Phytochemical and pharmacological properties of the genus Alpinia from 2016 to 2023.

Covering 2016 up to the end of 2023Alpinia is the largest genus of flowering plants in the ginger family, Zingiberaceae, and comprises about 500 species. Many Alpinia are commonly cultivated ornamental plants, and some are used as spices or traditional medicine to treat inflammation, hyperlipidemia, and cancers. However, only a few comprehensive reviews have been published on the phytochemistry and pharmacology of this genus, and the latest review was published in 2017. In this review, we provide an extensive coverage of the studies on Alpinia species reported from 2016 through 2023, including newly isolated compounds and potential biological effects. The present review article shows that Alpinia species have a wide spectrum of pharmacological activities, most due to the activities of diarylheptanoids, terpenoids, flavonoids, and phenolics.

Anti-Obesity Activities of the Compounds from Perilla frutescens var. acuta and Chemical Profiling of the Extract.

Perilla frutescens var. acuta (Lamiaceae) is widely used not only as an oil or a spice, but also as a traditional medicine to treat colds, coughs, fever, and indigestion. As an ongoing effort, luteolin-7-O-diglucuronide (1), apigenin-7-O-diglucuronide (2), and rosmarinic acid (3) isolated from P. frutescens var. acuta were investigated for their anti-adipogenic and thermogenic activities in 3T3-L1 cells. Compound 1 exhibited a strong inhibition against adipocyte differentiation by suppressing the expression of Pparg and Cebpa over 52.0% and 45.0%, respectively. Moreover, 2 inhibited the expression of those genes in a dose-dependent manner [Pparg: 41.7% (5 µM), 62.0% (10 µM), and 81.6% (50 µM); Cebpa: 13.8% (5 µM), 18.4% (10 µM), and 37.2% (50 µM)]. On the other hand, the P. frutescens var. acuta water extract showed moderate thermogenic activities. Compounds 1 and 3 also induced thermogenesis in a dose-dependent manner by stimulating the mRNA expressions of Ucp1, Pgc1a, and Prdm16. Moreover, an LC-MS/MS chromatogram of the extract was acquired using UHPLC-MS2 and it was analyzed by feature-based molecular networking (FBMN) and the Progenesis QI software (version 3.0). The chemical profiling of the extract demonstrated that flavonoids and their glycoside derivatives, including those isolated earlier as well as rosmarinic acid, are present in P. frutescens var. acuta.

Anti-Inflammatory Effect of Three Isolated Compounds of Physalis alkekengi var. franchetii (PAF) in Lipopolysaccharide-Activated RAW 264.7 Cells.

(1) Background: Three isolated compounds from Physalis alkekengi var. franchetii (PAF) have been investigated to possess a variety of biological activities. Their structures were elucidated by spectroscopic analysis (Ultraviolet (UV), High-resolution electrospray mass spectrometry (HR-ESI-Ms), and their anti-inflammatory effects were evaluated in vitro; (2) Methods: To investigate the mechanisms of action of PAF extracts and their isolated compounds, their anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). RAW 264.7 cells were treated with different concentrations of Physalis alkekengi var. franchetii three isolated compounds of PAF for 30 min prior to stimulation with or without LPS for the indicated times. The inflammatory cytokines, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were determined using reverse transcription-polymerase chain (RT-PCR); (3) Results Treatment of RAW 264.7 cells with LPS alone resulted in significant increases in inflammatory cytokine production as compared to the control group (p < 0.001). However, with the treatment of isophysalin B 100 µg/mL, there was a significant decrease in the mRNA expression levels of TNF-α in LPS-stimulated raw 264.7 cells (p < 0.001). With treatment of physalin 1−100 µg/mL, there was a markedly decrease in the mRNA expression levels of TNF-α in LPS stimulated raw 264.7 (p < 0.05). Moreover, TNF-α mRNA (p < 0.05) and IL-1ß mRNA (p < 0.001) mRNA levels were significantly suppressed after treatment with 3',7-dimethylquercetin in LPS stimulated Raw 264.7 cells; (4) Conclusions: These findings suggest that three isolated compounds from can suppress inflammatory responses in LPS stimulated macrophage.

Effects of oral contraceptive use on muscle strength, muscle thickness, and fiber size and composition in young women undergoing 12 weeks of strength training: a cohort study.

BACKGROUND: It is suspected that hormonal fluctuations during menstruation may cause different responses to strength training in women who use oral contraceptives (OC) versus those who do not. However, previous studies that investigated the existence of such differences produced conflicting results. In this study, we hypothesized that OC use has no effect on muscle strength and hypertrophy among women undergoing strength training. Thus, we compared the differences in muscle strength and thickness among women who used OCs and those who did not. METHODS: We investigated the influence of OC use on muscle strength (Fmax), muscle thickness (Mtk), type 1-to-type 2 muscle fiber (NO) ratio, muscle fiber thickness (MFT), and nuclear-to-fiber (N/F) ratio. Seventy-four healthy young women (including 34 who used OCs and 40 who did not) underwent 12 weeks of submaximal strength training, after which Fmax was evaluated using a leg-press machine with a combined force and load cell, while Mtk was measured using real-time ultrasonography. Moreover, the NO ratio, MFT, and N/F ratio were evaluated using muscle needle biopsies. RESULTS: Participants in the non-OC and OC groups experienced increases in Fmax (+ 23.30 ± 10.82 kg and + 28.02 ± 11.50 kg respectively, p = 0.073), Mtk (+ 0.48 ± 0.47 cm2 and + 0.50 ± 0.44 cm2 respectively, p = 0.888), Fmax/Mtk (+ 2.78 ± 1.93 kg/cm2 and + 3.32 ± 2.37 kg/cm2 respectively, p = 0.285), NO ratio (type 2 fibers: + 1.86 ± 6.49% and - 4.17 ± 9.48% respectively, p = 0.169), MFT (type 2 fibers: + 7.15 ± 7.50 µm and + 4.07 ± 9.30 µm respectively, p = 0.435), and N/F ratio (+ 0.61 ± 1.02 and + 0.15 ± 0.97 respectively, p = 0.866) after training. There were no significant differences between the non-OC and OC groups in any of these parameters (p > 0.05). CONCLUSIONS: The effects of 12 weeks of strength training on Fmax, muscle thickness, muscle fiber size, and composition were similar in young women irrespective of their OC use.

The impact of price transparency and competition on hospital costs: a research on all-payer claims databases.

BACKGROUND: Public reporting has been considered effective in reducing health care costs by mitigating information asymmetry in the market as payers have incorporated publicly available information mandates into pay-for-performance programs and value-based purchasing. Therefore, hospitals have faced increasing pressures to provide price transparency. Despite the widespread promotion of healthcare transparency, the effectiveness of public reporting has not yet been sufficiently understood. This study analyzed the impact of transparency policy and competition on hospital costs by taking the state operations of all-payer claims databases (APCDs) as a case of interest. METHODS: We employed a fixed-effects regression, which allows the generation of hospital-specific effects, in accordance with the suggestion by the Hausman test. The study samples comprise nonprofit and for-profit general acute care hospitals in the United States for 2011-2017. The finalized dataset ranges from 3547 observations in 2011 to 3405 observations in 2015 after removing missing values. RESULTS: We found that hospitals in the states with APCDs tend to bear higher average operating expenses than those without APCDs, which may indicate that states maintaining higher healthcare expenditures are more attentive to a price transparency initiative and tend to adopt APCDs. With regard to competition, the results showed that weak market competition is significantly associated with higher operating costs, supporting the traditional competition theory. However, the combined effect of APCDs and competition did not indicate a significant association with operating expenses. Further investigation showed a continued tendency for a weak intensity of competition to be linked to lower hospital operating costs in states without APCDs. For those located in non-APCD adopted states, market consolidation helped hospitals coordinate care more effectively, economize operating costs, and enjoy economies of scale due to their large size. Similar trends did not appear in APCD-adopted states except for in 2015. CONCLUSIONS: This study observed limited evidence of the impact of APCDs and market competition. Our findings suggest that states need to make multifaceted efforts to contain hospital costs, not solely depending on the rollout of cost information or market competition. Market concentration may lead to coordinated care or cost economization in some cases. Still, the existing literature also demonstrates some potentially harmful impacts of increased concentration in the healthcare market, such as inefficient use of resources, unilateral market power, and deterrence of innovation. The introduction of a price transparency tool may require additional policy actions that take market competition into consideration.

Comparative Analysis of Coumarin Profiles in Different Parts of Peucedanum japonicum and Their Aldo-Keto Reductase Inhibitory Activities.

Peucedanum japonicum (Umbelliferae) is widely distributed throughout Southeast Asian countries. The root of this plant is used in traditional medicine to treat colds and pain, whereas the young leaves are considered an edible vegetable. In this study, the differences in coumarin profiles for different parts of P. japonicum including the flowers, roots, leaves, and stems were compared using ultra-performance liquid chromatography time-of-flight mass spectrometry. Twenty-eight compounds were tentatively identified, including three compounds found in the genus Peucedanum for the first time. Principal component analysis using the data set of the measured mass values and intensities of the compounds exhibited distinct clustering of the flower, leaf, stem, and root samples. In addition, their anticancer activities were screened using an Aldo-keto reductase (AKR)1C1 assay on A549 human non-small-cell lung cancer cells and the flower extract inhibited AKR1C1 activity. Based on these results, seven compounds were selected as potential markers to distinguish between the flower part versus the root, stem, and leaf parts using an orthogonal partial least-squares discriminant analysis. This study is the first to provide information on the comparison of coumarin profiles from different parts of P. japonicum as well as their AKR1C1 inhibitory activities. Taken together, the flowers of P. japonicum offer a new use related to the efficacy of overcoming anticancer drug resistance, and may be a promising source for the isolation of active lead compounds.

High-yield synthesis and purification of recombinant human GABA transaminase for high-throughput screening assays.

Many studies have focussed on modulating the activity of γ-aminobutyric acid transaminase (GABA-T), a GABA-catabolizing enzyme, for treating neurological diseases, such as epilepsy and drug addiction. Nevertheless, human GABA-T synthesis and purification have not been established. Thus, biochemical and drug design studies on GABA-T have been performed by using porcine GABA-T mostly and even bacterial GABA-T. Here we report an optimised protocol for overexpression of 6xHis-tagged human GABA-T in human cells followed by a two-step protein purification. Then, we established an optimised human GABA-T (0.5 U/mg) activity assay. Finally, we compared the difference between human and bacterial GABA-T in sensitivity to two irreversible GABA-T inhibitors, gabaculine and vigabatrin. Human GABA-T in homodimeric form showed 70-fold higher sensitivity to vigabatrin than bacterial GABA-T in multimeric form, indicating the importance of using human GABA-T. In summary, our newly developed protocol can be an important first step in developing more effective human GABA-T modulators.

Inhibition of A549 Lung Cancer Cell Migration and Invasion by Ent-Caprolactin C via the Suppression of Transforming Growth Factor-ß-Induced Epithelial-Mesenchymal Transition.

The epithelial-mesenchymal transition (EMT) of cancer cells is a crucial process in cancer cell metastasis. An Aquimarina sp. MC085 extract was found to inhibit A549 human lung cancer cell invasion, and caprolactin C (1), a new natural product, α-amino-ε-caprolactam linked to 3-methyl butanoic acid, was purified through bioactivity-guided isolation of the extract. Furthermore, its enantiomeric compound, ent-caprolactin C (2), was synthesized. Both 1 and 2 inhibited the invasion and γ-irradiation-induced migration of A549 cells. In transforming growth factor-ß (TGF-ß)-treated A549 cells, 2 inhibited the phosphorylation of Smad2/3 and suppressed the EMT cell marker proteins (N-cadherin, ß-catenin, and vimentin), as well as the related messenger ribonucleic acid expression (N-cadherin, matrix metalloproteinase-9, Snail, and vimentin), while compound 1 did not suppress Smad2/3 phosphorylation and the expression of EMT cell markers. Therefore, compound 2 could be a potential candidate for antimetastatic agent development, because it suppresses TGF-ß-induced EMT.

Phytochemicals and Bioactivities of Zingiber cassumunar Roxb.

Zingiber cassumunar Roxb. (Zingiberaceae), is an important medicinal plant known as "Plai (Phlai)" in Thailand, "Bangle" in Indonesia, and "Bulei" in China. Traditionally, this plant has been used to treat inflammation, pain, and respiratory problems. The rhizomes are the primary part of the plant that has been used for medicinal purposes due to their constituents with therapeutic properties, including phenylbutenoids, curcuminoids, and essential oils. Since the 1970s, many studies have been conducted on the phytochemicals and bioactivities of Z. cassumunar to establish fundamental scientific evidence that supports its use in traditional medicine. The accumulated biological studies on the extracts, solvent fractions, and constituents of Z. cassumunar have described their diverse medicinal properties, including antioxidant, anti-inflammatory, anticancer, neuroprotective/neurotrophic, cosmeceutical, and antifungal/antimicrobial bioactivities. In this review, we summarize information on the phytochemicals of Z. cassumunar and the bioactivities of its extracts and constituents.

Eudesmane and Eremophilane Sesquiterpenes from the Fruits of Alpinia oxyphylla with Protective Effects against Oxidative Stress in Adipose-Derived Mesenchymal Stem Cells.

Alpinia oxyphylla Miquel (Zingiberaceae) has been reported to show antioxidant, anti-inflammatory, and neuroprotective effects. In this study, two new eudesmane sesquiterpenes, 7α-hydroperoxy eudesma-3,11-diene-2-one (1) and 7ß-hydroperoxy eudesma-3,11-diene-2-one (2), and a new eremophilane sesquiterpene, 3α-hydroxynootkatone (3), were isolated from the MeOH extract of dried fruits of A. oxyphylla along with eleven known sesquiterpenes (4-14). The structures were elucidated by the analysis of 1D/2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and optical rotation data. Compounds (1-3, 5-14) were evaluated for their protective effects against tert-butyl hydroperoxide (tBHP)-induced oxidative stress in adipose-derived mesenchymal stem cells (ADMSCs). As a result, treatment with isolated compounds, especially compounds 11 and 12, effectively reverted the damage of tBHP on ADMSCs in a dose-dependent manner. In particular, 11 and 12 at 50 µM improved the viability of tBHP-toxified ADMSCs by 1.69 ± 0.05-fold and 1.61 ± 0.03-fold, respectively.

18:0 Lyso PC Derived by Bioactivity-Based Molecular Networking from Lentil Mutant Lines and Its Effects on High-Fat Diet-Induced Obese Mice.

Lentil (Lens culinaris; Fabaceae), one of the major pulse crops in the world, is an important source of proteins, prebiotics, lipids, and essential minerals as well as functional components such as flavonoids, polyphenols, and phenolic acids. To improve crop nutritional and medicinal traits, hybridization and mutation are widely used in plant breeding research. In this study, mutant lentil populations were generated by γ-irradiation for the development of new cultivars by inducing genetic diversity. Molecular networking via Global Natural Product Social Molecular Networking web platform and dipeptidyl peptide-IV inhibitor screening assay were utilized as tools for structure-based discovery of active components in active mutant lines selected among the lentil population. The bioactivity-based molecular networking analysis resulted in the annotation of the molecular class of phosphatidylcholine (PC) from the most active mutant line. Among PCs, 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (18:0 Lyso PC) was selected for further in vivo study of anti-obesity effect in a high-fat diet (HFD)-induced obese mouse model. The administration of 18:0 Lyso PC not only prevented body weight gain and decreased relative gonadal adipose tissue weight, but also attenuated the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and leptin in the sera of HFD-induced obese mice. Additionally, 18:0 Lyso PC treatment inhibited the increase of adipocyte area and crown-like structures in adipose tissue. Therefore, these results suggest that 18:0 Lyso PC is a potential compound to have protective effects against obesity, improving obese phenotype induced by HFD.

N-Acetyldopamine derivatives from Periostracum Cicadae and their regulatory activities on Th1 and Th17 cell differentiation.

Bioassay-guided fractionation of a 90% ethanol extract of Periostracum Cicadae led to the isolation of two new N-acetyldopamine dimers (1a/1b) along with six known dimers (2a/2b, 3a/3b, and 4a/4b) and two monomers (5a/5b); compounds 2a/2b, 4a/4b and 5a/5b were newly isolated from this material. All compounds were isolated as enantiomeric mixtures and each enantiomer was successfully separated by chiral-phase HPLC. The structures including absolute configurations were confirmed by high-resolution electrospray ionization mass spectrometry (HR-ESIMS), 1D/2D nuclear magnetic resonance (NMR) spectroscopy, 1H iterative Full Spin Analysis (HiFSA), and electronic circular dichroism (ECD) spectroscopy. Subsequently, the bioactivities of these isolates were evaluated via CD4+ T cell differentiations, which are critical for immune responses and inflammation. The results revealed that compound 5b was observed to enhance the IFN-γ+ Th1 differentiation, which may have a potential for cancer immunotherapy.

Constituents of Coreopsis lanceolata Flower and Their Dipeptidyl Peptidase IV Inhibitory Effects.

A new polyacetylene glycoside, (5R)-6E-tetradecene-8,10,12-triyne-1-ol-5-O-ß-glucoside (1), was isolated from the flower of Coreopsis lanceolata (Compositae), together with two known compounds, bidenoside C (10) and (3S,4S)-5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-ß-glucopyranoside (11), which were found in Coreopsis species for the first time. The other known compounds, lanceoletin (2), 3,2'-dihydroxy-4-3'-dimethoxychalcone-4'-glucoside (3), 4-methoxylanceoletin (4), lanceolin (5), leptosidin (6), (2R)-8-methoxybutin (7), luteolin (8) and quercetin (9), were isolated in this study and reported previously from this plant. The structure of 1 was elucidated by analyzing one-dimensional and two-dimensional nuclear magnetic resonance and high resolution-electrospray ionization-mass spectrometry data. All compounds were tested for their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and compounds 2-4, 6 and 7 inhibited DPP-IV activity in a concentration-dependent manner, with IC50 values from 9.6 to 64.9 µM. These results suggest that C. lanceolata flower and its active constituents show potential as therapeutic agents for diseases associated with type 2 diabetes mellitus.

Moscatilin Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma Cells via JNK Signaling Pathway.

Dendrobii Herba is an herbal medicine that uses the stems of Dendrobium species (Orchidacea). It has been traditionally used to treat fever, hydrodipsomania, stomach disorders, and amyotrophia. In our previous study, a bibenzyl compound, moscatilin, which is isolated from Dendrobii Herba, showed potent cytotoxicity against a FaDu human pharyngeal squamous carcinoma cell line. Prompted by this finding, we performed additional studies in FaDu cells to investigate the mechanism of action. Moscatilin induced FaDu cell death by using 5 µM of concentration and by mediating apoptosis, whereas cell proliferation following treatment with 1 µM of moscatilin was not suppressed to the same levels as by the anti-cancer agent, cisplatin. Apoptosis-related protein expression (cleaved caspase-8, cleaved caspase-7, cytochrome c, cleaved caspase-9, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) was increased by treating with 5 µM of moscatilin. This suggests that moscatilin-mediated apoptosis is associated with the extrinsic and intrinsic apoptotic signaling pathways. In addition, moscatilin-induced apoptosis was mediated by the c-Jun N-terminal kinase (JNK) signaling pathway. Overall, this study identified additional biological activity of moscatilin derived from natural products and suggested its potential application as a chemotherapeutic agent for the management of head and neck squamous cell carcinoma.

Furanocoumarins from the Roots of Angelica dahurica with Inhibitory Activity against Intracellular Reactive Oxygen Species Accumulation.

Five new furanocoumarins, dahuribirin H (1), dahuribirin I (2), (2'S)-(+)-5-(2'-hydroxy-3'-methylbut-3'-enyloxy)-8-(3''-methylbut-2″-enyloxy)psoralen (3), (2'R)-(+)-5-(2',3'-epoxy-3'-methylbutoxy)-8-(3″-methylbut-2″-enyloxy)psoralen (4), and 5-methoxy-8-((Z)-4'-(3″-methylbutanoate)-3'-methylbut-2'-enyloxy)psoralen (5), along with 15 known compounds (6-20), were isolated from the roots of Angelica dahurica. The structures of the new compounds were elucidated by spectroscopic analysis, along with electronic circular dichroism calculations and Mosher ester analysis. Compounds 3, 4, 11, 13, and 16 reduced H2O2-induced cell death in HepG2 cells and attenuated reactive oxygen species (ROS) formation without showing cytotoxicity, suggesting that these compounds might have cytoprotective effects against H2O2-induced oxidative damage via ROS scavenging activities.

Anti-Inflammatory Effects of Catalpalactone Isolated from Catalpa ovata 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-α 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-ß (IFN-ß) production. Treatment with catalpalactone prevented interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB) 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-κB, and IFN-ß/STAT-1 activation.

Phytochemical Composition and Antioxidant Activities of Two Different Color Chrysanthemum Flower Teas.

Chrysanthemum morifolium Ramat is a perennial flowering plant widely cultivated for use in a tea infusion and as a popular beverage. To identify and evaluate the tea infusion made with a γ-irradiated mutant chrysanthemum cultivar with dark purple petals (cv. ARTI-Dark Chocolate), its phytochemical composition and antioxidant activity were tested and compared with those of the commercially available chrysanthemum cultivar with yellow petals (cv. Gamguk) by HPLC-DAD-ESIMS, as well as DPPH and ABTS radical scavenging assays. The purple chrysanthemum tea contained anthocyanins and linarin, which were not detected in the yellow chrysanthemum tea and the content of chlorogenic acid, acacetin-7-O-ß-glucoside, and luteolin was higher compared with the yellow chrysanthemum tea. In contrast, the yellow chrysanthemum tea had higher luteolin-7-O-ß-glucoside, 3,5-dicaffeoylquinic acid, apigenin-7-O-ß-glucoside, and apigenin contents in comparison with the purple chrysanthemum tea. In addition, the content and antioxidant activity of the two chrysanthemum teas were investigated according to different water temperatures and infusing time. The yellow chrysanthemum tea did not show any significant differences according to infusing time and temperature, while the purple chrysanthemum tea was more influenced by the infusing time than water temperature, showing the highest total compound content in the infusing condition of 100 °C and 4 min. Moreover, the floral scent volatiles of the two chrysanthemum tea sources were analyzed using HS-SPME-GC-MS. In the DPPH radical scavenging assay, the purple chrysanthemum tea broadly showed greater antioxidant activity than did the yellow chrysanthemum tea, corresponding to the high content of anthocyanins known as the powerful antioxidant. Further, both chrysanthemum flower teas exhibited strong ABTS radical scavenging effects ranging from 76% to 61% under all infusing conditions. Therefore, the purple chrysanthemum cultivar, ARTI-Dark Chocolate, is worthy of breeding as a new tea cultivar.

Identification of Two New Phenanthrenes from Dendrobii Herba and Their Cytotoxicity towards Human Hypopharynx Squamous Carcinoma Cell (FaDu).

Two new phenanthrenes, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxy-phenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with seven known phenanthrenes (3-9), two bibenzyls (10-12), and a lignan (13). Structures of 1 and 2 were elucidated by analyzing one-dimensional (1D) and two-dimensional (2D)-NMR and High-resolution electrospray ionization mass spectra (HR-ESI-MS) data. The absolute configuration of compound 1 was confirmed by the circular dichroism (CD) spectroscopic method. In cytotoxicity assay using FaDu human hypopharynx squamous carcinoma cell line, compounds 3-6, 8, 10, and 12 showed activities, with IC50 values that ranged from 2.55 to 17.70 µM.

Comparative Analysis of Phytochemical Composition of Gamma-Irradiated Mutant Cultivars of Chrysanthemum morifolium.

The flowers of chrysanthemum species are used as a herbal tea and in traditional medicine. In addition, members of the genus have been selected to develop horticultural cultivars of diverse floral colors and capitulum forms. In this research, we investigated the phytochemical composition of eight gamma-irradiation mutant cultivars of Chrysanthemum morifolium and their original cultivars. The mutant chrysanthemum cultivars were generated by treatment with various doses of 60Co gamma irradiation of stem cuttings of three commercial chrysanthemum cultivars as follows: 'ARTI-Dark Chocolate' (50Gy), 'ARTI-Purple Lady' (30 Gy), and 'ARTI-Yellow Star' (50 Gy) derived from 'Noble Wine'; 'ARTI-Red Star' (50 Gy) and 'ARTI-Rising Sun' (30 Gy) from 'Pinky'; 'ARTI-Purple' (40 Gy) and 'ARTI-Queen' (30 Gy) from 'Argus'; and 'ARTI-Rollypop' (70 Gy) from 'Plaisir d'amour'. Quantitative analysis of flavonoids, phenolic acids, anthocyanins, and carotenoids in the flowers of the 12 chrysanthemum cultivars was performed using high performance liquid chromatography-diode array detector-electrospray ionization mass spectrometry (HPLC-DAD-ESIMS). Essential oils from the flowers of these cultivars were analyzed by gas chromatography-mass spectrometry (GC-MS). The mutant cultivars, 'ARTI-Dark Chocolate', 'ARTI-Purple Lady', 'ARTI-Purple', and 'ARTI-Queen' showed higher total amounts of flavonoid and phenolic acid compared with those of the respective original cultivars. The mutant cultivars, 'ARTI-Dark Chocolate', 'ARTI-Purple Lady' and 'ARTI-Purple', which produce purple to pink petals, contained more than two-times higher amounts of anthocyanins compared with those of their original cultivars. Of the mutant cultivars, 'ARTI-Yellow Star' in which petal color was changed to yellow, showed the greatest accumulation of carotenoids. Ninety-nine volatile compounds were detected, of which hydrocarbons and terpenoids were abundant in all cultivars analyzed. This is the first report that demonstrated the phytochemical analysis of novel chrysanthemum cultivars derived from C. morifolium hydrid using HPLC-DAD-ESIMS and GC-MS. These findings suggest that the selected mutant chrysanthemum cultivars show potential as a functional source of phytochemicals associated with the abundance of health-beneficial components, as well as good source for horticulture and pigment industries.

The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism.

GTP and branched-chain amino acids (BCAAs) are metabolic sensors that are indispensable for the determination of the metabolic status of cells. However, their molecular sensing mechanism remains unclear. CodY is a unique global transcription regulator that recognizes GTP and BCAAs as specific signals and affects expression of more than 100 genes associated with metabolism. Herein, we report the first crystal structures of the full-length CodY complex with sensing molecules and describe their functional states. We observed two different oligomeric states of CodY: a dimeric complex of CodY from Staphylococcus aureus with the two metabolites GTP and isoleucine, and a tetrameric form (apo) of CodY from Bacillus cereus Notably, the tetrameric state shows in an auto-inhibitory manner by blocking the GTP-binding site, whereas the binding sites of GTP and isoleucine are clearly visible in the dimeric state. The GTP is located at a hinge site between the long helical region and the metabolite-binding site. Together, data from structural and electrophoretic mobility shift assay analyses improve understanding of how CodY senses GTP and operates as a DNA-binding protein and a pleiotropic transcription regulator.