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1.
Food Chem ; 446: 138891, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38432135

RESUMO

Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1-34), tannins (35-98), flavonoids (99-141), sterols (142-159), triterpenoids (160-175), lignans (176-183), alkaloids (184-197), alkanes (198-212), aromatic micromolecules (213-222), other compounds (223-239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future.


Assuntos
Botânica , Phyllanthus emblica , Plantas Medicinais , Phyllanthus emblica/química , Extratos Vegetais/química , Compostos Fitoquímicos , Etnofarmacologia
2.
Food Funct ; 14(22): 9974-9998, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37916682

RESUMO

Lycopene is an important pigment with an alkene skeleton from Lycopersicon esculentum, which is also obtained from some red fruits and vegetables. Lycopene is used in the food field with rich functions and serves in the medical field with multiple clinical values because it has dual functions of both medicine and food. It was found that lycopene was mainly isolated by solvent extraction, ultrasonic-assisted extraction, supercritical fluid extraction, high-intensity pulsed electric field-assisted extraction, enzymatic-assisted extraction, and microwave-assisted extraction. Meanwhile, it was also obtained via 2 synthetic pathways: chemical synthesis and biosynthesis. Pharmacological studies revealed that lycopene has anti-oxidant, hypolipidemic, anti-cancer, immunity-enhancing, hepatoprotective, hypoglycemic, cardiovascular-protective, anti-inflammatory, neuroprotective, and osteoporosis-inhibiting effects. The application of lycopene mainly includes food processing, animal breeding, and medical cosmetology fields. It is hoped that this review will provide some useful information and guidance for future study and exploitation of lycopene.


Assuntos
Carotenoides , Solanum lycopersicum , Licopeno/farmacologia , Licopeno/análise , Carotenoides/química , Antioxidantes/farmacologia , Antioxidantes/análise , Frutas/química
3.
Phytomedicine ; 115: 154831, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37094423

RESUMO

BACKGROUND: The intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue. PURPOSE: A new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed. METHOD: Platycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking. RESULTS: Results showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-ß-d-glucopyranosyl platycodigenin, 3-O-ß-d-glucopyranosyl isoplatycodigenin, 7­hydroxyl-3-O-ß-d-glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism. CONCLUSION: The proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity.


Assuntos
Antitussígenos , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Expectorantes , Citocromo P-450 CYP2C9 , Citocromo P-450 CYP2D6 , Ácido Linoleico , Farmacologia em Rede , Metabolômica/métodos , Glicerofosfolipídeos
4.
J Agric Food Chem ; 71(12): 4769-4788, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36930583

RESUMO

Hippophae rhamnoides L. (sea buckthorn), consumed as a food and health supplement worldwide, has rich nutritional and medicinal properties. Different parts of H. rhamnoides L. were used in traditional Chinese medicines for relieving cough, aiding digestion, invigorating blood circulation, and alleviating pain since ancient times. Phytochemical studies revealed a wide variety of phytonutrients, including nutritional components (proteins, minerals, vitamins, etc.) and functional components like flavonoids (1-99), lignans (100-143), volatile oils (144-207), tannins (208-230), terpenoids (231-260), steroids (261-270), organic acids (271-297), and alkaloids (298-305). The pharmacological studies revealed that some crude extracts or compounds of H. rhamnoides L. demonstrated various health benefits, such as anti-inflammatory, antioxidant, hepatoprotective, anticardiovascular disease, anticancer, hypoglycemic, hypolipidemic, neuroprotective, antibacterial activities, and their effective doses and experimental models were summarized and analyzed in this paper. The quality markers (Q-markers) of H. rhamnoides L. were predicted and analyzed based on protobotanical phylogeny, traditional medicinal properties, expanded efficacy, pharmacokinetics and metabolism, and component testability. The applications of H. rhamnoides L. in juice, wine, oil, ferment, and yogurt were also summarized and future prospects were examined in this review. However, the mechanism and structure-activity relationship of some active compounds are not clear, and quality control and potential toxicity are worth further study in the future.


Assuntos
Botânica , Hippophae , Óleos Voláteis , Hippophae/química , Compostos Fitoquímicos/farmacologia , Antioxidantes
5.
Nat Prod Res ; 37(4): 551-559, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35574640

RESUMO

Three new compounds, 4,5,6,7-tetramethoxy-3-benzoylbenzofuran (1), 4-hydroxy-3,5,6-trimethoxydihydrochalcone-2-O-ß-D-glucopyranoside (2) and 2-hydroxy-3,4,5,6-tetramethoxyphenylethyl benzoate (3) along with five known flavonoids were isolated from the dichloromethane fraction of the stems of Fissistigma acuminatissimum Merr.'s ethanol extracts. The compounds were obtained by chromatographic methods and the structure elucidation was completed primarily on the basis of spectroscopic analyses, all of these compounds were isolated from F. acuminatissimum for the first time. All the fractions and compounds were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) production in RAW264.7 cells in vitro. The dichloromethane fraction showed the most potent inhibition(38.2%) at 60 µg/mL, compound 1 (70.2%) and 3 (65.2%) showed significant inhibition at 10 µM.


Assuntos
Annonaceae , Annonaceae/química , Cloreto de Metileno , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Flavonoides/farmacologia , Flavonoides/química
6.
J Nat Prod ; 84(10): 2664-2674, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34546050

RESUMO

Biotransformation of betulonic acid (1) by Rhizopus arrhizus CGMCC 3.868 resulted in the production of 16 new (3, 5, 6, and 9-21) and five known compounds. Structures of the new compounds were established by analysis of spectroscopic data. Hydroxylation, acetylation, oxygenation, glycosylation, and addition reactions involved the C-20-C-29 double bond. Antineuroinflammatory activities of the obtained compounds in NO production were tested in lipopolysaccharides-induced BV-2 cells. Compared with the substrate betulonic acid, biotransformation products 3, 8, 9, 14, and 21 exhibited an improved inhibitory effect, with IC50 values of 10.26, 11.09, 5.38, 1.55, and 4.69 µM, lower than that of the positive control, NG-monomethyl-l-arginine.


Assuntos
Anti-Inflamatórios/farmacologia , Biotransformação , Ácido Oleanólico/análogos & derivados , Rhizopus oryzae/metabolismo , Acetilação , Animais , Linhagem Celular , Glicosilação , Hidroxilação , Camundongos , Estrutura Molecular , Neuroglia/efeitos dos fármacos , Óxido Nítrico , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia
7.
Trials ; 22(1): 485, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34496928

RESUMO

BACKGROUND: Insomnia is a common but frequently overlooked sleep disorder after stroke, and there are limited effective therapies for insomnia following stroke. Traditional Chinese medicine (TCM), including acupuncture and the Chinese herbal medication (CHM) Suanzaoren decoction (SZRD), has been reported as an alternative option for insomnia relief after stroke in China for thousands of years. Here, this study aims to investigate the efficacy and safety of electroacupuncture (EA) in combination with SZRD in the treatment of insomnia following stroke. METHODS: A total of 240 patients with post-stroke insomnia will be included and randomized into four groups: the EA group, SZRD group, EA & SZRD group, and sham group. The same acupoints (GV20, GV24, HT7, and SP6) will be used in the EA group, EA & SZRD group, and sham group, and these patients will receive the EA treatment or sham manipulation every other day for 4 consecutive weeks. SZRD treatments will be given to participants in the SZRD group and EA & SZRD group twice a day for 4 consecutive weeks. The primary outcome measures include Pittsburgh Sleep Quality Index scores and polysomnography. Secondary outcome measures include the Insomnia Severity Index, the National Institutes of Health Stroke Scale, the Hospital Anxiety and Depression Scale, brain magnetic resonance imaging, functional magnetic resonance imaging, and nocturnal melatonin concentrations. The primary and secondary outcomes will be assessed at baseline (before treatment), during the 2nd and 4th weeks of the intervention, and at the 8th and 12th weeks of follow-up. Safety assessments will be evaluated at baseline and during the 4th week of the intervention. DISCUSSION: This study will contribute to assessing whether the combination of these two therapies is more beneficial for post-stroke insomnia than their independent use, and the results of this clinical trial will improve our understanding of the possible mechanisms underlying the effects of combination therapies. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2000031413 . Registered on March 30, 2020.


Assuntos
Eletroacupuntura , Distúrbios do Início e da Manutenção do Sono , Acidente Vascular Cerebral , Medicamentos de Ervas Chinesas , Eletroacupuntura/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
8.
J Mater Chem B ; 9(10): 2457-2461, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33630990

RESUMO

Carboxylesterase 2 (CES 2) is a key enzyme in the activation of the prodrug irinotecan (CPT-11) in the treatment against colorectal cancer and also has some relationship with the side effect of CPT-11 in clinical applications. Herein, a near infrared (NIR) fluorescent probe (DSAB) has been designed for CES 2 which possesses the advantages of prominent selectivity and high sensitivity, and DSAB has been successfully applied for the imaging of endogenous CES 2 in living cells. Moreover, a high-throughput screening method for CES 2 inhibitors has been established using DSAB and discovered four novel CES 2 inhibitors from various herbal medicines. These results fully demonstrated that DSAB is a promising molecular tool for the investigation of the biological functions of CES 2 in living systems and the discovery of novel CES 2 inhibitors for the treatment of CES 2 related physiological diseases.


Assuntos
Carboxilesterase/química , Carboxilesterase/metabolismo , Ensaios Enzimáticos/métodos , Corantes Fluorescentes/química , Raios Infravermelhos , Carboxilesterase/antagonistas & inibidores , Linhagem Celular , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Limite de Detecção
9.
Phytochemistry ; 183: 112593, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33341664

RESUMO

The roots of Euphorbia fischeriana known as "Langdu" in traditional Chinese medicine have been used for the treatment of tuberculosis in China. Through a bioactive phytochemical investigation of the roots of E. fischeriana, 15 diterpenoids were obtained by various chromatographic techniques. On the basis of wide spectroscopic data, including NMR, UV, IR, HR-ESI-MS, ECD and X-ray crystallography, all of the isolated compounds were elucidated to be ent-abietane diterpenoid analogs, including undescribed eupholides A-H and seven known diterpenoids. In the bioassay for anti-tuberculosis, eupholides F-H moderately inhibited the proliferation of Mycobacterium tuberculosis H37Ra, with the MIC determined to be 50 µM. Furthermore, eupholides G, ent-11α-hydroxyabieta-8(14), 13(15)-dien-16,12α-olide, and jolkinolide F significantly inhibited the lyase activity of human carboxylesterase 2 (HCE 2), with IC50 values of 7.3, 150, and 34.5 nM, respectively.


Assuntos
Antineoplásicos Fitogênicos , Euphorbia , Abietanos/farmacologia , China , Diterpenos/farmacologia , Estrutura Molecular , Raízes de Plantas
10.
Phytomedicine ; 81: 153436, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360346

RESUMO

BACKGROUND: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain. PURPOSE: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE). STUDY DESIGN AND METHODS: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system. RESULTS: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 µg/ml. CONCLUSION: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Uncaria/química , Hormônio Adrenocorticotrópico/sangue , Animais , Antidepressivos/química , Biologia Computacional , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Depressão/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Receptor 5-HT1A de Serotonina , Serotonina/metabolismo , Estresse Psicológico
11.
Int J Biol Macromol ; 167: 1262-1272, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189757

RESUMO

Carboxylesterase 2 (CES 2), plays a pivotal role in endobiotic homeostasis and xenobiotic metabolism. Protostanes, the major constituents of the genus Alisma, display a series of pharmacological activities. Despite the extensive studies of pharmacological activities, the investigation on inhibitory effects of protostanes against CES 2 is rarely reported. In this study, the inhibitory activities of a library of protostanes (1-25) against human CES 2 were investigated for the first time, using 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB) as the specific fluorescent probe for human CES 2. Compounds 1, 2, 7, 8, 12, 13, 18, 19, and 25 showed strong inhibitory effects towards CES 2. For the most potent compounds 1, 7, 13, and 25, the inhibition kinetics were further investigated, and these four protostanes were all uncompetitive inhibitors against human CES 2 with the inhibition constant (Ki) values ranging from 0.89 µM to 2.83 µM. In addition, molecular docking and molecular dynamics stimulation were employed to analyze the potential interactions between these protostanes and CES 2, and amino acid residue Gln422 was identified to play a crucial role in the strong inhibition of protostanes towards CES 2.


Assuntos
Alisma/química , Carboxilesterase/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Acridinas/química , Benzoatos/química , Corantes Fluorescentes/química , Concentração Inibidora 50 , Cinética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Estrutura-Atividade
12.
Fitoterapia ; 146: 104716, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32866541

RESUMO

A phytochemical investigation on the MeOH extract of the red alga Laurencia composita Yamada led to the discovery of six new highly halogenated sesquiterpenoids, including two bisabolane-type sesquiterpenoids (1 and 2), one nerolidol derivative (7), and three chamigrane-type sesquiterpenoids (9, 10, and 18), together with 13 known sesquiterpenoids. Their structures, including relative configuration, were elucidated by extensive spectroscopic analysis, and by comparison with data for related known compounds. The absolute configuration at C-10 of laurecomposin A (1) was determined by the modified Mosher's method. Halonerolidol (7) is the first naturally occurring halogenated nerolidol derivative, while compositacin L (9) represents the third example of chamigranes having a C-10 carbonyl group. Antifungal, antibacterial, and receptor tyrosine kinase inhibitory activities of these isolates were evaluated. The results showed that compounds 1-3 and 5 exhibited significant antifungal activity against Microsporum gypseum (Cmccfmza) with MIC values of 4, 8, 8, and 4 µg/mL, respectively. Additionally, compounds 1-3 and 5 also displayed promising antibacterial activity against Gram-positive bacteria Staphylococcus aureus Newman strain with MIC values ranging from 10.9 to 26.8 µg/mL.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Laurencia/química , Sesquiterpenos/farmacologia , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Arthrodermataceae/efeitos dos fármacos , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , China , Estrutura Molecular , Proteínas Tirosina Quinases/metabolismo , Sesquiterpenos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos
13.
Eur J Med Chem ; 203: 112622, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32688203

RESUMO

Sesquiterpenoid oligomers, biogenetically assembled by at least two monomeric sesquiterpenoid units via diverse pathways, represent a unique class of natural products with distinct bioactivities. Herein, we provide a review covering the dimeric, trimeric, and tetrameric sesquiterpenoids categorized by reaction types in biosynthesis from a chemical perspective. Emphasis is focused on the biosynthetic oligomerization pathways of these interesting molecules and their related biological functions, which will supply inspiration for the total synthesis or biomimetic synthesis of more oligomeric sesquiterpenoids and further pharmacological investigations.


Assuntos
Desenho de Fármacos , Polimerização , Sesquiterpenos/química , Animais , Humanos , Sesquiterpenos/farmacologia
14.
Bioorg Chem ; 102: 104065, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32663670

RESUMO

Pulmonary fibrosis is a progressive, irreversible, and fatal fibrotic lung disease with a high mortality and morbidity, and commonly nonresponsive to conventional therapy. Inula japonica Thunb. is a traditional Chinese medicine, known as "Xuan Fu Hua" in Chinese, and has been widely applied to relieve cough and dyspnea and eliminate retained phlegm with a long history. In this study, we aimed to evaluate the anti-fibrosis effect and action mechanism of I. japonica extract (IJE) for the treatment of bleomycin (BLM)-induced pulmonary fibrosis in mice. IJE treatment significantly restored BLM-induced alterations in body weight loss and lung function decline, decreased the collagen deposition induced by BLM in lung tissues, and inhibited fibrotic and inflammatory factors, such as α-SMA, TGF-ß1, TNF-α, IL-6, COX-2, NF-κB, and GSK3ß, in a dose-dependent manner. We found that IJE could enhance the concentration of 8,9-epoxyeicosatrienoic acid (8,9-EET) and decrease concentrations of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET), 11,12-DHET, and 14,15-DHET in BLM-induced mice. Meanwhile, IJE suppressed protein and mRNA expression levels of soluble epoxide hydrolase (sEH), and significantly displayed the inhibition of sEH activity with an IC50 value of 0.98 µg/mL. Our results indicated that IJE exerted remarkable anti-fibrosis effect on BLM-induced pulmonary fibrosis in mice via inhibiting sEH activity, resulting in the regulation of GSK3ß signaling pathway. Our findings revealed the underlying action mechanism of I. japonica, and suggested that I. japonica could be regarded as a candidate resource for the treatment of pulmonary fibrosis.


Assuntos
Epóxido Hidrolases/antagonistas & inibidores , Inula/química , Medicina Tradicional Chinesa/métodos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Animais , Bleomicina/efeitos adversos , Humanos , Camundongos
15.
Int J Biol Macromol ; 159: 1022-1030, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428588

RESUMO

Cardiovascular diseases, such as hypertension and cardiac failure, have become the most major and global cause for threatening human health in recent years. Uncaria rhynchophylla as a traditional Chinese medicine is widely used to treat hypertension for a long history, whereas its medicinal effective components and potential action mechanism are uncertain. Therefore, twenty-four alkaloids (1-24) isolated from U. rhynchophylla were assayed for their relaxant effects against phenylephrine (Phe)-induced contraction of rat mesenteric arteries. Among them, we surprisingly found that uncarialin A (21) exhibited most potent relaxation effect against Phe-induced contraction (IC50 = 0.18 µM) in the manner of independent on endothelium-derived vasorelaxing factors and endothelium. All the experiments including measurement of Ca2+ in vascular smooth muscle cells (VSMCs) by fluorescence microscopy, whole-cell path clamp, molecular docking, and molecular dynamics, demonstrated that uncarialin A (21) could significantly inhibit L-type calcium channel subunit alpha-1C (Cav1.2) via the hydrogen bond interaction with amino acid residue Met1186, allowing the inhibition of Ca2+ inward current. Our results suggested that uncarialin A (21) could be served as a potential L-type Cav1.2 blocker in the effective treatment of cardiovascular diseases.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/metabolismo , Medicamentos de Ervas Chinesas/química , Vasodilatadores/farmacologia , Alcaloides/análise , Animais , Sítios de Ligação , Células CHO , Bloqueadores dos Canais de Cálcio/química , Canais de Cálcio Tipo L/química , Células Cultivadas , Cricetinae , Cricetulus , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Uncaria/química , Vasodilatadores/química
16.
Int J Biol Macromol ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32360461

RESUMO

The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat inflammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of traditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium were isolated to obtain eight compounds, including 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concentration (IC50) from 5.88 ±â€¯0.97 µM to 11.63 ±â€¯0.58 µM. The inhibition kinetics suggested that 4H-tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constant (Ki) values of 7.02 and 6.57 µM, respectively, and linoleic acid (3) was a competitive type inhibitor with a Ki values of 3.52 µM. The potential interactions of 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by molecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524.

17.
J Exp Bot ; 71(6): 1899-1914, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-31832647

RESUMO

In yam (Dioscorea spp) species, bulbils at leaf axils are the most striking species-specific axillary structure and exhibit important ecological niches. Genetic regulation underlying bulbil growth remains largely unclear so far. Here, we characterize yam (Dioscorea alata L.) bulbil development using histological analysis, and perform full transcriptional profiling on key developmental stages together with phytohormone analyses. Using the stage-specific scoring algorithm, we have identified 3451 stage-specifically expressed genes that exhibit a tight link between major transcriptional changes and stages. Co-expressed gene clusters revealed an obvious over-representation of genes associated with cell division and expansion at the initiation stage of bulbils (T1). Transcriptional changes of hormone-related genes highly coincided with hormone levels, indicating that bulbil initiation and growth are coordinately controlled by multiple phytohormones. In particular, localized auxin is transiently required to trigger bulbil initiation, and be further depleted or exported from bulbils to promote growth by up-regulation of genes involved in auxinconjugation and efflux. The sharp increase in supply of sucrose and an enhanced trehalose-6-phophate pathway at T1 were observed, suggesting that sucrose probably functions as a key signal and promotes bulbil initiation. Analysis of the expression of transcription factors (TFs) predicated 149 TFs as stage-specifically expressed; several T1-specific TFs (from Aux/IAA, E2F, MYB, and bHLH families) have been shown to play key roles in triggering bulbil formation. Together, our work provides a crucial angle for in-depth understanding of the molecular programs underlying yam's unique bulbil development processes. Stage-specific gene sets can be queried to obtain key candidates regulating bulbil growth, serving as valuable resources for further functional research.


Assuntos
Dioscorea , Dioscorea/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ácidos Indolacéticos , Folhas de Planta
18.
Zhongguo Zhong Yao Za Zhi ; 43(5): 959-963, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29676094

RESUMO

A new sesquiterpenes named glaucochinarol A (1) and a new phenylpropane glycoside named glcacochinaside A (2), together with six known ones, including trichothecolone (3), ß-D-(6-O-trans-feruloyl)fructofuranosyl-α-D-O-glucopyranoisde (4), 3,4,5-trimethoxyphenyl-ß-D-glucopyranoside (5), (4R)-p-menth-1-ene-7,8-diol-7-O-ß-D-glucopyranoside (6), naringenin (7), and emodin-8-O-ß-glucoside (8) were isolated from smilax glaucochina warb. Their structures were elucidated on the basis of NMR, MS and published data. Compounds 3-8 were isolated from the species for this first time.


Assuntos
Glicosídeos/química , Sesquiterpenos/química , Smilax/química , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Sesquiterpenos/isolamento & purificação
19.
Acta Pharm ; 68(1): 87-96, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29453916

RESUMO

Flow-injection mass spectrometry (FIMS) coupled with a chemometric method is proposed in this study to profile and distinguish between rhizomes of Smilax glabra (S. glabra) and Smilax china (S. china). The proposed method employed an electrospray-time-of-flight MS. The MS fingerprints were analyzed using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) with the aid of SIMCA software. Findings showed that the two kinds of samples perfectly fell into their own classes. Further predictive study showed desirable predictability and the tested samples were successfully and reliably identified. The study demonstrated that the proposed method could serve as a powerful tool for distinguishing between S. glabra and S. china.


Assuntos
Rizoma/química , Smilax/química , Cromatografia Líquida de Alta Pressão/métodos , Análise dos Mínimos Quadrados , Espectrometria de Massas/métodos , Análise de Componente Principal/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos
20.
Nat Prod Res ; 32(1): 91-96, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28602139

RESUMO

A new diaryl 1,2-diketone, named 1-(2,5-dihydroxy-4-methoxyphenyl)-2-phenylethane-1,2-dione (1), along with eight known compounds (2-9), were isolated from the heartwood of Dalbergia latifolia. They were identified on the basis of spectral data. Compounds 1-7 were obtained from the Dalbergia genus for the first time. Compounds 8 and 9 were firstly isolated from the plant. Compound 1 exhibited inactive against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 21530 with the minimum inhibitory concentrations of 10.0 and 10.0 mg/mL, respectively.


Assuntos
Antibacterianos/química , Dalbergia/química , Hidroquinonas/química , Cetonas/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Hidroquinonas/farmacologia , Cetonas/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Madeira/química
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