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1.
Phytomedicine ; 128: 155492, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38479258

RESUMEN

BACKGROUND: The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored. PURPOSE: This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms. METHODS: In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice. RESULTS: APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4+T, CD8+T, CD19+B, F4/80+CD11B+ macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80+CD11B+CD206+ cells. CONCLUSION: APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.


Asunto(s)
Planta del Astrágalo , Ácidos Grasos Insaturados , Fluorouracilo , Microbioma Gastrointestinal , Polisacáridos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Polisacáridos/farmacología , Ratones , Planta del Astrágalo/química , Ácidos Grasos Insaturados/farmacología , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Bazo/efectos de los fármacos , Trasplante de Microbiota Fecal , Colon/efectos de los fármacos
2.
Ecotoxicol Environ Saf ; 265: 115531, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37778238

RESUMEN

With changes in global climate, blooms are becoming more frequent and difficult to control. Therefore, the selection of algal suppressor agents with effective inhibition and environmental safety is of paramount importance. One of the main treatment strategies is to inhibit the release of harmful algal toxins. Tea polyphenols (TP) are natural products that have been widely used in medicine, the environment, and other fields due to their antibacterial and antioxidant properties. To investigate their potential application in the treatment of algal blooms, TP were applied to three different microalgae. TP exhibited strong inhibitory effects towards all three microalgae. They stimulate the accumulation of ROS in algal cells, leading to lipid peroxidation and subsequent damage to the cell membrane, resulting in the rupture and necrosis of Cyclotella sp. and Chlorella vulgaris cells. Remarkably, it was observed that lower concentrations of TP exhibited the ability to induce apoptosis in M. aeruginosa cells without causing any structural damage. This outcome is particularly significant as it reduces the potential risk of microcystin release resulting from cell rupture. Overall, blooms dominated by different algae can be treated by adjusting the concentration of TP, a new algal suppressor, indicating strong potential treatment applications.


Asunto(s)
Chlorella vulgaris , Polifenoles , Polifenoles/farmacología , Eucariontes , Eutrofización , Té/química , Floraciones de Algas Nocivas
3.
Nat Commun ; 14(1): 5451, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37673856

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Masculino , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , PPAR alfa/genética , Ácidos y Sales Biliares , Citoplasma , Ratones Noqueados , Ácidos Grasos
4.
Am J Chin Med ; 51(5): 1153-1188, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37403214

RESUMEN

COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-[Formula: see text], IL-6, and IL-1[Formula: see text] in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-[Formula: see text], MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK[Formula: see text]/[Formula: see text], and I[Formula: see text]B[Formula: see text] and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-[Formula: see text]B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.


Asunto(s)
COVID-19 , Interleucina-6 , Animales , Ratones , Interleucina-6/metabolismo , COVID-19/metabolismo , SARS-CoV-2 , Neutrófilos/metabolismo , Síndrome de Liberación de Citoquinas , Macrófagos/metabolismo , FN-kappa B/metabolismo
5.
Chin Med ; 17(1): 144, 2022 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-36572936

RESUMEN

BACKGROUND: Traditional Chinese Medicine (TCM) has been practiced and developed in China over thousands of years under the guidance of a series of complicated traditional theories. Herbs within TCM usually are classified according to their different properties ranging from cold, cool, warm to hot, which are simplified as Cold and Hot properties. TCM with either Cold or Hot properties are used in various formulae designed for the purpose of restoring the balance of patients. Emerging evidence has highlighted that an altered gut microbiota or host metabolism are critically involved in affecting the healing properties of TCM. However, at present the exact influences and crosstalk on the gut microbiota and host metabolism remain poorly understood. METHODS: In the present study, the divergent impacts of six TCMs with either Cold or Hot properties on gut microbiome and host metabolism during short- or long-term intervention in mice were investigated. Six typical TCMs with Hot or Cold properties including Cinnamomi Cortex (rougui, RG), Zingiberis Rhizoma (ganjiang, GJ), Aconiti Lateralis Radix Praeparata (fuzi, FZ), Rhei Radix et Rhizoma (dahuang, DH), Scutellariae Radix (huangqin, HQ), and Copitdis Rhizoma (huanglian, HL) were selected and orally administered to male C57BL/6J mice for a short- or a long-term (7 or 35 days). At the end of experiments, serum and cecal contents were collected for metabolomic and gut microbiome analyses using gas chromatography-tandem mass spectrometry (GC-MS) or 16S ribosomal deoxyribonucleic acid (16S rDNA) sequencing. RESULTS: The results revealed that the gut microbiome underwent divergent changes both in its composition and functions after short-term intervention with TCM possessing either Cold or Hot properties. Interestingly, the number of changed genus and bacteria pathways was reduced in Hot_LT, but was increased in Cold_LT, especially in the HL group. Increased α diversity and a reduced F/B ratio revealed the changes in Hot_ST, but a reduced Shannon index and increased altered bacteria function was evident in Cold_LT. The serum metabolic profile showed that the influence of TCM on host metabolism was gradually reduced over time. Glycolipid metabolism related pathways were specifically regulated by Hot_ST, but also surprisingly by Cold_LT. Reduced lactic acid in Cold_ST, increased tryptophan concentrations and decreased proline and threonine concentrations in Cold_LT perhaps highlighting the difference between the two natures influence on serum metabolism. These metabolites were closely correlated with altered gut microbiota shown by further correlation analyses. CONCLUSION: The results indicated that TCM properties could be, at least partially characterized by an alteration in the gut microbiota and metabolic profile, implying that the divergent responses of gut microbiome and host metabolism are involved in different responses to TCM.

6.
Phytomedicine ; 97: 153922, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35032732

RESUMEN

BACKGROUND: Although Qing-Fei-Pai-Du decoction (QFPDD) is extensively used clinically to treat COVID-19 patients, the mechanism by which it modulates the immunological and metabolic functions of liver tissue remains unknown. PURPOSE: The purpose of this study is to investigate the mechanism of action of QFPDD in the treatment of mice with coronavirus-induced pneumonia by combining integrated hepatic single-cell RNA sequencing and untargeted metabolomics. METHODS: We developed a human coronavirus pneumonia model in BALB/c mice by infecting them with human coronavirus HCoV-229E with stimulating them with cold-damp environment. We initially assessed the status of inflammation and immunity in model mice treated with or without QFPDD by detecting peripheral blood lymphocytes and inflammatory cytokines. Then, single-cell RNA sequencing and untargeted metabolomics were performed on mouse liver tissue. RESULTS: HCoV-229E infection in combination with exposure to a cold-damp environment significantly decreased the percentage of peripheral blood lymphocytes (CD4+ and CD8+ T cells, B cells) in mice, which was enhanced by QFPDD therapy. Meanwhile, the levels of inflammatory cytokines such as IL-6, TNF-α, and IFN-γ were significantly increased in mouse models but significantly decreased by QFPDD treatment. Single-cell RNA sequencing analysis showed that QFPDD could attenuate disease-associated alterations in gene expression, core transcriptional regulatory networks, and cell-type composition. Computational predictions indicated that QFPDD rectified the observed aberrant patterns of cell-cell communication. Additionally, the metabolic profiles of liver tissue in the Model group were distinct from mice in the Control group, and QFPDD significantly regulated hepatic purine metabolism. CONCLUSION: To the best of our knowledge, this study is the first to integrate hepatic single-cell RNA sequencing and untargeted metabolomics into a TCM formula and these valuable findings indicate that QFPDD can improve immune function and reduce liver injury and inflammation.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos , Metabolómica , Animales , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Hígado , Ratones , Ratones Endogámicos BALB C , Análisis de Secuencia de ARN , Análisis de la Célula Individual
7.
Chin Med ; 16(1): 109, 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34702323

RESUMEN

BACKGROUND: Traditional Chinese Medicine (TCM) is distinguished by Syndrome differentiation, which prescribes various formulae for different Syndromes of same disease. This study aims to investigate the underlying mechanism. METHODS: Using a strategy which integrated proteomics, metabolomics study for clinic samples and network pharmacology for six classic TCM formulae, we systemically explored the biological basis of TCM Syndrome differentiation for two typical Syndromes of CHD: Cold Congealing and Qi Stagnation (CCQS), and Qi Stagnation and Blood Stasis (QSBS). RESULTS: Our study revealed that CHD patients with CCQS Syndrome were characterized with alteration in pantothenate and CoA biosynthesis, while more extensively altered pathways including D-glutamine and D-glutamate metabolism; alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism, were present in QSBS patients. Furthermore, our results suggested that the down-expressed PON1 and ADIPOQ might be potential biomarkers for CCQS Syndrome, while the down-expressed APOE and APOA1 for QSBS Syndrome in CHD patients. In addition, network pharmacology and integrated analysis indicated possible comorbidity differences between the two Syndromes, that is, CCQS or QSBS Syndrome was strongly linked to diabetes or ischemic stroke, respectively, which is consistent with the complication disparity between the enrolled patients with two different Syndromes. These results confirmed our assumption that the molecules and biological processes regulated by the Syndrome-specific formulae could be associated with dysfunctional objects caused by the Syndrome of the disease. CONCLUSION: This study provided evidence-based strategy for exploring the biological basis of Syndrome differentiation in TCM, which sheds light on the translation of TCM theory in the practice of precision medicine.

8.
Phytomedicine ; 91: 153693, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34403877

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related metabolic disease that is highly associated with gut dysbiosis and inflammation. A botanical dietary supplement, mainly containing an herbal pair of white peony root and licorice as well as grape seeds and broccoli extracts (WLT), exerts auxiliary protection against chemical liver injury. However, it is unclear whether WLT protects against the development of NAFLD induced by a high energy diet. PURPOSE: To investigate the protective role of WLT against NAFLD development induced by a high-fat and high-sucrose (HFHS) diet and its mechanism of action. METHODS: We investigated the anti-NAFLD effects of WLT on a HFHS diet-induced NAFLD C57BL/6J mouse model by detecting the hepatic triglyceride (TG) level, performing histological examination of the liver tissue, and evaluating glucose tolerance and systemic inflammation. Then, we analyzed the impact of WLT on gut microbiota by 16S rRNA gene sequencing, followed by fecal microbiota transplantation. Furthermore, we performed hepatic transcriptomic analysis of mice with or without WLT treatment using the RNA sequencing approach. RESULTS: Our results showed that WLT supplement attenuated body weight gain, hepatic steatosis, glucose tolerance, and systemic inflammation in HFHS-fed mice. Moreover, WLT supplement altered the composition of gut microbiota, which contributed at least in part, to the anti-NAFLD effect. Meanwhile, WLT improved the intestinal integrity and comprehensively modulated the expression of hepatic genes in HFHS mice, particularly reducing the expression of genes in the toll-like receptor-mediated inflammatory pathway. CONCLUSION: WLT is protective against NAFLD formation induced by an HFHS diet, and its effect is associated with the modulation of gut microbiota and inflammation, highlighting the potential of WLT to reduce the risk of metabolic disorders as a functional dietary supplement.


Asunto(s)
Suplementos Dietéticos , Microbioma Gastrointestinal , Glycyrrhiza , Enfermedad del Hígado Graso no Alcohólico , Paeonia , Extractos Vegetales , Animales , Dieta Alta en Grasa/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Glycyrrhiza/química , Inflamación/tratamiento farmacológico , Hígado , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Paeonia/química , Extractos Vegetales/farmacología , ARN Ribosómico 16S
9.
Phytomedicine ; 85: 153544, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33773192

RESUMEN

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with few therapeutic options available currently. Traditional Chinese Medicine (TCM) has been practiced for thousands of years in China and Asian countries, and regarded as an important source for identifying novel medicines for diseases. Si Miao Formula (SMF) is a classical TCM formula for the treatment of gout disease by reducing serum uric acid concentrations, while high concentration of uric acid is also an independent risk factor for NAFLD. PURPOSE: To investigate the protective effect of SMF on NAFLD in a mouse model induced by a high fat/high sucrose (HFHS) diet. METHODS: Mice received a HFHS diet over a 16-week period to induce NAFLD with or without SMF intervention. Lipid levels were measured in both the liver and serum. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Liver transcriptomics was used to enrich differentially expressed genes and to predict regulatory pathways after gene set enrichment analysis. 16S rRNA gene sequencing was used to determine the microbial composition. Genes of liver lipid metabolism, inflammation and intestinal tight junctions were detected by qRT-PCR analysis. RESULTS: SMF attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, improved sensitivity to insulin and also tolerance to glucose, in mice fed an HFHS diet. Hepatic transcriptomics showed that SMF downregulated the biosynthesis of fatty acids and stimulated the insulin secretion pathway. SMF significantly altered the gut microbiota composition and in particular increased the proportion of Akkermansia muciniphila. In agreement with liver transcriptomics, SMF downregulated the expression of genes implicated in the metabolism of lipids (Acly, Fas, Acc, Scd-1) and pro-inflammatory cytokines (Il-1ß, Nlrp-3) in the livers. CONCLUSION: The results indicate that SMF attenuates HFHS diet-induced NAFLD and regulates hepatic lipid metabolism pathways. The anti-NAFLD effect of SMF was linked to modulation of the gut microbiota composition and in particular an increased relative abundance of Akkermansia muciniphila.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Metabolismo de los Lípidos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Dieta Alta en Grasa , Inflamación/metabolismo , Insulina/metabolismo , Resistencia a la Insulina , Intestinos/efectos de los fármacos , Lípidos/sangre , Hígado/efectos de los fármacos , Masculino , Medicina Tradicional China , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/uso terapéutico , ARN Ribosómico 16S , Uniones Estrechas , Ácido Úrico/metabolismo , Aumento de Peso
10.
Inflammation ; 44(4): 1620-1628, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33751358

RESUMEN

The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractive candidates for the next-generation biologic drug study. In this study, we established a simple prokaryotic expression system for a dual target-directed single domain-based fusion protein against the interleukin-6 receptor and human serum, albumin, the recombinant anti-IL-6R fusion protein (VHH-0031). VHH-0031 exhibited potent anti-inflammatory effects produced by LPS on cell RAW264.7, where the major cytokines and NO production were downregulated after 24 h incubation with VHH-0031 in a dose-dependent manner. In vivo, VHH-0031 presented significant effects on the degree reduction of joint swelling in the adjuvant-induced arthritis (AIA) rat, having a healthier appearance compared with the dexamethasone. The expression level of JNK protein in the VHH-0031 group was significantly decreased, demonstrating that VHH-0031 provides a low-cost and desirable effect in the treatment of more widely patients.


Asunto(s)
Antiinflamatorios/inmunología , Artritis Experimental/tratamiento farmacológico , Interleucina-6/antagonistas & inhibidores , Albúmina Sérica Humana/antagonistas & inhibidores , Anticuerpos de Dominio Único/inmunología , Animales , Antiinflamatorios/uso terapéutico , Especificidad de Anticuerpos , Artritis Experimental/inmunología , Citocinas/metabolismo , ADN Complementario/genética , Dexametasona/uso terapéutico , Evaluación Preclínica de Medicamentos , Inducción Enzimática/efectos de los fármacos , Humanos , Interleucina-6/inmunología , Lipopolisacáridos/toxicidad , MAP Quinasa Quinasa 4/biosíntesis , MAP Quinasa Quinasa 4/genética , Ratones , Modelos Moleculares , Terapia Molecular Dirigida , Óxido Nítrico/metabolismo , Conformación Proteica , Células RAW 264.7 , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Albúmina Sérica Humana/inmunología , Anticuerpos de Dominio Único/genética
11.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3726-3739, 2020 Aug.
Artículo en Chino | MEDLINE | ID: mdl-32893565

RESUMEN

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Bacterias/clasificación , Cromatografía Liquida , Metabolómica , Ratas , Espectrometría de Masas en Tándem
12.
Phytomedicine ; 77: 153291, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32739572

RESUMEN

BACKGROUND: SJP is the commercial Chinese medicine included in the Chinese Pharmacopoeia, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been clearly elucidated. AIMS: To investigate the underlying protective mechanisms of SJP in an acute myocardial infarction (AMI) rat model using comprehensive metabolomics. MATERIALS AND METHODS: The rat model of AMI was generated by ligating the left anterior descending coronary artery. After 2 weeks treatment with SJP, the entire metabolic changes in the serum, heart, urine and feces of the rat were profiled by HPLC-QTOF-MS/MS. RESULTS: The metabolic profiles in different biological samples (heart, serum, urine and feces) were significantly different among groups, in which a total of 112 metabolites were identified. AMI caused comprehensive metabolic changes in amino acid metabolism, galactose metabolism and fatty acid metabolism, while SJP reversed more than half of the differential metabolic changes, mainly affecting amino acid metabolism and fatty acid metabolism. Correlation analysis found that SJP could significantly alter the metabolic activity of 12 key metabolites, regarded as potential biomarkers of SJP treatment. According to the results of network analysis, 6 biomarkers were considered to be hub metabolites, which means that these metabolites may have a major relationship with the SJP therapeutic effects on AMI. CONCLUSION: The combined comprehensive metabolomics and network analysis, indicated that the protective effect of SJP on cardiovascular disease was associated with systemic metabolic modulation, in particular regulation of amino acid and fatty acid metabolism.


Asunto(s)
Aminoácidos/metabolismo , Cardiotónicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Ácidos Grasos/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Animales , Biomarcadores/sangre , Cromatografía Líquida de Alta Presión , Corazón/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Metaboloma , Metabolómica , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem
13.
J Ethnopharmacol ; 259: 113001, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32464316

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (SBP) is a commercial Chinese medicine included in the Chinese Pharmacopoeia with well-established cardiovascular protect effect in clinic. However, the mechanism of SBP underlying protective effect on cardiovascular disease has not been clearly elucidated yet. AIM OF THE STUDY: We aimed to investigate the underlying protective mechanisms of SBP on an acute myocardial infarction (AMI) rat model by using comprehensive metabolomics. MATERIALS AND METHODS: The rat model of AMI was generated by ligating the left anterior descending coronary artery. After two weeks of treatment with SBP, comprehensive metabolomics and echocardiography index was performed for a therapeutic evaluation. The wiff data were processed using Progenesis QI and metabolites were identified based on the database of HMDB and LIPIDMAPS. Meanwhile, the untargeted metabolomics data from LC-MS combined with correlation analysis to characterize the metabolic alterations. RESULTS: The metabolomics profiles of different groups in different biological samples (heart, serum, urine and feces) were significantly different, in which a total of 217 metabolites were identified. AMI caused comprehensive metabolic changes in amino acid metabolism, glycerophospholipid metabolism and pyrimidine metabolism, while SBP reversed more than half of the differential metabolic changes, mainly affecting amino acid metabolism, butanoate metabolism and glycerophospholipid metabolism. Correlation analysis found that SBP could significantly alter the metabolic activity of six key metabolites (5-hydroxyindoleacetic acid, glycerophosphocholine, PS (20:4/0:0), xanthosine, adenosine and L-phenylalanine) related to AMI. The key role of these metabolites was further validated with correlation analysis with echocardiography indexes. CONCLUSION: This study demonstrated that SBP was effective for protecting cardiac dysfunction by regulating amino acid, lipid and energy metabolisms. The results also suggested that the modulation on gut microbiota might be involved the cardioprotective effect of SBP.


Asunto(s)
Fármacos Cardiovasculares/farmacología , Medicamentos Herbarios Chinos/farmacología , Metabolismo Energético/efectos de los fármacos , Metaboloma/efectos de los fármacos , Metabolómica , Infarto del Miocardio/tratamiento farmacológico , Miocardio/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/patología , Ratas Sprague-Dawley , Recuperación de la Función , Función Ventricular Izquierda/efectos de los fármacos
14.
Front Pharmacol ; 10: 254, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30971921

RESUMEN

Traditional Chinese Medicine (TCM), a complex natural herbal medicine system, has increasingly attracted attention from all over the world. Most research has illustrated the mechanism of TCM based on the active components or single herbs. It was fruitful and effective but far from satisfactory as it failed to gain insights into the interactivity and combined effects of TCM. In this work, we used Bupleurum chinense (B. chinense DC, a species in the genus Bupleurum, family Apiaceae) and Scutellaria baicalensis (S. baicalensis Georgi, a species in the genus Scutellaria, family Lamiaceae), an herbal pair in TCM, to illustrate the combined effect. We compared the diverse effects between the B. chinense-S. baicalensis herbal pair and its compositions in an animal model of Alcoholic Liver Injury to highlight the advantages of the formula. Biochemical and histological indicators revealed that the effect of B. chinense-S. baicalensis was better than its individual parts. Furthermore, metabolite profiling of the serum, liver tissue, and feces were conducted to reveal that the herbal pair largely presented its effects through enhanced tissue penetration to maintain liver-located intervention with less global and symbiotic disturbance. Furthermore, we analyzed the distribution of the metal elements in extracts of the serum and liver tissue and found that the herbal pair significantly regulated the distribution of endogenous selenium in liver tissue. As selenium plays an important role in the anti-oxidative and hepatoprotective effects, it may be the reason for combined effects in BS formula. This research could open new perspectives for exploring the material basis of combined effects in natural herbal medicine.

15.
Artículo en Inglés | MEDLINE | ID: mdl-24348731

RESUMEN

Acupuncture is an efficient therapy method originated in ancient China, the study of which based on ZHENG classification is a systematic research on understanding its complexity. The system perspective is contributed to understand the essence of phenomena, and, as the coming of the system biology era, broader technology platforms such as omics technologies were established for the objective study of traditional chinese medicine (TCM). Omics technologies could dynamically determine molecular components of various levels, which could achieve a systematic understanding of acupuncture by finding out the relationships of various response parts. After reviewing the literature of acupuncture studied by omics approaches, the following points were found. Firstly, with the help of omics approaches, acupuncture was found to be able to treat diseases by regulating the neuroendocrine immune (NEI) network and the change of which could reflect the global effect of acupuncture. Secondly, the global effect of acupuncture could reflect ZHENG information at certain structure and function levels, which might reveal the mechanism of Meridian and Acupoint Specificity. Furthermore, based on comprehensive ZHENG classification, omics researches could help us understand the action characteristics of acupoints and the molecular mechanisms of their synergistic effect.

16.
Artículo en Inglés | MEDLINE | ID: mdl-23853661

RESUMEN

Xiao Chai Hu Tang (XCHT), a compound formula originally recorded in an ancient Chinese medical book Shanghanlun, has been used to treat chronic liver diseases for a long period of time in China. Although extensive studies have been demonstrated the efficacy of this formula to treat chronic hepatitis, hepatic fibrosis, and hepatocarcinoma, how it works against these diseases still awaits full understanding. Here, we firstly present an overview arranging from the entire formula to mechanism studies of single herb in XCHT and their active components, from a new perspective of "separation study," and we tried our best to both detailedly and systematically organize the antihepatocarcinoma effects of it, hoping that the review will facilitate the strive on elucidating how XCHT elicits its antihepatocarcinoma role.

17.
Artículo en Inglés | MEDLINE | ID: mdl-23737844

RESUMEN

Coronary heart disease (CHD) is one of the highest mortality diseases in the world. Traditional Chinese medicine compound Danshen dripping pills (CDDPs) have currently made a great achievement in treating CHD. However, the therapeutic mechanism of CDDP is often poorly interpreted. In this study, a GC-MS-based metabonomic study was conducted to assess the holistic efficacy of CDDP for myocardial infarction in male Sprague-Dawley rats, which were divided into the control group, the sham group, the model group, the control + CDDP group, and the model + CDDP, with CDDP at a dose of 107 mg/kg·d (equal to 1.8 mL/kg·d). The metabonomic findings demonstrated great differences of metabolic pattern among sham, model, and the model + CDDP in the orthogonal partial least squares discriminant analysis (OPLS-DA) models, which coordinated well with the assessment of plasma biochemistry and histopathological assay. Differentially expressed metabolites suggested that energy metabolism, glycolysis, and lipid metabolism might be disrupted by myocardial infarction. Both the potential metabolic biomarkers and the biochemical histopathological indices were regulated effectively by CDDP.

18.
Artículo en Inglés | MEDLINE | ID: mdl-23690837

RESUMEN

Tongue coating is one of the important foundations of tongue diagnosis in traditional Chinese medicine (TCM) and plays an important role in reflecting the occurrence, development, and prognosis of the disease. However, its material basis is still poorly understood. In this study, a urinary metabonomic method based on gas chromatography coupled to mass spectrometry (GC/MS) was developed. The distinct clustering in metabolic profile was observed from Group A (thick yellow coating in patients with chronic hepatitis B), Group B (thick white coating in patients with chronic hepatitis B), and Group C (thin white coating with healthy humans) using orthogonal projections to latent structures (OPLS). Based on the variable of importance in the project (VIP) values, some significantly changed metabolites have been identified. These changes were related to the disturbance in energy metabolism, amino acid metabolism, nucleotide metabolism, and gut microflora, which were helpful to understand the material basis leading to the formation of tongue coating. This study demonstrated that tongue coating may have an objective material basis.

19.
Artículo en Inglés | MEDLINE | ID: mdl-23690853

RESUMEN

The phenomenon that the same syndrome turns up in different diseases appears in the sight of people around the world, which raises the thought for possibility of "Same Treatment for Different Diseases." Actually, treatment based on ZHENG classification in Traditional Chinese Medicine could bring revelation for the former finding. The dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver is regarded as the breakthrough point. We discussed the molecular mechanism of similar connotation that exists in chronic hepatitis B and nonalcoholic fatty liver by metabonomics to give the modern understanding of dampness-heat syndrome. Both urine and serum metabolic profiling revealed that obvious differences existed between dampness-heat syndrome and non-dampness-heat syndrome but the commonality was proved to appear in chronic hepatitis B and nonalcoholic fatty liver patients with dampness-heat syndrome. Furthermore, disorder of body fluid metabolism, decline in digestive capacity, and imbalance of intestinal flora were found to be the new guiding for treatment, with the hope to provide the basis for Chinese personalized medicine.

20.
Artículo en Inglés | MEDLINE | ID: mdl-23662120

RESUMEN

With the hope to provide an effective approach for personalized diagnosis and treatment clinically, traditional chinese medicine (TCM) is being paid increasing attention as a complementary and alternative medicine. It performs treatment based on ZHENG (TCM syndrome) classification, which could be identified clinical special phenotypes by symptoms and signs of patients even if they have a different disease. However, it caused controversy because ZHENG classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which lacks objectivity and repeatability. Although researchers and scientists of TCM have done some work with a lot of beneficial methods, the results could not reach satisfactory with the shortcomings of generalizing the entire state of the body or ignoring the patients' feelings. By total summary, mining, and integration of existing researches, the present paper attempts to introduce a novel macro-microconcept of ZHENG-omics, with the prospect of bright future in providing an objective and repeatable approach for Chinese personalized medicine in an effective way. In this paper, we give the brief introduction and preliminary validation, and discuss strategies and system-oriented technologies for achieving this goal.

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