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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.
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Artemisia , Sesquiterpenos , Animais , Camundongos , Artemisia/química , Estrutura Molecular , Sesquiterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Células RAW 264.7RESUMO
Acute lung injury (ALI) is one of the representative "lung heat syndromes" in traditional Chinese medicine (TCM). Scutellaria baicalensis is an herbal medicine used in TCM for treating lung diseases, due to its remarkable anti-inflammatory and antiviral effects. When used in TCM, S. baicalensis root is divided into two categories: S. baicalensis pith-not-decayed root (SN) and S. baicalensis pith-decayed root (SD). Compared to SN, SD has a better effect on lung diseases. We constructed a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model to study the pharmacodynamic mechanism of SD. The ethanolic extract of Scutellaria baicalensis pith-decayed root (EESD) significantly affected LPS-induced ALI by reducing alveolar interstitial thickening, pulmonary edema, and other pathological symptoms, decreasing the infiltration of inflammatory cells, especially macrophages, and inhibiting IL-1ß, TNF-α, and IL-6 transcription and translation. Furthermore, in the THP-1 macrophage model induced by LPS, EESD inhibited the expression of phosphorylated nuclear factor inhibitory protein alpha (p-IκBα), phosphorylated nuclear factor-κB P65 (p-p65), cleaved-caspase-1, cleaved-IL-1ß protein, and the release of inflammatory factors in the NF-κB/NLRP3 pathway, inhibiting macrophage function. In vivo experiments yielded similar results. Therefore, the present study clarified the potential of EESD in the treatment of ALI and revealed its potential pharmacodynamic mechanism by inhibiting the NF-κB/NLRP3 inflammasome pathway and suppressing the pro-inflammatory phenotype activation of lung tissue macrophages.
Assuntos
Lesão Pulmonar Aguda , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Scutellaria baicalensis , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Macrófagos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pulmão/metabolismo , Pulmão/patologiaRESUMO
ObjectiveTo investigate the clinical efficacy of Niaoxue No.1 Prescription in treating Henoch-Schönlein purpura (HSP) nephritis with blood heat and stasis syndrome and its effect on urine erythrocyte, urine protein, blood neutrophils, and blood routine-derived indicators. MethodA multicenter, randomized controlled trial (RCT) was conducted involving 108 HSP nephritis patients from three hospitals. The patients were randomly divided into a control group (54 cases) and a treatment group (54 cases). The treatment group received Niaoxue No.1 prescription once daily, while the control group was treated with captopril and ferulic acid tablets. Both groups underwent a 4-week course of treatment. The urine erythrocyte, urine microalbumin (mAlb), urine sediment red blood cell count, traditional Chinese medicine (TCM) syndrome score, 24-hour urine protein, blood neutrophil count, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), D-dimer, and immunoglobulin A were detected. The recurrence rate of HSP nephritis was followed up for 6 months. ResultThe total effective rates were 88.9% (48/54) in the treatment group and 70.4% (38/54) in the control group, and the treatment group was superior to the control group (χ2=5.708, P<0.05). Compared with the results before treatment, after 14 days of treatment, the TCM syndrome total score, urine erythrocyte, urine mAlb, and 24-hour urine protein in both groups significantly decreased (P<0.05,P<0.01), and the improvement was more significant in the treatment group than the control group (P<0.05). After 28 days of treatment, compared with the results before treatment, the TCM syndrome total score, urine erythrocyte, urine mAlb, urine sediment red blood cell count, D-dimer, and 24-hour urine protein in both groups significantly decreased (P<0.05,P<0.01), with the treatment group showing a more significant reduction in urine mAlb than the control group (P<0.05). On the 14th and 28th days of treatment, the neutrophil percentage and NLR were lower in the treatment group than in the control group (P<0.05), while there was no statistically significant difference in PLR and LMR. The recurrence rate of nephritis in both groups showed no statistically significant difference after a 6-month follow-up. ConclusionNiaoxue No.1 Prescription in the treatment of HSP nephritis with blood heat and stasis syndrome can significantly improve clinical symptoms, shorten the course of the disease, and reduce urine erythrocyte, urine mAlb, 24-hour urine protein, blood neutrophils, and NLR, thereby effectively alleviating the inflammatory state and reducing kidney damage in children with HSP nephritis.
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As a promising source of biologically active substances, the Artemisia species from Kazakhstan have not been investigated efficiently. Considering the rich history, medicinal values, and availability of the Artemisia plants, systematic investigations of two Artemisia species growing in the East Kazakhstan region were conducted. In this study, one new germacrane-type sesquiterpene lactone (11), together with 10 known sesquiterpenes and its dimer, were characterized from A. nitrosa Weber. Additionally, one new chromene derivative (1') with another 12 known compounds, including coumarins, sesquiterpene diketones, phenyl propanoids, polyacetylenics, dihydroxycinnamic acid derivatives, fatty acids, naphthalene derivatives, flavones, and caffeic acid derivatives were isolated from A. marschalliana Spreng. All compounds were isolated and identified for the first time from these two Artemisia species. The structures of new compounds (11, 1') were established by using UV, TOFMS, LC-MS, 1D and 2D NMR spectroscopic analyses. The cytotoxicity of all isolated compounds was evaluated. As a result, all compounds did not show significant inhibition against HL-60 and A-549 cell lines. The sesquiterpenoids isolated from A. nitrosa were tested for their inhibitory activity against the LPS-induced NO release from the RAW624.7 cells, and neither of them exhibited significant activity.
Assuntos
Antineoplásicos , Artemisia , Flavonas , Sesquiterpenos , Artemisia/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/químicaRESUMO
Eight new sesquiterpenoid dimers, artatrovirenolides A-H (1-8), along with three known analogues (9-11), were isolated from Artemisia atrovirens by using the LC-MS guided isolation. Compound 1 was a compound dimerized from a guaianolide and a 1,10-seco-guaianolide unit while others were from two guaianolide units. Their structures were established by comprehensive analysis of spectroscopic data, and their absolute configurations were determined by the aid of time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. Compound 8 showed anti-inflammatory effect in LPS-stimulated BV-2 microglial cells at 1 µM, while compounds 1, 2, 5, and 6 inhibited microglial inflammation at 10 µM.
Assuntos
Artemisia , Sesquiterpenos , Anti-Inflamatórios/farmacologia , Artemisia/química , Microglia , Estrutura Molecular , Óxido Nítrico , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Atractylodes lancea (Thunb.) DC. is a herb widely used traditionally for the treatment of gastrointestinal diseases such as gastric ulcer, spleen deficiency, and diarrhea. In China, people fry raw A. lancea (SCZ) together with wheat bran to make bran-fried A. lancea (FCZ). Ancient Chinese texts have documented that FCZ can enhance the function of regulating the intestines and stomach. Nevertheless, the effect and mechanism of SCZ and FCZ on ulcerative colitis (UC) are still unclear. The aim of this study was to compare the therapeutic effects of SCZ and FCZ and their mechanisms on dextran sulfate sodium (DSS)-induced UC in mice. The chemical constituents of SCZ and FCZ were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with six reference compounds. The effects of SCZ and FCZ were investigated based on their effects on weight loss, disease activity index (DAI) score, colon length shortening, goblet cell loss, and pathological changes using the colons from a mouse model of DSS-induced UC. The effects of SCZ and FCZ on levels of the inflammatory cytokines (tumor necrosis factor-[Formula: see text], interleukin-6, interleukin-1[Formula: see text], mucoprotein (MUC2), tight protein (ZO-1, occludin), and the activation of macrophages were determined using immunohistochemistry (IHC) and immunofluorescence (IF). 16s RNA sequencing technology was used to detect the composition of the intestinal flora in each group. Nontargeted metabonomics was used to detect the serum metabolite levels of mice in each group. Pearson analysis was used to determine the correlation between the intestinal flora, metabolites, and pathological indices. Reverse transcription-polymerase chain reaction was used to detect the genes of different metabolite-related enzymes. A pseudogerm free (PGF) mouse model was used to verify whether the effect of SCZ and FCZ in UC depends on the regulation of intestinal flora. SCZ and FCZ could inhibit weight loss and decrease the DAI score, colon length shortening, goblet cell loss, and the extent of pathological changes in the colons of mice with DSS-induced colitis. Moreover, SCZ and FCZ inhibited the decrease in MUC2, ZO-1, occludin, production of pro-inflammatory factors, and activation of pro-inflammatory macrophages in colonic tissue. The effect of FCZ was better than that of SCZ. SCZ and FCZ not only inhibited the abundance of harmful bacteria and increased the abundance of beneficial bacteria, but also regulated the metabolism of disease-related metabolites such as amino acid and cholesterol metabolism. Both preparations inhibited the gene expression (Slc6A7, PRODH, Sdsl, HMGCR, SREBP-2) of different metabolite-related enzymes. In the PGF mouse model, the above effects were not observed. Rhizoma Atractylodes was effective in alleviating DSS-induced UC in mice, and FCZ was found to be superior to SCZ. The mechanism of action of FCZ and SCZ is mainly related to the regulation of intestinal flora and their associated metabolites.
Assuntos
Atractylodes , Colite , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Animais , Atractylodes/química , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Camundongos , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Atractylenolide-1, an active component of Atractylodes Lancea, which is widely used to improve the gastrointestinal function. However, the efficacy and mechanism remain unclear in treating ulcerative colitis (UC). PURPOSE: This study aimed to investigate the efficacy and the underlying mechanism of atractylenolide-1in UC. METHODS: A dextran sulfate sodium (DSS)-induced UC mouse model was used to investigate the efficacy of atractylenolide-1. 16S DNA sequencing, GC-MS technique and transcriptome sequencing were used to detect the composition of mouse intestinal flora, the changes of metabolites and gene expression in mouse intestine. Compound-reaction-enzyme-gene network was used to find drug targets. Recombinant plasmid overexpression was used to verify drug targets in DSS mouse models. RESULTS: The results showed that Atractylenolide-1 could significantly improve weight loss, diarrhea, blood in the stool, shortening of the colon, the loss of colonic goblet cells, reduction in mucoprotein MUC2, and tight junction proteins (zo-1, occludin) in mice with colitis. It reduced the inflammatory factors TNF-α, IL-6, IL-1ß as well. The 16S sequencing showed that Atractylenolide-1 regulated the diversity and abundance of the intestinal flora in mice with colitis, and the analysis of flora enrichment indicated that the regulation of intestinal flora by atractylenolide-1 may be related to the regulation of metabolism. Correlation analysis of metabolomics and transcriptome showed that two genes SPHK1 and B4GALT2 related to the metabolism of fructose and galactose were regulated by atractylenolide-1. Further verification showed that atractylenolide-1 significantly inhibited the aberrance of SPHK1 and B4GALT2 in the colon with colitis. Meanwhile, it inhibited the activation of the PI3K-AKT pathway. SPHK1 and B4GALT2 overexpressing reversed the therapeutic effect of atractylenolide-1 in mice with colitis. CONCLUSION: Atractylenolide-1 is a potential drug for the treatment of colitis by suppressing inflammation via the SPHK1/PI3K/AKT axis and by targeting SPHK1 and B4GAT2 to regulate fructose/galactose-related metabolism, thereby regulating the composition of the intestinal flora.
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Ten undescribed cadinane-type sesquiterpenes (1-10) were isolated from the whole plant of Eupatorium chinense. Their planar structures were mainly elucidated by extensive analysis of spectroscopic data and DFT NMR calculations. The absolute configurations of 1, 2, and 3 were determined by TDDFT ECD calculations while those of compounds 4-7 and 9 were confirmed by single crystal X-ray diffraction experiments. Compounds 2 and 3 are a pair of C-10 epimers, compounds 4 and 5 a pair of C-1 epimers, and compounds 9 and 10 a pair of compounds isomerized at both C-1 and C-10. A possible biosynthetic pathway for these new sesquiterpenes was proposed.
Assuntos
Asteraceae/química , Extratos Vegetais/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Rotação Ocular , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Scutellariae Radix is a commonly used Chinese medicinal first recorded in the Shennong's Classic of Materia Medica. In the ancient books of traditional Chinese medicine(TCM), Scutellariae Radix is used in two specifications, solid one(Ziqin) and hollow one(Kuqin). In the current rules and regulations of Chinese medicine, Scutellariae Radix is used without the specific requirements for the specifications applied. To clarify the evolution of Scutellariae Radix specifications and analyze the current specifications of Scutellariae Radix pieces, the present study reviews the Scutellariae Radix from ancient literature, modern rules and regulations, and differences between Ziqin and Kuqin in composition, efficacy, and transformation mechanism. According to the research on ancient books, Kuqin is effective in clearing the fire of the upper energizer, and Ziqin in purging the heat of the lower energizer. Modern studies have revealed that Kuqin and Ziqin are significantly different in chemical components, and Ziqin and Kuqin target the colon and lung, respectively, which are consistent with the relevant records in ancient books. The review study suggests that the two specifications of Scutellariae Radix are reasonable since they can facilitate the precise treatment of Scutellariae Radix.
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Medicamentos de Ervas Chinesas , Literatura Moderna , Materia Medica , Medicina Tradicional Chinesa , Scutellaria baicalensisRESUMO
Dicarabrols B and C (1 and 2), two new carabrane sesquiterpenoid dimers, along with one new carabrane sesquiterpenoid (3) were isolated from the whole plant of Carpesium abrotanoides L. Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Dicarabrol B possesses a novel C30 skeleton featuring a methylene-tethered bridge between two sesquiterpene moieties, while dicarabrol C presents the unique linkage of a cyclopentane ring in the molecule. Dicarabrol C exhibited potent inhibitory effects on HL-60 cells with an IC50 value of 3.7 µmol·L-1.
Assuntos
Asteraceae , Sesquiterpenos , Dicroísmo Circular , Humanos , Estrutura MolecularRESUMO
Sesquiterpene lactones supply a variety of scaffolds for the development of anti-inflammatory drugs. In this study, eight undescribed guaianolides, i.e., lavandolides AâH, were isolated from the whole plants of Artemisia codonocephala, together with five known analogues. Their planar structures and relative configurations were elucidated by spectroscopic measurements, and their absolute configurations were determined by electronic circulardichroism spectra and single crystal X-ray diffraction experiments. The nitric oxide inhibitory effect of all the isolates was assessed on lipopolysaccharide stimulated THP-1 macrophages. Lavandolide D showed a potent inhibitory effect on NO production, with IC50 values of 3.31 ± 0.74 µM. Furthermore, lavandolide D inhibited NOD-, LRR- and pyrin domain-containing protein 3 inflammasome-mediated interleukin-1ß production through activating autophagy.
Assuntos
Artemisia , Interleucina-1beta/biossíntese , Macrófagos/efeitos dos fármacos , Sesquiterpenos de Guaiano/farmacologia , Artemisia/química , Humanos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Células THP-1RESUMO
A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora, resulting in the characterization of five new 3, 4-seco-isopimarane (1-5) and one new 3, 4-seco-pimarane diterpenoid (6), together with four known compounds. The structures of the new compounds were fully elucidated by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and time-dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra, and DFT calculations for NMR chemical shifts and optical rotations.
Assuntos
Abietanos , Callicarpa , Diterpenos , Abietanos/química , Abietanos/isolamento & purificação , Callicarpa/química , Diterpenos/química , Diterpenos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de PlantaRESUMO
Unclear established standard of bran-fried Atractylodis Rhizoma (BFAR), a commonly used drug in Traditional Chinese Medicine (TCM), compromised its clinical efficacy. In this study, we explored the correlation between color and near-infrared spectroscopy (NIR) feature with content of atractylodin, then established a rapid recognition model for the optimal degree of processing for BFAR preparation. The results of the Pearson analysis indicated that the color values were significantly and positively correlated with atractylodin content. The back propagation artificial neural network algorithm and cluster analysis revealed the color of different BFAR could be accurately divided into three categories; subsequently, the color range for the optimal degrees of stir-frying was established as follows: R[red value (105.79-127.25)], G[green value(75.84-89.64)], B[blue value(33.33-42.73)], L[Lightness (81.26-95.09)].Using NIR, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and cluster analysis, three types of BFAR were accurately identified. The prediction model of atractylodin content was established using partial least squares regression analysis. The R2 of the validation set was 0.9717 and the root mean square error was 0.026. In the color judgment model, the processing degree of 8 batches of BFAR from the market is inferior. According to the NIR judgment model, the processing degree of all samples from the market is inferior. In conclusion, the best fire degree of BFAR can be identified quickly and accurately based on our established model. It is a potential method for quality evaluation of Chinese Materia Medica processing.
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Atractylodes , Mineração de Dados , Furanos , Análise dos Mínimos Quadrados , Rizoma , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Ten undescribed noreudesmane-type sesquiterpenoids, including eight 12,13-dinoreudesmanes and a pair of 11,12,13-trinoreudesmane epimers were isolated from the whole plant of Artemisia hedinii. Their structures were elucidated by extensive analysis of spectroscopic data, including MS, 1D and 2D NMR, and their absolute configurations were confirmed by X-ray diffraction experiments and DFT calculations. Compounds 1-5, 7-10 were evaluated for their anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells, and all of them could significantly inhibit the LPS induced CCL2 mRNA expression in a dose-dependent manner.
Assuntos
Anti-Inflamatórios/farmacologia , Artemisia/química , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Quimiocina CCL2 , China , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Células RAW 264.7 , Sesquiterpenos/isolamento & purificaçãoRESUMO
Four pairs of undescribed racemic bi(9,10-dihydro) phenanthrene and phenanthrene/bibenzyl atropisomers, bletistriatins A-D (1-4), along with 22 known compounds were isolated from the rhizomes of Bletilla striata. These dimeric derivatives were constructed through direct C-C connection or an oxygen bridge. The structures of new compounds were fully established by extensive analysis of MS, and 1D and 2D NMR spectroscopic data. Owing to sterically hindered rotation around the biaryl axis, these dimeric 9,10-dihydrophenanthrene derivatives can exist as a pair of enantiomers, but were isolated as racemates. Their racemates were separated to yield enantiomerically pure compounds by HPLC on an optically active stationary phase, and were stereochemically characterized on-line by circular dichroism (CD) spectroscopy (LC-CD coupling). Some isolates were evaluated for cytotoxicity against human cancer cell lines HL-60 and A549. Compounds 13, 17, and 20 showed cytotoxicity against HL-60 and A-549 cell lines with IC50 values ranging from 2.56 to 8.67 µM.
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Antineoplásicos Fitogênicos/farmacologia , Orchidaceae/química , Fenantrenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Fenantrenos/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Rizoma/química , EstereoisomerismoRESUMO
Fourteen new eudesmane sesquiterpenoids (1, 3-5, 7-16) and seven known analogues were isolated from the whole plant of Artemisia hedinii. Their structures were elucidated by spectroscopic data analysis and comparison with published NMR data, and their absolute configurations were confirmed by X-ray diffraction experiments and TDDFT ECD calculation. Compounds 1-15 were identified as eudesmane acids, which represent a kind of lactone ring-opening eudesmane-type sesquiterpenes with an acetoxyl or a hydroxy group attached to C-9. Compounds 1 and 2, 5 and 6, and 7 and 8 are three pairs of epimers isomerized at C-3, C-5, and C-11, respectively. Compounds 1-9, 11-13, 15-19, and 21 could influence the proinflammatory phenotype of the M1 macrophage. Among them, compounds 5, 8, 9, 12, 16, and 19 consistently exhibited anti-inflammatory effects, as evidenced by downregulating classic pro-inflammatory cytokines TNF-α, IL-12, IL-6, and IFN-γ in LPS-induced primary bone marrow derived M1 macrophages.
Assuntos
Anti-Inflamatórios/farmacologia , Artemisia/química , Macrófagos/efeitos dos fármacos , Sesquiterpenos de Eudesmano/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , China , Citocinas , Feminino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Sesquiterpenos de Eudesmano/isolamento & purificaçãoRESUMO
A phytochemical investigation of a medicinal plant Artemisia atrovirens was carried out, resulting in the characterization of a novel bis-nor seco-guaianolide, seco-atrovirenolide A (1), a new 1,10-seco-guaianolide derivative, seco-atrovirenoic acid A (2), and a new artifact 10-methanoyloxy-seco-atrovirenoic acid A (3), together with eight known guaianolide and seco-guaianolide derivatives (4-11). The structures of new compounds were fully established by extensive analysis of MS, 1D and 2D NMR spectroscopic data. The absolute configurations of the isolated compounds were confirmed by TDDFT ECD calculation, Mosher's method, and X-ray crystal diffraction experiment. All the compounds were tested in vitro for their cytotoxicity against HL-60 and A549 cell lines. Some of them showed moderate inhibitory activity against HL-60 cell lines with IC50 values ranging from 5.99 to 11.74 µM.
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Antineoplásicos Fitogênicos/farmacologia , Artemisia/química , Limoninas/farmacologia , Células A549 , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células HL-60 , Humanos , Limoninas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/químicaRESUMO
Sexual reproduction in angiosperms is siphonogamous, and the interaction between pollen tube and pistil is critical for successful fertilization. Our previous study demonstrated that mutation of the Arabidopsis turgor regulation defect 1 (TOD1) gene leads to reduced male fertility, a result of retarded pollen tube growth in the pistil. TOD1 encodes a Golgi-localized alkaline ceramidase, a key enzyme for the production of sphingosine-1-phosphate (S1P), which is involved in the regulation of turgor pressure in plant cells. However, whether TOD1s play a conserved role in the innovation of siphonogamy is largely unknown. In this study, we provide evidence that OsTOD1, which is similar to AtTOD1, is also preferentially expressed in rice pollen grains and pollen tubes. OsTOD1 knockout results in reduced pollen tube growth potential in rice pistil. Both the OsTOD1 genomic sequence with its own promoter and the coding sequence under the AtTOD1 promoter can partially rescue the attod1 mutant phenotype. Furthermore, TOD1s from other angiosperm species can partially rescue the attod1 mutant phenotype, while TOD1s from gymnosperm species are not able to complement the attod1 mutant phenotype. Our data suggest that TOD1 acts conservatively in angiosperms, and this opens up an opportunity to dissect the role of sphingolipids in pollen tube growth in angiosperms.
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Magnoliopsida/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Flores/genética , Flores/fisiologia , Ginkgo biloba/genética , Ginkgo biloba/fisiologia , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , Magnoliopsida/fisiologia , Nelumbo/genética , Nelumbo/fisiologia , Nymphaea/genética , Nymphaea/fisiologia , Oryza/genética , Oryza/fisiologia , Pinus taeda/genética , Pinus taeda/fisiologia , Proteínas de Plantas/genética , Pólen/genética , Pólen/fisiologia , Tubo Polínico/genética , Tubo Polínico/fisiologia , ReproduçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes lancea (Thunb.) DC. is a widely used traditional herb that is well known for treating spleen deficiency and diarrhea. According to traditional Chinese medicine (TCM) theory, diarrhea-predominant irritable bowel syndrome (IBS-D) is caused by cold and dampness, resulting in diarrhea and abdominal pain. Nevertheless, the effect and mechanism of Atractylodes on IBS-D are still unclear. AIM OF THE STUDY: This study was designed to confirm the therapeutic effect of Atractylodes lanceolata oil (AO) in a rat model of IBS-D, and to determine the mechanisms by which AO protects against the disease. MATERIALS AND METHODS: The chemical components in AO were determined using gas chromatography-mass spectrometry (GC-MS). The expression levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and surfactant protein (SP) in serum and colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR), western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) were used to elucidate the mechanism of action of AO toward inflammation and the intestinal barrier in a rat model of IBS-D. RESULTS: The 15 chemical substances of the highest concentration in AO were identified using GC-MS. AO was effective against IBS-D in the rat model, in terms of increased body weight, diarrhea grade score, levels of interleukin-10 (IL-10), aquaporin 3 (AQP3), and aquaporin 8 (AQP8), and reduced fecal moisture content, levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), 5-HT, VIP, and SP, while also reducing intestinal injury, as observed using hematoxylin-eosin (HE) staining. In addition, the results indicated that AO increased the mRNA and protein expression levels of stem cell factor (SCF) and c-kit and enhanced the levels of zonula occludens-1 (ZO-1) and occludin, as well as decreased the levels of myosin light chain kinase (MLCK) and inhibited the phosphorylation of myosin light chain 2 (p-MLC2). CONCLUSIONS: AO was found to be efficacious in the rat model of IBS-D. AO inhibited the SCF/c-kit pathway, thereby reducing inflammation and protecting against intestinal barrier damage via the MLCK/MLC2 pathway.
Assuntos
Atractylodes/química , Síndrome do Intestino Irritável/tratamento farmacológico , Cadeias Leves de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Óleos de Plantas/farmacologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fator de Células-Tronco/metabolismo , Animais , Aquaporinas/genética , Aquaporinas/metabolismo , Colite/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diarreia/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/patologia , Cadeias Leves de Miosina/genética , Quinase de Cadeia Leve de Miosina/genética , Óleos de Plantas/química , Óleos de Plantas/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Ratos Sprague-Dawley , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Células-Tronco/genética , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Twelve new sesquiterpene lactone dimers, lavandiolides A-L (1-12), were isolated from the whole plants of Artemisia lavandulifolia. Among them, compounds 1-6 are 1,3-linked Diels-Alder adducts between two guaianolide monomers, and 7-12 are 2,4-linked sesquiterpene lactone dimers. Their structures were elucidated by comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. Their absolute configurations were determined by ECD spectra and single-crystal X-ray diffraction analyses with Cu Kα radiation. The nitric oxide (NO) inhibitory effect of all the isolates was assessed on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 1, 3, 7 and 9 showed potent inhibitory effects on NO production, with IC50 values of 0.61 ± 0.15, 1.64 ± 0.04, 1.89 ± 0.16, and 1.40 ± 0.23 µM, respectively. Furthermore, compound 1 inhibited NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome-mediated interleukin-1ß (IL-1ß) production through activating autophagy.