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

Quantum-Mechanical Driven ¹H Iterative Full Spin Analysis Addresses Complex Peak Patterns of Choline Sulfate

Choline and choline esters are essential nutrients in biological systems for carrying out normal functions, such as the modulation of neurotransmission and the formation and maintenance of cell membranes. Choline sulfate is reportedly involved in the defense mechanism of accumulating sulfur resources against sulfur deficiency. Contrary to expectations, a full assignment of the 1H NMR spectrum of choline sulfate has not been reported. The present study pioneered a full assignment by quantum-mechanical driven 1H iterative full spin analysis. The complex peak patterns were analyzed in terms of heteronuclear and non-first-order coupling. The 1H–14N coupling constants, including two-bond coupling, which can be neglected, were accurately determined by iterative optimization. Non-first-order splitting has been described to be due to the presence of magnetically non-equivalent geminal protons. Moreover, in the comparison of the methylene proton resonance patterns of choline sulfate with choline and choline phosphate, the differences in the geminal and vicinal coupling constants were further examined through spectral simulation excluding the heteronuclear coupling. The precise spectral interpretation provided in this study is expected to contribute to future 1H NMR-based qualitative or quantitative studies of choline sulfate-containing sources

Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer

Quantum-Mechanical Driven ¹H Iterative Full Spin Analysis Addresses Complex Peak Patterns of Choline Sulfate

Choline and choline esters are essential nutrients in biological systems for carrying out normal functions, such as the modulation of neurotransmission and the formation and maintenance of cell membranes. Choline sulfate is reportedly involved in the defense mechanism of accumulating sulfur resources against sulfur deficiency. Contrary to expectations, a full assignment of the 1H NMR spectrum of choline sulfate has not been reported. The present study pioneered a full assignment by quantum-mechanical driven 1H iterative full spin analysis. The complex peak patterns were analyzed in terms of heteronuclear and non-first-order coupling. The 1H–14N coupling constants, including two-bond coupling, which can be neglected, were accurately determined by iterative optimization. Non-first-order splitting has been described to be due to the presence of magnetically non-equivalent geminal protons. Moreover, in the comparison of the methylene proton resonance patterns of choline sulfate with choline and choline phosphate, the differences in the geminal and vicinal coupling constants were further examined through spectral simulation excluding the heteronuclear coupling. The precise spectral interpretation provided in this study is expected to contribute to future 1H NMR-based qualitative or quantitative studies of choline sulfate-containing sources

Minor phenolics from Angelica keiskei and their proliferative effects on Hep3B cells.

A new coumarin, (-)-cis-(3'R,4'R)-4'-O-angeloylkhellactone-3'-O-β-d-glucopyranoside (1) and two new chalcones, 3'-[(2E)-5-carboxy-3-methyl-2-pentenyl]-4,2',4'-trihydroxychalcone (4) and (±)-4,2',4'-trihydroxy-3'-{2-hydroxy-2-[tetrahydro-2-methyl-5-(1-methylethenyl)-2-furanyl]ethyl}chalcone (5) were isolated from the aerial parts of Angelica keiskei (Umbelliferae), together with six known compounds: (R)-O-isobutyroyllomatin (2), 3'-O-methylvaginol (3), (-)-jejuchalcone F (6), isoliquiritigenin (7), davidigenin (8), and (±)-liquiritigenin (9). The structures of the new compounds were determined by interpretation of their spectroscopic data including 1D and 2D NMR data. All known compounds (2, 3, and 6-9) were isolated as constituents of A. keiskei for the first time. To identify novel hepatocyte proliferation inducer for liver regeneration, 1-9 were evaluated for their cell proliferative effects using a Hep3B human hepatoma cell line. All isolates exhibited cell proliferative effects compared to untreated control (DMSO). Cytoprotective effects against oxidative stress induced by glucose oxidase were also examined on Hep3B cells and mouse fibroblast NIH3T3 cells and all compounds showed significant dose-dependent protection against oxidative stress

A New 9,10-Dihydrophenanthrene and Cell Proliferative 3,4-δ-Dehydrotocopherols from Stemona tuberosa

A new compound, 9,10-dihydro-5-methoxy-8-methyl-2,7-phenanthrenediol (1), was isolated from the roots of Stemona tuberosa Lour. (Stemonaceae) together with two new optically active compounds, (2S,4'R,8'R)-3,4-δ-dehydrotocopherol (2) and (2R,4'R,8'R)-3,4-δ-dehydrotocopherol (3). The structures of compounds 1–3 were determined on the basis of spectroscopic data analysis. Compounds 2 and 3 were each purified from a stereoisomeric mixture of 2 and 3 by preparative HPLC using a chiral column for the first time. The absolute configurations at C-2 of 2 and 3 were determined by Circular Dichroism (CD) experiments. As a part of the research to find natural wound healing agents, all isolates and the mixture of 2 and 3 were evaluated for their cell proliferative effects using a mouse fibroblast NIH3T3 and a HeLa human cervical cancer cell line. As a result, 1, 2, 3, or the mixture of 2 and 3 showed 41.6%, 78.4%, 118.6%, 38.2% increases of cell proliferation in the mouse fibroblast NIH3T3 respectively, compared to 28.4% increase of δ-tocopherol. Moreover, none of them induced cancer cell proliferation. Therefore, 3,4-δ-dehydrotocopherols, especially pure isomers 2 and 3 can be suggested as potential wound healing agents

Angelica keiskei Impacts the Lifespan and Healthspan of Drosophila melanogaster in a Sex and Strain-Dependent Manner.

Angelica keiskei is a perennial plant, belonging to the Apiaceae family and originating from Japan. This plant has been reported to act as a diuretic, analeptic, antidiabetic, hypertensive, tumor, galactagogue, and laxative. The mechanism of action of A. keiskei is not known, but previous studies have suggested that it may act as an antioxidant. In this work, we used Drosophila melanogaster to evaluate the impact of A. keiskei on lifespan and healthspan and its potential anti-aging mechanism by conducting multiple assays on three fly strains: w1118, chico, and JIV. We observed that the extract extended lifespan and improved healthspan in a sex- and strain-dependent manner. A. keiskei extended lifespan and improved reproductive fitness in female flies and either had no effect or decreased survival and physical performance in males. The extract protected against the superoxide generator paraquat in both sexes. These sex-specific effects suggest that A. keiskei may act through age-specific pathways such as the insulin and insulin-like growth factor signaling (IIS) pathways. Upon examination, we found that the increased survival of A. keiskei-fed females was dependent on the presence of the insulin receptor substrate chico, supporting the role of IIS in the action of A. keiskei

Anti-Inflammatory Effects of Catalpalactone Isolated from <i>Catalpa ovata</i> in LPS-Induced RAW264.7 Cells

Catalpa ovata (Bignoniaceae) is widely distributed throughout Korea, China, and Japan. This study investigated the anti-inflammatory effects of catalpalactone isolated from C. ovata in lipopolysaccharide (LPS)-induced RAW264.7 cells. Catalpalactone significantly inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) expression in LPS-induced RAW264.7 cells. The levels of cytokines such as interleukin-6 and tumor necrosis factor-&#945; were reduced under catalpalactone exposure in LPS-induced RAW264.7 cells. Additionally, catalpalactone suppressed signal transducer and activator of transcription 1 (STAT-1) protein expression and interferon-&#946; (IFN-&#946;) production. Treatment with catalpalactone prevented interferon regulatory factor 3 (IRF3) and nuclear factor-&#954;B (NF-&#954;B) activation. Taken together, these results suggest that the anti-inflammatory effects of catalpalactone are associated with the suppression of NO production and iNOS expression through the inhibition of IRF3, NF-&#954;B, and IFN-&#946;/STAT-1 activation

Chalcones from <i>Angelica keiskei</i>: Evaluation of Their Heat Shock Protein Inducing Activities

Five new chalcones, 4,2′,4′-trihydroxy-3′-[(2<i>E</i>,5<i>E</i>)-7-methoxy-3,7-dimethyl-2,5-octadienyl]­chalcone (<b>1</b>), (±)-4,2′,4′-trihydroxy-3′-[(2<i>E</i>)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]­chalcone (<b>2</b>), 4,2′,4′-trihydroxy-3′-[(2<i>E</i>)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]­chalcone (<b>3</b>), 2′,3′-furano-4-hydroxy-4′-methoxychalcone (<b>4</b>), and (±)-4-hydroxy-2′,3′-(2,3-dihydro-2-methoxyfurano)-4′-methoxychalcone (<b>5</b>), were isolated from the aerial parts of <i>Angelica keiskei</i> Koidzumi together with eight known chalcones, <b>6</b>–<b>13</b>, which were identified as (±)-4,2′,4′-trihydroxy-3′-[(6<i>E</i>)-2-hydroxy-7-methyl-3-methylene-6-octenyl]­chalcone (<b>6</b>), xanthoangelol (<b>7</b>), xanthoangelol F (<b>8</b>), xanthoangelol G (<b>9</b>), 4-hydroxyderricin (<b>10</b>), xanthoangelol D (<b>11</b>), xanthoangelol E (<b>12</b>), and xanthoangelol H (<b>13</b>), respectively. Chalcones <b>1</b>–<b>13</b> were evaluated for their promoter activity on heat shock protein 25 (<i>hsp25</i>, murine form of human <i>hsp27</i>). Compounds <b>1</b> and <b>6</b> activated the <i>hsp25</i> promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by <b>1</b> and <b>6</b> were examined. Compound <b>6</b> increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas <b>1</b> did not induce any expression of these proteins. As a result, <b>6</b> seems to be a prospective HSP inducer