Yun-Seo Kil

Psoralidin, a coumestan analogue, as a novel potent estrogen receptor signaling molecule isolated from Psoralea corylifolia.

A novel biological activity of psoralidin as an agonist for both estrogen receptor (ER)α and ERβ agonist has been demonstrated in our study. Psoralidin has been characterized as a full ER agonist, which activates the classical ER-signaling pathway in both ER-positive human breast and endometrial cell lines as well as non-human cultured cells transiently expressing either ERα or ERβ. The estrogenic activity was determined using the relative expression levels of either reporter or the endogenous genes dependent on the agonist-bound ER to the estrogen response element (ERE). Psoralidin at 10 μM was able to induce the maximum reporter gene expression corresponding to that of E2-treated cells and such activation of the ERE-reporter gene by psoralidin was completely abolished by the cotreatment of a pure ER antagonist, implying that the biological activities of psoralidin are mediated by ER. Psoralidin was also able to induce the endogenous estrogen-responsive gene, pS2, in human breast cancer cells MCF-7. It was observed that activation of the classical ER-signaling pathway by psoralidin is mediated via induction of ER conformation by psoralidin and direct binding of the psoralidin-ER complex to the EREs present in the promoter region of estrogen-responsive genes, as shown by chromatin immunoprecipitation assay results. Finally, molecular docking of psoralidin to the ligand binding pocket of the ERα showed that psoralidin is able to mimic the binding interactions of E2, and thus, it could act as an ER agonist in the cellular environment.

Heat shock factor 1 inducers from the bark of Eucommia ulmoides as cytoprotective agents.

The barks of Eucommia ulmoides (Eucommiae Cortex, Eucommiaceae) have been used as a traditional medicine in Korea, Japan, and China to treat hypertension, reinforce the muscles and bones, and recover the damaged liver and kidney functions. Among these traditional uses, to establish the recovery effects on the damaged organs on the basis of phytochemistry, the barks of E. ulmoides have been investigated to afford three known phenolic compounds, coniferaldehyde glucoside (1), bartsioside (2), and feretoside (3), which were found in the family Eucommiaceae for the first time. The compounds 1–3 were evaluated for their inducible activities on the heat shock factor 1 (HSF1), and heat shock proteins (HSPs) 27 and 70, along with four compounds, geniposide (4), geniposidic acid (5), pinoresinol diglucoside (6), and liriodendrin (7), which were previously reported from E. ulmoides. Compounds 1–7 increased expression of HSF1 by a factor of 1.214, 1.144, 1.153, 1.114, 1.159, 1.041, and 1.167 at 3 μM, respectively. Coniferaldehyde glucoside (1) showed the most effective increase of HSF1 and induced successive expressions of HSP27 and HSP70 in a dose‐dependent manner without cellular cytotoxicity, suggesting a possible application as a HSP inducer to act as cytoprotective agent.

A new secoiridoid glycoside from the fruits of Cornus officinalis (Cornaceae).

Abstract A new secoiridoid glycoside, 7β-O-dimethyl butanedioate morroniside (1) was isolated from the fruits of Cornus officinalis (Cornaceae) along with the known compound, caffeoyltartaric acid dimethyl ester (2) which was isolated from the family Cornaceae for the first time. Their structures were elucidated by physical and spectroscopic data analysis, including 1D and 2D NMR, ESI-MS and CD experiments. Graphical Abstract

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.

Angelica keiskei , an emerging medicinal herb with various bioactive constituents and biological activities

Angelica keiskei (Miq.) Koidz. (Umbelliferae) has traditionally been used to treat dysuria, dyschezia, and dysgalactia as well as to restore vitality. Recently, the aerial parts of A. keiskei have been consumed as a health food. Various flavonoids, coumarins, phenolics, acetylenes, sesquiterpene, diterpene, and triterpenes were identified as the constituents of A. keiskei. The crude extracts and pure constituents were proven to inhibit tumor growth and ameliorate inflammation, obesity, diabetics, hypertension, and ulcer. The extract also showed anti-thrombotic, anti-oxidative, anti-hyperlipidemic, anti-viral, and anti-bacterial activities. This valuable herb needs to be further studied and developed not only to treat these human diseases but also to improve human health. Currently A. keiskei is commercialized as a health food and additives in health drinks. This article presents a comprehensive review of A. keiskei and its potential place in the improvement of human health.

Suppression of IL-2 production and proliferation of CD4(+) T cells by tuberostemonine O.

Tuberostemonine stereoisomers are natural alkaloids found in Stemona tuberosa, that are known to have anti‐inflammatory and anti‐infective properties. Tuberostemonine alkaloids inhibit inflammation by suppressing the expression of inflammatory mediators such as cyclooxygenase and nitric oxide synthase. However, the direct immunomodulatory properties of tuberostemonine alkaloids in T cells have not been elucidated so far. In this study, the activities in T cells of tuberostemonine N (TbN) and a novel alkaloid, tuberostemonine O (TbO), isolated from S. tuberosa, were investigated. Although TbN did not have a significant effect on cytokine production in splenic T cells, TbO selectively suppressed interleukin (IL)‐2 production. Moreover, TbO, but not TbN, significantly inhibited IL‐2 production by primary CD4+ T cells and delayed the T‐cell proliferation in a dose‐dependent manner. Addition of excess recombinant IL‐2 restored the decreased cell‐division rates in TbO‐treated CD4+ T cells to control levels. Collectively, these findings suggest that the immunomodulatory effects of TbO occurred by the suppression of IL‐2 expression and IL‐2‐induced T‐cell proliferation, suggesting a potential beneficial role of tuberostemonine alkaloids for the control of chronic inflammatory and autoimmune diseases caused by hyperactivated T cells.

Chemical Constituents of the Leaves of Vitis labruscana cv. Steuben

There are ten thousand grape varieties (the genus Vitis, the family Vitaceae) in the world. Vitis labruscana cv. Steuben (Wayne Sheridan) is one of them and was produced from an interspecific cross in New York, United States. It features large clusters of blue slipskin grapes with fruity and spicy tastes. The cultivar is also favored as an arbor grape due to its natural red fall color [1]. Thus far, there has been no study on the phytochemical constituents of this cultivar. As part of our ongoing research to find bioactive compounds from leaves of grapes [2, 3], we investigated V. labruscana cv. Steuben which were collected from the Oha Farm in Ansung, South Korea, in September 2010. A voucher specimen was identified by Prof. Nam Sook Lee (Ewha Womans University, Seoul 03760, Korea) and was deposited at the Natural Product Chemistry Laboratory, College of Pharmacy, Ewha Womans University, Korea, under accession number EA313. In the present study, the BuOH-soluble extract of the leaves of V. labruscana cv. Steuben was investigated, leading to the isolation of 12 known compounds: quercetin (1) [4], quercetin-3-O-D-glucoside (2) [5], quercetin-3-O-D-glucuronide (3) [4, 6], quercetin-3-O-D-glucuronide 6 -methyl ester (4) [3, 7], kaempferol-3-O-D-glucuronide (5) [3, 4], resveratrol (6) [8], icariside B1 (7) [9], (–)-(3R,9S)-3-hydroxy-7,8-dihydro-ionol 9-O-D-glucoside (8) [10–12], gentisic acid 5-OD-glucopyranoside (9) [13, 14], hydrangeifolin I (10) [15], (+)-cis-viniferin (11) [16], and (+)-viniferin (12) [17]. The structures of 1–12 were identified by interpretation of their physical ([ ]D) and spectroscopic (1H, 13C, COSY, NOESY, HSQC, and HMBC NMR, and HR-ESI-MS) data as well as by comparison with the published values. To the best of our knowledge, this is the first report on the phytochemical constituents of V. labruscana cv. Steuben. Furthermore, 8 has not been identified from the family Vitaceae.

Phytochemical Study of the Low Polar Constituents of Pinellia ternata

Tubers of Pinellia ternata (Thunb.) Makino (Araceae) have traditionally been used as an antiemetic and sedative in Korea, China, and Japan [1–4]. However, the raw materials should be processed by boiling them with the rhizomes of Zingiber officinale Roscoe (Zingiberaceae) and alum solution before use due to their irritating property [5]. Accordingly, there have been several studies to determine the reason for the irritation property of P. ternata [6, 7] and the effects of the traditional processing method for lowering the irritation [8, 9]. Previous phytochemical investigations on the crude drug reported the identification of nucleic acids [3, 10, 11], proteins [4], polysaccharides [1, 3], alkaloids [11, 12], phenylpropanoids, fatty acids, glycerides, cerebrosides, galactolipids, and sterols [3]. As part of our research project to standardize traditional medicines, a hexanes-soluble extract of the dried tubers of P. ternata was studied, leading to the isolation of seven known compounds, 2-linoleoyl-1,3-dioleoylglycerol (= 2-linoleoyl1,3-diolein) (1) [13], 3-oleoyl-1-palmitoylglycerol (2) [14], 1,3-dioleoylglycerol (3) [15], 1,3-dilinoleoylglycerol (4) [15], -tocospiro A (5) [16], -tocospiro B (6) [16], and squalene (7) [17]. The structures of 1–7 were identified by physical and spectroscopic analysis. Compounds 1–7 were isolated from P. ternate for the first time. To the best of our knowledge, 1–6 were not previously found in the family Araceae, although compound 7 was reported as one of the volatile components of P. fermentata by GC-MS analysis [18]. 2-Linoleoyl-1,3-diolein (1) was a major constituent of the lower polar fraction of P. ternata. It also showed a promotive effect on the gastrointestinal motility of mice in our previous study, which is relevant to the traditional use of P. ternata [19]. However, compound 1 was easily decomposed, probably from exposure to light, air, and temperature during the study. It seems not to be suitable as a standard compound of the traditional medicine due to its poor stability. The dried tubers of P. ternata (5 kg) were extracted with MeOH (18 L 3) overnight at room temperature. A concentrated MeOH extract (86 g) was suspended in a MeOH–H2O mixture (9:1, 1 L) and then fractionated with hexane (1 L 3), affording a hexane-soluble extract (32 g). The hexane-soluble extract was subjected to silica gel column chromatography (CC) by elution with a hexane–EtOAc gradient solvent system (999:1 0:1) to give 7 (1 mg) with 15 fractions (F01–F15). Fraction F06 (2.3 g) was purified by Sephadex LH-20 CC using CHCl3–MeOH (1:1) as eluent to afford 1 (2 g). Fraction F07 (3 g) was chromatographed over silica gel eluted by hexane–EtOAc (19:1) to yield 1 (400 mg) and 9 subfractions (F07.1–F07.9). Subfractions F07.5 (23 mg) and F07.6 (25 mg) were further separated by Sephadex LH-20 CC using MeOH 100% as eluent to afford 5 (5 mg) and 6 (7 mg), respectively. Fraction F11 (6 g) was subjected to RP-18 CC using gradient mixtures of MeCN–H2O (4:1 1:0) and CH2Cl2–MeCN (1:4) to give 13 subfractions (F11.01–F11.13). Subfraction F11.09 (900 mg) was chromatographed over silica gel by elution with CHCl3–acetone (49:1) to yield 4 (180 mg). Compounds 2 (1 mg) and 3 (1mg) were separated from subfraction F11.11 (290 mg) by silica gel CC using CHCl3–acetone (49:1) as eluent. 2-Linoleoyl-1,3-dioleoylglycerol (1). 1H NMR (400 MHz, CDCl3, , ppm, J/Hz): 5.31–5.42 (8H, m, H-(9, 10) 2, H-9 , 10 , and 12 , 13 ), 5.26 (1H, m, glyceryl H-2), 4.29 (2H, dd, J = 12.0, 4.4, glyceryl H-3), 4.14 (2H, dd, J = 11.8, 5.8, glyceryl H-1), 2.77 (2H, t, J = 6.6, H-11 ), 2.31 (6H, br.t, J = 7.8, H-2 2 and H-2 ), 2.04 (12H, m, H-(8, 11) 2, H-8 , 14 ), 1.61 (6H, m, H-3 2 and H-3 ), 1.40–1.24 (54H, m, CH2), 0.89 (6H, t, J = 6.8, H-18 2), 0.88 (3H, t, J = 6.8, H-18 ). 13C NMR (100 MHz, CDCl3, , ppm): 173.3 (C-1 2), 172.8 (C-1 ), 130.2 and 130.0 (C-(9, 10) 2), 128.1 and 127.9 (C-9 , 10 , 12 , 13 ), 68.9