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
·
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
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-19
·
IF 3.9
Liu Yunxiao,Wang Shuanghu,Younas Ayesha,Lv Jiaojian,Al Mamun Abdullah,Shao Chuxiao
Nonalcoholic Fatty Liver Disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes and is closely associated with metabolic disturbances such as obesity, dyslipidemia, and insulin resistance. Despite its increasing prevalence and potential progression to severe liver conditions, there is currently no approved pharmaceutical intervention for NAFLD. Traditional Chinese Medicine (TCM) formulations, such as Xiaoyao San (XYS), have shown therapeutic efficacy in treating NAFLD, but the underlying mechanisms remain unclear. This study employed a multi-omics approach to elucidate the therapeutic mechanisms of XYS in NAFLD. A rat model of NAFLD was established using a high-fat diet (HFD). The chemical constituents of XYS were analyzed using UPLC-MS/MS. Transcriptomics and proteomics analyses were performed to identify potential biological targets and signaling pathways involved in the therapeutic effects of XYS. The results were validated using ELISA and Western blotting. UPLC-MS/MS identified 225 prototype chemical components of XYS in the blood. XYS significantly reduced body weight, liver index, and Lee’s index in NAFLD model rats. It ameliorated HFD-induced hepatic steatosis, down-regulated serum levels of ALT, AST, GGT, TG, TC, LDL-C, FBG, IL-1β, IL-6, TNF-α, and ROS, and up-regulated HDL-C levels. Transcriptomics and proteomics analyses revealed that XYS modulated key signaling pathways, including cAMP, TGF-β, NF-κB, and necroptosis. Specifically, XYS down-regulated the expressions of NF-κB, p-NF-κB, FOXO1, TGF-β1, RIP3, and p-MLKL, while up-regulating cAMP, PKA, p-PKA, and PPARα. XYS improves NAFLD by regulating the cAMP/PKA-mediated PPARα, FOXO1, and NF-κB signaling pathways. This study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of XYS in NAFLD and supports its potential as a novel therapeutic intervention for this condition.
研究领域:
药理学
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代谢疾病
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系统生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Runjing Zhang,Tao Huang,Qiuyu Zhang,Yufeng Yao,Changhui Liu,Chaozhan Lin,Chenchen Zhu
Intrahepatic cholestasis is a clinical syndrome of liver damage with systemic circulation and intrahepatic accumulation of excessive toxic bile acids without effective therapeutic methods so far. Xiaoyan Lidan Formula (XYLDF), a traditional Chinese prescription, has long been clinically applied for hepatobiliary disorders due to cholestasis. But its mechanism remains unknown. In this study, a non-targeted metabolomics approach based on UHPLC-Q-TOF-MS/MS combined with a bile acids (BAs) - targeted metabolomics approach based on UHPLC-MS/MS were performed to elucidate the functional mechanisms of XYLDF on α-naphthylisothiocyanate(ANIT)-induced intrahepatic cholestasis rats. The results showed that a total of 39 endogenous metabolites with significant difference (VIP > 1.00, P < 0.05) were identified as biomarkers of ANIT-induced intrahepatic cholestasis in rats. After treatment by XYLDF, 22 biomarkers were reversed to the control-like levels, which involved in primary BA biosynthesis, bile acid metabolism and excretion, steroids metabolism, retinol metabolism, starch and sucrose metabolism, inter conversions between pentose and glucoronate as well as arachidonic acid metabolism. Meanwhile, the results of contents variation of BAs in liver and serum showed that both hydrophilic and hydrophobic BAs were markedly increased in the model rats, while XYLDF treatment could restore the increase induced by ANIT, which suggested that one of the mechanisms of XYLDF on cholestasis referred to regulation of metabolic homeostasis of cholic acid.
研究领域:
药理学
·
肝病学
·
代谢组学
·
中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOCHEMICAL ANALYSIS
·
2024
·
IF 3
Yanni Tai,Mintong Zhao,Feng Ding,Gelin Wu,Haibin Qu,Ping Gong,Yongjian Xie,Peng Zhou,Xingchu Gong
Introduction Despite numerous successful cases, there are still some challenges in using analytical quality by design (AQbD) for the development of analytical methods. Knowledge organization helps to enhance the objectivity of risk assessment, reduce the number of preliminary exploratory experiments, identify potential critical method parameters (CMPs) and their scope. Objective In the present study, we aimed to develop a simple, rapid, and robust analytical method for detecting phenolic compounds in Xiaochaihu capsule intermediates utilizing knowledge organization. Methods Knowledge organization and AQbD were combined to obtain the initial analytical conditions through knowledge collection, extraction, reorganization, and analysis. The quantitative relationship between critical method attributes (CMAs) and CMPs was then established by a definitive screening design. The method operable design region was calculated using an exhaustive Monte Carlo approach based on the probability of reaching the standard. Robustness investigation and methodological validation were finally performed. Results Analytical target profiles, CMAs, potential CMPs, and initial analytical conditions were initially identified, and the optimized ranges of operating parameters were obtained. A UHPLC method was successfully established for the analysis of phenolic compounds in ginger–ginger pinellia percolate, and the method validation outcomes were also satisfactory. Conclusion The developed method can be a reliable means to detect the phenolic compounds of Xiaochaihu capsule intermediates. Knowledge organization provides a new approach for making better use of prior knowledge, significantly enhancing the efficiency of analytical method development. The approach is versatile and can be similarly applied to the development of other methods.
研究领域:
分析化学
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药学
·
化学计量学
·
质量保证
✓ 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）