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Aim: To construct a prediction model for adverse pregnancy outcomes of preeclampsia (PE). Thus assisting clinicians to identify high-risk patients. Provide guidance for treatment intervention. Methods: A retrospective study was conducted on 319 PE patients admitted to the Huzhou Maternal and Child Health Hospital from April 2021 to December 2022, The patients were divided into an adverse group (93 cases) and a non-adverse group (226 cases) based on whether they had adverse pregnancy outcomes after admission. Collect clinical data from patients, using a single factor analysis to screen statistically significant indicators as input variables, the outcome of the analysis is dependent on the incidence of PE adverse pregnancy outcomes. Divide patients into training and testing sets in a 7:3 ratio, Logistic regression model and random forest model were constructed respectively. Evaluate the predictive performance of two statistical models. Results: Among the 319 PE patients included 93 had adverse pregnancy outcomes after admission. Among them, Age (OR: 1.702, 95%CI: 1.069~2.710), small gestational age (OR: 0.757,95%CI: 0.607~0.945), more clinical symptoms (OR: 3.618, 95%CI: 1.682~7.783), high 24 h proteinuria (OR: 2.532, 95%CI: 1.290~4.968), low PLT index (OR: 0.616, 95%CI: 0.419~0.906), high AST index (OR: 1.554, 95%CI: 1.012~2.387), high D-Dimer index (OR:1.966, 95%CI: 1.183~3.267) were the influencing factors of adverse pregnancy outcomes in PE patients. The test set found that the random forest model was superior to the Logistic regression model in predicting the risk of adverse pregnancy outcomes in PE patients. Conclusions: The random forest model has good stability in predicting the risk of adverse pregnancy outcomes in PE, and its prediction efficiency is better than the Logistic regression model.
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Pré-Eclâmpsia , Resultado da Gravidez , Feminino , Criança , Gravidez , Humanos , Resultado da Gravidez/epidemiologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/diagnóstico , Algoritmo Florestas Aleatórias , Estudos Retrospectivos , Modelos LogísticosRESUMO
Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.
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Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.
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Cardiopatias , Insuficiência Cardíaca , Animais , Medicina Tradicional Chinesa , Doença Crônica , Modelos AnimaisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic fibrosis is a major consequence of liver disease. Radix Paeoniae Rubra (RPR), the dry root of Paeonia lactiflora Pall., has a long history of clinical application in traditional Chinese medicine (TCM) for the treatment of liver diseases. The researches of RPR active ingredients are mainly focused on paeoniflorin. However, the functional roles of other ingredients have not been clarified sufficiently in the treatment of hepatic fibrosis with RPR. AIM OF THE STUDY: This study was to figure out the anti-hepatic fibrosis potential and mechanisms of CS-4, one of the paeoniflorin-free subfraction of RPR. MATERIALS AND METHODS: With the guide of bioassay, CS-4, a subfraction of RPR showed in vitro inhibition of hepatic stellate cell activation, was obtained using multiple chromatographic techniques. Its ingredients were determined by UPLC-Q-TOF-MS/MS. Then, the target profiles of ingredients were obtained from the HERB database, and the disease targets were collected from the DisGeNET database. Through the network pharmacology method, a protein-protein interaction network of CS-4 against hepatic fibrosis was established to analyze and excavate the potential therapeutic targets. Combined with the KEGG analysis, a series of signaling pathways were obtained, thereby validated by western blot analysis. RESULTS: The paeoniflorin-free subfraction of RPR, CS-4, was obtained and showed the most potential anti-fibrotic effect in vitro. A total of 20 main ingredients were identified from CS-4 and considered as its active ingredients. From HERB and DisGeNET databases, 1460 potential targets of CS-4 and 1180 disease targets were obtained, respectively. The overlapped 79 targets were considered to exert the potential anti-fibrosis effect of CS-4, such as JAK2, MYC, SMAD3, and IFNG. The gene enrichment analysis revealed that classical TGF-ß/Smad signaling pathway and nonclassical TGF-ß/PI3K-AKT signaling pathway may be two of the main mechanisms of CS-4 against hepatic fibrosis, which supported by western blot analysis. CONCLUSION: In this study, a paeoniflorin-free subfraction with potential anti-hepatic fibrosis activity in vitro, CS-4, was obtained from RPR. Its multiple ingredients, multiple targets, and multiple mechanisms against hepatic fibrosis were explained by network pharmacology and verified by western blot analysis to further support the clinical applications of RPR.
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Medicamentos de Ervas Chinesas , Paeonia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Glucosídeos , Humanos , Cirrose Hepática/tratamento farmacológico , Monoterpenos , Farmacologia em Rede , Paeonia/química , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Espectrometria de Massas em Tandem/métodos , Fator de Crescimento Transformador betaRESUMO
The pharmacodynamic substances of traditional Chinese medicine(TCM) are the basis for the research of TCM and the development of innovative drugs. However, the lack of clarity of targets and molecular mechanisms is the bottleneck problem that restricts the research of pharmacodynamic substances of TCM. Bioactive components are the material basis of the efficacy of TCM, which exert activity by regulating the corresponding targets. Therefore, it is very important to identify the targets of the bioactive components to elucidate the pharmacological mechanism of TCM. Proteins are the most important drug targets, and study of the interaction between the proteins and bioactive components of TCM plays a key role in the development of pharmacological mechanism of TCM. In recent years, the main techniques for detecting the interaction between the bioactive components and proteins include surface plasmon resonance, fluorescence resonance energy transfer, bio-layer interference, molecular docking, proteome chip, target fishing, target mutant, and protein crystallization techniques, etc. This review summarized the biological target detection techniques and their applications in locating the targets of the bioactive components in TCM in the last decade, and this paper will provide useful strategies to elucidate the pharmacological mechanisms of TCM.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , ProteomaRESUMO
The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
BACKGROUND: Non-alcoholic steatohepatitis (NASH) can develop into cirrhosis, liver failure, or hepatocellular carcinoma without effective treatment. However, there are currently no drugs for NASH treatment, and the development of new therapeutics has remained a major challenge in NASH research. Advances in traditional Chinese medicine to treat liver disease inspired us to search for new NASH candidates from Chi-Shao, a widely used traditional Chinese medicine. PURPOSE: In this research, we aimed to clarify the anti-NASH effect and the underlying mechanism of isopropylidenyl anemosapogenin (IA, 1), which was a new lead compound isolated from Chi-Shao. STUDY DESIGN AND METHODS: Isopropylidenyl anemosapogenin (IA, 1) was first discovered by collagen type I α 1 promoter luciferase bioassay-guided isolation and then characterized by single crystal X-ray diffraction analysis and enriched by semi-synthesis. Using various molecular biology techniques, the multiple anti-NASH efficacies and mechanisms of IA were clarified based on in vitro LX-2 and Huh7 cell models, along with the in vivo choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model and bile duct ligation (BDL)-induced rat model. The UPLC-MS/MS method was used to assess the plasma concentration of IA. RESULTS: A new lead compound IA was isolated from the traditional Chinese medicine Chi-Shao, which showed significant anti-liver fibrosis activity in TGF-ß1-treated LX-2 cells and anti-liver steatosis activity in oleic acid-treated Huh7 cells. Furthermore, IA could significantly ameliorate in vivo CDAHFD-induced liver injury by activating the farnesoid X receptor pathway, including its targets Nr0b2, Abcb11, and Slc10a2. Simultaneously, IA activated the autophagy pathway by activating the TFEB factor, thereby promoting lipid degradation. Its liver-protective and anti-fibrosis activities were verified by the BDL-induced rat model. Finally, with an oral administration of 100 mg/kg, IA achieved the maximum plasma concentration of 1.23 ± 0.18 µg/ml at 2.67 ± 0.58 h. CONCLUSION: IA, an unreported lupine-type triterpenoid isolated from Chi-shao, can significantly alleviate liver injury and fibrosis via farnesoid X receptor activation and TFEB-mediated autophagy, which indicates that IA could serve as a novel therapeutic candidate against NASH.
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Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Cromatografia Líquida , Modelos Animais de Doenças , Fibrose , Fígado , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ratos , Espectrometria de Massas em TandemRESUMO
Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 µmol·-1.
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Lignanas , Paeonia , Cromatografia Líquida de Alta Pressão , Humanos , Lignanas/química , Raízes de Plantas/química , EstereoisomerismoRESUMO
In a continuing search for biological natural products with structure diversity from traditional Chinese herbs, five new sesquineolignans (1-5) were isolated from an ethyl acetate extract of the twigs of Litsea cubeba. Their structures were elucidated based on MS, 1D and 2D NMR spectroscopic data, as well as experimental electronic circular dichroism (ECD) spectra. Compounds 1-5 showed moderate inhibitory effects against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 16.2, 20.2, 22.1, 15.1, and 16.6 µmol·L-1, respectively.
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Litsea , Macrófagos , Estrutura MolecularRESUMO
A new phenolic acid ester, 4'-hydroxyphenylethyl 4,8(R)-dihydroxyphenylpropionate(1), was isolated from an endophytic fungus Colletotrichum capsici of Paeonia lactiflora roots, along with eight known phenolic derivatives, tyrosol(2), 2-(4-hydroxyphenyl) ethyl acetate(3), methyl p-hydroxyphenylacetate(4), methyl m-hydroxyphenylacetate(5), 4-(4-hydroxyphene-thoxy)-4-oxobutanoic acid(6), 4-hydroxyphenethyl methyl succinate(7), trichodenol B(8) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl) acetate(9). Their structures were identified by a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) spectroscopy, ultraviolet(UV) spectroscopy and electronic circular dichroism(ECD) spectroscopy. Compounds 2-9 were isolated from this fungus for the first time.
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Colletotrichum , Paeonia , Ésteres , HidroxibenzoatosRESUMO
According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 µmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.
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Carboxilesterase , Carboxilesterase/antagonistas & inibidores , Carboxilesterase/metabolismo , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e HidrofílicasRESUMO
Purpurolides D-F (1-3), three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system, were isolated from the endophytic fungus Penicillium purpurogenum IMM 003. Their structures were unambiguously elucidated based on extensive spectroscopic data analyses, 13C NMR chemical shifts calculations coupled with the DP4+ probability method, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase (PL). The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.
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Lipase/antagonistas & inibidores , Penicillium/química , Penicillium/isolamento & purificação , Sesquiterpenos/química , Linhagem Celular Tumoral , Humanos , Estrutura MolecularRESUMO
Pain is a protective defense response of the body to harmful stimuli. Long-term pain not only seriously affects the body of the patient and brings great pain to the patient, but also brings huge economic burden to the patient's family and society. It has become one of the most serious problems affecting human health. At present, opioids and non-steroidal anti-inflammatory drugs(NSAIDs) are commonly used as painkillers, but they tend to cause a variety of adverse reactions or risk of addiction. To find and develop new analgesic drugs, which are safer and more effective, has become the hot spot and difficulty in medical research. A variety of alkaloids derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical analgesic medicines. Various alkaloids have been proved to have good analgesic effects, such as morphine and the related to opioids, the main analgesic active components from Corydalis Rhizoma and Aconiti Lateralis Radix Praeparata. Here we summarized the research progress of natural alkaloids with analgesic activity, in order to provide reference for the research and development of analgesic drugs based on natural products.
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Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Analgésicos , Humanos , RizomaRESUMO
Pain is a complex, unpleasant feeling and emotional experience associated with actual or potential tissue damage, and manifests itself in certain autonomous psychological and behavioral responses. The commonly used opioid and non-steroidal anti-inflammatory analgesics(NSAIDs) may cause adverse reactions to the kidney, liver, cardiovascular or gastrointestinal system and cause problems of drug abuse. Therefore, it is necessary to study new analgesic drugs with less side effects and significant analgesic effects. A variety of natural products derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical medicines and provide an inexhaustible resource for the development and innovation of modern medicines. Therefore, this paper mainly reviews the natural non-alkaloids with analgesic activity in order to provide reference for the research and development of analgesic drugs derived from natural products.
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Analgésicos , Produtos Biológicos , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Dor/tratamento farmacológicoRESUMO
Chemical investigation on the constituents of the ethyl acetate soluble extraction of Litsea cubeba has resulted in the isolation and structure elucidation of thirty compounds, including one sesquiterpene(1), four monoterpenes(2-5), two γ-butyrolactone derivatives(6 and 7), seven tyramine derivatives(8-14), fifteen aromatic compounds(15-29), and one pyrone derivative(30) via various chromatographic techniques and spectroscopic data analysis(MS, IR, 1 D and 2 D NMR). Compounds 1-7, 13 and 14 were obtained from the genus Litsea for the first time.
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Litsea , Sesquiterpenos , Acetatos , MonoterpenosRESUMO
Litsea cubeba, an important medicinal plant, is widely used as a traditional Chinese medicine and spice. Using cytotoxicity-guided fractionation, nine new lignans 1â»9 and ten known analogues 10â»19 were obtained from the EtOH extract of the twigs of L. cubeba. Their structures were assigned by extensive 1D- and 2D-NMR experiments, and the absolute configurations were resolved by specific rotation and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. In the cytotoxicity assay, 7',9-epoxylignans with feruloyl or cinnamoyl groups (compounds 7â»9, 13 and 14) were selectively cytotoxic against NCI-H1650 cell line, while the dibenzylbutyrolactone lignans 17â»19 exerted cytotoxicities against HCT-116 and A2780 cell lines. The results highlighted the structure-activity relationship importance of a feruloyl or a cinnamoyl moiety at C-9' or/and C-7 ketone in 7',9-epoxylignans. Furthermore, compound 11 was moderate active toward protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 13.5 µM, and compounds 4â»6, 11 and 12 displayed inhibitory activity against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 46.8, 50.1, 58.6, 47.5, and 66.5 µM, respectively.
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Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Lignanas/isolamento & purificação , Lipopolissacarídeos/efeitos adversos , Litsea/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Regulação para Baixo , Células HCT116 , Humanos , Lignanas/química , Lignanas/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
Dihydrochelerythrine was isolated from the ethanol extract of Corydalis yanhusuo by chromatographic and recrystallization techniques. To our knowledge, this is the first report that dihydrochelerythrine was found to be unstable. The NMR, HPLC, and LC-MS were applied to monitor the structural conversion process of dihydrochelerythrine. The results showed that when dissolved in polar deuteration solvent (e.g., DMSO-d6 & MeOD), dihydrochelerythrine is directly converted to chelerythrine gradually. However, if used non-polar reagent (e.g.,CD2Cl2), the sample of dihydrochelerythrine undergoes the formation of pseudobase, chelerythrine, and bimolecular ether then followed by oxidation to oxychelerythrine as the major final product. Which leads to this phenomenon maybe is that the C-6 in dihydrochelerythrine is highly reactive to nucleophiles, and is easily converted to different derivatives in different solvents attributed to the solvent effect. This finding will contribute to the extraction and isolation, bioactivity screening, and quality evaluation of medicinal materials containing dihydrochelerythrine and other similar derivatives.
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Benzofenantridinas/química , Corydalis/química , Extratos Vegetais/química , Solventes/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em TandemRESUMO
Nineteen compounds were isolated from the water-soluble extract of the dry roots of Paeonia lactiflora by using various chromatographic techniques. Their structures were identified by MSï¼ NMR and other spectroscopic analysis as paeoniflorin(1)ï¼ 4-O-ethylpaeoniflorin(2)ï¼ 2'-O-benzoylpaeoniflorin(3)ï¼ benzoylpaeoniflorin(4)ï¼ 4"-hydroxy-benzoyloxypaeoniflorin(5)ï¼ moudanpioside C(6)ï¼ 6'-O-benzoyl-4"-hydroxy-3"-methoxy-paeoniflorin(7)ï¼ paeoniflorin B(8)ï¼ 6-O-benzoylalbiflorin(9)ï¼ secoisolariciresinol (10)ï¼ (+)-lyoniresinol(11)ï¼ dihyrodehydrodiconiferyl alcohol(12)ï¼ (7Sï¼8S)-threo-7ï¼9ï¼9'-trihydroxy-3ï¼3'-dimethoxy-8-O-4'-neolignan(13)ï¼ (+)-neo-olivil (14)ï¼ [(3S)-5-methyl-2ï¼3-dihydro-1-benzofuran-3-yl]methanol(15)ï¼ 5-hydroxy-3S-hydroxymethyl-6-methyl-2ï¼3-dihydrobenzofuran(16)ï¼ (+)-(R)-2-hydroxy-1-(4-methoxyphenyl)-1-propan-1-one(17)ï¼ (+)-(2R)-1-(4-hydroxy-3-methoxyphenyl)-2-propanol(18)ï¼ (+)-(4S)-(2E)-4-hydroxy-2-nonenoic acid(19). Compounds 15 and 18 are new natural productsï¼ while compounds 10ï¼ 11ï¼ 13ï¼ 14ï¼ 17 and 19 are isolated from the genus Paeonia for the first time.
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Paeonia , Monoterpenos , Extratos Vegetais , Raízes de Plantas , ÁguaRESUMO
Ischemic brain injury impacts cardiac dysfunction depending on the part of the brain affected, with a manifestation of irregular blood pressure, arrhythmia, and heart failure. Generally called brain-heart syndrome in traditional Chinese medicine, few mechanistic understanding and treatment options are available at present. We hypothesize that considering the established efficacy for both ischemic stroke and myocardial infarction (MI), Danhong injection (DHI), a multicomponent Chinese patent medicine, may have a dual pharmacological potential for treating the brain-heart syndrome caused by cerebral ischemic stroke through its multi-targeted mechanisms. We investigated the role of DHI in the setting of brain-heart syndrome and determined the mechanism by which it regulates this process. We induced Ischemia/Reperfusion in Wistar rats and administered intravenous dose of DHI twice daily for 14 days. We assessed the neurological state, infarct volume, CT scan, arterial blood pressure, heart rhythm, and the hemodynamics. We harvested the brain and heart tissues for immunohistochemistry and western blot analyses. Our data show that DHI exerts potent anti-stroke effects (infarct volume reduction: ∗∗p < 0.01 and ∗∗∗p < 0.001 vs. vehicle. Neurological deficit correction: ∗p < 0.05 and ∗∗∗p < 0.001 vs. vehicle), and effectively reversed the abnormal arterial pressure (∗p < 0.05 vs. vehicle) and heart rhythm (∗∗p < 0.01 vs. vehicle). The phenotype of this brain-heart syndrome is strikingly similar to those of MI model. Quantitative assessment of hemodynamic in cardiac functionality revealed a positive uniformity in the PV-loop after administration with DHI and valsartan in the latter. Immunohistochemistry and western blot results showed the inhibitory effect of DHI on the ß-adrenergic pathway as well as protein kinase C epsilon (PKCε) (∗∗p < 0.01 vs. model). Our data showed the underlying mechanisms of the brain-heart interaction and offer the first evidence that DHI targets the adrenergic pathway to modulate cardiac function in the setting of brain-heart syndrome. This study has made a novel discovery for proper application of the multi-target DHI and could serve as a therapeutic option in the setting of brain-heart syndrome.
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Fractionation of an aqueous extract of the air-dried roots of a traditional Chinese medicinal plant, Paeonia lactiflora, yielded the new monoterpenoid glycosides 1-10. Their structures were assigned via spectroscopic techniques, and the absolute configurations of 1, 4-6, and 8 were verified via chemical methods, specific rotation, and electronic circular dichroism data. Compounds 1-4 are rare compared to the reported cage-like paeoniflorin derivatives; that is, they comprised two monoterpenoidal moieties. In the in vitro assay, compounds 5, 8, and 9 showed weak inhibitions against lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages, with IC50 values of 64.8, 60.1, and 97.5 µM, respectively.