Scopoletin from Cirsium setidens Increases Melanin Synthesis via CREB Phosphorylation in B16F10 Cells

Okba

Evidence-Based Complementary and Alternative Medicine

et al. 2019

Background. Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power. The aim of the study was to screen E. longifolia aqueous extract (AE) and isolates for ROCK-II inhibition. Results. The AE (1-10 μg/ml) showed a significant inhibition for ROCK-II activity (62.8-81%) at P < 0.001 with an IC50 (651.1 ± 32.9 ng/ml) compared to Y-27632 ([(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride]) (68.15-89.9 %) at same concentrations with an IC50 (192 ± 8.37 ng/ml). Chromatographic purification of the aqueous extract (AE) allowed the isolation of eight compounds; stigmasterol T1, trans-coniferyl aldehyde T2, scopoletin T3, eurycomalactone T4, 6α- hydroxyeurycomalactone T5, eurycomanone T6, eurycomanol T7, and eurycomanol-2-O-β-D-glucopyranoside T8. This is the first report for the isolation of T1 and T3 from E. longifolia and for the isolation of T2 from genus Eurycoma. The isolates (at 10 μg/ml) exhibited maximum inhibition % of ROCK-II 82.1 ± 0.63 (T2), 78.3 ± 0.38 (T6), 77.1 ± 0.11 (T3), 76.2 ± 3.53 (T4), 74.5 ± 1.27 (T5), 74.1 ± 2.97 (T7), 71.4 ± 2.54 (T8), and 60.3 ± 0.14 (T1), where the newly isolated compound trans-coniferyl aldehyde T2 showed the highest inhibitory activity among the tested isolated compounds and even higher than the total extract AE. The standard Y-27632 (10 μg/ml) showed 89.9 ± 0.42 % inhibition for ROCK-II activity when compared to control at P < 0.0001. Conclusion. The traditional use of E. longifolia as aphrodisiac and for male sexual disorders might be in part due to the ROCK-II inhibitory potential.

Section: Discussionsupporting

confidence: 88%

Rho-Kinase II Inhibitory Potential of Eurycoma longifolia New Isolate for the Management of Erectile Dysfunction

Okba

Evidence-Based Complementary and Alternative Medicine

et al. 2019

Molecular Medicine Reports

“…Therefore, identification of a strategy for the protection of transplanted MSCs is important for the development of MSCs-based therapy for regenerative medicine. C. setidens is a phenolic and flavonoid compound, which possesses anti-inflammatory, anticancer, anti-mutation, anti-fungal, hepatoprotective and neuroprotective activity, and is capable of immune enhancement ( 9 , 10 , 14 – 16 ). In the present study, the HPLC chromatogram detected pectolinarin in the C. setidens extract.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant effects of Cirsium setidens extract on oxidative stress in human mesenchymal stem cells

Lee

Jung

Han

et al. 2016

Human mesenchymal stem cells (MSCs) may be used in cell-based therapy to promote neovascularization for the treatment of ischemic diseases. However, high levels of reactive oxygen species (ROS) derived from the pathophysiological ischemic environment induce senescence and apoptosis of MSCs, resulting in reduced functionality and defective neovascularization. Therefore, the present study aimed to determine the protective effects of Cirsium setidens, a natural product, on oxidative stress-induced apoptosis in MSCs. The present study investigated for the change of ROS levels in MSCs using ROS assays. In addition, cell viability determined by MTT and TUNEL assays. Western blot analysis was performed to investigate the change of apoptosis-associated proteins in MSCs. Treatment of MSCs with hydrogen peroxide (H2O2; 200 µM) significantly increased intracellular ROS levels and cell death; however, pretreatment with C. setidens (100 µg/ml) suppressed H2O2-induced ROS generation and increased the survival of MSCs. H2O2-induced ROS production increased the levels of phosphorylated-p38 mitogen activated protein kinase, c-Jun N-terminal kinase, ataxia telangiectasia mutated and p53; these increases were inhibited by pretreatment with C. setidens. In addition, C. setidens inhibited ROS-induced apoptosis of MSCs by increasing the expression levels of the anti-apoptotic protein B-cell lymphoma 2 (BCL-2), and decreasing the expression levels of the proapoptotic protein BCL-2-associated X protein. These findings indicated that pretreatment of MSCs with C. setidens may prevent ROS-induced oxidative injury by regulating the oxidative stress-associated signaling pathway, and suppressing the apoptosis-associated signal pathway. Therefore, C. setidens may be developed as a beneficial broad-spectrum agent for enhancing the effectiveness of MSC transplantation in the treatment of ischemic diseases.

“…We found that carvone decreased melanin content in a concentration-dependent manner ( Figure 1B,C). We recently conducted a phenotype-based approach to screening for compounds in B16F10 melanoma cells to find small-molecule inhibitors of melanin synthesis [16,17]. By this method, we found that carvone treatment markedly decreases melanin content.…”

Section: Carvone Decreases Melanin Content Of B16f10 Melanoma Cellsmentioning

confidence: 99%

Carvone Decreases Melanin Content by Inhibiting Melanoma Cell Proliferation via the Cyclic Adenosine Monophosphate (cAMP) Pathway

2020

Melanin, which determines the color of the skin and hair, is initially synthesized to protect the skin from ultraviolet light; however, excessive melanin pigmentation caused by abnormal cell proliferation can result in various melanocytic lesions. Cyclic adenosine monophosphate (cAMP) is known to regulate cell cycle progression and consequently to inhibit the division of abnormally proliferating cells. In this work, we aimed to test whether carvone, a scent compound from plants, inhibits proliferation and subsequently reduces melanin content of melanoma cells and to determine whether its beneficial effects are mediated by the cAMP pathway. We found that carvone decreases melanin content and inhibits melanoma cell proliferation in a concentration-dependent manner. Meanwhile, it inhibited the activation of cell cycle-associated proteins such as cyclin-dependent kinase 1 (CDK1). Of note, the beneficial effects of carvone were abrogated by cAMP inhibition. Our findings indicate potential benefits of carvone for the treatment of melanomas and presumably other hyperpigmentation-related dermatological disorders such as melasmas, lentigines, and excessive freckles.