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1.
Front Endocrinol (Lausanne) ; 15: 1328748, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572474

RESUMO

Background: In observational studies, the relationship between coffee intake and bone mineral density (BMD) is contradictory. However, residual confounding tends to bias the results of these studies. Therefore, we used a two-sample Mendelian randomization (MR) approach to further investigate the potential causal relationship between the two. Methods: Genetic instrumental variables (IVs) associated with coffee intake were derived from genome-wide association studies (GWAS) of the Food Frequency Questionnaire (FFQ) in 428,860 British individuals and matched using phenotypes in PhenoScanner. Summarized data on BMD were obtained from 537,750 participants, including total body BMD (TB-BMD), TB-BMD in five age brackets ≥60, 45-60, 30-45, 15-30, and 0-15 years, and BMD in four body sites: the lumbar spine, the femoral neck, the heel, and the ultradistal forearm. We used inverse variance weighting (IVW) methods as the primary analytical method for causal inference. In addition, several sensitivity analyses (MR-Egger, Weighted median, MR-PRESSO, Cochran's Q test, and Leave-one-out test) were used to test the robustness of the results. Results: After Bonferroni correction, Coffee intake has a potential positive correlation with total body BMD (effect estimate [Beta]: 0.198, 95% confidence interval [Cl]: 0.05-0.35, P=0.008). In subgroup analyses, coffee intake was potentially positively associated with TB-BMD (45-60, 30-45 years) (Beta: 0.408, 95% Cl: 0.12-0.69, P=0.005; Beta: 0.486, 95% Cl: 0.12-0.85, P=0.010). In addition, a significant positive correlation with heel BMD was also observed (Beta: 0.173, 95% Cl: 0.08-0.27, P=0.002). The results of the sensitivity analysis were generally consistent. Conclusion: The results of the present study provide genetic evidence for the idea that coffee intake is beneficial for bone density. Further studies are needed to reveal the biological mechanisms and offer solid support for clinical guidelines on osteoporosis prevention.


Assuntos
Densidade Óssea , Café , Humanos , Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Colo do Fêmur
2.
J Tradit Chin Med ; 44(1): 131-144, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213248

RESUMO

OBJECTIVE: To investigate the potential pharmacological mechanism of Danlou tablet (, DLT) with a long-term clinical application in the treatment of myocardial ischemia/reperfusion (I/R) injury through network pharmacology, molecular docking and experimental verification. METHODS: The main chemical ingredients in DLT were retrieved from the Traditional Chinese Medicine (TCM) System Pharmacology Database, the TCM information database, the bioinformatics analysis tool for molecular mechanism of TCM, and HERB database. Disease targets of I/R were accessed from the databases of Online Mendelian Inheritance in Man, GeneCards, Therapeutic Target Database, and DisGeNET database. The overlaying genes of DLT and I/R were obtained from the Venny online platform. The core targets and protein-protein interaction network were constructed and analyzed via the Search Tool for the Retrieval of Interacting Genes Proteins database and Cytoscape software. Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by the Metascape platform. Based on the results, the component-target-pathway network was constructed and drafted via the Cytoscape software and the platform of Bioinformatics. Furthermore, we performed molecular docking to predict the binding information between chemical molecules and target proteins. Finally, oxygen-glucose deprivation/recovery (OGD/R)-induced H9c2 cardiomyocytes were used to validate the results of network pharmacology in vitro. RESULTS: A total of 189 active chemical components in DLT and 849 correlative targets of I/R were screened. Of note, 133 overlaying genes found from the Venny online platform were concentrated into 28 core genes. Furthermore, the GO and KEGG pathway enrichment analysis presented that DLT might participate in 42 types of GO molecular functions, 747 types of GO biological processes, 19 types of GO cellular components, and 140 kinds of pathways to treat I/R. In the component-target-pathway network, the indirect relationship between herbs and their possible effective pathways was clarified. Based on the molecular docking, we speculated that Baicalein-prostaglandin G/H synthase 2 (PTGS2) with -3.24 kcal/mol, Luteolin-heat shock protein 90 alpha family class A member 1 (HSP90AA1) with -3.22 kcal/mol, Baicalein-HSP90AA1 with -3.13 kcal/mol, and Quercetin-HSP90AA1 with -3.05 kcal/mol possessed the strongest binding force of less than -3 kcal/mol, sequentially. Experimental verification showed that Quercetin, Luteolin, and Baicalein could increase the relative cell viability of OGD/R-stimulated cardiomyocytes, probably by suppressing PTGS2, and activating HSP90AA1 and estrogen receptor 1 expression. CONCLUSIONS: We predicted the potential active compounds as the material basis of DLT that may provide a new approach to elucidate the novel pharmacological mechanism underlying the treatment of cardiac I/R damage.


Assuntos
Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/genética , Ciclo-Oxigenase 2 , Luteolina , Simulação de Acoplamento Molecular , Farmacologia em Rede , Quercetina , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa
3.
J Ovarian Res ; 17(1): 25, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279186

RESUMO

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.


Assuntos
Quempferóis , Farmacologia em Rede , Feminino , Humanos , Ácido Araquidônico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Endométrio , Simulação de Acoplamento Molecular
4.
Medicine (Baltimore) ; 102(48): e36349, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050247

RESUMO

This study aimed to investigate the active composition and mechanism of the Shuganfang (SGF) in treating drug-induced liver injury (DILI) using network pharmacology and molecular docking. The potential active ingredients and targets of SGF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. DILI-related targets were queried from various databases including GEO, GeneCards, OMIM, NCBI, and DisGeNET. The STRING database was used to establish a protein-protein interaction (PPI) network. DAVID was utilized for conducting gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The data visualization and analysis of herb-ingredient-target and disease-pathway-target-ingredient networks were conducted using Cytoscape software (version 3.7.2). PyMoL and AutoDock software was used to select the best binding target for molecular docking. A total of 177 active ingredients,126 targets and 10112 disease targets were obtained, including 122 intersection targets. The identified potential active ingredients consisted of quercetin, kaempferol, luteolin, tanshinone IIa, nobiletin, isorhamnetin, beta-sitosterol and naringenin. The core targets implicated in the study were IL6, estrogen receptor 1 (ESR1), hypoxia-inducible factor alpha subunit 1 (HIF1A), MYC and vascular endothelial growth factor A (VEGFA). KEGG analysis revealed that the treatment of DILI with SGF mainly acted through apoptosis, the PI3K-Akt signaling pathway, and the tumor necrosis factor (TNF) signaling pathway. Furthermore, the binding affinities between the potential ingredients and the core targets were subsequently confirmed through molecular docking experiments. The findings indicated that the docking outcomes remained consistent and demonstrated a favorable capacity for binding. SGF exerts a therapeutic effect on DILI through multiple active ingredients, multiple targets and multiple pathways. Our findings contribute to a positive investigation and establish a theoretical basis for further extensive exploration of SGF as a potential treatment for DILI in future research.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator A de Crescimento do Endotélio Vascular , Fosfatidilinositol 3-Quinases , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
6.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2233-2240, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282911

RESUMO

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.


Assuntos
Antipiréticos , Resfriado Comum , Faringite , Humanos , Antipiréticos/efeitos adversos , Antipiréticos/uso terapêutico , Cápsulas , Resfriado Comum/tratamento farmacológico , Resfriado Comum/diagnóstico , Método Duplo-Cego , Febre/tratamento farmacológico , Temperatura Alta , Resultado do Tratamento
7.
Fitoterapia ; 169: 105560, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37302761

RESUMO

Seven new sesquiterpenoids (1-7) and 19 known analogues were isolated from the whole plant of Artemisia verlotorum. Their structures were determined by extensive analysis of 1D and 2D NMR and HRESIMS data, electronic circular dichroism (ECD) spectra, density functional theory (DFT) NMR calculations, and time dependent density functional theory (TDDFT) ECD calculations. The absolute configurations of 1, 3, 5 and 7 were confirmed by single crystal X-ray diffraction experiments. Compounds 1 and 2 possess a rarely reported 5/8-bicyclic skeleton, while both compounds 3 and 4 were uncommon iphionane-type sesquiterpenoids. Eudesmane sesquiterpenoids (5-17) reported in this study are all 7,8-cis-lactones, of which, compound 7 represents the first eudesmane sesquiterpene with an oxygen bridge connecting C-5 and C-11. All the compounds were tested in vitro for their anti-inflammatory activities in LPS-stimulated RAW 264.7 murine macrophages. Compound 18 showed a potent inhibitory effect on NO production, with IC50 values of 3.08 ± 0.61 µM.


Assuntos
Artemisia , Sesquiterpenos , Animais , Camundongos , Artemisia/química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Compostos Fitoquímicos/farmacologia , Lactonas/farmacologia , Lactonas/química
8.
Zhongguo Zhen Jiu ; 43(6): 715-20, 2023 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-37313568

RESUMO

OBJECTIVE: To analyze the acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy by data mining technology. METHODS: The literature regarding acupuncture and moxibustion for post-stroke epilepsy included in CNKI, VIP, Wanfang, SinoMed and PubMed databases from the establishment of the database to August 1st 2022 was retrieved. Microsoft Excel 2019 software was used to establish a database to conduct the descriptive analysis of acupoints; SPSS Modeler 18.0 Apriori algorithm was used to conduct association rule analysis; high-frequency acupoint co-occurrence network diagrams were drawn by Cytoscape3.9.0 software; SPSS Statistics 25.0 software was used to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn. RESULTS: Totally 39 articles were included, and 63 prescriptions of acupuncture and moxibustion were extracted, involving 56 acupoints, with a total frequency of 516 times; the top three acupoints with the highest frequency of use were Baihui (GV 20), Fenglong (ST 40) and Neiguan (PC 6); the selected meridians were mainly the governor vessel, the hand and foot yangming meridians; the selection of acupoints were mostly in the head, neck and lower limbs; in terms of acupoint compatibility, Hegu (LI 4)-Shuigou (GV 26) and Neiguan (PC 6) had the highest confidence degree; The top 20 high-frequency acupoints could be divided into 4 effective clusters. CONCLUSION: Modern acupuncture and moxibustion treatment for post-stroke epilepsy attaches great importance to the use of yang meridians and meridians with enrich qi and blood; the core prescription is Shuigou (GV 26)-Neiguan (PC 6)-Hegu (LI 4)-Baihui (GV 20). In addition, the combination of distant and near acupoints is highly valued to improve clinical efficacy.


Assuntos
Terapia por Acupuntura , Epilepsia , Moxibustão , Acidente Vascular Cerebral , Humanos , Pontos de Acupuntura , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Mineração de Dados
9.
Molecules ; 28(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37241993

RESUMO

Artemisia divaricate belongs to the Artemisia genus of the family of Compositae, a sort of perennial herb endemic in most regions of China. For the first time, a phytochemical investigation was carried out on the whole plant of Artemisia divaricate, resulting in the identification of 39 sesquiterpenes, with 9 of them being new (1-9). The structures of the new compounds were fully established using extensive analysis of MS and 1D and 2D NMR spectroscopic data and density functional theory (DFT) NMR calculations. Their structures involve germacrane, eudesmane, and bisabolane types. All the new isolates were evaluated for their anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated murine macrophages of RAW 264.7 cells. Compounds 2 and 8 showed a significant inhibition effect on NO production, with IC50 values of 5.35 ± 0.75 and 7.68 ± 0.54 µM, respectively.


Assuntos
Artemisia , Sesquiterpenos , Animais , Camundongos , Artemisia/química , Macrófagos , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Estrutura Molecular
10.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1319-1329, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-37005816

RESUMO

This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mg·kg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mg·kg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in BALF were detected. The mRNA expression levels of IL-1ß, IL-6, and TNF-α, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.


Assuntos
Lesão Pulmonar Aguda , Microbioma Gastrointestinal , Ginsenosídeos , Panax , Camundongos , Masculino , Animais , Ginsenosídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Panax/genética , Lipopolissacarídeos/efeitos adversos , RNA Ribossômico 16S , Camundongos Endogâmicos C57BL , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Pulmão/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Folhas de Planta/metabolismo , RNA Mensageiro
11.
Fitoterapia ; 167: 105509, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37062345

RESUMO

The first phytochemical investigation of Artemisia nujianensis resulted in the isolation of eight new guaianolides (1-8) and six known analogs. Their structures were determined by extensive analysis of 1D and 2D NMR data, HRESIMS data, DFT NMR calculations, and X-ray diffraction studies. Some compounds were evaluated for their anti-inflammatory activities in LPS-stimulated RAW 264.7 cells. Compounds 5, 7 and 9 showed moderate inhibitory effects on LPS-induced NO production in RAW 264.7 cells, with IC50 values of 12.50 ± 0.21, 9.53 ± 0.14 and 6.85 ± 0.11 µM, respectively.


Assuntos
Artemisia , Sesquiterpenos , Animais , Camundongos , Artemisia/química , Estrutura Molecular , Sesquiterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Células RAW 264.7
12.
Acta Pharmacol Sin ; 44(6): 1122-1134, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36627343

RESUMO

Aggregation of α-synuclein, a component of Lewy bodies (LBs) or Lewy neurites in Parkinson's disease (PD), is strongly linked with disease development, making it an attractive therapeutic target. Inhibiting aggregation can slow or prevent the neurodegenerative process. However, the bottleneck towards achieving this goal is the lack of such inhibitors. In the current study, we established a high-throughput screening platform to identify candidate compounds for preventing the aggregation of α-synuclein among the natural products in our in-house compound library. We found that a small molecule, 03A10, i.e., (+)-desdimethylpinoresinol, which is present in the fruits of Vernicia fordii (Euphorbiaceae), modulated aggregated α-synuclein, but not monomeric α-synuclein, to prevent further elongation of α-synuclein fibrils. In α-synuclein-overexpressing cell lines, 03A10 (10 µM) efficiently prevented α-synuclein aggregation and markedly ameliorated the cellular toxicity of α-synuclein fibril seeds. In the MPTP/probenecid (MPTP/p) mouse model, oral administration of 03A10 (0.3 mg· kg-1 ·d-1, 1 mg ·kg-1 ·d-1, for 35 days) significantly alleviated behavioral deficits, tyrosine hydroxylase (TH) neuron degeneration and p-α-synuclein aggregation in the substantia nigra (SN). As the Braak hypothesis postulates that the prevailing site of early PD pathology is the gastrointestinal tract, we inoculated α-synuclein preformed fibrils (PFFs) into the mouse colon. We demonstrated that α-synuclein PFF inoculation promoted α-synuclein pathology and neuroinflammation in the gut and brain; oral administration of 03A10 (5 mg· kg-1 ·d-1, for 4 months) significantly attenuated olfactory deficits, α-synuclein accumulation and neuroinflammation in the olfactory bulb and SN. We conclude that 03A10 might be a promising drug candidate for the treatment of PD. 03A10 might be a novel drug candidate for PD treatment, as it inhibits α-synuclein aggregation by modulating aggregated α-synuclein rather than monomeric α-synuclein to prevent further elongation of α-synuclein fibrils and prevent α-synuclein toxicity in vitro, in an MPTP/p mouse model, and PFF-inoculated mice.


Assuntos
Doença de Parkinson , Camundongos , Animais , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Doenças Neuroinflamatórias , Substância Negra/metabolismo , Substância Negra/patologia , Encéfalo/metabolismo
13.
Chin J Nat Med ; 21(1): 65-80, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36641234

RESUMO

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 µmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 µmol·L-1, respectively.


Assuntos
COVID-19 , Flavonoides , Flavonoides/farmacologia , Flavonoides/química , SARS-CoV-2 , Rizoma , Peptídeo Hidrolases , Antivirais/farmacologia , Antivirais/química
14.
J Sci Food Agric ; 103(1): 213-220, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35871448

RESUMO

BACKGROUND: Roasting plays an important role in the formation of flavor of roasted green tea; however, the changes in chemicals during this process have not been systematically studied until now. To reveal the dynamic changes in chemicals in green tea during roasting, non-targeted metabolomics, coupled with chemometrics, was employed. RESULTS: A total of 101 non-volatile metabolites were identified in tea samples, and 29 metabolites were identified as characteristic metabolites of roasting. A significant increase in catechins and their derivatives, organic acids, and flavonoid glycosides was observed, while the content of some amino acids and their derivatives decreased over 50% during roasting. The content of theanine glucoside increased dramatically (by 21.23-fold at the roasting stage), and Maillard-derived compounds also increased to varying degrees. CONCLUSION: Glycosylation, oxidative polymerization, and pyrolysis were important reactions responsible for the formation and transformation of flavor compounds in roasted green tea during roasting. © 2022 Society of Chemical Industry.


Assuntos
Catequina , Chá , Chá/química , Temperatura Alta , Metabolômica
15.
Planta Med ; 89(5): 571-579, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36170857

RESUMO

Lasiocarpine (LAS) and heliotrine (HEL) are two different ester types of toxic pyrrolizidine alkaloids (PAs): open-chain diester and monoester. However, the pharmacokinetics of these two types of PAs in rats have not been reported. In the present study, two LC-MS/MS methods for determining LAS and HEL were established and validated. The methods exhibited good linearity, accuracy, and precision and were then applied to a comparative pharmacokinetic study. After intravenous administration to male rats at 1 mg/kg, the AUC0-t values of LAS and HEL were 336 ± 26 ng/mL × h and 170 ± 5 ng/mL × h. After oral administration at 10 mg/kg, the AUC0-t of LAS was much lower than that of HEL (18.2 ± 3.8 ng/mL × h vs. 396 ± 18 ng/mL × h), while the Cmax of LAS was lower than that of HEL (51.7 ± 22.5 ng/mL × h vs. 320 ± 26 ng/mL × h). The absolute oral bioavailability of LAS was 0.5%, which was significantly lower than that of HEL (23.3%). The results revealed that the pharmacokinetic behaviors of LAS differed from that of HEL.


Assuntos
Alcaloides de Pirrolizidina , Espectrometria de Massas em Tandem , Ratos , Animais , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Administração Oral
16.
Artigo em Chinês | WPRIM | ID: wpr-981465

RESUMO

Pseudostellaria heterophylla in large-scale cultivation needs to apply pesticides to control diseases, and non-standard use of pesticide may cause excessive pesticide residues in medicinal materials, increasing the risk of clinical medication. To accurately monitor the residual pesticides, this paper investigated the drug use during the process of P. heterophylla disease prevention in 25 P. he-terophylla planting enterprises or individual households in Guizhou province. It was found that there were 8 common diseases in P. he-terophylla planting, including leaf spot, downy mildew, virus disease, root rot, dropping disease, purple feather disease, white silk disease, and damping-off disease. Twenty-three kinds of pesticides were used in disease control, mainly chemical synthetic pesticides, accounting for 78.3%, followed by biological pesticides and mineral pesticides, accounting for 13.0% and 8.7%, respectively. The disease prevention and control drugs were all low-toxic pesticides, and there were no varieties banned in the Chinese Pharmacopoeia(2020 edition). However, the pesticides used have not been registered on P. heterophylla, and the excessive use of drugs was serious. The present monitoring of pesticide residues in P. heterophylla is mainly based on traditional pesticides such as organochlorine, organophosphorus, and carbamate, which does not effectively cover the production of drugs and had certain safety risks. It is suggested to speed up the research and registration of drug use in the production of P. heterophylla, increase the use of biological pesticides, and further improve the monitoring indicators of pesticide residues in combination with the actual production of drugs, so as to promote the high-quality development of P. heterophylla industry.


Assuntos
Agentes de Controle Biológico , Caryophyllaceae , Resíduos de Praguicidas , Praguicidas , Plantas Medicinais
17.
Artigo em Chinês | WPRIM | ID: wpr-981424

RESUMO

Based on the data of 56 kinds of diseases and drug use in 100 kinds of cultivated Chinese herbal medicines, this paper used frequency analysis method to count the types of diseases and their drug use characteristics, and systematically analyzed the status of drug registration and monitoring standards for disease prevention and control of Chinese herbal medicines. The results showed that 14 diseases such as root rot, powdery mildew, and drooping disease were common in the production of Chinese herbal medicines. Among the 99 pesticides reported, 67.68% were chemically synthesized, 23.23% were biological pesticides, and 9.09% were mineral pesticides. Among the reported pesticides, 92.93% of them were low toxic, with relative safety. However, 70% of the production drugs were not registered in Chinese herbal medicines, and the phenomenon of overdose was serious. The current pesticide residue monitoring standards does not match well with production drugs in China. Although the matching degree between Maximum Residue Limit of Pesticide in Food Safety National Standard(GB 2763-2021) and production drugs is more than 50%, there are few varieties of Chinese herbal medicines covered. The matching degree between Chinese Pharmacopoeia(2020 edition), Green Industry Standard of Medicinal Plants and Preparations(WM/T2-2004), and production drugs is only 1.28%. It is suggested to speed up the research and registration of Chinese herbal medicine production and further improve the pesticide residue limit standard combined with the actual production, so as to promote the high-quality development of Chinese herbal medicine industry.


Assuntos
Humanos , Agentes de Controle Biológico , Medicamentos de Ervas Chinesas , Resíduos de Praguicidas , Praguicidas
18.
Artigo em Chinês | WPRIM | ID: wpr-970603

RESUMO

This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mg·kg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mg·kg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in BALF were detected. The mRNA expression levels of IL-1β, IL-6, and TNF-α, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.


Assuntos
Camundongos , Masculino , Animais , Ginsenosídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Panax/genética , Lipopolissacarídeos/efeitos adversos , Microbioma Gastrointestinal , RNA Ribossômico 16S , Camundongos Endogâmicos C57BL , Lesão Pulmonar Aguda/genética , Pulmão/metabolismo , Superóxido Dismutase/metabolismo , Folhas de Planta/metabolismo , RNA Mensageiro
19.
Artigo em Chinês | WPRIM | ID: wpr-970591

RESUMO

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.


Assuntos
Panax notoginseng/química , Panax , Antioxidantes/farmacologia , Saponinas/farmacologia , Glutationa , Medição de Risco
20.
Front Endocrinol (Lausanne) ; 13: 1035929, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353235

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of reproductive age. Current standard treatment includes lifestyle change, oral pharmacological agents, and surgical modalities. However, the efficacy of current therapies is less than satisfactory. Clinical evidence has shown that acupuncture is effective for regulating hormone levels, promoting ovulation, and attenuating insulin resistance in patients with PCOS. Acupuncture may affect the production of ß-endorphin, which may lead to gonadotropin-releasing hormone secretion and then affect ovulation, menstrual cycle, and fertility. The mechanism of acupuncture for patients with PCOS has not been comprehensively reviewed so far. Better understanding of the mechanisms of acupuncture would help popularize the use of acupuncture therapy for patients with PCOS. In this narrative review, we aimed to overview the potential mechanisms and evidence-based data of acupuncture on PCOS, and analyze the most frequently used acupoints based on animal and clinical studies. The results of this study will contribute to a better understanding of the current situation in this field.


Assuntos
Terapia por Acupuntura , Resistência à Insulina , Síndrome do Ovário Policístico , Humanos , Animais , Feminino , Síndrome do Ovário Policístico/terapia , Síndrome do Ovário Policístico/etiologia , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Ovulação
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