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Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.
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ETHNOPHARMACOLOGICAL RELEVANCE: Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum Indicum L., is a popular traditional Chinese medicine (TCM) for treatment of inflammatory diseases in China. FCI is also a functional food, and is widely used as herbal tea for clearing heat and detoxicating. AIM OF THE STUDY: To explore quality control markers of FCI based on the optimal harvest period. MATERIALS AND METHODS: First, UPLC-Q-TOF/MS based untargeted metabolomics was applied to explore the chemical profiles of FCIs collected at bud stages (BS), initial stages (IS), full bloom stages (FS) and eventual stages (ES) from eight cultivated regions in China. Subsequently, lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model and carrageenan-induced rat paw edema model were used to confirm the anti-inflammatory effect of FCIs collected at IS/FS. Then, UPLC-PDA targeted metabolomics was used to quantitatively analyze 9 constituents with anti-inflammatory activity (7 flavonoids and 2 phenolic acids) changed significantly (VIP > 4) during flowering stages. Finally, ROC curves combined with PCA analysis based on the variation of 9 active constituents in FCIs from different flowering stages were applied to screen the quality markers of FCI. RESULTS: FCIs at IS/FS had almost same chemical characteristics, but quite different from those at BS and ES. A total of 32 constituents in FCIs including flavonoids and phenolic acids were changed during flowering development. Most of the varied constituents had the highest or higher contents at IS/FS compared with those at ES, indicating that the optimal harvest period of FCI should be at IS/FS. FCI extract could effectively suppress nitric oxide (NO) production in LPS-induced RAW264.7 cells and regulate the abnormal levels of cytokines and PGE2 in carrageenan-induced paw edema model rat. The results of quantitatively analysis revealed that the variation trends of phenolic acids and flavonoids in FCIs were different during flowering development, but most of them had higher contents at IS/FS than those at ES in all FCIs collected from eight cultivated regions, except one sample from Anhui. Finally, linarin, luteolin, apigenin and 3,5-dicaffeoylquinic acid were selected as the Q-markers based on the contribution of their AUC values in ROC and clustering of PCA analysis. CONCLUSIONS: Our study demonstrates the optimal harvest period of FCI and specifies the multi-constituents Q-markers of FCI based on the influence of growth progression on the active constituents using untargeted/targeted metabolomics. The findings not only greatly increase the utilization rate of FCI resources and improve quality control of FCI products, but also offer new strategy to identify the Q-markers of FCI.
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Antiinflamatorios , Chrysanthemum , Edema , Flores , Metabolómica , Control de Calidad , Ratas Sprague-Dawley , Animales , Chrysanthemum/química , Ratones , Metabolómica/métodos , Células RAW 264.7 , Masculino , Edema/tratamiento farmacológico , Edema/inducido químicamente , Antiinflamatorios/farmacología , Ratas , Quimiometría , Carragenina , Extractos Vegetales/farmacología , Extractos Vegetales/química , Inflamación/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , LipopolisacáridosRESUMEN
Herbal medicine pair, composed of two single herbs, is a relatively fixed minimum prescription unit in the traditional Chinese medicine's formula and has special significance in clinic. The combination of Xiangfu (the rhizoma of Cyperus rotundus L, XF) and Chuanxiong (the rhizoma of Ligusticum chuanxiong Hort, CX) has been recoded as an herbal medicine pair XF-CX in the Yuan Dynasty (1347 CE) of China and widely used in traditional Chinese medicine formula, including Chaihu Shugan San, which has been clinically used for treatment of depression. However, the optimal ratio of the XF-CX herbal medicine pair and its antidepressant constituents are still unclear. Herein, the antidepressive-like effects of XF-CX herbal medicine pairs with different ratios of XF and CX (2:1, 1:1, 1:2) were evaluated using behavioral despair animal models in mice, and then its potential antidepressant constituents were recognized by spectrum-effect relationship analyses. Finally, the potential antidepressant constituents of the XF-CX herbal medicine pair were validated by molecular docking with glucocorticoid receptor and corticosterone (CORT)-induced PC12 cell injury model. The results indicated that different ratios of XF-CX pairs had antidepressive-like effects, and the XF-CX (2:1) exhibited a more significant effect. Thirty-two potential antidepressant constituents in the XF-CX herbal medicine pair were screened out from the spectrum-effect relationship combined molecular docking analyses. Among them, senkyunolide A, cyperotundone, Z-ligustilide, and levistilide A were validated to have protective effects against CORT-induced injury in PC12 cells. Our findings not only obtained the optimal ratio of XF-CX in the herbal medicine pair for the treatment of depression but also its potential antidepressant constituents, which will benefit in elucidating the mechanism of action and promoting the application of the herbal medicine pair in the clinic.
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Antidepresivos , Corticosterona , Cyperus , Medicamentos Herbarios Chinos , Ligusticum , Simulación del Acoplamiento Molecular , Animales , Células PC12 , Antidepresivos/farmacología , Antidepresivos/aislamiento & purificación , Ratones , Ratas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ligusticum/química , Masculino , Cyperus/química , Depresión/tratamiento farmacológico , Estructura Molecular , Modelos Animales de Enfermedad , Rizoma/química , Ratones Endogámicos ICRRESUMEN
Eight new caffeoyl derivatives, elephantomentosides A-H (1 - 8), together with ten known ones (9 - 18), were isolated from the whole plant of Elephantopos tomentosus L. Their structures were elucidated using detailed spectroscopic analysis. Structurally, compounds 1 - 8 are composed of ß-D-glucopyranose, and almost all of the substituent positions are at the C-1' and C-4' of glucopyranose. The anti-inflammatory and antioxidant activities of all isolated compounds were evaluated in vitro. Compounds 9-10, 13-15, and 17-18 exhibited significant DPPH scavenging capacity with IC50 values in the range of 10.01-25.07 µM, in comparison with Vc (IC50, 17.98 µM).
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Antioxidantes , Asteraceae , Estructura Molecular , Antioxidantes/farmacología , Antioxidantes/química , Asteraceae/química , Antiinflamatorios/farmacología , Antiinflamatorios/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is one of the most prevalent gastrointestinal tract diseases that seriously affects health-related quality of human life and requires effective treatments without side effect. The rhizome of Atractylodes macrocephala Koidz. (Compositae), called Atractylodes Macrocephala Rhizome (AMR), a commonly used traditional Chinese medicine, has been used to relieve the clinical symptoms of patients with constipation. AIM OF THE STUDY: To reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. MATERIALS AND METHODS: Loperamide-induced constipation rat model was established and the dose-dependent laxative effect of AMR was investigated. Untargeted metabolomics based on an UPLC-Q/TOF-MS technique combined with western blot analysis was used to explain the potential mechanism of AMR relieve loperamide-induced constipation in rats. RESULTS: The results showed that medium dose of AMR (AMR-M, 4.32 g raw herb/kg) and high dose of AMR (AMR-H, 8.64 g raw herb/kg) treatments significantly increased the fecal water content, Bristol score, gastrointestinal transit rate, and recovered the damaged colon tissues of constipated rats, but low dose of AMR (AMR-L, 2.16 g raw herb/kg) did not show laxative effect. Both AMR-M and AMR-H treatments also remarkably reduced the serum levels of vasoactive intestinal peptide (VIP), somatostatin (SS) and dopamine (DA), and increased the levels of motilin (MTL), gastrin (GAS) and 5-hydroxytryptamine (5-HT). Urine metabolomics revealed that constipation development was mainly ascribed to the perturbed tryptophan metabolism, and AMR-M and AMR-H markedly corrected the abnormal levels of five urine tryptophan metabolites, namely 4,6-dihydroxyquinoline, indole, 4,8-dihydroxyquinoline, 5-hydroxytryptamine, and kynurenic acid. Additionally, western blot analysis confirmed that the abnormal expression of rate-limiting enzyme involving in tryptophan metabolism, including tryptophan hydroxylase (TPH), monoamine oxidase (MAO) and indoleamine-2,3-dioxygenase (IDO) in the colon of constipated rats, were mediated by AMR-M and AMR-H. CONCLUSIONS: The findings provide insight into the mechanisms of STC and AMR could be developed as new therapeutic agent for prevention or healing of constipation.
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Atractylodes , Loperamida , Ratas , Humanos , Animales , Loperamida/uso terapéutico , Laxativos/farmacología , Atractylodes/química , Triptófano , Rizoma/química , Serotonina , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológicoRESUMEN
Fifteen undescribed eudesmane-type sesquiterpenes, named atramacronoids D-R, along with fourteen known analogues were isolated from the rhizomes of Atractylodes macrocephala. The structures of atramacronoids D-R were elucidated based on extensive spectroscopic data analysis, Snatzke's rule, electronic circular dichroism (ECD) calculations, and X-ray crystallographic analysis. Notably, of the undescribed isolates, atramacronoids D and E are the first example of eudesmanolactam-phenol and eudesmanolactam-ethyl hybrids obtained from plants, respectively. A pair of enantiomers, (+)- and (-)-atramacronoids F, were successfully resolved by chiral-phase HPLC. Atramacronoid D exhibited weak cytotoxicity against SGC-7901 cells. Atramacronoid E significantly promoted the proliferation of LPS-induced IEC-6 cells.
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Atractylodes , Sesquiterpenos de Eudesmano , Sesquiterpenos , Sesquiterpenos de Eudesmano/farmacología , Sesquiterpenos de Eudesmano/análisis , Sesquiterpenos de Eudesmano/química , Atractylodes/química , Sesquiterpenos/química , Rizoma/química , Estructura MolecularRESUMEN
1H-NMR guided fractionation led to the isolation of twenty-two coumarin monoterpenes from the whole plant of Gerbera piloselloides, among which fourteen were undescribed. All coumarin monoterpenes were initially found to be racemates without optical activity. Subsequently, eleven pairs of optically pure enantiomers were successfully separated by chiral phase HPLC. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated/experimental electronic circular dichroism (ECD) data, and X-ray diffraction analysis. Bioassays in LPS-treated RAW 264.7 cells revealed that the four compounds possessed moderate anti-inflammatory activity. In addition, the correlations between the cotton effect (CE) from δ-lactone at approximately 210-220 nm in CD spectra and γ-C or the ring fused at γ-C of the skeleton were reported for the first time.
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Asteraceae , Monoterpenos , Antiinflamatorios/farmacología , Asteraceae/química , Cumarinas/química , Cumarinas/farmacología , Lactonas , Lipopolisacáridos/farmacología , Estructura Molecular , Monoterpenos/farmacología , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Aloin A/B and aloesin are the major bioactive constituents in Aloe vera, with diverse pharmacological activities, including anti-bacterial, anti-tumour, anti-inflammatory and intestinal regulation. However, the in vivo metabolism of aloin A/B and aloesin is still unclear. In this study, the metabolic processes of aloin A/B and aloesin in rats were investigated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and MetaboLynx™ software with the mass defect filter technique. Based on the proposed method, the prototype components of three compounds were all detected in rat plasma, urine and feces. Meanwhile, 25 aloin A/B metabolites (six phase I, three phase II, 16 phase I combined with phase II) and three aloesin metabolites (two phase I and one phase II) were detected in rats after oral administration of aloin A, aloin B and aloesin, and the main biotransformation reactions were hydroxylation, oxidation, methylation, acetylation and glucuronidation. In addition, aloin A and aloin B can be transformed into each other in vivo and the metabolic profiles of aloin A and aloin B are identical. These results provide essential data for further pharmaceutical research and clinical application of aloin A/B and aloesin.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Ratas , Animales , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Ratas Sprague-DawleyRESUMEN
The inherent structural instability of some physalins has hampered the isolation and identification of these compounds for approximately 50 years, and an effective method to overcome these challenges remains unavailable. In the present study, the unprecedented tautomerization mechanism of unstable physalins was elucidated by performing isotopic labeling experiments and DFT calculations, which led to the successful separation of tautomers and isolation of highly pure products for the first time. As a result, 15 new physalins, physaminins A-O (1-15), as well as 17 known analogues (16-32), were isolated from the whole plants of Physalis minima L. The chemical structures of the new compounds were established by performing a comprehensive analysis of spectroscopic data, and their absolute configurations were confirmed by using computational ECD calculations and/or single-crystal X-ray diffraction analyses. All obtained isolates were evaluated for their antiproliferative effects against four human cancer cell lines (A549, HepG2, MCF-7, and SCG-7901) and two noncancerous cell lines (RAW 264.7 and human normal hepatocytes L02), as well as their anti-inflammatory activities by measuring their abilities to inhibit NO production in LPS-stimulated murine RAW 264.7 cells in vitro. Compounds 1-5, 13, 16, 18, 19, 23, and 30 exerted significant antiproliferative effects on the four human cancer lines, with IC50 values ranging from 0.2(0) to 24.7(2) µM, and these compounds were not toxic to the two noncancerous cell lines at a concentration of 10 µM. Moreover, compounds 7, 10, 11, 12, 14, 17, 22, and 27 significantly inhibited NO production, with IC50 values ranging from 2.9(1) to 9.5(2) µM.
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Physalis , Animales , Antiinflamatorios/farmacología , Humanos , Ratones , Estructura Molecular , Physalis/química , Células RAW 264.7RESUMEN
Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.
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Artritis Reumatoide , Medicamentos Herbarios Chinos , Animales , Artritis Reumatoide/tratamiento farmacológico , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional Tibetana , Metabolómica , RatasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The dispensing granules of traditional Chinese medicines (TCMs) is an innovative form of medicinal material for TCMs decoction, which is gradually recognized in the clinic due to being suitable for production on a large scale and convenient to take for patients. However, the quality control of TCMs dispensing granules is being challenged, because they contain too many unrevealed hydrophilic components. AIM OF THE STUDY: Here, the dispensing granules produced from the rhizome of Atractylodes macrocephala (Baizhu dispensing granules), were explored as a case to explore the quality markers correlated to the clinical efficacy of TCMs dispensing granules by a comprehensive strategy of integrating chemical profiling, network pharmacology, and chemometric analysis. MATERIALS AND METHODS: First, the chemical profiling of Baizhu dispensing granules was characterized by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Subsequently, the potential active components responsible for the efficacy of Baizhu dispensing granules were screened via network pharmacology, and the ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was developed for quantitative analysis of the potential active components in 26 batches of Baizhu dispensing granules. Finally, the quality markers of Baizhu dispensing granules were deciphered based on content variations of potential active components and chemometric analysis. RESULTS: A total of 69 components were identified from Baizhu dispensing granules. Network pharmacology analysis further revealed that eight of them including five caffeoylquinic acids (31, 32, 36, 42, 44) and three sesquiterpenoids (63, 67, 76) were intimately connected to the core targets of dyspepsia, enteritis, gastritis and immunity. The contents of eight components differed greatly among 26 batches of Baizhu dispensing granules. Chlorogenic acid (31), cryptochlorogenic acid (32) and atractylenolide III (63) have higher concentrations and make great contributions to distinguish different batches of the Baizhu dispensing granules based on principal component analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA), and could be used as the quality markers of Baizhu dispensing granules. CONCLUSIONS: Our study defined the quality markers of Baizhu dispensing granules, which will benefit further investigation on the quality evaluation of TCMs dispensing granules containing Baizhu. The strategy used in this study will be helpful for discovering the quality markers of other TCMs dispensing granules.
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Atractylodes/química , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China/normas , Control de Calidad , Quimiometría , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/normas , Humanos , Espectrometría de Masas , Farmacología en Red , Análisis de Componente Principal , RizomaRESUMEN
Three new caffeoyl derivatives (1-3), together with two known ones (4-5), were isolated from the whole plant of Elephantopus scaber Linn. The structures of the new compounds were elucidated using detailed spectroscopic analysis. Compound 4 was obtained and its NMR data were given for the first time. All isolates were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and pro-inflammatory cytokines release in RAW 264.7 cells. Compounds 2-5 showed mild inhibitory activities with IC50 values ranging from 64.78 to 87.21 µM, and 3-4 could inhibit LPS-induced tumor necrosis factor-α (TNF-α) production.
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Asteraceae , Lipopolisacáridos , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Asteraceae/química , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico , Células RAW 264.7RESUMEN
Depression is a prevalent, life-threatening, and highly recurrent psychiatric illness. Several studies have shown that depression is associated with endogenous metabolites and the gut microbiota. However, it is unclear whether metabolites in different gut tissues play a role in the pathogenesis of depression and whether the gut microbiota has an impact on depression. Here, we investigated the metabolic signatures in the jejunum, ileum, and colorectum using metabolomics and explored the influence of the gut microbiota on both the development of chronic variable stress (CVS)-induced depression rat model and variations in gut tissue metabolites using a gnotobiotic rat model. The results showed that CVS induced disturbances in gut metabolites (29 differential metabolites) and had different effects on the different segments. When CVS rats were treated with antibiotics, depression-like ethological disorders disappeared, and the decreased catecholamine levels almost normalized. The depression recovery was attributed to the influence of antibiotics on the gut microbiota, especially inhibiting Clostridiaceae (F1), Candidatus arthromitus (G2), Lactobacillus (G6), and elevating Pseudomonadaceae (F6). Moreover, 16 of 29 varied metabolites in CVS rats were reversed with antibiotic treatment. Among them, 12 increased metabolites were decreased, suggesting a trigger for depression. However, four decreased metabolites were increased, indicating a potential therapeutic effect on depression. Based on the Pearson's correlation analysis, hypoxanthine, 3-hydroxypristanic acid, threonic acid, and L-carnitine were strongly associated with F6, F1, G2, and G6, which are involved in the development and prevention of depression. These findings provide a possibility for further exploration of the pathogenesis and prevention of depression.
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Microbioma Gastrointestinal , Animales , Antibacterianos , Depresión/prevención & control , Lactobacillus , Metabolómica , RatasRESUMEN
A phytochemical investigation on the 80% ethanol extract of the roots of Caragana stenophylla Pojark. resulted in the isolation of 20 compounds, including two new ones, named kompasinol P (2) and 3,5,7,2',3'-pentahydroxy-4'-methoxyisoflavanone (3). Among them, a pair of enantiomers, (7S, 8 R, 7'R, 8'S)-kompasinol A (1a) and (7 R, 8S, 7'S, 8'R)-kompasinol A (1b), were successfully separated by the chiral-phase HPLC resolution for the first time. The absolute configurations of 1a and 1b were determined by the experimental and calculated electronic circular dichroism (ECD) data. 15 isolates were evaluated for their anti-inflammatory activity via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Compounds 1a/1b, 6, 7, 9, 10, 12, 14, and 16-18 showed moderate inhibition with IC50 values ranging from 11.45 to 68.54 µM.
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Caragana , Lignanos , Animales , Antiinflamatorios/farmacología , Flavonoides/farmacología , Ratones , Estructura MolecularRESUMEN
Prevalence of acute-on-chronic liver failure (ACLF) patients is growing worldwide, associating with multi-organ failure and high short-term mortality rates. ACLF can be of varying entity manifestation, whereas it remains poorly defined. Traditional Chinese medicine (TCM) stratifies ACLF into two types, damp hot (DH) and cold damp (CD), by seasoned TCM practitioners, for specific treatment with different TCMs. The biggest challenge for the outcome of TCM therapy is the accuracy of diagnosis. However, it is difficult to guarantee it due to lack of the molecule classification of ACLF. Herein, we recruited 58 subjects including 34 ACLF patients (18 DH and 16 CD) and 24 healthy controls, and analyzed serum metabolic profiles using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics approach. A total of 10 serum metabolites were found as potential biomarkers for diagnosis of ACLF. Among them, taurochenodesoxycholic acid (N3), glycyldeoxycholic acid (N5) and 12-HETE-GABA (N7), varied between two types of ACLF and can be merged as a combination marker to differentiate CD from DH patients with area under the receiver operating curve (AUC) of 0.928 (95 % CI 0.8-1). CD patients possessed comparatively higher bile acid metabolism and lower arachidonic acid metabolism compared with DH patients. The results provide not only serum molecules for early accurate diagnosis of ACLF patients, but also potential clinical biomarkers for classification of CD and DH types. The findings clarify that molecular markers will be objective criteria for diagnosis of clinical types in TCM practice.
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Insuficiencia Hepática Crónica Agudizada , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Biomarcadores/metabolismo , Humanos , Espectrometría de Masas , Metaboloma , Metabolómica , Pronóstico , Suero/metabolismoRESUMEN
The root and rhizome of Polygonum cuspidatum (Hu-Zhang) has been used for treatment of various inflammatory disorders in China. In our pervious study, we found that three fractions (HZE-30, HZE-60 and HZE-95) from the ethanol extract of Hu-Zhang (HZE) all could inhibit NO production, and HZE-60 shows the most potent anti-inflammatory activity. In order to understand the major contribution constituents of Hu-Zhang responsible for its anti-inflammatory effect, quantitative composition-activity relationship method was performed. Firstly, the constituents in HZE-60 were characterized using an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) approach. Second, quantitative analyzed five major constituents identified in HZE-60 and compare the difference of five major constituents in HZE and three anti-inflammatory activity fractions. Finally, evaluated the anti-inflammatory effects of major constituents in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. The results showed that a total of 31 compounds were identified from HZE-60, including 12 anthraquinones, 7 diphenylethenes, 9 phenols and 3 others. The contents of five major constituents (polydatin (6), resveratrol (7), emodin-1-O-ß-d-glucoside (15), emodin-8-O-ß-d-glucoside (21) and emodin (31)) were simultaneously determined by UPLC-PDA with good linearity (correlation coefficients > 0.9990) and satisfactory repeatability (RSD < 0.99 %), precision (RSD < 0.01 %), stability (RSD < 0.67 %) and recoveries (99.52 %-101.23 %, RSD < 0.91 %). All five major constituents could be detected in HZE and HZE-60 fraction, but only 6 was detected in HZE-30, and 31 in HZE-95. Moreover, 7, 15 and 21 exhibited significant anti-inflammatory activity via suppressing supernatant pro-inflammatory mediators, such as NO, tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1). Therefore, we conclude that the bioactivity of HZE is the syngeneic effect of its constituents, and 7, 15 and 21 should make great contributions for the anti-inflammatory effect of Hu-Zhang. The findings define the anti-inflammatory chemical constituents of Hu-Zhang, which will benefit further investigation on its quality control and the mechanism of action.
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Fallopia japonica , Antiinflamatorios/farmacología , China , Cromatografía Líquida de Alta Presión , Lipopolisacáridos , Macrófagos , RizomaRESUMEN
Two new phenolic acids, ethyl 3,3',4,4'-tetrahydroxy-δ-truxinate (1), 3-O-p-coumaroyl-4-O-caffeoyl quinic acid methyl ester (2), together with three known compounds (3-5) were isolated from the whole plant of Elephantopus scaber Linn. The structures of the new compounds were elucidated using detailed spectroscopic analysis. Compound 3 was obtained and given its NMR data for the first time. All isolates were evaluated for their anti-inflammatory activity via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells, and 1, 4 and 5 showed a moderate inhibition with IC50 values ranging from 11.85 to 20.62 µM.
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Asteraceae , Animales , Antiinflamatorios/farmacología , Lipopolisacáridos , Macrófagos , Ratones , Óxido Nítrico , Células RAW 264.7RESUMEN
Overexpression of the histone acetyltransferase and the 1H NMR spectroscopic experiments of the endophytic fungus Monosporascus eutypoides resulted in the isolation of two new compounds, monosporasols A (1) and B (2), and two known compounds, pestaloficin C (3) and arthrinone (4). Their planar structures and absolute configurations were determined by spectroscopic analysis including high resolution electrospray ionization mass spectroscopy (HRESIMS), one-dimensional (1D) and two-dimensional (2D) NMR, and calculated electronic circular dichroism data. Compounds 1-2 were screened in cytotoxic bioassays against HeLa, HCT-8, A549 and MCF-7 cells. Our work highlights the enormous potential of epigenetic manipulation along with the NMR comparison as an effective strategy for unlocking the chemical diversity encoded by fungal genomes.
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Antineoplásicos/farmacología , Ascomicetos/química , Ascomicetos/genética , Endófitos/química , Epigénesis Genética , Células A549 , Cromatografía Líquida de Alta Presión , Dicroismo Circular , Evaluación Preclínica de Medicamentos , Fermentación , Células HeLa , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Estructura Molecular , Raíces de Plantas/microbiología , Policétidos/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum indicum L., is a common functional food and a well-known traditional Chinese medicine (TCM) for the treatment of inflammatory diseases. Previous studies have revealed that FCI has anti-inflammatory activity, but little is known about its anti-inflammatory chemical profile. In this study, the potential anti-inflammatory constituents of FCI were investigated by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with the network pharmacology approach, and further confirmed on a LPS activated RAW264.7 macrophage model. As a result, a total of forty-two compounds, including thirty-two flavonoids, nine phenolic acids and one sesquiterpene, were identified. Among them, fourteen compounds including eight flavonoids (11, 17, 24, 28, 32, 39, 41 and 42) and six caffeoylquinic acids (3, 4, 5, 13, 15 and 20) were recognized as potential key anti-inflammatory constituents of FCI through network pharmacology analysis, because they accounted for 92% of the relative peak area in the UPLC-Q-TOF/MS chromatogram and acted on 87 of 97 the inflammatory targets of FCI. However, only 16 targets were shared between the flavonoids and caffeoylquinic acids, indicative of both acting on more different targets. Further the anti-inflammatory effects of the fourteen constituents were validated with the decreased levels of NO, TNF-α, IL-6 and PGE2 in RAW264.7 macrophage cells treated with LPS. Our results indicated that both flavonoids and caffeoylquinic acids were responsible for the anti-inflammatory effect of FCI through synergetic actions on multi-targets. Moreover, 3,5-dicaffeoylquinic acid (15), luteolin (24) and linarin (28) were the most important active constituents of FCI and could be selected as chemical markers for quality control of FCI. Overall, the findings not only explore the anti-inflammatory chemical constituents of FCI, but also provide novel insights into the effective constituents and mechanism of TCMs.
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Antiinflamatorios/farmacología , Cromatografía Líquida de Alta Presión , Chrysanthemum/química , Medicamentos Herbarios Chinos/farmacología , Flores/química , Espectrometría de Masas en Tándem , Animales , Antiinflamatorios/química , Supervivencia Celular , Medicamentos Herbarios Chinos/química , Flavonoides/análisis , Glicósidos , Lipopolisacáridos/efectos adversos , Luteolina/análisis , Medicina Tradicional China/métodos , Ratones , Ácido Quínico/análogos & derivados , Células RAW 264.7RESUMEN
Nine new epipoly(thiodioxopiperazine) (ETP) analogues, chetocochliodins A-I (1-9), along with two known ones, chetoseminudins E and C (10 and 11), were purified from the fungus Chaetomium cochliodes. The planar structures and absolute configurations of these new compounds were determined by extensive NMR spectroscopic analysis, CD spectra, and chemical reactions. Shielding effects from the indole on the 3-SCH3/3-OCH3/3-OCH2- groups facilitated the determination of relative configuration of the analogues. Compound 9 was cytotoxic, suggesting the importance of the sulfide bridge for the diketopiperazine bioactivities.