Isolation and Characterization of Isofraxidin 7‐O‐(6′‐O‐p‐Coumaroyl)‐β‐glucopyranoside from Artemisia capillaris Thunberg: A Novel, Nontoxic Hyperpigmentation Agent That Is Effective In Vivo

Abstract

Abnormalities in skin pigmentation can produce disorders such as albinism or melasma. There is a research need to discover novel compounds that safely and effectively regulate pigmentation. To identify novel modulators of pigmentation, we attempted to purify compounds from a bioactive fraction of the Korean medicinal plant Artemisia capillaris Thunberg. The novel compound isofraxidin 7-O-(6′-O-p-coumaroyl)-β-glucopyranoside (compound 1) was isolated and its pigmentation activity was characterized in mammalian melanocytes. Compound 1 stimulated melanin accumulation and increased tyrosinase activity, which regulates melanin synthesis. Moreover, compound 1 increased the expression of tyrosinase and the key melanogenesis regulator microphthalmia-associated transcription factor (MITF) in melanocytes. Compared to the parent compound, isofraxidin, compound 1 produced greater effects on these pigmentation parameters. To validate compound 1 as a novel hyperpigmentation agent in vivo, we utilized the zebrafish vertebrate model. Zebrafish treated with compound 1 showed higher melanogenesis and increased tyrosinase activity. Compound 1 treated embryos had no developmental defects and displayed normal cardiac function, indicating that this compound enhanced pigmentation without producing toxicity. In summary, our results describe the characterization of novel natural product compound 1 and its bioactivity as a pigmentation enhancer, demonstrating its potential as a therapeutic to treat hypopigmentation disorders.

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

“…Artemisia capillaris was evaluated for its toxicity based on embryotoxicity, and isofraxidine 7-O-(6′-O-p-coumaroyl)-β-glucopyranoside was isolated from this plant. The toxicity, death, and cardiac rates of handled zebrafish embryos are used to diagnose safe and effective concentrations [ 157 ].…”

Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties

“…The UV absorption range of coumarins' basic structure is about 220-310 nm (in EtOH), which this range for IF was reported λ max (in MeOH) 212-228-344 nm [39,70,90,91]. Additionally, the IR spectroscopy of IF showed several prominent absorption spectra (KBr) including 3200-3500 cm −1 (the broad peak related to the hydroxyl group (OH − ), 2900-3000 cm −1 (medium, C-H), 1675-1705 cm −1 (strong, C=O), 1570-1600 cm −1 (medium, C=C aromatic), 1600-1680 cm −1 (weak, C=C), and 1030-1300 cm −1 (medium, C-O) [92,93]. In another study, the noticeable results of IR spectroscopy of IF isolated from Sarcandra glabra were included 3298, 2981, 2941, 1705, 1606, 1574, 1302, 1036 that could be interpreted based on the aforementioned results [94].…”

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…Moreover, TYR pigmentation, melanosome transfer, and phagocytosis of melanosomes by keratinocytes are enhanced in the presence of keratinocyte‐derived growth factor, SCF . On the other hand, the addition of 12‐0‐tetradecanoylphorbol acetate (TPA), cholera toxin (CT), isobutylmethylxanthine (IBMX), and bFGF NHM growth medium led to an increase in intracellular cAMP level and melanocyte proliferation …”

“…77 Even though previous mechanisms of melanosomal transfer based on membrane fusion, direct inoculation-like means, endocytosis as well as phagocytosis have been proposed, recent process of melanosomal transfer explained that the pigment globules contained a number of melanosomes that are actually discharged from dendrites tips of NHM after collection by the microvilli of keratinocytes. 78 Although RWJ-50353, a serine protease inhibitor, reduced pigment deposition and led to the accumulation of immature melanosomes inside melanocytes of epidermal equivalents and causes the formation of abnormal dendrite as illustrated by TEM [58]. It is worthy to note that the expression of PAR2 is present only in keratinocytes, due to its importance in melanosome cleavage phagocytosis.…”

“…78 On the other hand, the addition of 12-0-tetradecanoylphorbol acetate (TPA), cholera toxin (CT), isobutylmethylxanthine (IBMX), and bFGF NHM growth medium led to an increase in intracellular cAMP level and melanocyte proliferation. 31,53,58,73,96 Melanoma cell lines were normally grown in medium such as…”