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1.
J Sep Sci ; 46(14): e2300094, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37339806

RESUMEN

Coptis chinensis Franch. and Sophora flavescens Ait. is a herbal pair frequently used in treating ulcerative colitis. However, the bio-disposition profile of the major components in the inflamed gut remains unclear, which is essential to understand the pharmacological material basis of this herb pair. Here we established an integral quantitative and chemometric method to deduce the colonic metabolism differences of this herbal pair in normal and colitis mice. With this LC-MS method, a total of 41 components have been found in the Coptis chinensis Franch. and Sophora flavescens Ait. extract, and 28 metabolites were found in the colon after oral administration. Alkaloid and its phase I metabolites were the main components in the colon of normal and colitis mice. The results of principal component analysis at 6 h after oral administration showed significant colonic metabolism differences between normal and colitis mice. Heamap results showed that colitis induced significant changes in the colonic bio-disposition of this herbal pair extract. In particular, in the context of colitis, the phase I metabolism of berberine, coptisine, jatrorrhizine, palmatine,and epiberberine has been inhibited. These results may provide a basis for understanding the pharmacological material basis of Coptis chinensis Franch. and Sophora flavescens Ait. in treating ulcerative colitis.


Asunto(s)
Alcaloides , Colitis Ulcerosa , Coptis , Medicamentos Herbarios Chinos , Animales , Ratones , Coptis chinensis , Sophora flavescens , Colitis Ulcerosa/tratamiento farmacológico , Quimiometría , Coptis/química , Cromatografía Líquida de Alta Presión/métodos , Alcaloides/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Cromatografía Liquida , Medicamentos Herbarios Chinos/química
2.
Comb Chem High Throughput Screen ; 26(14): 2437-2451, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36872360

RESUMEN

INTRODUCTION: Sijunzi Decoction (SJZD) is a classical prescription in traditional Chinese medicine that enhances neuroimmune endocrine function to alleviate inflammatory aging, a key pathogenic mechanism underlying premature ovarian insufficiency (POI). However, the mechanism through which SJZD alleviates POI remains unknown. Hence, we aimed to identify the active components of SJZD and its mechanism of therapeutic action against POI. METHODS: We identified compounds in SJZD using liquid chromatography-linear trap quadrupole- Orbitrap-mass spectrometry (LC-LTQ-Orbitrap-MS). Traditional Chinese Medicine Systems (TCMSP) and HERB databases were used to identify the ingredients and potential targets of SJZD. We analyzed Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using RStudio and constructed a visual network using Cytoscape3.9.1. RESULTS: We identified 98 compounds using LC-LTQ-Orbitrap-MS, among which 29 were bioactive. The screen outputted yielded 151 predicted targets of these compounds that were associated with POI. The results of the GO and KEGG analyses showed that these compounds play key roles in cell growth, division, migration, and survival signaling pathways. Therefore, phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and epidermal growth factor receptor (EGFR) pathways might be closely associated with the pharmacological effects of SJZD on the pathological processes of POI. CONCLUSION: Our findings provide a scientific basis for rapidly analyzing bioactive compounds in SJZD and their pharmacological mechanisms.


Asunto(s)
Medicamentos Herbarios Chinos , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Medicamentos Herbarios Chinos/farmacología , Espectrometría de Masas , Simulación del Acoplamiento Molecular
3.
Phytomedicine ; 109: 154595, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36610135

RESUMEN

BACKGROUND: Increasing hepatic insulin signaling is found to be an important mechanism of Platycodon grandiflorus root to alleviate metabolic syndrome (MetS) symptoms such as insulin resistance, obesity, hyperlipidemia and hepatic steatosis, but the details are not yet clear. Since the main constituents of Platycodon grandiflorus root were hard to be absorbed by gastrointestinal tract, getting opportunity to interact with gut microbiota, we speculate the gut microorganisms may mediate its effect. PURPOSE: Our work aimed to confirm the critical role of gut microbes in the intervention of Platycodon grandiflorus root extract (PRE) on MetS, and investigate the mechanism. METHODS: Biochemical analyses, glucose tolerance test and hepatic lipidomics analysis were used to evaluate the anti-MetS effect of PRE on high fat diet (HFD) fed mice. Perform 16S rDNA analysis, qPCR analysis and in vitro co-incubation experiment to study its effect on gut microbes, followed by fecal microbiota transplantation (FMT) experiment and antibiotics intervention experiment. Also, the effect of Akkermansia muciniphila treatment on HFD mice was investigated. RESULTS: PRE alleviated lipid accumulation and insulin resistance in HFD mice and remodeled the fecal microbiome. It also increased the gene expression of colonic tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced TNF-α induced hepatic JNK-dependent IRS-1 serine phosphorylation and the impairment of PI3K/PIP3/Akt insulin signaling pathway. A. muciniphila was one of the most significantly enriched microbes by PRE treatment, and its administration to HFD mice showed similar effects to PRE, repairing the gut barrier and activating hepatic PI3K/PIP3/Akt pathway. Finally, anti-MetS effect of PRE could be delivered to FMT recipients, and PRE could not further attenuate MetS in gut microbiota depleted mice. CONCLUSION: We demonstrated for the first time that PRE alleviated MetS in a gut microbiota dependent manner, and found activation of hepatic insulin signaling mediated by gut A. muciniphila was a potential mechanism of it.


Asunto(s)
Resistencia a la Insulina , Síndrome Metabólico , Platycodon , Animales , Ratones , Insulina/metabolismo , Dieta Alta en Grasa/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal , Ratones Endogámicos C57BL
4.
J Pharm Biomed Anal ; 222: 115086, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36219926

RESUMEN

Dalitong Granules, a potent gastrointestinal motility promoting traditional Chinese medicine, is used to treat functional dyspepsia clinically. It shows good effect on alleviating gastrointestinal motility disorders and has a broad prospect of clinical application. However, there is no comprehensive study on its in vivo and in vitro chemical analysis. UPLC-Q-TOF-MS combined with the non-targeted characteristic filter analysis and in silico prediction strategies (NCFS) were used to deduce and identify the chemical components and in vivo metabolites in the bio-samples of rats following oral administration of Dalitong Granules. In this study, 108 chemical components were identified in Dalitong granules, including 50 flavonoids, 22 alkaloids, 13 terpenes, 11 organic acids, 10 coumarins and 2 volatile oils. In the plasma, tissue, urine and fecal samples of rats after administration of Dalitong granules, a total of 147 compounds were speculated (60 prototype compounds and 87 metabolites). The main metabolic pathways in vivo include methylation, demethylation, deglycosylation, hydrogenation, hydroxylation, sulfonation and glucuronidation as there are many flavonoids existing in Dalitong Granules. In conclusion, the chemical components and metabolites of Dalitong Granules were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Dalitong Granules efficacy and its further comprehensive development and utilization.


Asunto(s)
Alcaloides , Medicamentos Herbarios Chinos , Ratas , Animales , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Alcaloides/análisis , Flavonoides/análisis , Administración Oral
5.
J Ethnopharmacol ; 297: 115545, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-35843411

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis (SB) and Coptis chinensis (CC) are widely used traditional Chinese medicine (TCM) for "heat-clearing and damp-drying" and "purging fire and detoxifying". SB-CC are commonly used as a herbal pair for synergistic treatment of various diseases such as bacteria-related infections, metabolic syndromes, and some inflammatory disorders. This herbal pair is commonly used in many famous TCM formula, like Huang-Lian-Jie-Du, Gegen-Qinlian, Banxia Xiexin decoction. Aryl hydrocarbon receptor (AHR) plays an essential role in the disposition of both xenobiotics and endogenous substances through the induction of cytochrome P450 1A (CYP1A) enzymes. Regulation of the AHR-CYP1A axis is increasingly implicated in drug-drug and drug-herb interactions. Research on SB-CC for regulatory effect on the AHR-CYP1A axis is only limited to few compounds. AIM OF THE STUDY: This study aimed to systematically investigate the regulatory effect of SB-CC and its main constitutes on the AHR-CYP1A axis in vitro and in vivo. MATERIALS AND METHODS: The livers of mice treated with SB-CC extract were subjected to RNA-sequencing (RNA-seq). The key target genes related to drug metabolism were screened, and the differential expression genes (DEGs) were validated by qRT-PCR, Western blot, and enzyme activity assay. Luciferase reporter gene, qRT-PCR, and Western blot assays were used to determine whether SB-CC and their main constituents could activate AHR and regulate CYP1A expression in HepG2 cells. The effect of SB-CC on the pharmacokinetics of phenacetin, a CYP1A substrate, were further observed in mice to test the net effect of SB-CC on CYP1A functions. The potential CYP1A inhibitors in SB-CC were screened and their inhibitory mechanisms were also studied using human liver microsomes. RESULTS: AHR and drug metabolism system, especially CYP1A1 and CYP1A2, were strongly affected in the liver of SB-CC-treated mice. These results were further validated by the findings that SB-CC increased CYP1A's mRNA, protein expression and activity in mouse liver. In HepG2 cells, SB, CC, baicalin, baicalein, chrysin, oroxylin A, berberine, coptisine and epiberberine increased CYP1A1 mRNA expression in an AHR-dependent way. Interestingly, SB-CC treatment for 14 days only slightly increased the systemic exposure of paracetamol in mice. In the CYP1A inhibition assay, SB, CC, baicalin, baicalein, wogonoside, wogonin, chrysin, oroxylin A, scutellarein, columbamine, coptisine, palmatine, epiberberine, and berberrubine inhibited CYP1A activity in different degree. CONCLUSIONS: These results suggested that SB-CC exerted dual regulatory effect on the AHR-CYP1A axis by increasing CYP1A expression but simultaneously inhibiting CYP1A activity, which may contribute to a tight modulation of AHR signaling for homeostatic control.


Asunto(s)
Receptores de Hidrocarburo de Aril , Scutellaria baicalensis , Animales , Coptis chinensis , Citocromo P-450 CYP1A1/genética , Humanos , Ratones , Extractos Vegetales , ARN Mensajero , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Scutellaria baicalensis/química
6.
J Ethnopharmacol ; 295: 115401, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35623504

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandia lappa Decne. (ALDE) is the general name for Asteraceae plants Yunmuxiang, which has traditionally been proven to have the efficacy in relieving depression by regulating qi, alleviating cold by warming, attenuating pain in stomach and relieving diarrhea in intestines. Therefore, ALDE is always recommended as an herbal remedy for gastrointestinal dysfunction. AIM OF THE STUDY: The purpose of this study was to explore the therapeutic potential and mechanism of action of the sesquiterpene lactone-rich fraction (SLRF) of ALDE extracts in vivo and in vitro. MATERIALS AND METHODS: An aqueous extract (AE) and SLRF of ALDE were prepared and the contents of the main components were quantified by high performance liquid chromatography (HPLC). The therapeutic effects of the extracts were evaluated in C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Body weight, disease activity index (DAI), and colon length were recorded, and histopathological changes in the colon were characterized using hematoxylin and eosin (H&E) staining. The in vitro anti-inflammatory activity and possible mechanisms of the two main sesquiterpene lactones in ALDE (costunolide and dehydrocostus lactone) were studied by quantitative proteomic analysis. Finally, based on bioinformatic analysis, we used polymerase chain reaction (PCR), immunofluorescence, and western blot experiments to verify the anti-inflammatory mechanism of the extracts in C57BL/6 mice. RESULTS: The SLRF of ALDE significantly improved the pathological symptoms and inflammatory pathology of UC, whereas the AE had a weak protective effect. In RAW264.7 cells stimulated with lipopolysaccharide (LPS), costunolide and dehydrocostus lactone significantly reduced the mRNA levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, suggesting that these two sesquiterpene lactones had strong anti-inflammatory activity. Quantitative proteomics results indicated that the anti-inflammatory mechanism of these lactones was associated with the NF-κB/MAPK and Nrf2-Hmox-1 pathways. These results were further validated in SLRF-treated mice. CONCLUSION: This study confirmed that the SLRF of ALDE exerted protective activity against UC by regulating the Nrf2-Hmox-1, NF-κB, and MAPK pathways.


Asunto(s)
Colitis Ulcerosa , Saussurea , Sesquiterpenos , Animales , Antiinflamatorios/efectos adversos , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colon , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Lactonas/farmacología , Lactonas/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Fitoquímicos/farmacología , Proteómica , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 47(2): 437-443, 2022 Jan.
Artículo en Chino | MEDLINE | ID: mdl-35178987

RESUMEN

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 µm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 µL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.


Asunto(s)
Scutellaria , Espectrometría de Masas en Tándem , Quimiometría , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos
8.
J Sep Sci ; 45(9): 1600-1609, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35192736

RESUMEN

Scutellaria barbata D. Don (S. barbata) is one of the most frequently used anticancer herb medicine in China. Mechanistic understanding of the biological activities of S. barbata is hindered by limited knowledge regarding its components and metabolic profile. In this study, ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry (quadrupole time-of-flight mass spectrometry) was used to identify the chemical constituents in S. barbata and their metabolic profiles in rats. By applying cleavage rules and comparison with reference substances, 89 components were identified in S. barbata, which included 45 flavonoids, 28 diterpenoids, 10 phenolics, and 6 others. A total of 110 compounds, including 32 prototype compounds and 78 metabolites, were identified or tentatively characterized in vivo. Methylation, sulfonation, and glucuronidation were the main metabolic pathways, which could be attributed to the fact that several of the compounds in S. barbata have phenolic hydroxyl groups. This is the first systematic study on the chemical constituents and in vivo metabolic profile of S. barbata. The analytical method features a quick and comprehensive dissection of the chemical composition and metabolic profile of S. barbata and provides a basis for exploring its various biological activities.


Asunto(s)
Medicamentos Herbarios Chinos , Scutellaria , Animales , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Flavonoides/análisis , Espectrometría de Masas , Metaboloma , Ratas , Scutellaria/química , Scutellaria/metabolismo
9.
J Ethnopharmacol ; 283: 114700, 2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-34600076

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese and Korean medicine, Jowiseungki-tang (JST) is a prescription for diabetes mellitus (DM) treatment. However, little scientific evidence is known of its effect in diabetic condition. AIMS: We assessed the effects of JST on high-fat diet (HFD)-induced obesity with inflammatory condition in mice and to analyze the therapeutic function of JST on network pharmacology as well as targeted metabolomics. MATERIALS AND METHODS: JST administration at 100 mg/kg and 500 mg/kg for a period of 4 weeks in HFD-induced obese mice, body weight gain, energy utility, calorie intake, and levels of glucose, insulin, total cholesterol, triglyceride, LDL-cholesterol as well as interleukin-6 were measured. Measurements of HDL-cholesterol (HDL-C) were performed and compared to those of the control group. Moreover, the therapeutic function of JST on obesity was analyzed furtherly based on network pharmacology and targeted metabolomics methods. RESULTS: Administration of JST at 100 mg/kg and 500 mg/kg for a period of 4 weeks in HFD-induced obesity mice significantly decreased the body weight gain, energy utility, calorie intake, and levels of insulin, total cholesterol, LDL-cholesterol, triglyceride, and interleukin-6. However, HDL-cholesterol (HDL-C) levels showed marked elevation relative to control groups. JST administration strongly inhibited expressions of inducible nitric oxide synthase, inflammatory proteins, and cyclooxygenase-2 in the pancreas, stomach, and liver tissues, and reduced hepatic steatosis and pancreatic hyperplasia. In network pharmacological analysis, the putative functional targets of JST are underlie on modulation of cofactor-, coenzyme-, and fatty acid-bonding, insulin resistance, and inflammatory response, fine-tuned the phosphatase binding and signal pathway activation, such as mitogen activated protein kinases, phosphatidylinositol 3-kinases/protein kinase B, protein kinase C, and receptor of glycation end products as well-advanced glycation end products. According to the metabolomics analysis, the contents and energy metabolites, and medium and long chain fatty acids was significantly changed in mice pancreases. CONCLUSIONS: JST is a valuable prescription for treatment of patients with DM in traditional clinics through inhibition of obesity, inflammatory condition and metabolism.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Farmacología en Red , Obesidad/inducido químicamente , Obesidad/tratamiento farmacológico , Fitoterapia , Animales , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Metabolómica , Ratones , Ratones Endogámicos C57BL
10.
Front Immunol ; 12: 628358, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34025639

RESUMEN

Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11-induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1ß, and IL-6 in the colonic tissue of CPT-11-treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11-treated mice to near normal level. TFGU also effectively reversed the CPT-11-induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman's correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11-induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11-induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant.


Asunto(s)
Antiinflamatorios/farmacología , Bacterias/efectos de los fármacos , Colitis/prevención & control , Colon/efectos de los fármacos , Heces/microbiología , Flavonoides/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Glycyrrhiza uralensis , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Bacterias/metabolismo , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/microbiología , Colon/metabolismo , Colon/microbiología , Colon/patología , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Disbiosis , Flavonoides/aislamiento & purificación , Glycyrrhiza uralensis/química , Inflamasomas/metabolismo , Mediadores de Inflamación/metabolismo , Irinotecán , Masculino , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Extractos Vegetales/aislamiento & purificación
11.
Eur J Histochem ; 65(1)2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33634679

RESUMEN

Rheumatoid arthritis (RA) is featured by a variety of physical symptoms and fibroblast-like synoviocytes (FLSs) abnormal proliferation. Increasing evidence has demonstrated that traditional Chinese medicine exerts an important role in RA treatment. New bitongling (NBTL) as one of the traditional Chinese medicine has been reported to be involved in the progression of RA, but the exact mechanism is unclear. In our study, we intended to investigate the effect of NBTL on RA to identify the mechanisms related to JAK2/STAT3 signaling pathway. Extracts of Tripterygium wilfordii (TW), a traditional Chinese herbal medicine, have been widely used for treating RA in China for several decades, so, TW was used as a positive control drug for TBNL. RA rats were constructed by immunization with collagen type II to evaluate the action of NBTL in vivo. Body weight and arthritic index were evaluated. Hematoxylin and Eosin staining was performed to analysis the morphological changes of ankle joints tissue. TUNEL and flow cytometry were performed to examine cell apoptosis, while CCK8 and Ethynyl-2'-deoxyuridine (EdU) were performed to examine cell proliferation. In addition, the markers of inflammation were detected by Western blot, ELISA, and RT-qPCR. Firstly, we find that rats treated with NBTL or TW not only reduced swelling degree and bone destruction, but also repressed IL-1 ß and IL-6 levels. In addition, NBTL and TW could increase the weight of rats, and promote the level of IL-10 and IL-4 in vivo. Furthermore, NBTL inhibited inflammation of FLS, induced cell apoptosis and hindered cell proliferation, which was reversed by dipeptidyl peptidase (DPP), a JAK2/STAT3 pathway activator. Taken together, NBTL potentially retarded RA via JAK2/STAT3 pathway, highlighting novel mechanisms associated with RA.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Proliferación Celular/efectos de los fármacos , Femenino , Inflamación/tratamiento farmacológico , Inflamación/etiología , Ratas Sprague-Dawley , Sinoviocitos/efectos de los fármacos
12.
J Ethnopharmacol ; 267: 113489, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33091498

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia kansui (EK) is the dried root of Euphorbia kansui S.L.Liou ex S.B.Ho. Clinically, processing with vinegar is for reducing toxicity of EK, and EK stir-fried with vinegar (VEK) is used to treat ascites and edema. VEK has been confirmed to reduce ascites by accelerating the promotion of intestinal contents. AIM OF THE STUDY: The study aimed to investigate whether gut microbiota could affect the expelling water retention effects and the intestinal oxidative damage of EK and VEK on malignant ascites effusion (MAE) rats. MATERIALS AND METHODS: Pseudo-germ-free (PGF) MAE rats or probiotic intervented MAE rats were treated with EK/VEK. Related indicators such as serum, ascites, urine, feces, gastrointestinal tissues were analyzed, and the structure of the gut microbiota were also studied. The relationship between gut microbiota and the expelling water retention effects of EK/VEK where then further investigated. RESULTS: VEK reduce the volume of ascites by promoting urine and feces excretion, AQP8 protein and mRNA expression, when comparing with the MAE rats, also VEK could regulate the disordered gut microbiota in MAE rats. Mixed antibiotics could diminish VEK's expelling water retention effects in MAE rats, but increased oxidative damage in intestine. While existence of gut microbiota (especially probiotics) played an important role in the protection of intestines in VEK treated MAE rats. CONCLUSION: VEK had obvious pharmacological effect on MAE and could regulate gut microbiota, but gut microbiota was not a necessary condition for its pharmacological effects. The probiotics played a synergistic role with VEK in the effects of expelling water retention and intestinal protection.


Asunto(s)
Ácido Acético/química , Ascitis/prevención & control , Bacterias/efectos de los fármacos , Culinaria , Euphorbia , Microbioma Gastrointestinal/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Acuaporinas/genética , Acuaporinas/metabolismo , Ascitis/etiología , Ascitis/microbiología , Ascitis/patología , Bacterias/crecimiento & desarrollo , Línea Celular Tumoral , Defecación/efectos de los fármacos , Euphorbia/química , Calor , Intestino Delgado/metabolismo , Intestino Delgado/microbiología , Intestino Delgado/patología , Masculino , Neoplasias/complicaciones , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Probióticos/farmacología , Ratas Sprague-Dawley , Micción/efectos de los fármacos
13.
Pharm Biol ; 58(1): 367-373, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32351153

RESUMEN

Context: As a toxic traditional Chinese medicine for edoema, Euphorbia kansui S.L. Liou ex S.B. Ho (Euphorbiaceae) (EK) stir-fried with vinegar for detoxification was associated with alterations of gut microbiota. However, the evidence of correlation between short-chain fatty acids (SCFAs) and toxicity of EK has not been confirmed.Objective: In order to study the biological basis of detoxification of EK stir-fried with vinegar (VEK), a rapid, sensitive and validated GC-MS method was developed to determine SCFAs in normal rat faeces after given EK and VEK.Materials and methods: Sprague Dawley rats were orally administered 0.5% CMC-Na (control group), EK (EK-treated group) and VEK powder (VEK-treated group) at 680 mg/kg for six consecutive days (eight rats each group). Fresh faeces samples were promptly collected, derivatized and then analyzed by GC-MS.Results: The ranges of LOD and LOQ were within 0.13-1.79 and 0.45-5.95 µg/mL, respectively. The RSD values of intra-day and inter-day precisions were less than 15%. Four SCFAs were generally stable under four storage conditions. The extraction recoveries were ranged from 53.5% to 97.3% with RSD values lower than 15%. The concentrations of four SCFAs in EK and VEK were decreased significantly compared with those not administered (EK-treated, p < 0.01; VEK-treated, p < 0.05 and p < 0.01). After being stir-fried with vinegar, the concentrations were all increased (p < 0.05 and p < 0.01).Discussion and conclusions: The negative correlation between SCFAs and toxicity of EK may provide evidence for biological mechanism and toxic Chinese medicine.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Edema/tratamiento farmacológico , Euphorbia , Ácidos Grasos Volátiles/análisis , Heces/química , Extractos Vegetales/uso terapéutico , Animales , Medicamentos Herbarios Chinos/aislamiento & purificación , Edema/metabolismo , Masculino , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Sprague-Dawley
14.
J Ethnopharmacol ; 249: 112423, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31765764

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia kansui is a toxic Chinese herbal medicine and exhibits promising treatment to the malignant ascites (MA) in its traditional use. Ingenane-type and jastrophane-type diterpenes are demonstrated to be responsible for the toxicity and efficacy of kansui. Two representative compounds, kansuiphorin C (KPC) and kansuinin A (KA) in each type were proved to effectively reduce the ascites. The biological and toxicological effects are closely associated with the gastrointestinal tract, but the possible mechanism and related metabolic functions of KPC and KA treating MA through modulating the gut microbiota remain unclear. AIM OF THE STUDY: To investigate the possible mechanism and related metabolism of KPC and KA ameliorating malignant ascites through modulating gut microbiota. MATERIALS AND METHODS: MA rats and normal rats were divided into different groups and administrated with KPC, KA, and positive drug, respectively. 16S rDNA gene sequencing and metagenomes analysis combined with the quantification of short-chain fatty acids of feces were performed to reflect the modulation of gut microbiota. Then, the metabolites of KPC and KA in rat feces under the normal and pathological circumstances were detected by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) to explore the in-vivo bacterial biotransformation. RESULTS: KPC and KA were modulatory compounds for gut microbiota. The richness of Lactobacillus and the decreased abundance of Helicobacter involved in the carbohydrate metabolism and amino acid metabolism could be responsible for their prohibitory effects on malignant ascites. KPC exhibited stronger modulation of gut microbiota through making the abundance of Helicobacter about 3.5 times lower than KA. Besides, in-vivo microbial biotransformation of KPC and KA contained oxidation, hydrolysis, dehydration, and methylation to form metabolites of lower polarity. Besides, at the dosage of 10 mg kg-1, the toxicity of both compounds had weaker influences on the gut microbiota of normal rats. CONCLUSION: KPC and KA could ameliorate malignant ascites by modulating gut microbiota mainly containing the increase of Lactobacillus and the decrease of Helicobacter and related carbohydrate and amino acid metabolism, providing a basis for their promising clinical usage.


Asunto(s)
Ascitis/tratamiento farmacológico , Diterpenos/farmacología , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias Peritoneales/tratamiento farmacológico , Animales , Ascitis/etiología , Ascitis/metabolismo , ADN Bacteriano/aislamiento & purificación , Modelos Animales de Enfermedad , Diterpenos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Euphorbia/química , Heces/microbiología , Microbioma Gastrointestinal/fisiología , Helicobacter/genética , Helicobacter/aislamiento & purificación , Humanos , Lactobacillus/genética , Lactobacillus/aislamiento & purificación , Masculino , Metagenoma/genética , Neoplasias Peritoneales/complicaciones , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/secundario , ARN Ribosómico 16S/genética , Ratas , Pruebas de Toxicidad
15.
J Pharm Biomed Anal ; 179: 112984, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-31759764

RESUMEN

Xiao-Ai-Jie-Du decoction (XAJDD), a traditional Chinese medicine formula, has long been used for the treatment of hepatocarcinoma, gastric cancer and colorectal cancer. It is composed of six herbal medicines, including Scutellariae Barbatae Herba, Pseudostellariae Radix, Ophiopogonis Radix, Cremastrae Pseudobulbus, Curcumae Rhizoma and Akebiae Fructus. Despite the in-depth study on its pharmacological effects on cancer prevention and treatment, the comprehensive analysis of the chemical components and the absorbed bioactive constituents are not well studied. Thus, an ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was established to detect and identify the chemical constituents in XAJDD. The absorbed components and metabolites after oral administration of XAJDD in rats were also studied. In total, 102 components were identified or tentatively characterized in XAJDD, including 30 flavonoids, 19 triterpenoids, 12 organic acids, 9 steroidal saponins, 9 cyclic peptides, 7 phenanthrenes, 5 amino acids, 3 alkaloids and 8 other compounds. After analysing the metabolites in rat plasma and urine after oral administration of XAJDD, a total of 70 compounds were identified, including 15 primary components and 55 metabolites, and metabolic pathways, including hydrogenation, hydroxylation, methylation, sulfonation, and glucuronidation were evaluated. Among these, methylation and glucuronidation were the main metabolic pathways. In conclusion, the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of XAJDD in vitro and characterizing the primary components and their metabolites in vivo; moreover, the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of XAJDD.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Espectrometría de Masas en Tándem/métodos , Ácidos/análisis , Animales , Flavonoides/análisis , Masculino , Ratas , Saponinas/análisis , Distribución Tisular , Triterpenos/análisis
16.
J Pharm Biomed Anal ; 175: 112762, 2019 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-31336286

RESUMEN

As a triterpene saponin, pedunculoside is one of the most abundant, representative and active components in plants of genus Ilex (Aquifoliaceae). Pedunculoside has been used to treat myocardial ischemia, ameliorate hyperlipidemia and prevent liver injury. In this paper, a systemic in vitro liver microsomes / S9 and intestinal bacteria incubation, and in vivo animal experiment were performed, using LC-Q-TOF/MS analysis and a three-step data processing protocol. As a result, Bifidobacterium adolescentis and Bifidobacterium breve were identified to potentially metabolize pedunculoside among the intestinal bacteria tested. A total of 11 metabolites were found and tentatively identified, with 6 in both microsomal and bacterial incubation systems, and 9 after rats orally administered with pedunculoside. The metabolites detected involving both phase I and phase II metabolism, mainly through deglycosylation (hydrolyzation), dehydrogenation, hydroxylation and conjugation, and some of them underwent more than one-step metabolic reactions. Most of the metabolites have not been reported before. In vitro, liver microsome and intestinal bacteria prefer to metabolize pedunculoside in totally different ways; while in vivo, intestinal tract is the most important site for the metabolism and excretion of pedunculoside, where both intestinal bacteria and the host metabolic enzymes participate in its metabolism and disposition. The importance of intestinal bacteria should be highlighted. This study would contribute to a better understanding of pedunculoside metabolism, which can provide scientific evidence for its pharmacodynamic mechanism research and prove its clinical application.


Asunto(s)
Biotransformación/fisiología , Glucosa/análogos & derivados , Metaboloma/fisiología , Triterpenos/química , Triterpenos/metabolismo , Animales , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/metabolismo , Heces/química , Glucosa/química , Glucosa/metabolismo , Hidroxilación/fisiología , Ilex/metabolismo , Intestinos/fisiología , Masculino , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-Dawley , Saponinas/química , Saponinas/metabolismo , Espectrometría de Masas en Tándem/métodos
17.
Oxid Med Cell Longev ; 2019: 8636835, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30911351

RESUMEN

Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.


Asunto(s)
Amnesia/tratamiento farmacológico , Donepezilo/uso terapéutico , Ginkgo biloba/química , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Acetilcolina/metabolismo , Acetilcolinesterasa , Amnesia/patología , Animales , Benzotiazoles/química , Compuestos de Bifenilo/química , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Inhibidores de la Colinesterasa/farmacología , Trastornos del Conocimiento/tratamiento farmacológico , Donepezilo/farmacología , Quimioterapia Combinada , Ginkgólidos/química , Ligandos , Malondialdehído/metabolismo , Ratones Endogámicos ICR , Simulación del Acoplamiento Molecular , Picratos/química , Extractos Vegetales/farmacología , Receptor trkB/metabolismo , Escopolamina , Ácidos Sulfónicos/química , Superóxido Dismutasa/metabolismo , Comprimidos
18.
Front Pharmacol ; 10: 1600, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32047436

RESUMEN

Rhein is one of active anthraquinone components in traditional Chinese herbal medicine Rheum palmatum L., possessing anti-inflammatory, antioxidant, antitumor, antiviral, and hepatoprotective activities. Human respiratory syncytial virus (RSV), a common virus, is able to result in pneumonia and bronchitis, which usually can be seen in infants. However, so far the effects of Rhein on RSV-induced pneumonia are still unknown. As the NLRP3 inflammasome is activated excessively, it is able to lead to inflammatory response and tissue injury in most viral infection process (including RSV infection) of respiratory tract. Therefore, we designed experiments to reveal whether Rhein can treat RSV-induced pneumonia by inhibiting NLRP3 inflammasome activation. In present research, we established the pneumonia model of BALB/C mice caused by RSV. First of all, the pathology of lung tissue and the weight of mice were evaluated, and the corresponding lung index was calculated. Additionally, the expression of pro-inflammatory mediators in serum and lung tissues, and related proteins (NLRP3, ASC and Caspase-1) of NLRP3 inflammasome and NF-κB pathway were detected by Enzyme-linked immunosorbent assay (ELISA), Real-time PCR (RT-PCR), Immunohistochemistry (IHC), and Western blot (WB), respectively. The determination of lung index and lung tissue pathological evaluation revealed that Rhein was able to alleviate lung infection and injury caused by RSV. The results of ELISA showed that Rhein was able to reduce the release of pro-inflammatory cytokines in the serum and lung tissues of RSV-induced BALB/c mice, including IL-1ß, IL-6, TNF-α, IL-18, and IL-33. Additionally, it was revealed that Rhein inhibited the immune inflammatory response of RSV-infected mice, which was likely to be associated with the inhibition the NLRP3 inflammasome activation via NF-κB pathway. To sum up, our results indicated that Rhein may inhibit RSV-induced pulmonary inflammatory response effectively; meanwhile, it is emphasized that Rhein therapy is likely to be a promising treatment on the RSV-infected lung inflammation and avoidance of lung tissue damage.

19.
J Tradit Chin Med ; 39(1): 139-152, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-32186035

RESUMEN

Behcet's disease is a condition with a complicated and unclear etiology that comprises multi-systemic, chronic, inflammatory vasculitis. Behcet's disease can affect every tissue and organ in the body, and is characterized by recurrent oral and genital ulcers, ocular inflammation, skin lesions, and other manifestations. The incidence of Behcet's disease has a distinct regional specificity, and is most prevalent along the Silk Road, a route that stretched between the Mediterranean, Middle East and Far East. This article reviews the recent literature to evaluate the prevalence, clinical manifestations, pathogenesis and mechanism, and current treatments of Behcet's disease. Furthermore, the etiology of Behcet's disease will be evaluated from the aspect of Traditional Chinese Medicine (TCM) syndrome differentiation. As Behcet's disease is complex and intractable, its treatment warrants further research. Traditionally, Behcet's disease is treated with Western Medicine (WM) via medications that act locally and systemically; this WM treatment protocol usually has a good effect, but relapse can occur after reducing the dosage. Thus, it may be ideal to treat Behcet's disease via a combination of WM and TCM. Recent studies have indicated that such a combination of Chinese and Western treatments has a better effect than either treatment alone. The aim of the present review is to describe the clinical features of Behcet's disease, and to outline its possible pathogenesis in terms of both TCM and WM. Based on these findings, the present review proposes a Behcet's disease treatment protocol composed of a combination of Chinese and WM that can effectively improve the occurrence of relapse caused by the reduction of the dosage of Western medication.


Asunto(s)
Síndrome de Behçet/tratamiento farmacológico , Medicina Tradicional China/métodos , Humanos
20.
Molecules ; 23(8)2018 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-30104552

RESUMEN

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.


Asunto(s)
Alantoína/química , Alantoína/farmacología , Diferenciación Celular/efectos de los fármacos , Dioscorea/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mioblastos/citología , Mioblastos/efectos de los fármacos , Rizoma/química , Adenosina Trifosfato/biosíntesis , Animales , Línea Celular , Metabolismo Energético/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Mitocondrias/genética , Fibras Musculares Esqueléticas/citología , Biogénesis de Organelos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos
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