Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 16 de 16
Filter
1.
Environ Sci Pollut Res Int ; 31(10): 16028-16047, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38308166

ABSTRACT

Pathogenic bacteria, the major causative agents of aquaculture diseases, are a serious impediment to the aquaculture industry. However, the bioinformatics of pathogenic bacteria and virulence factors (VFs) in sediments, an important component of freshwater aquaculture ecosystems, are not well characterized. In this study, 20 sediment samples were collected from fish pond sediments (FPS), shrimp field sediments (SFS), fish pond sediment control (FPSC), and shrimp field sediment control (SFSC). Molecular biological information was obtained on a total of 173 pathogenic bacteria, 1093 virulence factors (VFs), and 8475 mobile genetic elements (MGEs) from these samples. The results indicated that (1) aquaculture patterns and sediment characteristics can affect the distribution of pathogenic bacteria. According to the results of the Kruskal-Wallis H test, except for Mycobacterium gilvum, there were significant differences (P < 0.05) among the four sediment types in the average abundance of major pathogenic bacteria (top 30 in abundance), and the average abundance of major pathogenic bacteria in the four sediment types followed the following pattern: FPS > SFS > FPSC > SFSC. (2) Pathogenic bacteria are able to implement a variety of complex pathogenic mechanisms such as adhesion, invasion, immune evasion, and metabolic regulation in the host because they carry a variety of VFs such as type IV pili, HSI-I, Alginate, Colibactin, and Capsule. According to the primary classification of the Virulence Factor Database (VFDB), the abundance of VFs in all four types of sediments showed the following pattern: offensive VFs > non-specific VFs > defensive VFs > regulation of virulence-related genes. (3) Total organic carbon (TOC), total phosphorus (TP), available phosphorus (AP), nitrite, and nitrate were mostly only weakly positively correlated with the major pathogenic bacteria and could promote the growth of pathogenic bacteria to some extent, whereas ammonia was significantly positively correlated with most of the major pathogenic bacteria and could play an important role in promoting the growth and reproduction of pathogenic bacteria. (4) Meanwhile, there was also a significant positive correlation between CAZyme genes and major pathogenic bacteria (0.62 ≤ R ≤ 0.89, P < 0.05). This suggests that these pathogenic bacteria could be the main carriers of CAZyme genes and, to some extent, gained a higher level of metabolic activity by degrading organic matter in the sediments to maintain their competitive advantage. (5) Worryingly, the results of correlation analyses indicated that MGEs in aquaculture sediments could play an important role in the spread of VFs (R = 0.82, P < 0.01), and in particular, plasmids (R = 0.75, P < 0.01) and integrative and conjugative elements (ICEs, R = 0.65, P < 0.05) could be these major vectors of VFs. The results of this study contribute to a comprehensive understanding of the health of freshwater aquaculture sediments and provide a scientific basis for aquaculture management and conservation.


Subject(s)
Ecosystem , Fresh Water , Animals , Bacteria , Aquaculture , Phosphorus , Virulence Factors/genetics
2.
Nat Mater ; 22(7): 853-859, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37349395

ABSTRACT

III-nitride wide bandgap semiconductors are promising materials for modern optoelectronics and electronics. Their application has progressed greatly thanks to the continuous quality improvements of heteroepitaxial films grown on large-lattice-mismatched foreign substrates. But compared with bulk single crystals, there is still tremendous room for the further improvement of the material quality. Here we show a paradigm to achieve high-quality III-nitride heteroepitaxial films by the controllable discretization and coalescence of columns. By adopting nano-patterned AlN/sapphire templates with regular hexagonal holes, discrete AlN columns coalesce with uniform out-of-plane and in-plane orientations guaranteed by sapphire nitridation pretreatment and the ordered lateral growth of cleavage facets, which efficiently suppresses the regeneration of threading dislocations during coalescence. The density of dislocation etch pits in the AlN heteroepitaxial film reaches 3.3 × 104 cm-2, close to the present available AlN bulk single crystals. This study facilitates the growth of bulk-class quality III-nitride films featuring low cost and scalability.


Subject(s)
Aluminum Oxide , Electronics , Semiconductors , Software
3.
Nat Prod Res ; 37(13): 2135-2143, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35067130

ABSTRACT

In the course of our continuing search for biologically active compounds from medicinal herbs, four undescribed terpenoids including one monoterpenoid glycoside, (1 R, 3S, 4S, 5 R)-(-)-1,8-epoxy-p-menthan-5-ethoxycarbonyl-3-O-ß-D-glucopyranoside (1), one iridoid glycoside, 3'-O-ß-D-glucopyranosyl-melampyroside (2), one sesquiterpene, 1-(2-methylbutanol)-2-pentyl-1,3-cyclohexadiene (3), and one triterpenoid, 28-nor-3ß,18ß-dihydroxyurs-12-ene (4), together with nine known terpenoids (5-13) were isolated from the dried aerial parts of Dracocephalum moldavica (Lamiaceae). Their chemical structures were elucidated by detailed spectroscopy (1 D and 2 D NMR), HRESIMS data analysis and acid hydrolysis. Among them, compounds 9 and 10 were isolated from the family Lamiaceae, compounds 5, 6 and 11-13 were identified from the genus Dracocephalum and compounds 7 and 8 were reported from the D. moldavica for the first time. The biological evaluation of anti-complementary activity revealed that some compounds, 4, 6 and 12 exhibited anti-complementary activity with CH50 and AP50 values ranging from 0.67-1.43 and 1.12-1.55 mM, respectively.


Subject(s)
Lamiaceae , Terpenes , Terpenes/pharmacology , Lamiaceae/chemistry , Magnetic Resonance Spectroscopy , Plant Components, Aerial
4.
Eur J Nutr ; 60(6): 3013-3027, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33469697

ABSTRACT

PURPOSE: Previous population studies on the associations between dietary fatty acids (FAs), plasma FAs levels, and the risk of age-related macular degeneration (AMD) have yielded inconclusive results. Herein, we conducted a dose-response meta-analysis to quantitatively evaluate the associations between specific type of dietary FAs, plasma FAs on early and advanced AMD risk. METHODS: PubMed, Web of Science, and EMBASE were systematically searched for observational cohort studies published through May 2020. For highest versus lowest comparison and dose-response analyses, the relative risk (RR) estimates with a 95% confidence interval (CI) were analyzed using random effects model. RESULTS: 11 studies with 167,581 participants were included in the meta-analysis. During the follow-up periods (ranging from 3 to 28 years), 6,318 cases of AMD were recorded. Dietary intake of docosahexaenoic acid (DHA) and eicosatetraenoic acid (EPA) combined (per 1 g/day increment) were found to be negatively associated with early AMD (RR: 0.67, 95% CI [0.51, 0.88]). Each 1 g/day increment of DHA (RR: 0.50, 95% CI [0.32, 0.78]) and EPA (RR: 0.40, 95% CI [0.18, 0.87]) was associated with a 50% and 60% reduction of early AMD risk, respectively. Plasma DHA (RR: 0.72, 95% CI [0.55, 0.95]) and EPA (RR: 0.57, 95% CI [0.40, 0.81]) indicated significant negative relationship with advanced AMD. CONCLUSION: Increasing dietary intake of ω-3 polyunsaturated fatty acids (PUFAs), specifically DHA and EPA, were associated with a reduced risk of early subtype of AMD, while other types of FAs did not present significant results. Further research is warranted to explore the potential association between dietary FA, plasma FA levels, and advanced subtype of AMD.


Subject(s)
Fatty Acids, Omega-3 , Macular Degeneration , Cohort Studies , Fatty Acids , Humans , Macular Degeneration/epidemiology , Macular Degeneration/etiology , Macular Degeneration/prevention & control , Prospective Studies
5.
Nat Prod Res ; 35(22): 4423-4432, 2021 Nov.
Article in English | MEDLINE | ID: mdl-32037886

ABSTRACT

Sanguisorba officinalis L. is a traditional herbal plant that belongs to the genus Sanguisorba and the family Rosaceae. Two new phenolic glycosides (1-2), ten known phenolics (3-12), and six known monoterpenoid glycosides (13-18) were isolated from the roots of S. officinalis using silica gel column and preparative middle pressure liquid chromatography (MPLC). The chemical structures were elucidated based on extensive spectroscopic experiments, including 1D and 2D NMR as well as HR-ESI-MS, and comparison with those reported in the literature. Compounds 3-5, and 13 were isolated from the Rosaceae family and compound 7 was obtained from the genus Sanguisorba for the first time. Additionally, all compounds were evaluated for their anti-complementary activities against the classical pathway. Furthermore, compounds 1, 5, 9, and 14 showed significant anti-complementary activities with the 50% haemolytic inhibition concentrations (CH50) values of 0.40 ± 0.03, 0.57 ± 0.01, 0.51 ± 0.07, and 0.53 ± 0.05 mM, respectively.


Subject(s)
Sanguisorba , Glycosides/pharmacology , Phenols/pharmacology , Plant Extracts/pharmacology , Plant Roots
6.
Nat Prod Res ; 35(8): 1331-1339, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31385536

ABSTRACT

Two new flavonoids, (2S)-6,8-dimethyl-5,7,3',4'-tetrahydroxyflavanone 4'-O-ß-D-glucopyranoside (1) and quercetin 3-O-ß-D-(6''-p-methoxybenzoyl)-galactopyranoside (2), together with ten known flavonoids (3-12) were isolated from the leaves of Rhododendron dauricum L. The structures of the flavonoids were characterized from spectroscopic data (1D and 2D NMR and HR-ESI-MS). The isolated flavonoids were evaluated for their inhibitory effects on the production of tumour necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 cells. Compound 11 exhibited inhibitory activity against TNF-α production with an IC50 value of 46.2 ± 1.2 µM.


Subject(s)
Flavonoids/isolation & purification , Lipopolysaccharides/pharmacology , Plant Leaves/chemistry , Rhododendron/chemistry , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Carbon-13 Magnetic Resonance Spectroscopy , Flavonoids/chemistry , Mice , Plant Extracts/chemistry , Quercetin/analysis , RAW 264.7 Cells , Rhododendron/drug effects
7.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2063-2072, 2020 May.
Article in Chinese | MEDLINE | ID: mdl-32495555

ABSTRACT

Bawei Chenxiang Powder is a traditional Tibetan folk medicine formula, consisting of resinous wood of Aquilaria sinensis, kernel of Myristica fragrans, fruit of Choerospondias axillaris, travertine, resin of Boswellia carterii or B. bhaw-dajiana, stem of Aucklandia lappa, fruit of Terminalia chebula(roasted), and flower of Gossampinus malabarica. It has the function of clearing heart heat, nourishing heart, tranquilizing mind, and inducing resuscitation, which has been used for the treatment of coronary heart disease and angina pectoris. Modern research shows that the medicine materials of this formula mainly contain terpenoids like sesquiterpenes and triterpenes and polyphenols like flavonoids, lignans, and tannins, displaying some pharmacological activities such as anti-myocardial ischemia, anti-cerebral ischemia, and spatial learning and memory promotion. This review summaries the traditional uses, chemical constituents, and pharmacological activities research progress, hopefully to provide a reference for clarification of its pharmacological active ingredients.


Subject(s)
Drugs, Chinese Herbal , Terminalia , Flavonoids , Medicine, Tibetan Traditional , Tibet
8.
Nat Prod Res ; 34(23): 3313-3319, 2020 Dec.
Article in English | MEDLINE | ID: mdl-30810367

ABSTRACT

A new pentacyclic triterpenoid, 3-oxo-urs-11,13(18)-dien-28-oic acid (1), along with twelve known triterpenoids, α-amyrin (2), 19α-hydroxy-α-amyrin (3), triptohypol E (4), uvaol (5), 2α,3α-dihydroxyurs-11-en-13ß,28-olide (6), 3ß-hydroxyurs-11-en-13ß,28-olide (7), ursolic acid (8), asiatic acid (9), oleanolic acid (10), aegiceradienol (11), obtusalin (12) and betulinic acid (13) were isolated from the leaves of Rhododendron dauricum L. Their structures were established from spectroscopic data and comparison with reported values. Among them, compounds 3, 4, 6, 7 and 11 were isolated from the Ericaceae family for the first time. Compounds 2, 5, 9, 12 and 13 were obtained from R. dauricum for the first time. Additionally, compounds 6, 10 and 11 significantly inhibited the levels of NO in LPS-stimulated RAW 264.7 cells at 3 µM.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Nitric Oxide/biosynthesis , Rhododendron/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Drug Evaluation, Preclinical , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Oleanolic Acid/analysis , Pentacyclic Triterpenes/analysis , Plant Extracts/chemistry , Plant Leaves/chemistry , RAW 264.7 Cells , Triterpenes/analysis , Betulinic Acid , Ursolic Acid
9.
Nat Prod Res ; 34(2): 225-232, 2020 Jan.
Article in English | MEDLINE | ID: mdl-30580619

ABSTRACT

One new aryldihydronaphthalene-type lignan (1) together with eight known lignans (2-4, 7-11) as well as two caffeic-acid dimers (5, 6) were isolated from an ethanol extract of the whole plant of Corispermum mongolicum Iljin (Chenopodiaceae). The chemical structures of these compounds were determined from 1D and 2D NMR and HR-ESI-MS spectra, and results were compared with data from the literature. This study is the first demonstration of nine compounds (2 and 4-11) isolated from the Chenopodiaceae family, with one of these (3) from the genus Corispermum. Anti-inflammatory effects of the isolated compounds were evaluated in terms of inhibition of production of nitric oxide, tumour necrosis factor-α, and interleukin-6 in lipopolysaccharide-induced RAW 264.7 cells.


Subject(s)
Anti-Inflammatory Agents/isolation & purification , Chenopodiaceae/chemistry , Lignans/isolation & purification , Plant Extracts/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Chenopodiaceae/metabolism , Interleukin-6/biosynthesis , Lignans/chemistry , Lignans/pharmacology , Lipopolysaccharides , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/drug effects
10.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3830-3836, 2019 Sep.
Article in Chinese | MEDLINE | ID: mdl-31602960

ABSTRACT

The peeled root,stem or twig of Syringa pinnatifolia is a representative Mongolian folk medicine with the effects of antidepression and pain relief. It has been used for the treatments of heart tingling,heart palpitations,upset,insomnia and other symptoms. Inspired by Mongolian medical theory and clinical practices,this study evaluated the analgesic effect of S. pinnatifolia ethanol extract( T) through three analgesic models including acetic acid writhing test,formalin test,and hot plate test,and the sedative effect of T was evaluated by locomotor activity and synergistic sleeping experiments,and furthermore the effects of T on the GABAergic nervous system were investigated by ELISA,immunohistochemistry,Western blot,and PCR methods. The results showed that T can significantly reduce the number of writhing,the time of paw licking and extend the thermal threshold of mice,suggesting the analgesic effect of T.T also can indicate its sedative effect by reducing the number of activities,decreasing latency of sleeping and extending sleeping time of mice. ELISA results showed that T can increase the content of GABA/Glu in rat cortex,hippocampus,and hypothalamus,and the most significant increase in hypothalamus. The immunohistochemistry and Western blot results showed that T can up-regulate the expression of GAD67 protein in hypothalamus,and the PCR results showed that T can up-regulate the expression of GABAA Rα1,α2,α3,α5,ß1-3,γ1-3 genes,suggesting a sedative effect through the GABAergic nervous system. In conclusion,this study shed insight into the theoretical basis and clinical application of S. pinnatifolia,and also provides inspiration for subsequent development and application.


Subject(s)
Analgesics/pharmacology , Hypnotics and Sedatives/pharmacology , Plant Extracts/pharmacology , Syringa/chemistry , Animals , Medicine, Mongolian Traditional , Mice , Pain , Rats
11.
Planta Med ; 84(8): 536-543, 2018 May.
Article in English | MEDLINE | ID: mdl-29202512

ABSTRACT

Nardostachys jatamansi is a well-documented herbal agent used to treat digestive and neuropsychiatric disorders in oriental medicinal systems. However, few simple, rapid, and comprehensive methods were reported for quality assessment and control of N. jatamansi. Herein, a UPLC with photodiode array detection method was developed for both fingerprint investigation of N. jatamansi and simultaneous quantitative analysis of the six serotonin transporter modulatory constituents in N. jatamansi. For chromatographic fingerprinting, 24 common peaks were selected as characteristic peaks to assess the consistency of N. jatamansi samples from different retail sources. Six of the common peaks (5, 7, 12: , and 16:  - 18: ) were identified as desoxo-narchinol A, buddleoside, isonardosinone, nardosinone, kanshone H, and (-)-aristolone, respectively, by phytochemical investigation. Five of the six compounds significantly either enhanced or inhibited serotonin transporter activity, while (-)-aristolone (18: ) didn't show any serotonin transporter activity. In quantitative analysis, the six compounds showed good linearity (r > 0.999) within test ranges. The precision, expressed as relative standard deviation, was in the range of 0.25 - 2.77%, and the recovery of the method was in the range of 92 - 105%. The UPLC-photodiode array detection-based fingerprint analysis and quantitative methods reported here could be used for routine quality control of N. jatamansi.


Subject(s)
Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Nardostachys/chemistry , Quality Control
12.
Pathol Res Pract ; 211(12): 948-54, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26471217

ABSTRACT

Rhizoma Paridis saponins combined with turmeric (RT) showed well anti-hepatocarcinoma activities in our previous research. The aim of this study was to investigate the progression of the biochemical response to RT and capture metabolic variations during intragastric administration of their compatibility. In the experiment, histopathological examination and (1)H NMR method were developed and validated for the metabolic profiling of RT intervention in H22 tumor growth. Data were analyzed with principal components analysis (PCA) and partial least-squares discrimination analysis (PLS-DA). As a result, Rhizoma paridis saponins (RPS) or RT induced inflammatory cell infiltration in tumors. RT also mediated the tumor microenvironment to promote anti-tumor immunity of mice. RT significantly inhibited tumor growth rate through suppressing levels of amino acids containing alanine, asparagine, glutamine, putrescine, and sarcosine, lipid compounds, and carbohydrates like myo-inositol and arabinose in the tumor tissues. In conclusion, these results uncovered unexpectedly poor nutritional conditions in the RT-treated tumor tissues whose effect was stronger than RPS's. Therefore, RT could be a novel anticancer agent that targets on cancer metabolism through starving tumors reducing viability of cancer cells.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/pathology , Curcuma , Liver Neoplasms/pathology , Plant Extracts/pharmacology , Saponins/pharmacology , Animals , Disease Models, Animal , Female , Magnetic Resonance Spectroscopy , Mice , Phytotherapy/methods , Principal Component Analysis , Rhizome
13.
Planta Med ; 77(14): 1631-8, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21484673

ABSTRACT

Phytochemical investigation of the EtOH extract of the leaves of Erythrophleum fordii led to the isolation of two oleanane-type triterpene saponins (1-2) and five cassaine-type diterpenoids (4-8) along with one known methyl 3 ß-hydroxy-erythrosuamate (3). Their structures were established by extensive NMR, as well as ESI-MS analyses and acid hydrolysis. Biological evaluation of compounds 3- 8 against five human cancer cell lines revealed that compounds 5-7 exhibited potent cytotoxic activity with IC50 values ranging from 1.51 to 8.68 µM.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Drugs, Chinese Herbal/chemistry , Fabaceae/chemistry , Oleanolic Acid/pharmacology , Abietanes , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Survival , Diterpenes/chemistry , Diterpenes/isolation & purification , Drug Screening Assays, Antitumor , Female , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Humans , Magnetic Resonance Spectroscopy , Medicine, Chinese Traditional , Molecular Structure , Oleanolic Acid/chemistry , Oleanolic Acid/isolation & purification , Plant Leaves/chemistry , Plants, Medicinal/chemistry , Saponins/chemistry , Saponins/isolation & purification , Saponins/pharmacology
14.
Phytochemistry ; 71(14-15): 1749-55, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20678783

ABSTRACT

Detailed phytochemical investigation from the leaves of Erythrophleum fordii resulted in the isolation of 13 compounds, including three cassaine diterpenoid-diterpenoid amide dimers (1, 3 and 5), and seven cassaine diterpenoid amides (6 and 8-13), together with three previously reported ones, erythrophlesins D (2), C (4) and 3beta-hydroxynorerythrosuamide (7). Compounds 1, 3 and 5 are further additions to the small group of cassaine diterpenoid dimers represented by erythrophlesins A-D. Their structures were determined by analysis of extensive one- and two-dimensional NMR experiments and ESIMS methods. Cytotoxic activities of the isolated compounds were tested against HCT-8, Bel-7402, BGC-823, A549 and A2780 human cancer cell lines in the MTT test. Results showed that compounds 1 and 3-5 exhibited significantly selective cytotoxic activities (IC(50)<10 microM) against these cells, respectively.


Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Amides/isolation & purification , Amides/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/isolation & purification , Diterpenes/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Fabaceae/chemistry , Abietanes , Alkaloids/chemistry , Amides/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Diterpenes/chemistry , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Leaves/chemistry
15.
J Nat Prod ; 73(5): 818-24, 2010 May 28.
Article in English | MEDLINE | ID: mdl-20411974

ABSTRACT

Five new neolignans (1-4 and 9), two pairs of neolignan epimers (5-8), and two new aromatic glycosides (10 and 11) have been isolated from the stem bark of Illicium difengpi. Their structures were determined by spectroscopic methods, including 1D and 2D NMR, HRESIMS, CD experiments, and chemical methods. The absolute configurations of the 3,4-diol moiety in 1 and 1,3-diol moiety in 2 were confirmed by Snatzke's method, observing the induced circular dichroism after addition of dimolybdenum tetraacetate in DMSO. Compounds 3, 4, and 11 exhibited moderate anti-inflammatory activities with IC(50) values ranging from 1.62 to 24.4 microM, while compound 3 displayed antioxidant activity with an IC(50) value of 42.3 microM.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Illicium/chemistry , Lignans/isolation & purification , Plants, Medicinal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Glycosides/chemistry , Inhibitory Concentration 50 , Lignans/chemistry , Lignans/pharmacology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Bark/chemistry , Plant Stems/chemistry , Stereoisomerism
16.
Hypertension ; 43(5): 993-1002, 2004 May.
Article in English | MEDLINE | ID: mdl-15007034

ABSTRACT

The metabolic syndrome is a common precursor of cardiovascular disease and type 2 diabetes that is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood pressure. In humans, mutations in the peroxisome proliferator-activated receptor-gamma (PPARgamma) have been reported to cause the full-blown metabolic syndrome, and drugs that activate PPARgamma have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes. Here we report that telmisartan, a structurally unique angiotensin II receptor antagonist used for the treatment of hypertension, can function as a partial agonist of PPARgamma; influence the expression of PPARgamma target genes involved in carbohydrate and lipid metabolism; and reduce glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet. None of the other commercially available angiotensin II receptor antagonists appeared to activate PPARgamma when tested at concentrations typically achieved in plasma with conventional oral dosing. In contrast to ordinary antihypertensive and antidiabetic agents, molecules that can simultaneously block the angiotensin II receptor and activate PPARgamma have the potential to treat both hemodynamic and biochemical features of the metabolic syndrome and could provide unique opportunities for the prevention and treatment of diabetes and cardiovascular disease in high-risk populations.


Subject(s)
Angiotensin II Type 1 Receptor Blockers , Benzimidazoles/pharmacology , Benzoates/pharmacology , Receptors, Cytoplasmic and Nuclear/agonists , Transcription Factors/agonists , Adipocytes/drug effects , Animals , Benzimidazoles/chemistry , Benzoates/chemistry , Biphenyl Compounds/pharmacology , Blood Glucose/analysis , Cell Differentiation/drug effects , Cells, Cultured/drug effects , Chlorocebus aethiops , Drug Evaluation, Preclinical , Gene Expression Regulation/drug effects , Imidazoles/pharmacology , Insulin/blood , Irbesartan , Losartan/pharmacology , Male , Mice , Models, Molecular , Myoblasts/drug effects , Protein Conformation/drug effects , Rats , Rats, Sprague-Dawley , Receptors, Cytoplasmic and Nuclear/chemistry , Receptors, Cytoplasmic and Nuclear/genetics , Rosiglitazone , Structure-Activity Relationship , Telmisartan , Tetrazoles/pharmacology , Thiazoles/pharmacology , Thiazolidinediones/pharmacology , Thiazolidines , Transcription Factors/chemistry , Transcription Factors/genetics , Triglycerides/blood , Valine/analogs & derivatives , Valine/pharmacology , Valsartan , Weight Gain/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL