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1.
BMC Genomics ; 22(1): 714, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600494

RESUMO

BACKGROUND: As one of the largest genera in Apiaceae, Bupleurum L. is well known for its high medicinal value. The genus has frequently attracted the attention of evolutionary biologist and taxonomist for its distinctive characteristics in the Apiaceae family. Although some chloroplast genomes data have been now available, the changes in the structure of chloroplast genomes and selective pressure in the genus have not been fully understood. In addition, few of the species are endemic to Southwest China, a distribution and diversity center of Chinese Bupleurum. Endemic species are key components of biodiversity and ecosystems, and investigation of the chloroplast genomes features of endemic species in Bupleurum will be helpful to develop a better understanding of evolutionary process and phylogeny of the genus. In this study, we analyzed the sequences of whole chloroplast genomes of 4 Southwest China endemic Bupleurum species in comparison with the published data of 17 Bupleurum species to determine the evolutionary characteristics of the genus and the phylogenetic relationships of Asian Bupleurum. RESULTS: The complete chloroplast genome sequences of the 4 endemic Bupleurum species are 155,025 bp to 155,323 bp in length including a SSC and a LSC region separated by a pair of IRs. Comparative analysis revealed an identical chloroplast gene content across the 21 Bupleurum species, including a total of 114 unique genes (30 tRNA genes, 4 rRNA genes and 80 protein-coding genes). Chloroplast genomes of the 21 Bupleurum species showed no rearrangements and a high sequence identity (96.4-99.2%). They also shared a similar tendency of SDRs and SSRs, but differed in number (59-83). In spite of their high conservation, they contained some mutational hotspots, which can be potentially exploited as high-resolution DNA barcodes for species discrimination. Selective pressure analysis showed that four genes were under positive selection. Phylogenetic analysis revealed that the 21 Bupleurum formed two major clades, which are likely to correspond to their geographical distribution. CONCLUSIONS: The chloroplast genome data of the four endemic Bupleurum species provide important insights into the characteristics and evolution of chloroplast genomes of this genu, and the phylogeny of Bupleurum.


Assuntos
Apiaceae , Bupleurum , Genoma de Cloroplastos , Bupleurum/genética , China , Ecossistema , Filogenia
2.
Biomed Res Int ; 2021: 5845554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513994

RESUMO

Objective: Neuroblastoma (NB) is a highly metastatic tumor in children that develops in the sympathetic nervous system and has a low curative rate. Saikosaponin A (SSA), an active ingredient isolated from the root of Radix Bupleuri, is a natural compound with various pharmacological activities and shows good application prospects in antitumors. This study investigated the antihuman NB activity of SSA and underlying mechanisms associated with its actions. Materials and Methods: The MTT method was used to detect the activity of SSA in inhibiting human NB cell SK-N-AS proliferation. Cell morphology was observed. The flow cytometry technology was used in analyzing the cell apoptosis rate. The Transwell assay evaluated cell migration and invasion following SSA treatment, apoptosis-related protein expression, and angiogenesis-related protein expression, and EMT-related proteins were detected by western blot analysis. Results: SSA showed an inhibitory effect on SK-N-AS cells with the IC50 values of 14.14 µM at 24 h and 12.41 µM at 48 h. Results indicated that SSA has proapoptotic activity, and its proapoptotic activity is positively correlated with the Bax/Bcl-2/caspase-9/caspase-7/PARP pathway. Furthermore, SSA inhibited the invasion and migration of SK-N-AS cells via regulating the angiogenesis-related VEGFR2/Src/Akt pathway and the epithelial-mesenchymal transition- (EMT-) related protein expression. Conclusion: SSA exerts an antihuman NB effect and thus provides foundations for NB treatment.


Assuntos
Neuroblastoma/metabolismo , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Apoptose/efeitos dos fármacos , Bupleurum/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Humanos , Concentração Inibidora 50 , Neuroblastoma/tratamento farmacológico , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Extratos Vegetais/farmacologia , Saponinas/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4222-4229, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467736

RESUMO

Bupleuri Radix, serving as the sovereign medicinal in many antidepressant compound preparations, has been proved effective in treating depression in mice, but its effect on the intestinal flora remains unclear. The present study aimed to investigate the effects of Bupleurum chinense(one of the original materials of Bupleuri Radix) on the behaviors and the diversity of intestinal flora of depressed mice. A depression mouse model was induced by repeated social defeat stress. Specifically, C57 BL/6 J male mice were exposed to the attack from the CD-1 mice. Then, C57 BL/6 J male mice were divided into a depression group and a B. chinense group, with normal saline and B. chinense administered(ig) respectively. Sucrose preference test and tail suspension test were conducted during and after the experiment respectively, to analyze the effects of B. chinense on the behaviors of the depressed mice. The feces were collected after the experiment. The V3-V4 16 S rDNA regions of intestinal flora of mice in each group were sequenced by Ion S5 TMXL for the analysis of the number of operational taxonomic units(OTUs), richness, alpha and beta diversity indexes, and differential phyla and genera. The results indicated that B. chinense could decrease depressive-like behaviors of mice, increase sucrose preference, and shorten the time of immobility in tail suspension test. After B. chinense intervention, the relative abundance of Firmicutes was significantly decreased, while that of Bacteroidetes was increased at the phylum level. At the genus level, the relative abundance of Lactobacillus and Lachnoclostridium decreased(P<0.05), while that of Bacteroides, Alistopes, etc. was elevated(P<0.05). The findings demonstrate that B. chinense can regulate the intestinal flora and improve the depressive-like behaviors of mice with depression.


Assuntos
Bupleurum , Microbioma Gastrointestinal , Animais , Fezes , Lactobacillus , Camundongos , Camundongos Endogâmicos C57BL
4.
Poult Sci ; 100(9): 101302, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34289428

RESUMO

Heat stress can affect the poultry production and immune status of broilers. Heat stress disrupts intestinal integrity and increases intestinal inflammation, which is related with body immune dysfunction. Chai Hu oral liquid used as an antipyretic and anti-inflammatory drug is widely used in exogenous fever of poultry, but its resistance to heat stress and the mechanism is still unclear. In this study, a chronic heat stressed broilers model was established to explore the mechanisms of broilers' immune function changes and the effects of Chai Hu oral liquid. In this study, a total of 480 broilers were randomly divided into 6 groups with 80 replicates. Heat stress (HS) group broilers were stressed at 35 ± 2°C for 5 or 10 consecutive d with 6 h/d. Heat stressed (for 5 or 10 d) broilers were given with Jieshu KangreSan (Positive), Chai Hu oral liquid high, middle and low dosage (CH-High, CH-Mid, CH-Low) by oral administration. Birds in control group were treated with the same volume of PBS only in 25 ± 2°C. All birds were sacrificed at last heat stress challenged day. Changes in immune function were assessed by immune organs index, serum IFN-γ level, gene and protein expressions of immune factors in spleen and bursa of Fabricius. Results from this experiment showed that heat stress enhanced the immune organs' edema by directly increased the organs indexes of spleen and bursa of Fabricius in broilers. Heat stress for 10 d also increased bursa of Fabricius HSP70 protein level and significantly lowered the spleen and bursa of Fabricius proteins expressions of IFN-α, IFN-ß, and IFN-γ in broilers. The IFN-ß and IFN-γ protein levels in spleen and bursa of Fabricius also decreased in heat stressed broilers for 5 d. The gene and protein expressions of TLR4 and TBK1 markedly decreased in spleen and bursa of Fabricius of broilers treated with chronic heat stress. Chai Hu oral liquid reduced edema of immune organs and elevated TLR4-TBK1 signaling pathway to release immune factors. Above results indicated that chronic heat stress induced impaired immune function by inhibiting TLR4-TBK1 signaling pathway, and Chai Hu oral liquid had effective protection of body's immune ability by enhancing this signaling pathway.


Assuntos
Bupleurum , Bolsa de Fabricius , Animais , Galinhas , Suplementos Nutricionais , Resposta ao Choque Térmico , Imunidade , Transdução de Sinais , Baço , Receptor 4 Toll-Like
5.
Gene ; 798: 145801, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34175392

RESUMO

Bupleurum sikangense is an endemic species to China distributed in Xizang (Tibet), which has high saikosaponin content and potential medicinal value. Morphologically, it extremely resembles B. commelynoideum. In order to get a better understanding of the relationship between B. sikangense and B. commelynoideum, and on the phylogenetic status of the two species in the genus, the complete chloroplast (cp) genomes of them were sequenced. The genome organization, repeat sequences, codon usage, RNA-editing sites, and variation of their cp genomes revealed high similarity between the species. Some highly variable regions like trnK-UUU_rps16, rps16_trnQ-UUG, ndhC_trnV-UAC, petA_psbJ, accD_psaI, and petL_psbE were identified, providing potential molecular markers for differentiating the two species. Phylogenetic analysis indicated that B. commelynoideum has a closer relationship to B. chinese than that to B. sikangense. Overall, this study will not only improve our knowledge about cp genomes of these two species, and but also provide data for further research on species identification, safe medical application, conservation genetics, etc., of Bupleurum plants.


Assuntos
Bupleurum/classificação , Bupleurum/genética , Genoma de Cloroplastos , Genoma de Planta , Filogenia , Edição de RNA , RNA de Plantas , Análise de Sequência de DNA
6.
Planta ; 253(6): 128, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037846

RESUMO

MAIN CONCLUSION: We identified IAA13 negatively associated with lateral root number by comparing the differential expressed genes between Bupleurum chinense and B. scorzonerifolium. Dried roots of the genus Bupleurum L. are used as a herbal medicine for diseases in Asia. Bupleurum chinense has a greater number of lateral roots than B. scorzonerifolium, but the genetic mechanisms for such differences are largely unknown. We (a) compared the transcriptome profiles of the two species and (b) identified a subset of candidate genes involved in auxin signal transduction and explored their functions in lateral root development. By isoform sequencing (Iso-Seq) analyses of the whole plant, more unigenes were found in B. scorzonerifolium (118,868) than in B. chinense (93,485). Given the overarching role of indole-3-acetic acid (IAA) as one of the major regulators of lateral root development, we identified 539 unigenes associated with auxin signal transduction. Fourteen and 44 unigenes in the pathway were differentially expressed in B. chinense and B. scorzonerifolium, respectively, and 3 unigenes (LAX2, LAX4, and IAA13) were expressed in both species. The number of lateral root primordia increased after exogenous auxin application at 8 h and 12 h in B. scorzonerifolium and B. chinense, respectively. Since overexpression of IAA13 in Arabidopsis reduced the number of lateral roots, we hypothesized that IAA13 is involved in the reduction of the number of lateral roots in B. scorzonerifolium.


Assuntos
Arabidopsis , Bupleurum , Plantas Medicinais , Ásia , Bupleurum/genética , Raízes de Plantas/genética
7.
Biomed Chromatogr ; 35(9): e5133, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33811357

RESUMO

The overall chemical composition of Bupleurum marginatum var. stenophyllum and Bupleurum chinense DC. was compared in this study. Metabolites were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Multivariate statistical analysis techniques such as principal component analysis were used to conduct metabonomics analysis and study the correlation between different components. Principal component analysis results showed a clear distinction among medicinal materials of different origins and divided them into different categories, consistent with the results of hierarchical cluster analysis. Both partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that the two materials could be distinguished clearly. Using PLS-DA and OPLS-DA combined with the S-plot and a variable importance in the projection (VIP) score >1, 24 differential metabolites were screened and identified; all of the metabolites were triterpenoid saponins. In addition, SPSS 25.0 and Metabo Analyst 4.0 were used to analyze significant differences in the relative contents of different compounds in the two materials. This study has successfully provided not only a new direction for research based on the chemical substances identified and the quality evaluation of Bupleuri Radix but also a better theoretical basis for the expansion of medicinal sources and their clinical application.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Metaboloma/fisiologia , Metabolômica/métodos , Bupleurum/química , Bupleurum/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas/métodos , Análise de Componente Principal
8.
Planta ; 253(4): 81, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765202

RESUMO

MAIN CONCLUSION: The chloroplast genomes of Mediterranean Bupleurum species are reported for the first time. Phylogenetic analysis supports the species as a basal clade of Bupleurum with divergence time at 35.40 Ma. Bupleurum is one of the most species-rich genus with high medicinal value in Apiaceae. Although infrageneric classifications of Bupleurum have been the subject of numerous studies, it still remains controversial. Chloroplast genome information will prove essential in advancing our understanding on phylogenetic study. Here we report cp genomes of two woody Bupleurum species (Bupleurum gibraltaricum and B. fruticosum) endemic to Mediterranean. The complete cp genomes of the two species were 157,303 and 157,391 bp in size, respectively. They encoded 114 unique genes including 30 tRNA genes, 4 rRNA genes and 80 protein coding genes. Genome structure, distributions of SDRs and SSRs, gene content exhibited similarities among Bupleurum species. High variable hotspots were detected in eight intergenic spacers and four genes. Most of genes were under purifying selection with two exceptions: atpF and clpP. The phylogenetic analysis based on 80 coding genes revealed that the genus was divided into 2 distinct clades corresponding to the 2 subgenera (subg. Penninervia, subg. Bupleurum) with divergence time at the end of collision of India with Eurasia. Most species diversified mainly during the later period of uplift of Qinghai-Tibetan Plateau. The cp genomes of the two Bupleurum species can be significant complementary to insights into the cp genome characteristics of this genus. The comparative chloroplast genomes and phylogenetic analysis advances our understanding of the evolution of cp genomes and phylogeny in Bupleurum.


Assuntos
Bupleurum , Genoma de Cloroplastos , Filogenia , Bupleurum/classificação , Bupleurum/genética , Região do Mediterrâneo , Repetições de Microssatélites
9.
Biomed Pharmacother ; 135: 111187, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33556916

RESUMO

BACKGROUND: Obesity and its comorbidities are associated with abnormal lipid metabolism and gut microbiota dysbiosis. Bupleuri Radix is a medicinal plant used in traditional Chinese medicine with the prevention and treatment of obesity-related diseases. In this study, we aim to validate the regulation of Bupleuri Radix Extract (BupE) on lipid metabolism in obese mice, and try to find out the potential active components and reveal the underlying mechanisms. METHODS: Ingredients in BupE, their circulating metabolites in mice and fecal biotransformation products were analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Western blotting, RT-PCR and ELISA were used for tests of objective genes and proteins. 16 s rRNA sequencing was performed to examine intestinal bacteria composition and microbes' functional changes were predicted with PICRUSt software. An absolute quantification method was set up via the construction of recombinant plasmid for the assays of intestinal flora. Specific microbial strains were cultured in anaerobic conditions and oral administrated to mice for intestinal mono-colonization. RESULTS: BupE attenuated obesity, liver steatosis, and dyslipidemia in HFD-fed mice by up-regulating the expression of FGF21 in liver and white adipose tissue (WAT) as well as the downstream proteins of FGF21 signal pathway including ß-klotho, GLUT1 and PGC-1α, etc. UPLC/Q-TOF-MS fingerprints showed no compounds from BupE or their metabolites or biotransformation products were detected in rodent serum samples. High-throughput pyrosequencing data indicated that BupE reversed obesity-induced constructional and functional alterations of intestinal flora. Two bacterial strains, Bacteroides acidifaciens (B. acidifaciens) and Ruminococcus gnavus (R. gnavus), were separated and identified from the feces of obese mice and by intestinal mono-colonization they were verified to intervene in the anti-obesity effects of BupE on mice. CONCLUSION: These data suggest that BupE protects against diet-induced obesity and counteracts metabolic syndrome features consistent with a mechanism involving the gut-liver axis that boosts hepatic FGF21 secretion and consequent down-stream proteins expression relating to lipid metabolism. And in this gut-liver axis, intestinal microbes such as B.acidifaciens and R.gnavus play an indispensable role.


Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Bactérias/metabolismo , Bupleurum , Fatores de Crescimento de Fibroblastos/metabolismo , Microbioma Gastrointestinal , Intestinos/microbiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Tecido Adiposo Branco/metabolismo , Animais , Fármacos Antiobesidade/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Bupleurum/química , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Transdução de Sinais
10.
Poult Sci ; 100(3): 100803, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33516464

RESUMO

Ammonia (NH3) at a high concentration has been recognized as a highly poisonous pollutant affecting both air and water quality. NH3, as a stimulus, exerts negative impact on broiler growth and production, but the molecular mechanisms are not clear yet. This study was designed to evaluate the effects of dietary supplementation of Bupleurum falcatum L saikosaponins (SP) on the growth and ileum health status in broilers exposed to NH3. Day-old Arbor Acers broilers (n = 480) were randomly allocated into 1 of 4 treatments. The main factors were dietary SP supplementation (0 or 80 mg/kg of diet) and NH3 challenge (with or without 70 ± 5 ppm NH3). The data of growth, intestinal morphology, and mRNA expression related to ileal function were collected from broilers exposed to NH3 for 7 d. Results showed that NH3 remarkably suppressed growth performance and intestinal development as well as induced biological injuries in the ileum of broilers, resulting from oxidative stress, mucous barrier damage, and immune dysfunction as well as upregulated apoptosis. These negative effects of NH3 were alleviated by the SP supplement. In conclusion, dietary supplementation of SP may be helpful in alleviating the detrimental effects of NH3 on the ileum development in broilers.


Assuntos
Bupleurum , Galinhas , Suplementos Nutricionais , Ácido Oleanólico/análogos & derivados , Saponinas , Amônia/toxicidade , Animais , Bupleurum/química , Dieta/veterinária , Poluentes Ambientais/toxicidade , Íleo/efeitos dos fármacos , Masculino , Ácido Oleanólico/farmacologia , Saponinas/farmacologia
11.
Curr Pharm Biotechnol ; 22(3): 329-340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32957882

RESUMO

BACKGROUND: Chaihu is a popular traditional Chinese medicine that has been used for centuries. It is traditionally used to treat cold fever and liver-related diseases. Saikosaponins (SSs) are one of the main active components of chaihu, in addition to essential oils, flavonoids, and polysaccharides. Considerable effort is needed to reveal the biosynthesis and regulation of SSs on the basis of current progress. OBJECTIVE: The aim of this study is to provide a reference for further studies and arouse attention by summarizing the recent achievements of SS biosynthesis. METHODS: All the data compiled and presented here were obtained from various online resources, such as PubMed Scopus and Baidu Scholar in Chinese, up to October 2019. RESULTS: A few genes of the enzymes of SSs participating in the biosynthesis of SSs were isolated. Among these genes, only the P450 gene was verified to catalyze the SS skeleton ß-amyrin synthase. Several UDP-glycosyltransferase genes were predicted to be involved in the biosynthesis of SSs. SSs could be largely biosynthesized in the phloem and then transported from the protoplasm, which is the biosynthetic site, to the vacuoles to avoid self-poisoning. As for the other secondary metabolites, the biosynthesis of SSs was strongly affected by environmental factors and the different species belonging to the genus of Bupleurum. Transcriptional regulation was studied at the molecular level. CONCLUSION: Profound discoveries in SSs may elucidate the mechanism of diverse the monomer formation of SSs and provide a reference for maintaining the stability of SS content in Radix Bupleuri.


Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Bupleurum/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Ácido Oleanólico/análogos & derivados , Saponinas/biossíntese , Animais , Bupleurum/genética , Flavonoides/biossíntese , Flavonoides/genética , Humanos , Ácido Oleanólico/biossíntese , Ácido Oleanólico/genética , Raízes de Plantas , Saponinas/genética , Especificidade da Espécie
12.
J Ethnopharmacol ; 267: 113471, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075440

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Vinegar-baked Radix Bupleuri (VBRB) is a processed form of Bupleurum chinense DC. As a well-known meridian-guiding drug, it is traditionally used as a component of traditional Chinese medicine formulations indicated for the treatment of liver diseases. However, the liver targeting component in VBRB remains unclear. Therefore, this study aims to explore the efficacy and mechanism of PSS (polysaccharides in Vinegar-baked Radix Bupleuri) in enhancing liver targeting. MATERIALS AND METHODS: Drug distribution of OM alone or combined with PSS was investigated in vivo. Relative uptake efficiency (RUE) and relative targeting efficiency (RTE) were calculated to evaluate liver targeting efficiency. The mRNA and protein expression of organic cation transporter 1 (OCT1), multi-drug resistance protein 2 (Mrp2), and hepatocyte nuclear factor 4α (HNF4α) in the liver were determined by q-PCR and Western blot. Then, AZT, the inhibitor of OCT1 and BI6015, the inhibitor of HNF4α were used to investigate regulatory mechanisms involved in the uptake of OM in the cell. At last, the role of PSS in the anti-hepatitis B virus (HBV) was explored on HepG2.2.15. RESULTS: PSS increased the AUC of OM in the liver and increase the RUE and RTE in the liver which indicated a liver targeting enhancing effect. The mRNA and protein expression of OCT1 was increased while Mrp2 and HNF4α decreased. PSS could increase the uptake of OM in HepG2 by increasing the protein expression of HNF4α and OCT1, while inhibited Mrp2. Moreover, PSS combined with OM could enhance the anti-HBV effect of OM. CONCLUSION: PSS enhanced the liver targeting efficiency and the underlying mechanism related to up-regulating the expression of OCT1 and HNF4α, while down-regulating of Mrp2. These results suggest that PSS may become a potential excipient and provide a new direction for new targeted research.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Ácido Acético/química , Alcaloides/farmacologia , Alcaloides/farmacocinética , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/metabolismo , Culinária , Fator 4 Nuclear de Hepatócito/metabolismo , Fígado/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Quinolizinas/farmacologia , Quinolizinas/farmacocinética , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Bupleurum/química , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/genética , Regulação da Expressão Gênica , Células Hep G2 , Fator 4 Nuclear de Hepatócito/genética , Temperatura Alta , Humanos , Fígado/metabolismo , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Extratos Vegetais/química , Polissacarídeos/química , Ratos Sprague-Dawley , Distribuição Tecidual
13.
J Ethnopharmacol ; 269: 113736, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33359917

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Pain is an unpleasant sensory and emotional experience, often accompanied by the occurrence of a variety of diseases. More than 800 kinds of traditional Chinese medicines (TCM) has now been reported for pain relief and several monomers have been developed into novel analgesic drugs. Bupleurum chinense and Angelica biserrata were representatives of the TCM that are currently available for the treatment of pain. AIM OF THE STUDY: The study aims to detect the potential analgesic activity of each monomer of Bupleurum chinense and Angelica biserrata and to explore whether Nav1.7 is one of the targets for its analgesic activity. MATERIALS AND METHODS: In this study, five monomers from Bupleurum chinense (Saikosaponin A, Saikosaponin B1, Saikosaponin B2, Saikosaponin C, Saikosaponin D) and five monomers from the Angelica biserrata (Osthole, Xanthotoxin, Imperatorin, Isoimperatorin, Psoralen) were examined by whole-cell patch-clamp on Nav1.7, which was closely associated with pain. Classical mouse pain models were also used to further verify the analgesic activity in vivo. RESULTS: The results showed that monomers of Saikosaponins and Angelica biserrata all inhibited the peak currents of Nav1.7, indicating that Nav1.7 might be involved in the analgesic mechanism of Saikosaponins and Angelica biserrata. Among them, Saikosaponin A and Imperatorin showed the strongest inhibitory effect on Nav1.7. Furthermore, both Saikosaponin A and Imperatorin showed inhibitory effects on thermal pain and formalin-induced pain in phase II in vivo. CONCLUSION: The results provide valuable information for future studies on the potential of TCM in alleviating pain.


Assuntos
Analgésicos/farmacologia , Angelica/química , Bupleurum/química , Medicamentos de Ervas Chinesas/farmacologia , Canal de Sódio Disparado por Voltagem NAV1.7/efeitos dos fármacos , Dor/tratamento farmacológico , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Células CHO , Cricetulus , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Formaldeído/toxicidade , Furocumarinas/farmacologia , Furocumarinas/uso terapêutico , Temperatura Alta/efeitos adversos , Masculino , Medicina Tradicional Chinesa , Camundongos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Dor/etiologia , Raízes de Plantas/química , Saponinas/farmacologia , Saponinas/uso terapêutico , Sódio/fisiologia
14.
J Ethnopharmacol ; 264: 113281, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32810624

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The compatibility of Bupleurum chinense DC (Chaihu)-Paeonia lactiflora Pall (Baishao) is one of the most accepted herb pairs in traditional Chinese medicine (TCM) prescriptions for treating depression. However, the combination mechanisms of this herb pair for anti-depression remain unclear. MATERIALS AND METHODS: In this study, the combined effect of Chaihu-Baishao was evaluated by the chronic unpredictable mild stress (CUMS) rat model. Secondly, network pharmacology was constructed to dissect the united mechanisms. Based on the results of network pharmacology analysis, plasma metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was performed to discover the collaborative effect on metabolite regulation. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA. RESULTS: The antidepressant effect of Chaihu-Baishao herb pair was significantly better than Chaihu or Baishao in sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). In network pharmacology, herb pair played synergetic effect through regulating shared pathways, such as MAPK signaling pathway and arachidonic acid metabolism, etc. Besides, by metabolomics, the herb pair improved more metabolites (14) than a single herb (10 & 9) and has a stronger regulation effect on metabolites. Correspondingly, herb pair adjusted more metabolism pathways (5) than individual herb (4 & 4). Furthermore, the arachidonic acid metabolism was selected as crucial metabolism pathways by a joint analysis of 199 targets and 14 metabolites. The results showed that herb pair regulated arachidonic acid metabolism by synergetic reducing the level of arachidonic acid, and inhibiting the enzyme activity of prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxide synthase 2 (PTGS2). CONCLUSIONS: This work provided an integrated strategy for revealing the combination mechanisms of Chaihu-Baishao herb pair for treating depression, and also a rational way for clarifying the composition rules of TCM.


Assuntos
Antidepressivos/uso terapêutico , Bupleurum , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica/métodos , Paeonia , Animais , Antidepressivos/isolamento & purificação , Depressão/metabolismo , Depressão/psicologia , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/isolamento & purificação , Masculino , Ratos , Ratos Sprague-Dawley
15.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4853-4860, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33350256

RESUMO

Bupleuri Radix is a traditional staple Chinese medicinal material which has a wide range of medicinal values. However, with the increase of the international trade of Bupleuri Radix, its quality and safety issues have attracted much attention. Therefore, the establishment of international standards for Bupleuri Radix has important practical significance. In view of this, based on our foundation work on the standardization of Chinese medicine and international standards, this review systematically collates the quality standards of the major countries(regions) in which Bupleuri Radix is used, including the origin, macroscopic characteristics, microscopic characteristics, determination of marker compounds and extrinsic harmful contaminants. The existing problems and suggestions are also discussed in this review, which may provide reference for the study of the quality standard of Bupleuri Radix.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Comércio , Internacionalidade , Padrões de Referência
16.
Zhongguo Zhong Yao Za Zhi ; 45(17): 4238-4245, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164409

RESUMO

The aim of this study was to predict the anti-microbial components in the aerial part of Bupleurum chinense fermented by Lactobacillus plantarum through analyzing the correlation between contents of bioactive components and their inhibitory action for pathogenic bacteria. In this study, the UPLC-MS-MS detection method was established for eight flavonoids(kaempferol-3-O-ß-D-rutinoside, isoquercitrin, quercetin, isorhamnetin, rutin, iridin, quercetin-3-O-ß-L-arabinoside, kaempferol) and DL-3-phenyllactic acid, and the dynamic change of their contents at fermentation course were monitored. Meanwhile, the experiment employed five common no-naquatic pathogenic bacteria(Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus subtilis), and four common aquatic pathogenic bacteria(Aeruginosa hydrophila, Delayed Edwards, Vibrio alginolyticus, and Vibrio harveyi) to validate in vitro anti-microbial activity of the fermented aerial part of B. chinense at different fermentation time points. Finally, the Pearson correlation analysis was applied to predict the anti-microbial components of the fermented aerial part of B. chinense.The established UPLC-MS-MS method showed a good linearity and the widest linear range was from 0.19 µg·mL~(-1) to 50 µg·mL~(-1). The limit of quantitation and the limit of detection were 0.19-1.56 µg·mL~(-1) and 0.1-0.78 µg·mL~(-1) respectively. During the fermentation within 48 h, the contents of three flavonoids(rutin, quercetin-3-O-ß-L-arabinoside, isoquercitrin) and DL-3-phenyllactic acid from the fermented aerial part of B. chinense increased sharply. In the process of fermentation, the anti-microbial effect of the fermented aerial part of B. chinense on aquatic pathogens was significantly stronger than that on non-aquatic pathogens. Furthermore, Pearson correlation analysis predicted that isoquercitrin, rutin, quercetin-3-O-ß-L-arabinoside and DL-3-phenyllactic acid showed significant correlation with the four aquatic pathogens. This study revealed that the fermented aerial part of B. chinense had a high sensitivity to aquatic pathogens, which may be caused by the increased contents of isoquercitrin, rutin, quercetin-3-O-ß-L-arabinoside and DL-3-phenyllactic acid. In conclusion, this study provides a theoretical basis and new idea for the further development of the large amount of wasteful aerial part of Bupleurum chinense.


Assuntos
Anti-Infecciosos , Bupleurum , Cromatografia Líquida , Componentes Aéreos da Planta , Espectrometria de Massas em Tandem , Vibrio
17.
Fish Shellfish Immunol ; 107(Pt A): 379-384, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33059009

RESUMO

A 56-day feeding trial was conducted to investigate the effects of dietary supplementation of Astragalus membranaceus or/and Bupleurum chinense on the growth performance, immune enzymes, and related gene expression of Pacific white shrimp (Litopenaeus vanammei). Six experimental diets were formulated and supplemented with two levels (0.25% and 0.5%) of each herb and their combination. At the end of the trial, the specific growth rate and feed conversion ratio of shrimp were significantly (P < 0.05) improved by herbal diets. Besides, the activities of immune-related enzymes such as superoxide dismutase (SOD), alkaline phosphatase (AKP), and lysozyme in serum and hepatopancreas were significantly (P < 0.05) elevated in shrimp fed A. membranaceus or/and B. chinense. The high expression levels of immune deficiency (IMD), lysozyme, and Toll-like receptor mRNA directly or indirectly reflected the activation effect of innate immune in shrimp by dietary A. membranaceus or/and B. chinense. However, no significant difference (P > 0.05) among the herbal incorporated treatments was detected on the growth performance and immune response. In conclusion, the results suggest that A. membranaceus and B. chinense could be used as a beneficial feed additives and alternatives to antibiotics for white shrimp aquaculture.


Assuntos
Astragalus propinquus/química , Bupleurum/química , Suplementos Nutricionais/análise , Expressão Gênica/imunologia , Imunidade Inata/genética , Penaeidae/imunologia , Ração Animal/análise , Animais , Dieta/veterinária , Relação Dose-Resposta a Droga , Penaeidae/enzimologia , Penaeidae/genética , Penaeidae/crescimento & desenvolvimento , Distribuição Aleatória
18.
Fitoterapia ; 147: 104739, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33031867

RESUMO

Four new flavonoids (1-4) and fourteen known compounds (5-18), were isolated from the aerial part of Bupleurum chinense DC. The structural determination of the new flavonoids was accomplished using comprehensive spectroscopic methods, including 1D and 2D NMR spectra with references to the literatures, as well as high-resolution mass spectrometric analysis. The anti-proliferative activities of the flavonoids (1-18) against HeLa cells were evaluated using the MTT assay with cisplatin as the positive control.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Bupleurum/química , Flavonoides/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , China , Flavonoides/isolamento & purificação , Células HeLa , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Plantas Medicinais/química
19.
Biomed Pharmacother ; 131: 110679, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32858498

RESUMO

Bupleuri Radix (BR) is the dry root of Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. It has the functions of evacuation and antipyretic, soothing liver and relieving depression and often used to treat cold fever, chest and rib swelling pain, irregular menstruation, uterine prolapse, rectocele and other diseases. In this paper, the botany, traditional application, phytochemistry, pharmacology and toxicity of BR were reviewed. On the basis of limited literature, the analytical method, quality control, processing method, processing effect and pharmacokinetics of BR were summarized and analyzed for the first time. This review makes an in-depth discussion on the shortcomings of the current research on BR, and puts forward its own views and solutions. This has never been summarized in the previous review of BR. It is of great practical significance for future scholars to find a breakthrough point in the study of BR. So far, its mechanism has not been satisfactorily explained. Moreover, the comprehensive quality evaluation and multi-target network pharmacology of BR need to be further studied. In the future, more in vitro and in vivo experiments are needed to give full play to the therapeutic potential of BR.


Assuntos
Botânica/métodos , Bupleurum , Medicamentos de Ervas Chinesas/farmacocinética , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/farmacocinética , Raízes de Plantas , Bupleurum/química , Medicamentos de Ervas Chinesas/análise , Humanos , Compostos Fitoquímicos/análise , Raízes de Plantas/química
20.
Medicine (Baltimore) ; 99(29): e20980, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702837

RESUMO

BACKGROUND: Insomnia and hypertension are diseases with a high prevalence and a known association with each other. Sihogayonggolmoryeo-tang (SYM) is an herbal medicine traditionally used for the treatment of insomnia disorder concurrent with hypertension. However, no scientific clinical evidence exists supporting the effects of SYM on these disorders. This study aims to explore the feasibility, effectiveness, and safety of SYM for the treatment of insomnia disorder with concurrent prehypertension or stage 1 hypertension. METHODS: A prospective, randomized, wait-list controlled, parallel, pilot clinical trial has been designed for a study to be conducted in Daejeon, Republic of Korea. Thirty insomnia disorder patients with prehypertension or stage 1 hypertension will be randomly assigned to a SYM or wait-list group at a 1:1 ratio. The SYM group will be administered SYM granules twice a day for 4 weeks and followed-up for 2 weeks while the wait-list group will not receive SYM granules. All participants in both groups will be given brochures with instructions for maintaining sleep hygiene and lifestyle modifications to reduce hypertension. Data will be collected at baseline and at 2, 4, and 6 weeks after allocation. The primary outcome is the Insomnia Severity Index score at 4 weeks post-treatment. The secondary outcomes will consist of the Pittsburgh Sleep Quality Index, sleep diary, systolic and diastolic blood pressure, brachial-ankle pulse wave velocity, ankle-brachial index, atherosclerosis biomarkers, the Hospital Anxiety and Depression Scale, the 5-level EuroQol-5 dimensions, and the Patient Global Impression of Change. Adverse events and laboratory test results will be monitored to assess the safety. Data will be recorded in electronic case report forms and analyzed using SPSS Statistics, Version 24.0. DISCUSSION: This is the first clinical trial to explore the effectiveness and safety of SYM for the treatment of insomnia disorder concurrent with prehypertension or stage 1 hypertension. The results of this study can form the foundation for a future multicenter, large-scale, confirmatory clinical trial. TRIAL REGISTRATION: Clinical Research Information Service, KCT0005001 (registered on May 8, 2020).


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Hipertensão/complicações , Fitoterapia , Pré-Hipertensão/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/terapia , Ansiedade/diagnóstico , Depressão/diagnóstico , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários , Escala Visual Analógica
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