration resulting in a 50% reduction in cell viability (IC 50 ) after 24 h of treatment was calculated as 448.9 mg/mL (Fig. 1A).…”

“…Lupenone was able to increase tyrosinase mRNA expression via inhibiting the phosphorylation of extracellular signal-regulated kinases 1 and 2 by mitogen-activated protein kinase in B16 murine melanoma cells. 49,50 Additionally, lupenone exhibited weak cytotoxicity against human colorectal cancer (HT-29) and mammary breast cancer (MDA-MB) cell lines. 46,47 b-sitosterol is one of the most common phytosterols in higher plants and presents several pharmacological activities, including anti-tumor activities.…”