ANALYTICAL SCIENCES
·
2021
·Vol. 37
·期 10
·1413-1418
·
IF 2.081
Hua ZHAO,Xiaohui WANG,Yuli ZHANG,Xiaowan HUANG,Yaling JIANG,Huan MA,Li AN,Xujin WU,Qiang WANG
Saikosaponin a and saikosaponin d are used as chemical standards for the quality evaluation of Bupleurum chinense DC. by the high-performance liquid chromatography method in current Chinese Pharmacopoeia. However, other saikosaponins, such as saikosaponin c and saikosaponin b2, also possess pharmaceutical activity, but are not used as chemical standards. In this study, a quantitative proton nuclear magnetic resonance (1H NMR) method was developed to determine the total mass percentage (mg/g) of SSa, SSb1, SSb2 and SSd in B. chinense DC., using the H-24 (δH 0.71) signal. Furthermore, the molality (mol/kg) of type I saikosaponins (epoxy-ether structure) was also determined by quantitative 1H NMR in the area of H-11 (δH 5.95) for a more accurate quality evaluation. Validation of the method confirmed that it has acceptable selectivity, precision, stability, and repeatability. The results indicated that this method has the potential to be a reliable method for the quantification of saikosaponins in Bupleurum scorzonerifolium Willd., vinegar baked B. chinense DC. and B. scorzonerifolium Willd., Chaihu Koufuye (oral liquid of Chaihu).
研究领域:
药学化学
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分析化学
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生药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2020
·
IF 3.216
Hongfang Li,Yunyan Tang,Yang Wang,Weipeng Wei,Chengchen Yin,Fushang Tang
Background Bupleurum is one of the most important traditional Chinese medicines and an ingredient in many compound preparations. It is widely used together with other drugs in clinical practice, and thus there is great potential for drug–drug interactions. Saikosaponin D (SsD) is a major bioactive triterpenoid saponin extracted from Bupleurum with anti-inflammatory, anticancer, antioxidative, and antihepatic fibrosis effects. Effects of the main components of Bupleurum on cytochromes P450 (CYPs) need to be clarified in the clinical application of combination therapies of formulations containing SsD or Bupleurum . Purpose This study aimed to investigate the effects of SsD on the CYP1A2 and CYP2D6 mRNAs, protein expression, and relative enzyme activities in HepaRG cells. Methods HepaRG cells were cultured with SsD at concentrations of 0.5, 1, 5 and 10 μM for 72 hours. mRNA and protein expression of CYP1A2 and CYP2D6 were analyzed with real-time PCR and Western blot analysis. Relative enzyme activities were analyzed with HPLC based on consumption of the specific probe substrate. Results SsD significantly induced expression of mRNA and increased relative activity of CYP1A2 in HepaRG cells after the cells had been treated with SsD at concentrations of 1, 5 and 10 μM. SsD also induced protein expression of CYP1A2 at concentrations of 5 and 10 μM. SsD exhibited an inductive effect on CYP2D6 mRNA and protein expression, while increasing the relative activity of CYP2D6 at concentrations of 5 and 10 μM. Conclusion This study is the first to investigate the effect of SsD on CYP1A2 and CYP2D6 in HepaRG cells, and the results may provide some useful information on potential drug–drug interactions related to clinical preparations containing SsD or Bupleurum .
研究领域:
药理学
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毒理学
·
分子生物学
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中药学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2020
·
IF 2.673
Siqi Ren,Jingjing Liu,Yunwen Xue,Mei Zhang,Qiwei Liu,Jie Xu,Zunjian Zhang,Rui Song
Saikosaponins (SSs) are the main active components extracted from Bupleuri Radix (BR) which has been used as an important herbal drug in Asian countries for thousands of years. It has been reported that the intestinal bacteria plays an important role in the in vivo disposal of oral SSs. Although the deglycosylated derivatives (saikogenins, SGs) of SSs metabolized by the intestinal bacteria are speculated to be the main components absorbed into the blood after oral administration of SSs, no studies have been reported on the characteristics of SGs for their intestinal absorption, and those for SSs are also limited. Therefore, a rapid UHPLC-MS/MS method was developed to investigate and compare the apparent permeability of three common SSs (SSa, SSd, SSb 2 ) and their corresponding SGs (SGF, SGG, SGD) through a bidirectional transport experiment on Caco-2 cell monolayer model. The method was validated according to the latest FDA guidelines and applied to quantify the six analytes in transport medium samples extracted via liquid-liquid extraction (LLE). The apparent permeability coefficient ( P app ) determined in this study indicated that the permeability of SGs improved to the moderate class compared to the corresponding parent compounds, predicting a higher in vivo absorption. Moreover, the efflux ratio (ER) value demonstrated an active uptake of SSd and the three SGs, while a passive diffusion of SSa and SSb 2 .
研究领域:
药理学
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药剂学
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分析化学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 70
·41088-41098
·
IF 3.049
Danqi Li,Da Liu,Dandan Yue,Pinyi Gao,Cheng Du,Xuegui Liu,Lixin Zhang
Breast cancer remains the most commonly diagnosed malignancy among women, which is frequently associated with adverse side-effects and high metastasis. Bupleurum chinense DC. has been empirically and extensively used as the core prescription for more than half of Chinese formulations for the adjuvant therapy of breast cancer, and its biological activity against breast cancer has been proven by both in vitro and in vivo experiments. Saikosaponin compounds are the characteristic constituent of B. chinense, which exhibit significant cytotoxicity toward several cancer cells. However, the specific mechanisms of these compounds in the treatment of breast cancer have not been comprehensively understood. Therefore, we aimed to determine more potentially therapeutic targets and investigate the biological mechanisms of B. chinense. In the present study, we adopted network pharmacology and bioinformatics analysis to facilitate this requirement. Consequently, the network analysis revealed that saikosaponin-f (39), saikosaponin-d (14), saikosaponin-c (26), saikosaponin-h (54), saikosaponin-g (41), 3′′,6′′-O-diacetylsaikosaponin-d (20), 11α-methoxy-saikosaponin-f (40), and 6′′-O-acetylsaikosaponin-b1 (48) might play important roles in the treatment of breast cancer. In addition, the apoptosis regulator Bcl-2 (BCL-2), C-X-C chemokine receptor type 4 (CXCR4), probable ATP-dependent RNA helicase DDX5 (DDX5), protein kinase C alpha (PRKCA), and proto-oncogene tyrosine-protein kinase Src (SRC) were the potential therapeutic targets that exhibited intense interactions. Mechanistically, a gene enrichment analysis revealed that the action of B. chinense against breast cancer was achieved by the regulation of several biological signaling pathways, such as pathways in cancer, PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, microRNAs in cancer, etc. More importantly, we verified that the predictions involving saikosaponin-d by the cytotoxicity assay, apoptosis analysis, and RNA sequencing methods were partly consistent with those obtained from the network pharmacology prediction.
研究领域:
药理学
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生物信息学
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癌症研究
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分子生物学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2015
·
IF 2.998
Zhen-Yu Li,Hui-Min Sun,Jie Xing,Xue-Mei Qin,Guan-Hua Du
Ethnopharmacological relevance Radix Bupleuri (RB) is a commonly used herbal drug in Traditional Chinese Medicine (TCM), and it can be baked with vinegar to afford vinegar-baked Radix Bupleuri (VBRB), which is used in TCM for liver diseases treatment. In this study, the chemical compositions and biological effects between raw and two processed RBs by different vinegars were systematically compared. Materials and methods The chemical compositions of raw and two processed RBs were analyzed by 1 H NMR spectroscopy coupled with multivariate analysis. Two different extraction procedures were used, including direct extraction and liquid–liquid partition. Then HPLC was applied to determine the changes of saikosaponin contents. In addition, their liver protective effects against CCl 4 induced liver injury were also investigated, and the biochemical parameters and histopathology were measured after treatment of mice with raw RB and two processed RBs (5 g/kg/day) for 14 days. Results Multivariate analysis showed clear differences between the raw and the two processed RBs, and the vinegar-baking process induced elevated contents of ssb1, ssb2, acetic acid, malic acid , citric acid, 5-HMF, and ligustrazine , as well as the decreased contents of ssa, ssd, sucrose, glycine, succinic acid etc. In addition, both raw and processed RBs showed liver protective effects against CCl 4 induced liver injury, and the vinegar-baked RBs showed better effects than that of raw RB. Conclusions The raw and vinegar-baked RBs differed not only in the chemical compositions but also in the pharmacological effects. And two processed RBs also showed chemical differences, suggesting that the type of vinegar had an important effect on vinegar baking. In order to ensure the therapeutic effect and safety of TCM, the effect of different vinegars on processing of herbal drugs should be further studied.
研究领域:
中药学
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药理学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
CURRENT TOPICS IN MEDICINAL CHEMISTRY
·
2024
·
IF 2.9
Su Hongbing,Lei Hong,Cao Ling,Zhou Xiaoying,Liu Yumeng,Li Ying,Yan Lili,Shaowa Lv,Wang Yanhong,Guan Qingxia
Background: Self-emulsifying nano-phase of traditional Chinese medicine are a research
hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice,
which is of great research significance. The aim of this study was to isolate and characterize
the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects
of each phase on acute liver injury.
Methods: The liquid medicine was prepared employing centrifugation followed by dialysis. Single-
factor investigation methodology was utilized to optimize the preparation parameters for both
phases. Characterization of the formulated phase involved analyses such as surface morphology assessment,
measurement of nanoparticle size and Zeta potential using an analyzer, observation of
the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and
structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver
injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal-
N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase
(ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and
malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each
group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections
from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined
microscopically under light conditions. These revisions aim to enhance clarity, correct minor
grammatical errors (such as capitalization of “HE” to “H&E”), and ensure a smoother flow of
information without altering the scientific content of your original text.
Results: Successful establishment and separation of four distinct phases were achieved, including
the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase.
The self-emulsifying nano-phase was characterized as spherical particles with an average diameter
of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction
and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase
(ALT) levels compared to controls (P<0.05). However, no statistically significant differences
were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde
(MDA) content, or superoxide dismutase (SOD) activity between the treatment groups
and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying
nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically
distinguishable efficacy between them (P>0.05).
Conclusion: The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is
confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating
acute liver injury.
研究领域:
中药学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2025
·
IF 3.4
Xuedi Kang,Ting Wang,Haiping Wan,Wenjun Fu,Songjun Lin
Background Corticosterone stimulation has profound physiological and neurological effects on individuals, necessitating effective interventions to mitigate its impact. Current therapeutic approaches for corticosterone stimulation injury have limitations, including addiction and tolerance issues. In contrast, historical formulations such as Xiao Yao San, a traditional Chinese medicine formula, have shown promise in addressing changes in corticosterone stimulation-related neuroplasticity. This study aimed to explore the potential of Xiao Yao San in modulating the glucocorticoid receptor (GR) signaling pathway and its downstream effects on hippocampal neuroplasticity under corticosterone stimulation conditions. Methods Primary hippocampal neurons were cultured and exposed to corticosterone to establish a corticosterone stimulation model. Cellular viability, apoptosis, and protein expression were assessed via CCK-8 assays, flow cytometry, and immunoblotting, respectively. Interactions between FK506 binding protein 51 (FKBP51), GR, and p-GR were analyzed via coimmunoprecipitation and GST pull-down assays. The influence of FKBP4 on the competitive binding of GR was explored via similar techniques. The functional consequences of gene knockdown and overexpression were evaluated through cellular assays. Results Xiao Yao San attenuated corticosterone-induced reductions in cell viability and apoptosis, counteracting the detrimental effects of corticosterone stimulation. It downregulated FKBP51 expression and suppressed GR phosphorylation and nuclear translocation. Additionally, it hindered the interaction between FKBP51 and GR/p-GR. FKBP4 overexpression rescued hippocampal neuron viability and protected against the GR phosphorylation and nuclear translocation induced by corticosterone. Conclusion Xiao Yao San exhibited promising effects in ameliorating changes in corticosterone stimulation-induced neuroplasticity through the modulation of the GR signaling pathway. By inhibiting FKBP51-mediated GR phosphorylation and nuclear translocation, Xiao Yao San has potential as an alternative therapeutic strategy for corticosterone stimulation-related conditions. Further clinical investigations and mechanistic studies are warranted to validate its therapeutic efficacy and elucidate its mechanisms of action.
研究领域:
神经生物学
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药理学
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传统中医
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产品关联
DOI
PubMed
高影响因子
Chemosensors
·
2024
·Vol. 12
·期 8
·161
·
IF 3.7
Mintong Zhao,Yanni Tai,Gelin Wu,Feng Ding,Haibin Qu,Xingchu Gong
Risk management should run through the entire process of method development, utilization, and maintenance. Based on the analytical quality by design (AQbD) concept, various integrated risk management techniques were used in this study to develop an analysis method for the percolation solution of Xiaochaihu capsules. During the development of the analysis method, risk assessment was conducted using an Ishikawa diagram and failure mode effects analysis, followed by method optimization using experimental design. The probability of nonconformance calculated via an exhaustive Monte Carlo method quantitatively characterized the risk magnitude of method parameter failures, leading to the establishment of a operable design region method based on risk magnitude. Validation experiments and robustness tests of the data were utilized for model refinement and initial risk review. Methodological validation of the developed method was performed, and control strategies for the analysis method were presented through a decision tree. Stability experiments demonstrated that the samples remained stable at 4 °C for 24 h. The average recovery rate fell between 98.8% and 105%, with relative standard deviations ranging from 2.73% to 4.48%. The results showed that the established analysis method exhibited robustness. This analysis method can simultaneously determine the contents of uridine, adenine, 5-hydroxymethylfurfural, and guanosine. This method can also be employed for process control during percolation. This study integrated various risk management techniques to develop and maintain the analysis method, and this approach can potentially be extended to other analytical methods.
研究领域:
药学
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质量控制
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风险分析
✓ 已验证
产品关联
DOI
高影响因子
Chinese Journal of Natural Medicines
·
2019
·
IF 1.773
Yu-Xin WANG,Yi DU,Xia-Fei LIU,Fang-Xiu YANG,Xiao WU,Li TAN,Yi-Hong LU,Jing-Wei ZHANG,Fang ZHOU,Guang-Ji WANG
ABSTRACT We investigated the potential hepatoprotective effect of Radix Bupleuri (RB) by inducing acute liver injury (ALI) in an animal model using acetaminophen (APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serumaspartate transaminase (AST) and alanine transaminase (ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine (APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione (GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2E1 and CYP3A activity. Further investigation revealed the increasing of CYP2E1 and CYP3A protein was significantly inhibited in pretreatment group, while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription.
研究领域:
药理学
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毒理学
·
肝脏研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
·
2024
·
IF 2.3
Jun Meng,Bo Yang,Chang Shu,Shuai Jiang
Background Prostate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment. Methods Bioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression. Results FOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway. Conclusion This work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Ping Yin,Xi Han,Li Yu,Huifen Zhou,Jiehong Yang,Ying Chen,Ting Zhang,Haitong Wan
Bupleurum and Paeonia are common compatibilities for the treatment of depression, most of which are used in classical prescriptions. The main active ingredients saikosaponin A (SSA) and paeoniflorin (PF) have significant therapeutic effects on poststroke depression (PSD). However, the pharmacokinetic (PK) behavior based on the combination of the two components has not been reported in rats. The aim of this study was to compare the pharmacokinetic characteristics of combined administration of SSA and PF in normal and PSD rats. Plasma samples were collected after SSA and PF were injected into the rat tail vein, and plasma pretreatments were analyzed by HPLC. Based on the concentration levels of SSA and PF in plasma, Drug and Statistics 3.2.6 (DAS 3.2.6) software was used to establish the blood drug concentration model. PK data showed that compared with the normal rats, the values of related parameters t 1/2α , AUC (0−t) , AUC (0-∞) were decreased in diseased rats, while the values of CL 1 was increased. These findings suggest that PSD can significantly affect the PK parameters of SSA-PF. This study established a PK model to explore the time-effect relationship, in order to provide experimental and theoretical support for clinical application.
研究领域:
药理学
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神经科学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROTOXICOLOGY
·
2018
·
IF 3.076
Jing Zheng,Juan Chen,Xiaohan Zou,Fang Zhao,Mengqi Guo,Hongbo Wang,Tian Zhang,Chunlei Zhang,Wei Feng,Isaac N. Pessah,Zhengyu Cao
Saikosaponins (SSs) are a class of naturally occurring oleanane-type triterpenoid saponins found in Radix bupleuri that has been widely used in traditional Chinese medicine. As the main active principals of Radix bupleuri , SSs have been shown to suppress mouse motor activity, impair learning and memory, and decrease hippocampal neurogenesis. In the present study, we investigated the effect of five SSs (SSa, SSb1, SSb2, SSc, and SSd) on neuronal viability and the underlying mechanisms in cultured murine neocortical neurons. We demonstrate that SSa, SSb1 and SSd produce concentration-dependent apoptotic neuronal death and induce robust increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) at low micromolar concentrations with a rank order of SSd > SSa > SSb1, whereas SSb2 and SSc have no detectable effect on both neuronal survival and [Ca 2+ ] i . Mechanistically, SSd-induced elevation in [Ca 2+ ] i is the primary result of enhanced extracellular Ca 2+ influx, which likely triggers Ca 2+ -induced Ca 2+ release through ryanodine receptor activation, but not SERCA inhibition. SSd-induced Ca 2+ entry occurs through a non-selective mechanism since blockers of major neuronal Ca 2+ entry pathways, including L-type Ca 2+ channel, NMDA receptor, AMPA receptor, Na + -Ca 2+ exchanger, and TRPV1, all failed to attenuate the Ca 2+ response to SSd. Further studies demonstrate that SSd increases calcein efflux and induces an inward current in neocortical neurons. Together, these data demonstrate that SSd elevates [Ca 2+ ] i due to its ability to increase membrane permeability, likely by forming pores in the surface of membrane, which leads to massive Ca 2+ influx and apoptotic neuronal death in neocortical neurons.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）