<i>Nelumbo nucifera</i> Leaf Extracts Inhibit Melanogenesis in B16 Melanoma Cells and Guinea Pigs through Downregulation of CREB/MITF Activation

Abstract

Nelumbo nucifera leaves extracts (NLE) has been suggested to provide antioxidant, anti-obesity and anticancer effects. However, the research on the anti-melanogenetic effect of NLE was little. Here, we reported that NLE and Gallic acid (GA, major ingredients of NLE) exhibit the hypopigmentary effect in B16F1 cells. NLE and GA showed potent inhibitory effects on tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein-1 (TRP-1) protein production. The phosphorylation of intracellular protein kinase A (PKA) and cAMP response element-binding protein (CREB) were also decreased, revealing potent anti-melanogenic effects of NLE and GA. However, NLE showed the better effect than GA on reducing melanin formation, implying the importance of the synergism of polyphenolic compounds of NLE. Furthermore, NLE inhibited skin melanogenesis and epidermal hyperplasia of guinea pigs caused by irradiation through attenuating ERK and CREB activation. NLE reduced skin melanogenesis and epidermal hyperplasia induced by UVB in guinea pigs through downregulation ERK and CREB pathways, and the following decreasing of MITF, tyrosinase and TRP-1 expression. These results demonstrated the potential which NLE as an ingredient of hypopigmentary cosmetics.

Lotus (Nelumbo nucifera Gaertn.) and Its Bioactive Phytocompounds: A Tribute to Cancer Prevention and Intervention

“…Mechanistic studies using an immunoblotting assay revealed that both treatments reduced the expressions of tyrosinase, microphthalmia-associated transcription factor (MITF), TRP-1, phosphorylated protein kinase A (p-PKA), and phosphorylated cAMP response element-binding protein (p-CREB) (Lai et al, 2020). In another study, Liu et al [138] demonstrated that 7hydroxydehydronuciferine, a compound isolated from a methanolic extract of the leaves of N. nucifera Gaertn. cv.…”

“…The mice treated with the procyanidin-rich extract also displayed an increased spleen and thymus index, indicating immunomodulatory activities. Lai et al [138] also conducted an in vivo study using ultra-violet B (UVB)-radiation exposed female guinea pigs and topically treated them with 1-2% NLE. The test agent was found to reverse UVB-induced epidermal hyperplasia and decrease melanin content, as evidenced by hematoxylin and eosin staining and Fontana-Masson staining, respectively.…”

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

“…Moreover, CREB was activated by cirsimaritin, a dimethoxyflavone, isolated from the branches of Lithocarpus dealbatus [ 101 ], hesperetin, a flavanone glycoside, from Citrus sinensis , Citrus aurantium and Citrus reticulata extract [ 102 ] and scopoletin, a hydroxycoumarin, from the aerial parts of Cirsium setidens [ 103 ]. The opposite effect on phosphorylation of PKA and CREB are interfered with by Nelumbo nucifera leaf extract [ 104 ]. Rhodiola rosea root extract [ 105 ], Elaeagnus umbellate branches and leaves [ 106 ], Oenothera laciniata extracts [ 107 ] and Kadsura coccinea roots, stems, leaves, fruits [ 108 ] extracts inhibited the phosphorylation of CREB followed by downregulation of MITF and TYR expression.…”

Plants as Modulators of Melanogenesis: Role of Extracts, Pure Compounds and Patented Compositions in Therapy of Pigmentation Disorders

“…Nelumbo nucifera extract, used at 1% or 2% concentration and administered to UVB-irradiated guinea pigs on the back region for 2 weeks demonstrates similar activity. The main identified constituent was gallic acid [ 106 ]. Data show that 200 μL of Nymphaea nouchali extract, applied on UVB-irradiated HRM-2 hairless mice at a concentration 100 µg/mL to a 3 cm × 3 cm designated area on the dorsal skin for 4 weeks exhibit antimelanogenic effects [ 107 ].…”

“…The first one exerts an anti-melanogenic effect, whereas the other one-melanogenic effect. Regulation of cAMP/CREB/MAPKs/MITF and PKA/CREB/MITF axis and suppression of melanogenesis takes place by Nymphaea nouchali [ 107 ] and Nelumbo nucifera [ 106 ] extracts. Pueraria montana var.…”