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BACKGROUND: The plant Smilax china L., also known as Jingangteng, is suspected of regulating glucose and lipid metabolism. Jingangteng capsules (JGTCs) are commonly used to treat gynecological inflammation in clinical practice. However, it is not clear whether JGTCs can regulate glucose and lipid metabolism, and the mechanism is unclear. PURPOSE: To investigate the impact and mechanism of action of JGTCs on diabetes and liver lipid disorders in rats. METHODS: The chemical constituents of JGTCs were examined using ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. A high-fat diet and streptozotocin-induced diabetes model was used to evaluate anti-diabetic effects by assessing blood glucose and lipid levels and liver function. The mechanism was explored using fecal 16S rRNA gene sequencing and metabolomics profiling, reverse transcription-quantiative polymerase chain reaction (RT-qPCR), and Western blot analysis. RESULTS: Thirty-three components were identified in JGTCs. The serological and histomorphological assays revealed that JGTC treatment reduced levels of blood glucose and lipids, aspartate aminotransferase, alanine aminotransferase, and lipid accumulation in the liver of diabetic rats. According to 16S rDNA sequencing, JGTCs improved species richness and diversity in diabetic rats' intestinal flora and restored 22 dysregulated bacteria to control levels. Fecal metabolomics analysis showed that the altered fecal metabolites were rich in metabolites, such as histidine, taurine, low taurine, tryptophan, glycerophospholipid, and arginine. Serum metabolomics analysis indicated that serum metabolites were enriched in the metabolism of glycerophospholipids, fructose and mannose, galactose, linoleic acid, sphingolipids, histidine, valine, leucine and isoleucine biosynthesis, and tryptophan metabolism. Heatmaps revealed a strong correlation between metabolic parameters and gut microbial phylotypes. Molecular biology assays showed that JGTC treatment reversed the decreased expression of farnesoid X receptor (FXR) in the liver of diabetic rats and inhibited the expression of lipogenic genes (Srebp1c and FAS) as well as inflammation-related genes (interleukin (IL)-ß, tumor necrosis factor (TNF)-α, and IL-6). Liver metabolomics analysis indicated that JGTC could significantly regulate a significant number of bile acid metabolites associated with FXR, such as glyco-beta-muricholic acid, glycocholic acid, tauro-beta-muricholic acid, and tauro-gamma-muricholic acid. CONCLUSIONS: This was the first study to investigate the mechanisms of JGTCs' effects on liver lipid disorders in diabetic rats. JGTCs inhibited liver lipid accumulation and inflammatory responses in diabetic rats by affecting intestinal flora and metabolic disorders and regulating FXR-fat synthesis-related pathways to alleviate diabetic lipid disorders.
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Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Hígado , Ratas Sprague-Dawley , Receptores Citoplasmáticos y Nucleares , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratas , Receptores Citoplasmáticos y Nucleares/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Glucemia/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Cápsulas , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológicoRESUMEN
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
BACKGROUND: Metabolic and alcohol-associated liver disease (MetALD) shows a high prevalence rate in liver patients, but there is currently no effective treatment for MetALD. As a typical edible traditional Chinese medicinal herb, the anti-inflammatory, antioxidant, and hepatoprotective properties of water extract of Chrysanthemum morifolium Ramat. (WECM) has been demonstrated. However, its therapeutic effect on MetALD and the associated mechanisms remain unclear. PURPOSE: To investigate the underlying mechanisms of WECM against MetALD. METHODS: We constructed a MetALD rat model following a high-fat & high-sucrose plus alcohol diet (HFHSAD). MetALD rats were treated with WECM at 2.1, 4.2, and 8.4 g/kg/d for six weeks. Efficacy was determined, and pathways associated with WECM against MetALD were predicted through serum and hepatic biochemical marker measurement, histopathological section analysis, 16S rDNA sequencing of the gut microbiota and untargeted serum metabolomics analyses. Changes in genes and proteins in the peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) signaling pathways were detected by RTâPCR and Western blotting. RESULTS: WECM treatment significantly attenuated hepatic steatosis, hyperlipidemia and markers of liver injury in MetALD rats. Moreover, WECM improved vascular endothelial function, hypertension, and systematic oxidative stress. Mechanistically, WECM treatment altered the overall structure of the gut microbiota through maintaining Firmicutes/Bacteroidota ratio and reducing harmful bacterial abundances such as Clostridium, Faecalibaculum, and Herminiimonas. Notably, WECM promoted 15-deoxy-â³12, 14-prostaglandin J2 (15d-PGJ2) release and further activated the PPARγ to reduce serum TNF-α, IL-1ß, and IL-6 levels. Additionally, WECM upregulated PPARα and downregulated the levels of CD36 and FABP4 to improve lipid metabolism. CONCLUSION: Our findings provide the first evidence that WECM treatment significantly improved hepatic steatosis, oxidative stress and inflammation in MetALD rats by regulating the gut microbiota and activating the 15d-PGJ2/PPARγ and PPARα signaling pathway.
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Chrysanthemum , Microbioma Gastrointestinal , Hepatopatías Alcohólicas , PPAR alfa , PPAR gamma , Ratas Sprague-Dawley , Chrysanthemum/química , Animales , Microbioma Gastrointestinal/efectos de los fármacos , PPAR gamma/metabolismo , PPAR alfa/metabolismo , Masculino , Hepatopatías Alcohólicas/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Ratas , Hígado/efectos de los fármacos , Hígado/metabolismo , Extractos Vegetales/farmacología , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Estrés Oxidativo/efectos de los fármacosRESUMEN
The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments. UPLC-Q-TOF-MS/MS was employed to chara-cterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma, and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology. The "drug-component-target-disease" network was constructed. Protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma. Finally, the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer. Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma, among which gymnoside â , gymnoside â ¡, militarine, bletilloside A, and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer. PPI network analysis revealed core targets such as albumin(ALB), serine/threonine kinase 1(AKT1), tumor necrosis factor(TNF), and epidermal growth factor receptor(EGFR). The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras signaling pathway. The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate, decrease the levels of TNF-α, interleukin(IL)-1ß, IL-6, vasoactive intestinal peptide(VIP), and thromboxane B2(TXB2), elevated the le-vels of IL-10, prostaglandin E2(PGE2), epidermal growth factor(EGF), and vascular endothelial growth factor(VEGF), down-re-gulate the protein levels of PI3K and AKT, and up-regulate the protein levels of p-PI3K and p-AKT. This study indicates that Bletillae Rhizoma may play a role in the treatment of gastric ulcer through multiple components, targets, and pathways and verifies partial prediction results of network pharmacology. The findings of this study provide a scientific and experimental basis for clinical application.
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Experimentación Animal , Medicamentos Herbarios Chinos , Úlcera Gástrica , Animales , Ratones , Úlcera Gástrica/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Espectrometría de Masas en Tándem , Factor A de Crecimiento Endotelial Vascular , Factor de Necrosis Tumoral alfa , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
Poria cocos alkali-soluble polysaccharide (PCAP), a water-insoluble ß-glucan, is the main component of the total dried sclerotia of Poria cocos. However, its gelation behaviour and properties have yet to be comprehensively studied. In this study, an acid-induced physical hydrogel based on natural PCAP is fabricated. The acid-induced gelation in PCAP is explored with respect to the pH and polysaccharide concentration. PCAP hydrogels are formed in the pH range of 0.3-10.5, and the lowest gelation concentration is 0.4 wt%. Furthermore, dynamic rheological, fluorescence, and cyclic voltammetry measurements are performed to elucidate the gelation mechanism. The results reveal that hydrogen bonds and hydrophobic interactions play a dominant role in gel formation. Subsequently, the properties of the PCAP hydrogels are investigated using rheological measurements, scanning electron microscopy, gravimetric analysis, free radical scavenging, MTT assays, and enzyme-linked immunosorbent assays. The PCAP hydrogels exhibit a porous network structure and cytocompatibility, in addition to good viscoelastic, thixotropic, water-holding, swelling, antioxidant, and anti-inflammatory activities. Furthermore, using rhein as a model drug for encapsulation, it is demonstrated that its cumulative release behaviour from the PCAP hydrogel is pH dependent. These results indicate the potential of PCAP hydrogels for application in biological medicine and drug delivery.
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Hidrogeles , Wolfiporia , Hidrogeles/química , Sistemas de Liberación de Medicamentos , Polisacáridos/farmacología , Polisacáridos/química , Agua/químicaRESUMEN
Chrysanthemi Flos (Juhua), an edible herbal medicine that possesses efficacies of dispersing wind, clearing heat and detoxifying. Studies have demonstrated that the health benefits of Chrysanthemi Flos are largely attributable to its anti-inflammatory effects. However, the correlation between the compounds monitored by the current quality control methods and the anti-inflammatory effects of Chrysanthemi Flos is unclear. In order to better control the quality of Chrysanthemi Flos, the identification of anti-inflammatory quality markers (Q-markers) of Chrysanthemi Flos was performed. The chemical components of Chrysanthemi Flos were profiled by HPLC fingerprints combined with chemometrics methods. Simultaneously, the anti-inflammatory activities of 10 batches of water extracts of Chrysanthemi Flos were evaluated in lipopolysaccharide-activated RAW 264.7 macrophages cells. Gray correlation analysis was performed to assess the relationship between the anti-inflammatory activity and chemical properties. The results showed that 13 common peaks were closely correlated with the anti-inflammatory effect, and further bioactivity re-evaluation confirmed that 10 known compounds exerted a strong anti-inflammatory effect. The quantitative analysis of the 10 Q-markers showed that the 25 batches of samples could be discriminated into different zones according to their producing areas. Conclusively, the present work identified 10 anti-inflammatory Q-markers of Chrysanthemi Flos using spectrum-effect relationships combined with bioactivity re-evaluation.
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Chrysanthemum , Medicamentos Herbarios Chinos , Cromatografía Líquida de Alta Presión/métodos , Chrysanthemum/química , Medicamentos Herbarios Chinos/química , Antiinflamatorios/análisis , Antiinflamatorios/farmacología , Control de CalidadRESUMEN
Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/ß/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.
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Poria , Animales , Ratas , Bazo , Albúminas , Cromatografía Liquida , Proteína de Unión a Elemento de Respuesta al AMP CíclicoRESUMEN
Owing to the irreplaceable role of traditional Chinese medicine in the history of human resistance to diseases, medicine food homology teas (MFHTs) have emerged as a widely-consumed daily drink, although they may contain toxic or excessive trace elements. This study aims to determine the total and infused concentrations of nine trace elements (Fe, Mn, Zn, Cd, Cr, Cu, As, Pb, and Ni) in 12 MFHTs collected from 18 provinces in China, to evaluate their potential risks to human health, and to explore the factors affecting the trace element enrichment in traditional MFHTs. The exceedances of Cr (82%) and Ni (100%) in 12 MFHTs were higher than those of Cu (32%), Cd (23%), Pb (12%), and As (10%). The high values of the Nemerow integrated pollution index of dandelions and Flos sophorae (25.96 and 9.06, respectively) indicate severe trace metal pollution. The health risk assessment results showed that As, Cr, and Mn in the 12 types of MFHTs posed high non-carcinogenic risk. Honeysuckle and dandelion teas may be hazardous to human health through trace element exposure when consumed daily. The enrichment of Cr, Fe, Ni, Cu, Zn, Mn, and Pb in MFHTs is influenced by the MFHT type and producing area, whereas As and Cd are mainly controlled by the MFHT type. Environmental factors such as soil background values, rainfall, and temperature also affect the enrichment of trace elements in MFHTs collected from different producing areas.
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Metales Pesados , Contaminantes del Suelo , Oligoelementos , Humanos , Monitoreo del Ambiente/métodos , Oligoelementos/análisis , Cadmio , Plomo , Contaminantes del Suelo/análisis , Suelo , Medición de Riesgo , China , Metales Pesados/análisisRESUMEN
The chemical components in rats after oral administration of the water extract of Chrysanthemum morifolium cv. Fubaiju(CMF) were analyzed by UPLC-Q-TOF-MS/MS technique. Forty-four compounds were identified from the water extract of CMF and 11 components were identified from the rat serum. A total of 264 potential anti-inflammatory targets were identified by network pharmacology based on serum components. The "component-target" network and protein-protein interaction(PPI) network were constructed, and GO function enrichment and KEGG pathway enrichment analyses were performed. The molecular docking was carried out to validate the results of network pharmacology. The results showed that CMF might act on AKT1, TNF, TP53, IL6, INS, and other core targets through apigenin, luteolin, acacetin, diosmetin, 3,4-O-dicaffeoylquinic acid, and other active components, and exert anti-inflammatory effects by regulating PI3 K-AKT signaling pathway, FoxO signaling pathway, cAMP signaling pathway, Ras signaling pathway, and other pathways. The pharmacodynamic materials basis of CMF was identified by UPLC-Q-TOF-MS/MS technology, and the core anti-inflammatory targets and the underlying mechanism of action were analyzed by network pharmacology and molecular docking, which provided a reference for comprehensively clarifying the pharmacodynamic materials basis and quality control of CMF.
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Chrysanthemum , Medicamentos Herbarios Chinos , Animales , Antiinflamatorios/análisis , Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/química , Simulación del Acoplamiento Molecular , Farmacología en Red , Ratas , Espectrometría de Masas en Tándem/métodos , AguaRESUMEN
BACKGROUND: Poria cocos is an ancient medicine and modern functional food, which exerts excellent effects on anxiety, although its mechanism is unknown. PURPOSE: To explore the mechanisms of the aqueous extract of P. cocos (PCD) in ameliorating anxiety-like behavior caused by chronic sleep deprivation (CSD). METHODS: PCD chemical composition was analyzed by UPLC-QTOF-MS/MS. A CSD rat model was established over 21 days. We examined the effects and mechanisms after 10 days of CSD using open-field tests (OFTs), enzyme-linked immunosorbent assays, 16S rDNA, non-targeted metabolomics, and Western blot analyses. RESULTS: Sixty-two triterpenoids were identified in PCD. CSD-induced anxiety-like behavior was significantly attenuated by PCD treatment. PCD improved hypothalamic neurotransmitters, decreased proinflammatory cytokines, and depressed the proteins expression of tumor necrosis factor (TNF)-α/nuclear factor (NF)-κB signaling pathway. The full-length 16S rDNA sequence of bacterial cells was also sequenced by high-throughput analysis. CSD caused significant changes in the intestinal flora. PCD improved the species diversity and bacterial abundance in the intestines of rats with anxiety. Metabolomics analysis indicated that 12 PCD-related metabolites in serum and 32 PCD-related metabolites in feces were identified, respectively. Metabolite analysis in serum, PCD treatment affected taurine, hypotaurine, cysteine, methionine, glycine, serine, and threonine metabolism, among others. Metabolite analysis in feces showed significant effects of PCD treatment on the metabolism of vitamin B6, tyrosine, drugs, and glycerophospholipid. Additionally, the correlation analysis of heatmaps showed a tight relationship between inflammatory factors, metabolic parameters, and gut microbial phylotypes. CONCLUSIONS: PCD relieved anxiety by regulating intestinal flora, regulating metabolic disorders, and inhibiting inflammatory pathways in chronic sleep-deprived rats.
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Wolfiporia , Animales , Ansiedad/tratamiento farmacológico , ADN Ribosómico/farmacología , Metabolómica , FN-kappa B/metabolismo , ARN Ribosómico 16S , Ratas , Transducción de Señal , Espectrometría de Masas en Tándem , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Poria cocos (P. cocos) has been traditionally used as folk medicine and functional food in China for more than 2000 years. The water-soluble polysaccharide is the main component of P. cocos decoction. The effects and mechanisms of the water-soluble polysaccharide from P. cocos (PCWP) were investigated in chronic sleep deprivation (CSD)-induced anxiety in rats. CSD induced anxiety, gut dysbiosis, and inflammatory responses, and reduced neurotransmitter levels, whereas PCWP intervention ameliorated anxiety-like behaviors, increased the levels of 5-hydroxytryptamine, dopamine, norepinephrine, and γ-aminobutyric acid in the hypothalamus, regulated gastrointestinal peptide levels, reduced inflammatory factors, and inhibited the tumor necrosis factor (TNF)-α/nuclear factor (NF)-κB signaling pathway in rats with CSD. The changes in the intestinal flora composition were determined using 16S rDNA sequencing, and indicated that PCWP significantly improved species richness and diversity in the intestinal flora of rats with anxiety, and adjusted the abundance of the following dysregulated bacteria closer to that of the normal group: Rikenellaceae_RC9_gut_group, Ruminococcus, Prevotellaceae_UCG-001, Prevotellaceae_NK3B31_group, Fusicatenibacter. Metabolomics was used to analyze fecal samples to identify significantly altered metabolites in the PCWP-treated groups. Thirty-eight PCWP-related metabolites and four metabolic pathways such as sphingolipid metabolism, taurine and hypotaurine metabolism, vitamin B6 metabolism, and glycerophospholipid metabolism were explored. The results of serum metabolomics showed that 26 biomarkers were significantly changed after PCWP intervention compared with the model group. The regulatory effects of metabolic pathway enrichment on sphingolipid, phenylalanine, and taurine and hypotaurine metabolism, and validation results showed that PCWP intervention regulated the activity of enzymes involved in the above metabolic pathways. A strong correlation between intestinal bacteria and potential biomarkers was found. Our findings present new evidence supporting the potential effect of PCWP in preventing the progression of anxiety by inhibiting the TNF-α/NF-κB signaling pathway, alleviating metabolic disorders, and ameliorating the gut microflora imbalance.
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Enfermedades Metabólicas , Wolfiporia , Animales , Ansiedad/tratamiento farmacológico , Biomarcadores/metabolismo , Disbiosis/microbiología , Enfermedades Intestinales/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Polisacáridos/farmacología , Ratas , Transducción de Señal , Privación de Sueño , Esfingolípidos , Taurina/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología , Agua/farmacología , Wolfiporia/químicaRESUMEN
Purpose: Wolfiporia cocos is frequently used in traditional Chinese medicine to treat depression. However, antidepressant-like effects of the main active ingredients of Wolfiporia cocos, total triterpenes of Wolfiporia cocos (TTWC), are not well studied. This study aimed to investigate those effects and explore their specific mechanisms of action in depth. Methods: Chemical components of TTWC were analyzed using LC-MS. Depression-like behavior in rats were induced by chronic unpredictable mild stress (CUMS). The suppressive effects of TTWC (60, 120, 240 mg/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). Levels of 5-hydroxytryptamine (5-HT), glutamate (GLU), corticotropin-releasing hormone (CRH), interleukin-1 beta (IL-1beta), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in different groups were determined by ELISA. Western blotting (WB) was used to detect the expression of NLRP3, ASC, pro-caspase-1, caspase-1, pro-IL-1beta, IL-1beta, pro-IL-18, and IL-18 in the prefrontal cortex. Additionally, the mRNA levels of NLRP3, ASC, caspase-1, IL-1beta and IL-18 were detected by RT-PCR. Results: A total of 69 lanostane-type triterpene acids of TTWC were identified. The results showed that TTWC exhibited an antidepressant-like effect in CUMS rats, reversed the decreased sugar preference in the SPT, reduction of immobility time in the FST, reduced the rest time, increased the total moving distance in the OFT. TTWC increased 5-HT levels and decreased GLU levels in the hippocampus. Moreover, TTWC decreased CRH levels in serum, indicating the regulation of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, reduced serum levels of IL-1beta, IL-18, IL-6, and TNF-alpha. The WB results implied that TTWC inhibited the expression of NLRP3, ASC, caspase-1, IL-1beta, and IL-18 in the prefrontal cortex and enhanced the expression of pro-caspase-1, pro-IL-1beta, and pro-IL-18. Although most of the results were not significant, PCR results showed that TTWC inhibited the expression of NLRP3, ASC, caspase-1, IL-1beta, and IL-18 in the prefrontal cortex. Conclusion: TTWC treatment exerted an antidepressant-like effect and regulates neurotransmitters, HPA axis and NLRP3 signaling pathway. These results indicated the potential of TTWC in preventing the development of depression.
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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
BACKGROUND: Poria cocos (Schw.) Wolf (PC), a fungus, has been used for more than 2000 years as a food and medicine in China. It has a very good therapeutic effect for functional dyspepsia (FD). However, the material basis and mechanism of PC on FD were not reported. PURPOSE: To investigate the function and potential mechanisms of PC including its three extracts (triterpenoid, PCT; water-soluble polysaccharide, PCWP; acidic polysaccharide, PCAP) on FD. STUDY DESIGN: The study explored the therapeutic effect of PC and its three extracts on FD in rats for the first time and discussed its mechanisms based on brain-gut peptides, immunity and repair of the gastrointestinal mucosa. METHODS: The chemical components of PC extracts were analyzed and quantified using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and gel permeation chromatography coupled with size exclusion chromatography (GPC/SEC). The FD rat models were established using weight-loaded forced swimming and alternate-day fasting for 42 days. After 14 days of treatment, the effect and mechanisms were investigated using ELISA, histopathology, immunohistochemistry as well as Western blot. RESULTS: Seventy-seven triterpenoids in PCT were identified. PCWP was primarily composed of component A (Mw: 3.831 × 107 Da), component B (Mw: 5.650 × 106 Da) and component C (Mw: 113,117 Da). PCAP was a homogeneous composition with an average Mw of 74,320 Da. PCT, PCWP and PCAP alleviated the symptoms of FD. These extracts promoted the repair of gastrointestinal mucosa and regulated the balance between the T helper cell (Th)1/Th2 axis and the Th17/Treg axis. PCT and PCWP regulated brain-gut peptides more effectively, PCWP and PCAP enhanced immunity more effectively. Further study demonstrated that these extracts may have enhanced immunity via the Toll-like receptor (TLR) and c-Jun N-terminal kinase (JNK) signaling pathways. CONCLUSIONS: PC extracts showed therapeutic effects on FD rats, and the mechanism of action involved multiple pathways. PCAP, which is often discarded in traditional applications, was effective. Our study provides new ideas for the application and development of PC extracts.
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Dispepsia , Poria , Wolfiporia , Animales , Encéfalo , Membrana Mucosa , Péptidos/farmacología , Extractos Vegetales/farmacología , RatasRESUMEN
Morinda officinalis, a well-known traditional herbal medicine in China, is used to treat deficiency of kidney-yang syndrome. Although this medicine has the property of "reinforcing kidney to strengthening Yang," the chemical constituents responsible for this effect remain to be elucidated. Here, we aimed to identify the main active compounds responsible for reinforcing kidney to strengthening Yang, based on spectrum-effect relationships combined with chemometrics. We used the UPLC-diode array detection method to establish the chromatography fingerprint of M. officinalis. Hydrocortisone-induced and adenine-induced kidney-yang deficiency patterns were established to evaluate the efficacy of M. officinalis. Serum triiodothyronine, free thyroxine, thyrotropin, testosterone, cortisol, luteinizing hormone, follicle-stimulating hormone, corticotropin-releasing hormone, and adrenocorticotropic hormone levels were determined as pharmacodynamic indices. Analytic hierarchy process was used to determine the weight of each index to the total pharmacodynamic contribution. Lastly, the spectrum-effect between the fingerprint and the pharmacological effects were established using grey relational analysis and partial least squares. Our findings indicated that peaks 1, 2, 3, 5, 6, 7, 8, 9, 11, 13, 15, 17, and 20 might represent the main components that positively correlated to the total effect, of which four were identified by comparison with reference standards. The identified components were monotropein (peak 1), deacetyl asperulosidic acid (peak 3), asperulosidic acid (peak 8), and asperuloside (peak 9). Our results suggest that the "reinforce kidney to strengthening Yang" effects were attributable to the combined effects of the multiple chemical components of M. officinalis and provide a valuable method to identify the active "reinforce kidney to strengthening Yang" components of M. officinalis and establish the quality control of M. officinalis.
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Medicamentos Herbarios Chinos , Morinda , Medicamentos Herbarios Chinos/uso terapéutico , Riñón , Fitoterapia , Deficiencia Yang/tratamiento farmacológicoRESUMEN
The rats were exposed to chronic unpredictable mild stress(CUMS) and kept in separate cages for inducing depressive disorder, which was judged by behavioral indicators. The number and morphology of neurons in hippocampal CA3 area and prefrontal cortex were observed by hematoxylin-eosin(HE) staining. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), norepinephrine(NE), glutamic acid(GLU), interleukin-1ß(IL-1ß), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(RT-PCR) and Western blot were conducted to determine the mRNA and protein expression levels of related molecules in NLRP3 pathway. The results showed that compared with the model group, acidic polysaccharides from Poria at the low-, medium-, and high-doses(0.1, 0.3 and 0.5 g·kg~(-1)·d~(-1)) all improved the depression-like behavior of rats, increased the number of neurons and the levels of BDNF, 5-HT, 5-HIAA, DA, and NE in the hippocampus, and reduced GLU and serum IL-1ß, IL-18, and TNF-α levels. The mRNA expression levels of ASC, caspase-1, IL-1ß, and IL-18 and the protein expression levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in each medication group were down-regulated, whereas the protein expression levels of pro-caspase-1, pro-IL-1ß, and pro-IL-18 were up-regulated. All these have indicated that acidic polysaccharides from Poria exerted the antidepressant effect possibly by regulating neurotransmitters and NLRP3 inflammasome signaling pathway.
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Proteína con Dominio Pirina 3 de la Familia NLR , Poria , Animales , Antidepresivos , Depresión/tratamiento farmacológico , Interleucina-1beta , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Neurotransmisores , Polisacáridos/farmacología , RatasRESUMEN
BACKGROUND: Traditional Chinese medicine Smilax is the rhizome of liliaceous plant Smilax china L., which is used to treat pelvic inflammatory disease and anxieties. PURPOSE: To investigate the mechanism of anti-inflammatory activity of the extract from Smilax china L. (ES). METHODS: The components of ES were identified by UPLC-QTOF-MS/MS. The anti-inflammatory activities were evaluated in xylene-induced ear oedema and egg white-induced plantar swelling test. Cell viability was examined by CCK-8 assay. The inflammatory mediators, proinflammatory cytokines, and MAPK and NF-κB signals in LPS-stimulated THP-1 cells were determined using ELISA, real-time PCR, and Western blot, respectively. RESULTS: 20 compounds of ES were confirmed by comparing with the reference substance. ES displayed more prominent anti-inflammatory activity than the positive control "Jin Gang Teng" capsule in the in vivo acute inflammatory model. ES suppressed the expression of PGE2 and 6-Keot-PGF1 α, and the ratio of IC50 (COX-1)/IC50 (COX-2) of ES was 3.15, which indicated that ES could selectively inhibit COX-2. ES dose-dependently (12.5, 25, and 50 mg/L) decreased the production and mRNA levels of proinflammatory cytokines IL-1ß, IL-6, and TNF-α. Furthermore, ES significantly decreased LPS-induced phosphorylation of p38, JNK, ERK1/2, and p65, inhibiting the expression of IKKα and the degradation of IκBα. CONCLUSION: The results suggested that ES could selectively inhibit the activity of COX-2, and the anti-inflammatory effect of ES was associated with the inhibition of IL-1ß, IL-6, and TNF-α via negative regulation of MAPK and NF-κB signaling pathways in LPS-induced THP-1 cells.
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Alpinia/química , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Extractos Vegetales/farmacología , Acetatos/química , Animales , Gastritis/enzimología , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/enzimología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
To study the correlation between ultra high performance liquid chromatography( UPLC) fingerprint of Smilax china and its anti-pelvic inflammatory effect,and to explore the pharmacodynamic material basis of S. china against pelvic inflammatory disease.UPLC fingerprints of 10 batches of S. china from different habitats were established,and the values of SOD,MDA,TNF-α,and IL-6 in rats with pelvic inflammation were measured. The weight of each single pharmacodynamics index to the total efficacy was determined by analytic hierarchy process,and the contribution of each peak in fingerprints to the each single pharmacodynamics index and total efficacy was analyzed by the grey relational analysis. Then the structures of chemical constituents at the identified peaks were confirmed by comparing with the reference substance. The 27 common characteristic peaks of UPLC fingerprints were all related to the anti-pelvic inflammation effect of S. china,of which 13 peaks were identified as peak 2( 3,5-dihydroxy-2-methylbenzoic acid-3-O-glucoside),peak 3( chlorogenic acid),peak 5( 2,7,4-trihydroxydihydroflavone-5-O-glucoside),peak 6( 7,4-dihydroxydihydroflavonol-5-O-glucoside),peak 7( taxifolin-7-O-glucoside),peak 9( taxifolin),peak 10( polydatin),peak 11( oxyresveratrol),peak 12( astilbin),peak15( resveratrol),peak 16( quercitrin),peak 18( engeletin) and peak 24( kaempferol). The correlation degree of 21 peaks and the total efficacy was greater than 0. 8,and the top 10 ranked by correlation degree were as follows: peak 1,3,7,19,18,17,4,11,16,and 21. The results showed that the anti-pelvic inflammation effect of S. china was achieved by the combined action of pharmacodynamic substances. In order to control the quality of S. china and its prepared slices more effectively,the index components of content detection should be selected reasonably.
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Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Extractos Vegetales/farmacología , Smilax/química , Animales , China , Cromatografía Líquida de Alta Presión , Femenino , Fitoquímicos/farmacología , RatasRESUMEN
In vitro and in vivo studies indicate that scutellarin (SCU) exerts anti-inflammatory effects in the central nervous system (CNS) and inhibits microglia activation. This study investigated the anti-neuroinflammation molecular mechanisms exerted by scutellarin in LPS-induced BV-2 cells. The results showed that production of TNF-α, IL-1ß, IL-6, and NO and TNF-α, IL-1ß, IL-6, and iNOS mRNA were inhibited by scutellarin, which was independent of cytotoxicity as assessed by a CCK8 assay. Western blot analysis indicated that NF-κB-p65 phosphorylation was suppressed by scutellarin via inhibition of IκB degradation and IKKß activation, which coincided with blockage of nuclear translocation of NF-κB as shown by immunofluorescent staining. Consistent with the inhibition of NF-κB, scutellarin inhibited the phosphorylation of p38, JNK, and AKT without affecting phosphorylation of ERK1/2 or PI3K in LPS-induced BV-2 cells. Overall, the present study suggests that scutellarin inhibits the production of pro-inflammatory mediators via inhibition of the IKK-dependent NF-κB and p38/JNK signaling pathway, which inhibits microglia activation and exerts anti-inflammation, indicating its potential therapeutic effect for neurodegenerative and cerebrovascular diseases.