Ui Joung Youn

Cytoprotective effect of the fruits of Lycium chinense Miller against oxidative stress-induced hepatotoxicity.

AIM OF THE STUDY Fruits of Lycium chinense Miller (Solanaceae), distributed in northeast Asia, have gained attraction for their hepatoprotective role in traditional oriental medicine. The excessive production of reactive oxygen species (ROS) is hazardous for living organisms and damage major cellular constituents such as DNA, lipid, and protein. The cytoprotective effect of Lycium chinense fruits (Lycium extract) was assessed against H(2)O(2)-induced Chang liver cell damage. MATERIALS AND METHODS The effect of Lycium extract against H(2)O(2)-induced cell death was determined by the MTT assay. Radical scavenging activity was determined through the assessments of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, intracellular ROS, hydroxyl radicals, and superoxide. The inductions of antioxidant enzymes were determined via their protein expressions and activities. DNA damage was measured using comet assay and expression of phospho-histone H2A.X. Lipid peroxidation was measured using 8-isoprostane level and fluorescent probe. Protein modification was measured using protein carbonyl moiety. RESULTS AND CONCLUSION Lycium extract scavenged the DPPH free radicals, intracellular ROS, hydroxyl radicals, and superoxide. Lycium extract recovered activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased by H(2)O(2). Lycium extract decreased DNA damage, lipid peroxidation and protein carbonyl values increased by H(2)O(2) exposure. In addition, Lycium extract increased the cell viability of Chang liver cells exposed to H(2)O(2) via inhibition of apoptosis. These results show that Lycium extract protected Chang liver cells against oxidative stressed cell damage by H(2)O(2) via scavenging ROS and enhancing antioxidant enzyme activity.

Inhibition of matrix metalloproteinase-1 induced by oxidative stress in human keratinocytes by mangiferin isolated from Anemarrhena asphodeloides.

Oxidative stress is related to the synthesis of matrix metalloproteinases (MMPs), which cause skin aging. The protective effects of mangiferin derived from Anemarrhena asphodeloides were investigated against hydrogen peroxide (H2O2)-induced damage using human skin keratinocyte (HaCaT) cells. Mangiferin was found to scavenge intracellular reactive oxygen species (ROS), superoxide radicals, and hydroxyl radicals. ROS regulate MMPs gene expression and activation of proenzymes. Mangiferin inhibited H2O2-induced MMP-1 gene expression and protein levels as well as its activity. Moreover, it abrogated mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway and stress-activated protein kinase/extracellular signal-regulated kinase (SEK)-c-JUN N-terminal kinase (JNK) pathway, which are induced by H2O2 treatment. And, it inhibited DNA binding activity of activator protein-1 (AP-1), a transcription factor of MMP-1 and downstream of ERK and JNK. Finally, it protected the human skin keratinocytes from H2O2-induced cell death. Taken together, these results indicate that mangiferin attenuated H2O2-induced MMP-1 activation via inhibition of ERK and JNK pathway and AP-1.

Inhibition of UVB-induced wrinkle formation and MMP-9 expression by mangiferin isolated from Anemarrhena asphodeloides.

Chronic exposure of human skin to solar ultraviolet (UV) radiation causes photoaging. Naturally occurring phytochemicals are known to have anti-photoaging effects. The present study examined the effect of mangiferin isolated from Anemarrhena asphodeloides on wrinkle formation, skin thickness, and changes in collagen fibers in hairless mice. The in vitro effects and possible mechanism of mangiferin on UVB irradiation were determined in human keratinocyte (HEKa) cells. In vitro results showed that mangiferin reduced UVB-induced matrix metalloproteinase (MMP)-9 protein expression and enzyme activity and subsequent attenuation of UVB-induced phosphorylation of mitogen-activated protein kinase kinase1 (MEK) and extracellular signal-regulated kinase (ERK). In the in vivo studies, mangiferin inhibited UVB-induced mean length and mean depth of skin wrinkle based on skin replica, epidermal thickening, and damage to collagen fiber. Taken together, these results indicate that mangiferin exerts anti-photoaging activity in UVB-irradiated hairless mice by regulating MMP-9 expression through inhibition of MEK and ERK.

Regulation of the 5-HT3A Receptor-Mediated Current by Alkyl 4-Hydroxybenzoates Isolated from the Seeds of Nelumbo nucifera

Four known alkyl 4‐hydroxybenzoates, i.e., methyl 4‐hydroxybenzoate (1), ethyl 4‐hydroxybenzoate (2), propyl 4‐hydroxybenzoate (3), and butyl 4‐hydroxybenzoate (4), were isolated from the seeds of Nelumbo nucifera Gaertner (Nymphaeaceae) for the first time. The structures of the isolates were identified by 1D‐ and 2D‐NMR spectroscopy and comparison with published values. The compounds were evaluated for their effects on the 5‐HT‐stimulated inward current (I5‐HT) mediated by the human 5‐HT3A receptors expressed in Xenopus oocytes. Compounds 1 and 2 enhanced the I5‐HT, but 4 reduced it. These results indicate that 4 is an inhibitor of the 5‐HT3A receptors expressed in Xenopus oocytes.

Identification of new pyrrole alkaloids from the fruits of Lycium chinense

Three new minor pyrrole alkaloids, 3-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]pentanedioic acid (1), (2R)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-1-methoxy-1-oxobutanoic acid (2), and methyl (2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-4-methylpentanoate (3) were isolated from the fruits of Lycium chinense Miller (Solanaceae), along with the known compound, methyl (2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate (4). The structures of 1–4 were elucidated by analysis of their 1D- and 2D-NMR and HRMS data. The absolute configurations of 2–4, possessing a stereogenic center in each structure, were determined by comparison of their experimental electronic circular dichroism (ECD) with those of calculated ECD values.

Suppression of inducible nitric oxide synthase expression by nyasol and broussonin A, two phenolic compounds from Anemarrhena asphodeloides, through NF-κB transcriptional regulation in vitro and in vivo.

Anemarrhena asphodeloides is widely used in traditional Chinese medicine, and is known to possess antidiabetic and anti‐inflammatory properties. Because inducible nitric oxide synthase (iNOS) plays an important role in inflammation, we investigated the inhibitory effects of two known phenolic compounds, nyasol (1) and broussonin A (2), from A. asphodeloides, on iNOS and its plausible mechanism of action. Compounds 1 and 2 exhibited inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophage cells. Compounds 1 and 2 also suppressed the expressions of iNOS protein and mRNA. Moreover, compounds 1 and 2 suppressed the expression of inflammatory cytokines such as interleukin‐1β (IL‐1β) and interferon‐β (IFN‐β). They also inhibited the transcriptional activity of NF‐κB and degradation of IκB‐α, as well as the activation of Akt and ERK in LPS‐stimulated RAW 264.7 cells. In in vivo animal model, compounds 1 and 2 significantly inhibited TPA‐induced mouse ear edema. These results suggest that 1 and 2 suppress LPS‐stimulated iNOS expression at the transcriptional level through modulating NF‐κB and down‐regulation of the Akt and ERK signaling pathways. Taken together, these findings indicate that the suppressive effects of 1 and 2 on iNOS expression might provide one possible mechanism for their anti‐inflammatory activities.

Oligostilbenoids from Vitis vinifera cv. Muscat of Alexandria

The genus Vitis, consisting of about perennial 60 species, is distributed in Asia, Europe, and North America [1]. The species occur in widely different geographical areas and show a remarkable diversity of form. They are related to allow easy interbreeding, and the resultant inter specific hybrids are fertile and vigorous. Thus, thousands of cultivars have been developed by hybridization and selection [2]. In the present study, stems and leaves of Vitis vinifera L. cv. Muscat of Alexandria were collected from the Oha Farm in Ansung, South Korea, in September 2010 and identified by Prof. Nam Sook Lee (Ewha Womans University, Seoul 120-750, Korea). A voucher specimen (No. EA312) was deposited at the Natural Product Chemistry Laboratory, College of Pharmacy, Ewha Womans University, Korea. Previous phytochemical reports on the original species V. vinifera L. and its cultivar reveal several flavonoids [3], stilbenoids [4], monoterpenes [5], and polyphenols [6] and these compounds have been reported to show antioxidant [7], anti-inflammation [8], and antiproliferation [9]. As a part of our ongoing research to find bioactive compounds from higher plants, we studied the EtOAc extracts of the combined stems and leaves of V. vinifera L. cv. Muscat of Alexandria, which resulted in the isolation of two known oligostilbenoids, which were identified as isohopeaphenol (1) [10, 11] and ampelopsin H (2) [12, 13] by analyses of their physical and spectroscopic data as well as by comparison of their data with the published values. Compounds 1 and 2 were isolated from V. vinifera L. cv. Muscat of Alexandria for the first time.

Sesquiterpene Lactones from Vernonia cinerea

A new hirsutinolide-type sesquiterpene lactone, 8α-(2′Z-tigloyloxy)-1α-methoxyhirsutinolide (1), and a new naturally occurring 8α-(2′-hydroxymethylacryloyloxy)-1α-methoxyhirsutinolide-13-O-acetate (2) were isolated from the CHCl3 extract of the aerial parts of Vernonia cinerea (Asteraceae). The structures of the new compounds were determined by 1D and 2D NMR and MS experiments, as well as by comparison of their data with the published values.