Inhibition of melanogenesis by Aster yomena callus pellet extract in melanoma cells and patients with skin pigmentation

Abstract

Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena . This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. Excessive melanogenesis was induced in B16F10 melanoma cells using α-melanocyte stimulating hormone (α-MSH). The effects of AYC-P-E treatment on melanin biosynthesis inducers and melanin synthesis inhibition were assessed. Based on the results, a clinical study was conducted in subjects with skin pigmentation. AYC-P-E inhibited melanogenesis in α-MSH-treated B16F10 cells, accompanied by decreased mRNA and protein expression of melanin biosynthesis inducers, including cyclic AMP response element-binding protein (CREB), tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), and TRP-2. This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK) / extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment.

The Modulation of Melanogenesis in B16 Cells Upon Treatment with Plant Extracts and Isolated Plant Compounds

“…ERK may be suppressed by Ardisia crenata leaf and small branch extract [ 130 ] and by lupenone, a triterpenoid, isolated from Erica multiflora leaf [ 131 ]. In contrast, ERK may be upregulated, and melanogenesis suppressed, by Astragalus membranaceus whole plant extract [ 132 ], Aster yomena callus pellet extract [ 133 ], Melochia corchorifolia whole plant extract [ 134 ], Artemisia capillaris whole plant extract [ 135 ], Orostachys japonicus whole plant extract [ 136 ], and Aster spathulifolius leaf extract treatment [ 137 ]. Similar effects are also triggered by 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol isolated from Juglans mandshurica fruits [ 138 ], 1-O-acetylbritannilactone from Inula britannica flowers [ 139 ], zerumbone, a sesquiterpenoid, from Zingiber officinale [ 140 ], octaphlorethol A, a phenolic compound, from Ishige foliacea [ 141 ], 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol from Juglans mandshurica fruits [ 138 ], loganin, an iridoid monoterpenoid, from Cornus officinalis [ 111 ], neobavaisoflavone, a 7-hydroxyisoflavone, from aerial parts of Pueraria lobata [ 142 ], 6-O-isobutyrylbritannilactone from Inula britannica flowers [ 128 ] and quercitrin, a quercetin O-glycoside, from Lindera obtusiloba leaves [ 143 ].…”

“…In B16 melanoma cells, Musa sapientum peel extract [ 160 ], Aster yomena callus pellet extract [ 133 ] and Orostachys japonicus whole plant [ 136 ] treatment reduced phosphorylation of AKT, and these might act as anti-melanogenesis agents. Upregulation of AKT by Phragmites communis leaf extract [ 149 ], Aster spathulifolius leaf extract treatment [ 137 ] and Ginkgo biloba leaf extract [ 161 ] may also inhibit melanin synthesis.…”

“…Treatment of subjects with skin pigmentation with Aster yomena callus pellet extract-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvements in melanin levels at 2, 4, and 8 weeks, respectively. These results suggest that Aster spathulifolius, Nelumbo nucifera and Aster yomena extracts might be vulnerable and promising therapeutics as agents for hyperpigmentation [ 133 ].…”

Chrysoeriol Enhances Melanogenesis in B16F10 Cells Through the Modulation of the MAPK, AKT, PKA, and Wnt/β-Catenin Signaling Pathways

“…[6][7][8][9] Thus, modulating the activity of enzyme cascades consisting of several key enzymes, such as TRY, TRP-1, and TRP-2, is considered an important strategy in the development of skin pigmentation treatments. 10,11 Microphthalmia-associated transcription factor (MITF) is involved in the survival, proliferation, and differentiation of melanocytes and is an important transcriptional regulator of TRY, TRP-1, and TRP-2. 12,13 The key players in UV-mediated MITF regulation are propiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH), stem cell factor (SCF), and endothelin-1 (ET-1), all of which induce melanogenesis through four major signaling pathways: the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, and (4) Wnt/β-catenin signaling pathway.…”

Immunological Effects of Aster yomena Callus-Derived Extracellular Vesicles as Potential Therapeutic Agents against Allergic Asthma

“…Recently, we established a callus culture system for Aster yomena ( A. yomena ) and demonstrated the various bioactivities of substances derived from A. yomena callus, such as anti-photoaging, anti-melanogenic, and anti-inflammatory effects [ 22 , 23 ]. We found that the A. yomena callus culture system could induce EV formation, resembling the induction of EV formation in other plant species, and that these EVs contained secondary metabolites with various immunological effects.…”