Jaeyoung Kwon

Neuroprotective Xanthones from the Root Bark of Cudrania tricuspidata

Seventeen new prenylated xanthones (1-17) were isolated from an ethyl acetate-soluble extract of root bark of Cudrania tricuspidata together with 17 previously identified xanthones. The structures of the new compounds were elucidated by spectroscopic methods. Six new compounds (3, 7, 8, 9, 15, and 16) and six known compounds (18-23) showed neuroprotective effects against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells, with EC50 values of 0.7-16.6 μM.

Isoflavones with neuroprotective activities from fruits of Cudrania tricuspidata

Ten isoflavones, cudraisoflavones B-K (1-10), together with 27 known isoflavones, were isolated from the EtOAc soluble extract of fruits of Cudrania tricuspidata. The structures of compounds 1-10 were elucidated on the basis of MS and NMR spectroscopic data, including 2D NMR experiments. Compounds 7-9 and three known (11-13) compounds showed neuroprotective activity against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells, with EC50 values of 0.5-9.2 μM.

Metabolomics approach for the discrimination of raw and steamed Gastrodia elata using liquid chromatography quadrupole time-of-flight mass spectrometry

A liquid chromatography quadrupole time-of-flight mass spectrometry-based metabolomics approach was applied to metabolite profiling of Gastrodia elata in order to identify raw and steamed G. elata and explore potential biomarkers for each processing state. A statistical classification method, significant analysis of microarrays, was used to select influential metabolites from the different forms. Through metabolite selection, several potential biomarkers were determined and assigned by matching mass information with that of reference compounds or by comparing it with data in the literature. Furthermore, the developed method was cross-checked using two validation procedures. The first validation was performed simultaneously with the metabolite profiling of G. elata using all detected metabolites, and the second was performed after the metabolite profiling using representative standard compounds of G. elata. Overall, this study can be applied to quality assurance of G. elata.

Chemical Constituents Isolated from the Root Bark of Cudrania tricuspidata and Their Potential Neuroprotective Effects

Seventy-five compounds, including 21 new compounds (1-21), were isolated from the root bark of Cudrania tricuspidata. The structures of the isolated compounds were elucidated by interpretation of their spectroscopic data. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced cell death, and nine compounds had activities with EC50 values of 1.9-30.2 μM. The 75 isolated compounds along with 34 previously reported xanthones were tested also for neuroprotective effects against the 1-methyl-4-phenylpyridinium ion (MPP(+)) and oxygen glucose deprivation (OGD)-induced cell death. Three compounds were active against MPP(+)-induced cell death with EC50 values of 0.2-10.3 μM, and 23 compounds were active in the OGD model with EC50 values of 2.9-35.5 μM.

Neuroprotection against 6-OHDA-induced oxidative stress and apoptosis in SH-SY5Y cells by 5,7-Dihydroxychromone: Activation of the Nrf2/ARE pathway☆

AIMS The aim of this study was to prove the neuroprotective effect of 5,7-Dihydroxychromone (DHC) through the Nrf2/ARE signaling pathway. To elucidate the mechanism, we investigated whether 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells could be attenuated by DHC via activating the Nrf2/ARE signal and whether DHC could down-regulate 6-OHDA-induced excessive ROS generation MAIN METHODS To evaluate the neuroprotective effect of DHC against 6-OHDA-induced apoptosis, FACS analysis was performed using PI staining. The inhibitory effect of DHC against 6-OHDA-induced ROS generation was evaluated by DCFH-DA staining assay. Additionally, translocation of Nrf2 to the nucleus and increased Nrf2/ARE binding activity, which subsequently resulted in the up-regulation of the Nrf2-dependent antioxidant gene expressions including HO-1, NQO1, and GCLc, were evaluated by Western blotting and EMSA. KEY FINDINGS Pre-treatment of DHC, one of the constituents of Cudrania tricuspidata, significantly protects 6-OHDA-induced neuronal cell death and ROS generation. Also, DHC inhibited the expression of activated caspase-3 and caspase-9 and cleaved PARP in 6-OHDA-induced SH-SY5Y cells. DHC induced the translocation of Nrf2 to the nucleus and increased Nrf2/ARE binding activity which results in the up-regulation of the expression of Nrf2-dependent antioxidant genes, including HO-1, NQO1, and GCLc. The addition of Nrf2 siRNA abolished the neuroprotective effect of DHC against 6-OHDA-induced neurotoxicity and the expression of Nrf2-mediated antioxidant genes. SIGNIFICANCE Activation of Nrf2/ARE signal by DHC exerted neuroprotective effects against 6-OHDA-induced oxidative stress and apoptosis. This finding will give an insight that activating Nrf2/ARE signal could be a new potential therapeutic strategy for neurodegenerative disease.

Characterization of Arabidopsis thaliana FLAVONOL SYNTHASE 1 (FLS1) -overexpression plants in response to abiotic stress

Flavonoids are an important group of secondary metabolites that are involved in plant growth and contribute to human health. Many studies have focused on the biosynthesis pathway, biochemical characters, and biological functions of flavonoids. In this report, we showed that overexpression of FLS1 (FLS1-OX) not only altered seed coat color (resulting in a light brown color), but also affected flavonoid accumulation. Whereas fls1-3 mutants accumulated higher anthocyanin levels, FLS1-OX seedlings had lower levels than those of the wild-type. Besides, shoot tissues of FLS1-OX plants exhibited lower flavonol levels than those of the wild-type. However, growth performance and abiotic stress tolerance of FLS1-OX, fls1-3, and wild-type plants were not significantly different. Taken together, FLS1 can be manipulated (i.e., silenced or overexpressed) to redirect the flavonoid biosynthetic pathway toward anthocyanin production without negative effects on plant growth and development.

Drastic anthocyanin increase in response to PAP1 overexpression in fls1 knockout mutant confers enhanced osmotic stress tolerance in Arabidopsis thaliana

Key messagepap1-D/fls1kodouble mutant plants that produce substantial amounts of anthocyanin show tolerance to abiotic stress.AbstractAnthocyanins are flavonoids that are abundant in various plants and have beneficial effects on both plants and humans. Many genes in flavonoid biosynthetic pathways have been identified, including those in the MYB-bHLH-WD40 (MBW) complex. The MYB gene Production of Anthocyanin Pigment 1 (PAP1) plays a particularly important role in anthocyanin accumulation. PAP1 expression in many plant systems strongly increases anthocyanin levels, resulting in a dark purple color in many plant organs. In this study, we generated double mutant plants that harbor fls1ko in the pap1-D background (i.e., pap1-D/fls1ko plants), to examine whether anthocyanins can be further enhanced by blocking flavonol biosynthesis under PAP1 overexpression. We also wanted to examine whether the increased anthocyanin levels contribute to defense against osmotic stresses. The pap1-D/fls1ko mutants accumulated higher anthocyanin levels than pap1-D plants in both control and sucrose-treated conditions. However, flavonoid biosynthesis genes were slightly down-regulated in the pap1-D/fls1ko seedlings as compared to their expression in pap1-D seedlings. We also report the performance of pap1-D/fls1ko seedlings in response to plant osmotic stresses.

Spiroindole Alkaloids and Spiroditerpenoids from Aspergillus duricaulis and Their Potential Neuroprotective Effects

Six new spiroindole alkaloids (1-6) and two new spiroditerpenoids (7 and 8) were isolated from an EtOAc extract of Aspergillus duricaulis culture media together with five known compounds. The structures of the isolated compounds were elucidated by analysis of NMR and MS data, and the absolute configurations of compounds 1-8 were confirmed by CD spectroscopic methods. All isolated compounds were evaluated for their inhibition of beta-amyloid (Aβ) aggregate-induced toxicity in PC12 cells and Aβ aggregation. Compounds 8-11 efficiently protected PC12 cells against Aβ aggregate-induced toxicity, but only compound 9 inhibited Aβ aggregation. On the other hand, compounds 4 and 5 exhibited moderate inhibitory effects on Aβ aggregation, but did not protect the cells from Aβ aggregate-induced toxicity. Preincubating Aβ monomers with compounds 4 and 5 rescued PC12 cells against Aβ aggregate-induced toxicity by reducing neurotoxic Aβ aggregates. Compound 9 inhibited both Aβ aggregate-induced toxicity and Aβ aggregation.

A new canthinone-type alkaloid isolated from Ailanthus altissima Swingle

The present investigation of the chemical constituents of the stem barks of Ailanthus altissima has resulted in the isolation of six canthinone-type alkaloids, including a new compound, (R)-5-(1-hydroxyethyl)-canthine-6-one (1), and five known compounds (2–6). Moreover, four phenyl propanoids (7–10), two lignans (11 and 12), two triterpenoids (13 and 14) and a fatty acid (15) having previously known chemical structures were isolated during the same course of this study. The structure of the new compound was elucidated by physical (m.p., [α]D) and spectroscopic data (1H-NMR, 13C-NMR, 2D NMR, and HR-DART-MS) interpretation and its absolute configuration was determined by electronic circular dichroism (ECD) data and quantum chemical calculations. The inflammatory activities of the isolates were screened on lipopolysaccharide (LPS)-induced nitric oxide (NO), a proinflammatory mediator, in RAW 264.7 cells. Among these isolated compounds, six compounds exhibited significant inhibition of NO production, with IC50 values in the range of 5.92 ± 0.9 to 15.09 ± 1.8 μM.

Mulberrofuran G Protects Ischemic Injury-induced Cell Death via Inhibition of NOX4-mediated ROS Generation and ER Stress

The aim of this study was to investigate the neuroprotective effect of mulberrofuran G (MG) in in vitro and in vivo models of cerebral ischemia. MG was isolated from the root bark of Morus bombycis. MG inhibited nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme activity and oxygen–glucose deprivation/reoxygenation (OGD/R)‐induced NOX4 protein expression in SH‐SY5Y cells. MG inhibited the expression of activated caspase‐3 and caspase‐9 and cleaved poly adenine dinucleotide phosphate‐ribose polymerase in OGD/R‐induced SH‐SY5Y cells. In addition, MG protected OGD/R‐induced neuronal cell death and inhibited OGD/R‐induced reactive oxygen species generation in SH‐SY5Y cells. In in vivo model, MG‐treated groups (0.2, 1, and 5 mg/kg) reduced the infarct volume in middle cerebral artery occlusion/reperfusion‐induced ischemic rats. The MG‐treated groups also reduced NOX4 protein expression in middle cerebral artery occlusion/reperfusion‐induced ischemic rats. Furthermore, protein expression of 78‐kDa glucose‐regulated protein/binding immunoglobulin protein, phosphorylated IRE1α, X‐box‐binding protein 1, and cytosine enhancer binding protein homologous protein, mediators of endoplasmic reticulum stress, were inhibited in MG‐treated groups. Taken together, MG showed protective effect in in vitro and in vivo models of cerebral ischemia through inhibition of NOX4‐mediated reactive oxygen species generation and endoplasmic reticulum stress. This finding will give an insight that inhibition of NOX enzyme activity and NOX4 protein expression could be a new potential therapeutic strategy for cerebral ischemia. Copyright