Antioxidant Compounds, Kirenol and Methyl ent-16α, 17-dihydroxy-kauran-19-oate Bioactivity-Guided Isolated from Siegesbeckia glabrescens Attenuates MITF-Mediated Melanogenesis via Inhibition of Intracellular ROS Production.

Sun-Yup Shim,Ye Eun Lee,Mina Lee

doi:10.3390/molecules26071940

Abstract

Siegesbeckia glabrescens (Compositae), an annual herb indigenous to Korean mountainous regions and has been eaten as a food in Korea. This study investigated ABTS, DPPH and nitric oxide (NO) radical-scavenging activities, and melanin production and TYR inhibitory effects-guided fractionation to identify therapeutic phytochemicals from S. glabrescens that can attenuate oxidation and melanogenesis in murine melanoma B16F10 cells. Nine compounds with inhibitory effects on melanin production, and TYR activity, and ABTS, DPPH, and NO radical scavenging activity were isolated from the 100% ethanol fraction from S. glabrescens. Among the nine compounds, kirenol (K), methyl ent-16α, 17-dihydroxy-kauran-19-oate (MDK) had strong inhibitory effects on melanin production and TYR activity with antioxidant effects. Western blot analysis revealed that K and MDK suppressed tyrosinase-related protein (TYRP)-1, TYRP-2 and microphthalmia-associated transcription factor (MITF) expression. Moreover, these two compounds inhibited intracellular reactive oxygen species (ROS) level in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. Our results suggest that S. glabrescens containing active compounds such as K and MDK, which has antioxidant and antimelanogenesis effects, is the potent therapeutic and functional material for the prevention of oxidation-induced hyperpigmentation.

Highlights

Oxidative stress, which is defined as the generation of reactive oxygen species (ROS)and toxic free-radical species creates an imbalance between antioxidant and prooxidant homeostasis and is associated with the progression of various diseases [1]
Our study assessed the application of S. glabrescens, which is used as a food material on ABTS, DPPH and nitric oxide (NO) radical scavenging activities and melanin production and TYR activity-guided fractionation to discover natural therapeutic products that can reduce hyperpigmentation
We investigated the optimal conditions of extraction regarding the anti-oxidant effects (ABTS, DPPH, and NO radical scavenging activities) and anti-melanogenesis effects (TYR activity and melanin production)

Summary

Introduction

Oxidative stress, which is defined as the generation of reactive oxygen species (ROS)and toxic free-radical species creates an imbalance between antioxidant and prooxidant homeostasis and is associated with the progression of various diseases [1]. Hyperpigmentation is related to melanin generation which is produced by melanocytes that are surrounded by keratinocytes and is a major factor that determines skin color and one of the defense systems that protects the skin from UV-induced skin damage. Melanoblasts are unpigmented precursor cells of melanocytes [5,6] These cells migrate to various regions of the body and develop into melanocytes, and are identified by the expression of melanocyte-specific markers such as tyrosinase (TYR), tyrosinase-related protein (TYRP)-1, TYRP-2, and L-3,4-dihydroxyphenylalanine (DOPA) chrome tautomerase. TYRP-1 has a role in the activation and stabilization of TYR, melanosome synthesis, increased eumelanin: pheomelanin ratio, and protects against oxidative stress by mediating peroxidase activity [7,8,9,10,11]. Cellular melanin synthesis can be modulated by the catalytic activity of TYR and TYR expression

Methods

Results

Conclusion