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1.
PLoS One ; 19(6): e0304503, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843246

RESUMO

Drought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting biomass and secondary metabolite production, thus affecting yield and quality. To investigate the molecular mechanism underlying the response of B. chinense seedlings under drought stress, this study employed comprehensive physiological, transcriptomic, and metabolomic analyses. The results revealed that under drought stress, the root soluble sugar and free proline content in B. chinense seedlings significantly increased, while the activities of SOD, POD, and CAT increased in the leaves. These findings indicate the presence of distinct response mechanisms in B. chinense to cope with drought stress. Integrated analysis further identified significant correlations between genes and metabolites related to amino acid biosynthesis in the leaves, as well as genes and metabolites associated with acetaldehyde and dicarboxylic acid metabolism. In the roots, genes and metabolites related to plant hormone signaling and the tricarboxylic acid (TCA) cycle showed significant correlations. These findings provide vital views into the molecular-level response mechanisms of B. chinense under drought stress. Moreover, this study establishes the groundwork for identifying drought-tolerant genes and breeding drought-resistant varieties, which could improve the drought tolerance of medicinal plants and have broader implications for agriculture and crop production in water-scarce areas.


Assuntos
Bupleurum , Secas , Regulação da Expressão Gênica de Plantas , Metabolômica , Plântula , Estresse Fisiológico , Bupleurum/genética , Bupleurum/metabolismo , Plântula/metabolismo , Plântula/genética , Estresse Fisiológico/genética , Transcriptoma , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Folhas de Planta/metabolismo , Folhas de Planta/genética , Perfilação da Expressão Gênica , Metaboloma
2.
J Mass Spectrom ; 59(6): e5035, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38726730

RESUMO

Bupleuri Radix is an important medicinal plant, which has been used in China and other Asian countries for thousands of years. Cultivated Bupleurum chinense DC. (B. chinense) is the main commodity of Bupleuri Radix. The benefits of intercropping with various crops for B. chinense have been recognized; however, the influence of intercropping on the chemical composition of B. chinense is still unclear yet. In this study, intercropping with sorghum and maize exhibited little effect on the root length, root diameter, and single root mass of B. chinense. Only the intercropping with sorghum increased the root length of B. chinense slightly compared to the monocropping. In addition, 200 compounds were identified by UHPLC-Q-TOF-MS, and metabolomic combined with the Venn diagram and heatmap analysis showed apparent separation between the intercropped and monocropped B. chinense samples. Intercropping with sorghum and maize could both increase the saikosaponins, fatty acyls, and organic acids in B. chinense while decreasing the phospholipids. The influence of intercropping on the saikosaponin biosynthesis was probably related with the light intensity and hormone levels in B. chinense. Moreover, we found intercropping increased the anti-inflammatory activity of B. chinense. This study provides a scientific reference for the beneficial effect of intercropping mode of B. chinense.


Assuntos
Bupleurum , Metabolômica , Ácido Oleanólico , Raízes de Plantas , Saponinas , Sorghum , Zea mays , Sorghum/metabolismo , Sorghum/química , Bupleurum/química , Bupleurum/metabolismo , Zea mays/metabolismo , Zea mays/química , Saponinas/análise , Saponinas/metabolismo , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análise , Ácido Oleanólico/metabolismo , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Raízes de Plantas/metabolismo , Raízes de Plantas/química , Espectrometria de Massas/métodos , Agricultura/métodos , Espectrometria de Massa com Cromatografia Líquida
3.
J Pharm Biomed Anal ; 246: 116239, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38777665

RESUMO

The dried root of Bupleurum marginatum var. stenophyllum (H. Wolff) R.H. Shan & Y. Li (BM), which has been used as a Bupleuri radix in Guizhou Province and is listed in the 2003 edition of the Guizhou Quality Standard for Traditional Chinese Medicines and Ethnic Materia Medica, is effective at dispersing the liver and relieving depression and often used in the form of raw or vinegar-processed product (VBM). However, the potential depression-relieving components of BM are unclear. The aim of this study was to determine the potential antidepressant constituents of BM and investigate the effect of vinegar processing on these components. The antidepressant effect and mechanism of BM and VBM were investigated in depressed mice and BV2 cells, respectively. The pharmacodynamic constituents were screened through serum pharmacochemistry, which combined the results of metabolomics analysis of BM and VBM, high-performance liquid chromatography (HPLC) content determination, and verification of the antidepressant effect and mechanism of differential components of SSb2 to clarify the connotation of vinegar processing. Our results demonstrated that BM can exert a significant antidepressant effect by inhibiting microglia polarization and that this effect was enhanced after vinegar processing. Thirty-eight components were identified in the BM, 13 of which were blood-absorbable, mainly saponins, and defined as potential antidepressant components of the BM. The contents of 17 components-6 of which were absorbed into the blood-changed considerably after processing. It was finally determined that vinegar processing can enhance the antidepressant effect of BM by increasing the contents of SSb1 and SSb2. SSb2 exerts this effect via the samemechanism as BM. In conclusion, in this study we clarified the antidepressant effects and potential active components of BM and examined the mechanism of vinegar processing. These findings lay a foundation for the future research on the antidepressant effects of BM as well as for the complete development and application of BM's ethnomedicinal resources.


Assuntos
Ácido Acético , Antidepressivos , Bupleurum , Depressão , Medicamentos de Ervas Chinesas , Metabolômica , Animais , Bupleurum/química , Antidepressivos/farmacologia , Camundongos , Metabolômica/métodos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Depressão/tratamento farmacológico , Depressão/metabolismo , Raízes de Plantas/química
4.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1802-1808, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812192

RESUMO

The effects of humic acid water-soluble fertilizer on the growth and physiological characteristics of Bupleurum chinense seedlings(Zhongchai No.1) were studied by using a single factor experiment design. When the seedling age was 60 days, the humic acid water-soluble fertilizer was diluted 1 200 times(T1), 1 500 times(T2), 1 800 times(T3), and 2 100 times(T4) for seedling treatment, respectively, and water was used as the control(CK). The effects of different treatments on growth indexes, biomass accumulation, root activity, antioxidant enzyme activity, membrane lipid peroxidation, and photosynthetic characteristics of B. chinense seedlings were analyzed after 30 days. The results showed that compared with CK, stem height, leaf number, root diameter, and root length of the B. chinense seedlings under T3 treatment were significantly increased by 36.82%, 37.03%, 42.78%, and 22.38%, respectively. Root fresh weight, leaf fresh weight, root dry weight, and leaf dry weight under T3 treatment were significantly increased by 90.36%, 98.68%, 123.84%, and 104.38%, respectively. In addition, humic acid water-soluble fertilizer also enhanced TTC reducing activity of the root of B. chinense seedlings, inhibited malonaldehyde(MDA) content, increased superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) enzyme activities, improved chlorophyll content, and enhanced P_n, G_s, T_r, and other photosynthetic parameters. In conclusion, the application of humic acid water-soluble fertilizer diluted 1 800 times can significantly promote the growth of B. chinense seedlings, enhance root vitality, improve seedling stress resistance, and enhance photosynthesis. The results of this study can provide a theoretical basis for fertilization of B. chinense seedlings.


Assuntos
Bupleurum , Fertilizantes , Substâncias Húmicas , Raízes de Plantas , Plântula , Substâncias Húmicas/análise , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Plântula/metabolismo , Fertilizantes/análise , Bupleurum/crescimento & desenvolvimento , Bupleurum/química , Bupleurum/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Fotossíntese/efeitos dos fármacos , Água/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Solubilidade , Superóxido Dismutase/metabolismo
5.
Int J Biol Macromol ; 266(Pt 2): 131171, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574920

RESUMO

This study explored the structures of three polysaccharides from Bupleurum chinense DC. (BCPRs), and evaluated their antioxidant and anti-aging properties. The HPGPC and ion chromatography analyses revealed that the molecular weights of the BCPRs ranged from 12.05 to 21.20 kDa, and were primarily composed of rhamnose, arabinose, xylose, galactose, glucose and galacturonic acid. Methylation and NMR studies identified 10 PMAAs, establishing the various backbones of BCPRs 1-3. BCPR-3 demonstrated potent antioxidant activities, including DPPH, ABTS, hydroxy, and superoxide radicals scavenging in vitro. At concentrations between 125 and 500 µg/mL, BCPR-3 increased T-AOC, SOD and GSH-Px activities, while decreasing MDA levels in H2O2-induced SH-SY5Y cells. In addition, RNA-seq results indicated that BCPR-3 considerably downregulated the expression of 49 genes and upregulated five genes compared with the control group. KEGG analysis suggested that these differentially expressed genes (DEGs) were predominantly involved in the TNF and PI3K/Akt signaling pathways. Furthermore, in vivo experiment with Drosophila melanogaster showed that BCPR-3 could extend the average lifespan of flies. In conclusion, polysaccharides from B. chinense exhibited potential antioxidant and anti-aging activities, which could be developed as new ingredients to combat oxidative stress damage and slow the aging process.


Assuntos
Antioxidantes , Bupleurum , Polissacarídeos , Espécies Reativas de Oxigênio , Transdução de Sinais , Polissacarídeos/farmacologia , Polissacarídeos/química , Bupleurum/química , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Transdução de Sinais/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Envelhecimento/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peróxido de Hidrogênio
6.
J Ethnopharmacol ; 330: 118244, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38663781

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Hepatopatias , Animais , Humanos , Bupleurum/química , Doença Crônica , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/química
7.
J Asian Nat Prod Res ; 26(7): 858-864, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38572987

RESUMO

A new triterpenoid saponin (1), along with five known compounds (2-6), was isolated from Bupleurum marginatum Wall. ex DC, of which compounds 2-4 were obtained for the first time from this plant. The structures were confirmed by the analysis of 1D, 2D NMR, and HR-ESIMS data, and comparison with previous spectral data. Anti-liver fibrotic activities of the isolates were determined as proliferation inhibition of LPS-induced activation of HSC-T6 in vitro.


Assuntos
Bupleurum , Saponinas , Triterpenos , Saponinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Bupleurum/química , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Estrutura Molecular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Cirrose Hepática/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Animais , Ressonância Magnética Nuclear Biomolecular
8.
J Ethnopharmacol ; 328: 118038, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38479544

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC.-Scutellaria baicalensis Georgi (BS) is a classic drug pair that has good clinical effects on depression and many tumors. However, the concurrent targeting mechanism of how the aforementioned drug pair is valid in the two distinct diseases, has not been clarified yet. AIM OF THE STUDY: The components of BS were detected by LC-MS, combined with network pharmacology to explore the active ingredients and common targeting mechanism of its multi-pathway regulation of BS in treating depression and CRC, and to validate the dual effects of BS using the CUMS mice model and orthotopic transplantation tumor mice model of CRC. RESULTS: Twenty-nine components were screened, 84 common gene targets were obteined, and the top 5 key targets including STAT3, PIK3R1, PIK3CA, AKT1, IL-6 were identified by PPI network. GO and KEGG analyses revealed that PI3K/AKT and JAK/STAT signaling pathways might play a crucial role of BS in regulating depression and CRC. BS significantly modulated CUMS-induced depressive-like behavior, attenuated neuronal damage, and reduced serum EPI and NE levels in CUMS model mice. BS improved the pathological histological changes of solid tumors and liver tissues and inhibited solid tumors and liver metastases in tumor-bearing mice. BS significantly decreased the proteins' expression of IL-6, p-JAK2, p-STAT3, p-PI3K, p-AKT1 in hippocampal tissues and solid tumors, and regulated the levels of IL-2, IL-6 and IL-10 in serum of two models of mice. CONCLUSION: BS can exert dual antidepressant and anti-CRC effects by inhibiting the expression of IL-6/JAK2/STAT3 and PI3K/AKT pathway proteins and regulating the release of inflammatory cytokines.


Assuntos
Bupleurum , Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Animais , Camundongos , Farmacologia em Rede , Depressão/tratamento farmacológico , Interleucina-6 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Scutellaria baicalensis , Modelos Animais de Doenças , Neoplasias Colorretais/tratamento farmacológico , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
9.
Int J Biol Macromol ; 266(Pt 1): 131096, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522695

RESUMO

Polysaccharides of vinegar-baked Radix Bupleuri (VBCP) have been reported to exhibit liver-targeting and immunomodulatory activities through oral administration, but the absorption behavior and mechanism of VBCPs have not been extensively studied. In this study, a novel HG type pectin polysaccharide, VBCP1-4, with a high molecular weight of 2.94 × 106 Da, was separated from VBCP. VBCP1-4 backbone was contained 1,4-α-D-GalpA, 1,4-α-D-GalpA6OMe, 1,3,4-α-D-GalpA and 1,2,4-α-D-Rhap. The branches were mainly contained 1,5-α-L-Araf, 1,3,5-α-L-Araf, t-α-L-Araf and t-α-D-Galp, which linked to the 3 position of 1,3,4-α-D-GalpA and the 4 position of 1,2,4-α-D-Rhap. VBCP1-4 could self-assemble to nanoparticles in water, with CMC values of 106.41 µg/mL, particle sizes of 178.20 ± 2.82 nm and zeta potentials of -23.19 ± 1.44 mV. The pharmacokinetic study of VBCP1-4, which detected by marking with FITC, revealed that it could be partially absorbed into the body through Peyer's patches of the ileum. In vitro absorption study demonstrated that VBCP1-4 was difficult to be absorbed by Caco-2 cell monolayer, but could be absorbed by M cells in a time and concentration dependent manner. The absorption mechanism was elucidated that VBCP1-4 entered M cells through clathrin-mediated endocytosis in the form of nanoparticles. These findings provide valuable insights into the absorption behavior of VBCP and contribute to its further development.


Assuntos
Ácido Acético , Bupleurum , Nanopartículas , Pectinas , Pectinas/química , Bupleurum/química , Ácido Acético/química , Nanopartículas/química , Humanos , Animais , Células CACO-2 , Tamanho da Partícula , Peso Molecular , Células M
10.
Biomed Pharmacother ; 172: 116267, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364739

RESUMO

Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function of Radix Bupleuri aqueous extract in SCZ in mouse models. The SCZ mouse model was established by MK-801 injection and feeding of Radix Bupleuri aqueous extract or combined antibiotics. Radix Bupleuri aqueous extract significantly improved the aberrant behaviors and neuronal damage in SCZ mice, upregulated SYP and PSD-95 expression and BDNF levels in hippocampal homogenates, down-regulated DA and 5-HT levels, and suppressed microglial activation in SCZ mice. Moreover, Radix Bupleuri aqueous extract improved the integrity of the intestinal tract barrier. The 16 S rRNA sequencing of feces showed that Radix Bupleuri extract modulated the composition of gut flora. Lactobacillus abundance was decreased in SCZ mice and reversed by Radix Bupleuri aqueous extract administration which exhibited a significant negative correlation with IL-6, IL-1ß, DA, and 5-HT, and a significant positive correlation with BDNF levels in hippocampal tissues. The abundance of Parabacteroides and Alloprevotella was increased in SCZ mice. It was reversed by Radix Bupleuri aqueous extract administration, which exhibited a positive correlation with IL-6, IL-1ß, and 5-HT and a negative correlation with BDNF. In conclusion, Radix Bupleuri aqueous extract attenuates the inflammatory response in hippocampal tissues and modulates neurotransmitter levels, exerting its neuroprotective effect in SCZ. Meanwhile, the alteration of intestinal flora may be involved in this process, which is expected to be an underlying therapeutic option in treating SCZ.


Assuntos
Bupleurum , Microbioma Gastrointestinal , Extratos Vegetais , Esquizofrenia , Humanos , Animais , Camundongos , Maleato de Dizocilpina , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo , Interleucina-6 , Serotonina , Modelos Animais de Doenças , Interleucina-1beta
11.
Drug Des Devel Ther ; 18: 375-394, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38347958

RESUMO

Background: Gastric cancer (GC) is a common fatal malignancy. The aim of this study was to explore and validate the tumor-suppressive role and mechanism of Radix Bupleuri in GC. Methods: The active constituents of Radix Bupleuri were screened using TCMSP database. SwissTargetPrediction database was used to predict potential target genes of the compounds. GeneCards, TTD, DisGeNET, OMIM, and PharmGKB databases were used to search for GC-related targets. STRING database and Cytoscape 3.10 software were used for protein-protein interaction network construction and screening of core targets. DAVID database was used for GO and KEGG analyses. Core targets were validated using molecular docking. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry after GC cells were treated with isorhamnetin. The mRNA and protein expression levels of genes were detected using qRT PCR and Western blot. The metastasis potential of GC cells was evaluated in a nude mouse model. Results: A total of 371 potential targets were retrieved by searching the intersection of Radix Bupleuri and GC targets. Petunidin, 3',4',5',3,5,6,7-Heptamethoxyflavone, quercetin, kaempferol, and isorhamnetin were identified as the main bioactive compounds in Radix Bupleuri. SRC, HSP90AA1, AKT1, and EGFR, were core targets through which Radix Bupleuri suppressed GC. The tumor-suppressive effect of Radix Bupleuri on GC was mediated by multiple pathways, including PI3K-AKT, cAMP, and TNF signaling. The key compounds of Radix Bupleuri had good binding affinity with the core target. Isorhamnetin, a key component of Radix Bupleuri, could inhibit proliferation and metastasis, and induces apoptosis of GC cells. In addition, isorhamnetin could also reduce the mRNA expression of core targets, and the activation of PI3K/AKT pathway. Conclusion: This study identified potential targets and pathways of Radix Bupleuri against GC through network pharmacology and molecular docking, providing new insights into the pharmacological mechanisms of Radix Bupleuri in GC treatment.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Extratos Vegetais , Neoplasias Gástricas , Animais , Camundongos , Neoplasias Gástricas/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Mensageiro , Medicamentos de Ervas Chinesas/farmacologia
13.
Chem Biodivers ; 21(4): e202301733, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38217462

RESUMO

Bupleurum scorzonerifolium willd. (BS) and its vinegar-baked product (VBS) has been frequently utilized for depression management in clinical Chinese medicine. This paper aims to elucidate the antidepressant mechanism of BS and VBS from the perspectives of metabonomics and gut microbiota. A rat model of depression was established by CUMS combined with feeding alone to evaluate the antidepressant effects of BS and VBS. UPLC-Q-TOF-MS/MS-based metabolomics and 16S rRNA sequencing of rat feces were applied and the correlation of differential metabolic markers and intestinal floras was analyzed. The result revealed that BS and VBS significantly improved depression-like behaviors and the levels of monoamine neurotransmitters in CUMS rats. There were 27 differential endogenous metabolites between CUMS and normal rats, which were involved in 8 metabolic pathways. Whereas, BS and VBS could regulate 18 and 20 metabolites respectively, wherein fifteen of them were shared metabolites. On the genus level, BS and VBS could regulate twenty-five kinds of intestinal floras in CUMS rats, that is, they increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria. In conclusion, both BS and VBS exert excellent antidepressant effects by regulating various metabolic pathways and ameliorating intestinal microflora dysfunction.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Ratos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Ácido Acético , Espectrometria de Massas em Tandem , RNA Ribossômico 16S , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Metabolômica/métodos
14.
Nutr Cancer ; 76(1): 63-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37909316

RESUMO

OBJECTIVE: This study investigated how Radix Bupleuri-Radix Paeoniae Alba (BP) was active against hepatocellular carcinoma (HCC). METHODS: Traditional Chinese medicine systems pharmacology (TCMSP) database was employed to determine the active ingredients of BP and potential targets against HCC. Molecular docking analysis verified the binding activity of PTEN with BP ingredients. H22 cells were used to establish an HCC model in male balb/c mice. Immunofluorescence staining, immunohistochemistry, flow cytometry, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative PCR were used to study changes in proliferation, apoptosis, PTEN levels, inflammation, and T-cell differentiation in male balb/c mice. RESULTS: The major active ingredients in BP were found to be quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol. Molecular docking demonstrated that these five active BP ingredients formed a stable complex with PTEN. BP exhibited an anti-tumor effect in our HCC mouse model. BP was found to increase the CD8+ and IFN-γ+/CD4+ T cell levels while decreasing the PD-1+/CD8+ T and Treg cell levels in HCC mice. BP up-regulated the IL-6, IFN-γ, and TNF-α levels but down-regulated the IL-10 levels in HCC mice. After PTEN knockdown, BP-induced effects were abrogated. CONCLUSION: BP influenced the immune microenvironment through activation of the PTEN/PD-L1 axis, protecting against HCC.


Assuntos
Bupleurum , Carcinoma Hepatocelular , Neoplasias Hepáticas , Extratos Vegetais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Medicina Tradicional Chinesa , Microambiente Tumoral/efeitos dos fármacos , Humanos , Animais , Camundongos , Camundongos Endogâmicos BALB C , Bupleurum/química , Extratos Vegetais/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas , Espectrometria de Massa com Cromatografia Líquida , Linfócitos T/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia
15.
Biochem Biophys Res Commun ; 691: 149322, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38039833

RESUMO

BACKGROUND: Bupleurum (Bup), is a traditional effective medicine to treat colds and fevers in clinics. Multiple studies have demonstrated that Bup exhibites various biological activities, including cardioprotective effects, anti-inflammatory, anticancer, antipyretic, antimicrobial, and antiviral effects, etc. Currently, the effects of Bup on cardiac electrophysiology have not been reported yet. METHODS: Electrocardiogram recordings were used to investigate the effects of Bup on aconitine-induced arrhythmias. Patch-clamp techniques were used to explore the effects of Bup on APs and ion currents. RESULTS: Bup reduced the incidence of ventricular fibrillation (VF) and delayed the onset time of ventricular tachycardia (VT) in mice. Additionally, Bup (40 mg/mL) suppressed DADs induced by high-Ca2+ and shortened action potential duration at 50 % completion of repolarization (APD50) and action potential duration at 90 % completion of repolarization (APD90) to 60.89 % ± 8.40 % and 68.94 % ± 3.24 % of the control, respectively. Moreover, Bup inhibited L-type calcium currents (ICa.L) in a dose-dependent manner, with an IC50 value of 25.36 mg/mL. Furthermore, Bup affected the gated kinetics of L-type calcium channels by slowing down steady-state activation, accelerating the steady-state inactivation, and delaying the inactivation-recovery process. However, Bup had no effects on the Transient sodium current (INa.T), ATX II-increased late sodium current (INa.L), transient outward current (Ito), delayed rectifier potassium current (IK), or inward rectifier potassium current (IK1). CONCLUSION: Bup is an antiarrhythmic agent that may exert its antiarrhythmic effects by inhibiting L-type calcium channels.


Assuntos
Bupleurum , Canais de Cálcio Tipo L , Camundongos , Animais , Bupleurum/metabolismo , Miócitos Cardíacos/metabolismo , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas , Sódio/metabolismo , Potássio/farmacologia , Potenciais de Ação
16.
Phytochem Anal ; 35(2): 336-349, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37787024

RESUMO

INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.


Assuntos
Bupleurum , Espectrometria de Massas em Tandem , Camundongos , Animais , Peixe-Zebra , Cromatografia Líquida de Alta Pressão , Bupleurum/química , Células RAW 264.7 , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/análise , Inflamação/tratamento farmacológico , Componentes Aéreos da Planta/química
17.
J Chromatogr A ; 1714: 464544, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38142618

RESUMO

Comprehensive and rapid analysis of secondary metabolites like saponins remains challenging. This study aimed to establish a semi-automated workflow for filtration, identification, and characterization of saikosaponins in six Bupleurum species. Radix Bupleuri, a high-sales herbal medicine, is often adulterated, restricting its quality control and applications. Two authentic Radix Bupleuri species and four major adulterants were analyzed through UHPLC-LTQ-Orbitrap-MS for targeted saikosaponin analysis. To reveal trace saikosaponins and obtain quality fragment data, a MATLAB-based process automatically enumerating "sugar chain + aglycone + side chain" combinations and deduplicating generated a predicted saikosaponin database covering all possible saikosaponins as a precursor ion list for comprehensive targeted acquisition. To focus on informative ions and reduce MS analysis workload, we utilized MATLAB to automatically filtrate the false positive ions by MS1 and MS2 spectrometry. The newly established MATLAB-assisted data acquisition approach exhibited 50 % improvement in characterization of targeted saikosaponins. Furthermore, positive and negative ionization workflows were designed for accurate saikosaponins characterization based on fragmentation rules. In total, 707 saikosaponins were characterized, including over 500 potential new compounds and previously unreported C29 aglycones. We identified 25 saikosaponins present in both authentic species but absent in adulterants as potential markers. This unprecedented comprehensive multi-origin species differentiation demonstrates the promise of MATLAB-assisted acquisition and processing to advance saponin identification and standardize the Radix Bupleuri market.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Ácido Oleanólico , Saponinas , Medicamentos de Ervas Chinesas/química , Bupleurum/química , Extratos Vegetais , Saponinas/análise , Ácido Oleanólico/análise , Cromatografia Líquida , Espectrometria de Massas , Íons , Cromatografia Líquida de Alta Pressão/métodos
18.
Fitoterapia ; 173: 105778, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38128620

RESUMO

Saikosaponin d (SSd) is the main component of Bupleuri Radix, a famous traditional Chinese herbal medicine, with high medicinal value. An endophytic fungus (CHS3) was isolated from Bupleurum scorzonerifolium Willd. in the early stage of our research, and we found that CHS3 could promote the accumulation of SSd in Bupleurum scorzonerifolium Willd. suspension cells (BSS cells). It is of practical significance to identify the mechanism that CHS3 promoted the accumulation of SSd and increased the production of SSd in suspension cells. To search the influence of CHS3 on SSd synthesis in the BSS cells, we co-cultured CHS3 with the BSS cells and compared the SSd content in BSS cells before and after co-culture using high-performance liquid chromatography (HPLC). Then the Illumina HiSeq 2500 was performed to detect the transcriptome of the BSS cells before and after co-culture and analyzed for the KEGG enrichment. The expression of genes involved in SSd synthesis was finally corroborated by qPCR analysis. Among which 11 key genes in connection with SSd synthesis were increased in BSS cells of co-cultured group compared with the BSS cells of the control group. In conclusion, CHS3 could promote the accumulation of SSd in BSS cells, and the molecular mechanism was related to its ability to regulate the MVA pathway, the calcium signaling pathway, and the AMPK signaling pathway by upregulating the expressions of ANT, CypD, CaM, AMPK, AATC, HMGS, HMGR, MVK, MVD, SS, and SE.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Ácido Oleanólico/análogos & derivados , Saponinas , Bupleurum/química , Medicamentos de Ervas Chinesas/química , Proteínas Quinases Ativadas por AMP , Estrutura Molecular , Saponinas/química , Perfilação da Expressão Gênica
19.
Molecules ; 28(15)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37570602

RESUMO

Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. have different clinical efficacies, with the former typically used to treat typhoid fever and the latter mainly used to clear liver heat. The differences in their clinical efficacy are closely related to their complex chemical composition, especially the active components. In this study, the saponins and volatile oils in two varieties of Radix Bupleuri grown in different regions were extracted and analyzed using high-performance liquid chromatography (HPLC) and gas chromatography coupled with mass spectrometry (MS), and the absolute contents of five saikosaponins were accurately quantified using an established HPLC-MS method in the multiple reaction monitoring mode. Multivariate statistical analysis was performed to reveal the difference in the active components between the two varieties. The saikosaponin content was significantly affected by variety and growing region, with all five saikosaponins being significantly higher in Bupleurum chinense DC. than in Bupleurum scorzonerifolium Willd. The results of principal component analysis and hierarchical cluster analysis show a clear distinction between the two varieties in terms of both saponins and volatile oils. Twenty-one saponins, including saikosaponin b2 and b1, and fifty-two volatile oils, including 2-tetradecyloxirane and chloromethyl cyanide, were screened and identified as differential compounds contributing to the significant difference between the two varieties. These compounds may also be responsible for the difference in clinical efficacy between Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. All the results suggest that the accumulation and diversity of active components in Radix Bupleuri are significantly affected by the variety. In contrast to previous reports, this study provides the absolute contents of five saikosaponins in Radix Bupleuri of different varieties and reduces the influence of the growing region on the analytical results by collecting samples from different regions. The results of this study may provide a reference for the identification and quality evaluation of different varieties of Radix Bupleuri.


Assuntos
Bupleurum , Óleos Voláteis , Ácido Oleanólico , Saponinas , Bupleurum/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Saponinas/análise , Ácido Oleanólico/análise , Óleos Voláteis/análise , Raízes de Plantas/química
20.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1815-1823, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282956

RESUMO

It is generally believed that high-quality Bupleurum scorzonerifolium roots possess specific morphological characteristics, being red, robust, and long with strong odor. However, the scientific connotation of these characteristics has not been elucidated. According to the theory of "quality evaluation through morphological identification", we studied the correlations between appearance traits(the RGB value of root surface, root length, root diameter, dry weight, and ratio of phloem to xylem) and content of main chemical components(volatile oils, total saponins, total flavonoids, total polysaccharides, and seven saikosaponins) of B. scorzonerifolium roots. Epson Scanner and ImageJ were used to scan the root samples and measure the appearance traits. Ultraviolet spectrophotometry and HPLC were employed to determine the content of chemical components. The correlation, regression, and cluster analyses were performed to study the correlations between the appearance traits and the content of chemical components. The results showed that the content of volatile oils and saikosaponins were significantly correlated with RGB value, root length, and root diameter, indicating that within a certain range, the roots being redder, longer, and thicker had higher content of volatile oils and saikosaponins. According to the appearance traits and chemical component content, the 14 samples from different producing areas were classified into four grades, and the differences in morphological traits and chemical component content were consistent among different grades. The findings in this study demonstrate that appearance traits(RGB value, root length, and root diameter) can be used to evaluate the quality of B. scorzonerifolium roots. Meanwhile, this study lays a foundation for establishing an objective quality evaluation method for B. scorzonerifolium roots.


Assuntos
Bupleurum , Óleos Voláteis , Ácido Oleanólico , Saponinas , Bupleurum/química , Saponinas/análise , Ácido Oleanólico/análise , Óleos Voláteis/análise , Raízes de Plantas/química
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