Frontiers in Pharmacology
·
2023
·
IF 5.6
Zhou Shengnan,Liu Liwei,Zhang Yuanyuan,Zhang Zhibo,Li Hanbing,Fan Feng,He Jiuming,Kang Jian,Zuo Lihua
Introduction: Alpiniae oxyphyllae Fructus (AOF) has been abundantly utilized for the treatment of diarrhea, dyspepsia, kidney asthenia, and abdominal pain in China. AOF is effective for treating AD in clinical trials, but its exact mode of action is yet unknown.Methods: In this study, metabolomics was combined to ascertain the alterations in plasma metabolism in APP/PS1 transgenic mice, the therapy of AOF on model mice, and the dynamic variations in 15 bile acids (BAs) concentration.Results: 31 differential biomarkers were finally identified in APP/PS1 group vs. the WT group. The levels of 16 metabolites like sphinganine (Sa), lyso PE (20:2), lysoPC (17:0), glycocholic acid (GCA), deoxycholicacid (DCA) were increased in APP/PS1 group, and those of 15 metabolites like phytosphingosine, cer (d18:0/14:0), and fumaric acid were reduced in APP/PS1 group. After AOF treatment, 29 of the 31 differential metabolites showed a tendency to be back-regulated, and 15 metabolites were significantly back-regulated, including sphinganine (Sa), lyso PE (20:2), glycocholic acid (GCA), deoxycholic acid (DCA). The relationship between BAs level and AD had been received increasing attention in recent years, and we also found notable differences between DCA and GCA in different groups. Therefore, a BAs-targeted metabonomic way was established to determine the level of 15 bile acids in different groups. The consequence demonstrated that primary BAs (CA, CDCA) declined in APP/PS1 model mice. After 3 months of AOF administration, CA and CDCA levels showed an upward trend. Conjugated primary bile acids (TCA, GCA, TCDCA, GCDCA), and secondary bile acids (DCA, LCA, GDCA, TDCA, TLCA GLCA) ascended in APP/PS1 group. After 3 months of AOF treatment, the levels of most BAs decreased to varying degrees. Notably, the metabolic performance of DCA and GCA in different groups was consistent with the predictions of untargeted metabolomics, validating the correctness of untargeted metabolomics.Discussion: According to metabolic pathways of regulated metabolites, it was prompted that AOF ameliorated the symptom of AD mice probably by regulating bile acids metabolism. This study offers a solid foundation for further research into the AOF mechanism for the therapy of AD.
研究领域:
药理学
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神经科学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2016
·Vol. 8
·期 9
·2069-2081
·
IF 1.915
Qi Wen,Hai-Long Li,Yin-Feng Tan,Xu-Guang Zhang,Zhen-Miao Qin,Wei Li,Yong-Hui Li,Jun-Qing Zhang,Feng Chen
Alpiniae oxyphyllae Fructus (Yizhi in Chinese) is commonly used for the treatment of diarrhea, intestinal disorders and urinary incontinence symptoms. To date, little information is available on the pharmacokinetic (PK) properties of this herb. We have identified the known active chemicals (including nootkatone, yakuchinone A, yakuchinone B, oxyphyllacinol, tectochrysin, chrysin, izalpinin, apigenin-4′,7-dimethylether, and kaempferide) and their metabolites (phase II metabolites and oxidized product such as kaempferol) from Yizhi extract in rat plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring. In the present study, an LC-MS/MS-based method was developed and validated for the simultaneous quantitation of the Yizhi chemicals and their metabolites in rat plasma after enzymatic treatment. A mixture of β-glucuronidase and sulfatase was used to liberate parent chemicals from their phase II metabolites. A post-extraction spike method, as well as a post-column infusion method, was conducted to investigate matrix-effects. Particularly, the ion suppression effect for all the analytes was overcome through combining a liquid–liquid extraction method for clean-up, elution gradient optimization for separation and inclusion of very low concentration of HCOOH into the mobile phase. Mean accuracies were obtained in the range of 84.7–112% at three different quality control levels for the ten analytes, with intra- and inter-day variations within 13.6% (1.76–13.6%). This validated method was successfully applied to a PK investigation in rats after a single oral administration of Yizhi extract. These results supply a suitable reference for further PK studies of the Yizhi chemicals and their metabolites in the future.
研究领域:
中药学
·
分析化学
·
药理学
✓ 已验证
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Yue Sun,Juntao Wang,Shiqiong Chen,Qin Yang,Sixin Liu,Congfa Li
This study presents a comprehensive characterization and comparison of polyphenols in Alpiniae oxyphyllae fructus extracted using ultrasound-assisted deep eutectic solvents (DESs) versus traditional solvents. The contents of total polyphenols in Choline chloride -malic acid (ChCl-MA) (1:1) , ChCl-MA (1:2) , L-proline-Lactic acid (Pro-LA) (1:1) , Pro-LA (1:3) , and L-proline-citric acid (Pro-CA) (1:3) extracts were the highest, ranging from 17.67 to 19.37 mg/g, and were significantly higher than those in water extract (10.35 mg/g) and ethanol extract (14.78 mg/g) ( p < 0.05). Pro-LA extract exhibited high levels of 3,4-dihydroxybenzoic acid and protocatechualdehyde, and possessed strong antioxidant activity. Density functional theory (DFT) calculations indicated that the mechanism of DESs' efficient extraction of polyphenols was mainly reflected in the unique structural configuration of Pro-LA, which facilitated the formation of strong hydrogen bonds with the hydroxyl functional groups of polyphenols, enhancing the intermolecular interaction, and thus improving the extraction efficiency. Our study provided a novel approach for the efficient extraction of plant polyphenols.
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DOI
高影响因子
CURRENT DRUG METABOLISM
·
2021
·Vol. 22
·期 1
·70-82
·
IF 3.731
Zuo Lihua,Li Jia,Xue Lianping,Jia Qingquan,Li Zhuolun,Zhang Mengya,Zhao Mengfan,Wang Mengli,Kang Jian,Du Shuzhang,Sun Zhi
Background: Alpiniae oxyphyllae Fructus (AOF), a traditional Chinese medicine (TCM), is widely used in the treatment of urinary, gastrointestinal and neurologic diseases in China. Although terpenoids are the main active ingredients of AOF, there are few researches on their pharmacokinetics
and metabolism. Methods: In this study, a sensitive, rapid, accurate and novel ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to evaluate the pharmacokinetic behavior of five terpenoids (oxyphyllenodiol B, (4S* ,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4β-ol,
7-epi-teucrenone, (+)- (4R,5S,7R)-13-hydroxynootkatone, (E)-labda-12,14-dien-15(16)-olide-17-oic acid) in rats after oral administration of AOF extracts. 27 metabolic metabolites of the five terpenoids were identified by ultra high performance liquid chromatography -Q Exactive hybrid quadrupole-orbitrap
high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) based on precise mass and fragment ions. Results: The established pharmacokinetic analysis method showed good linearity over a wide concentration range, and the lower quantitative limit (LLOQ) ranged from 0.97 to 4.25
ng/mL. Other validation parameters were within the acceptable range. In addition, 27 metabolites were identified in plasma, urine and feces samples, and the metabolic pathways of five terpenoids were mainly focused on glucoside conjugation, dehydration, desaturation and glycine conjugation.
Conclusion: This is the first study on the pharmacokinetics and metabolism of five terpenoids in AOF, illuminating the disposal process of terpenoids in vivo. It was expected that the results of this study would provide some references for the apprehension of the action mechanism and
the further pharmacological study of five terpenoids in AOF.
研究领域:
中药学
·
分析化学
·
药理学
✓ 已验证
DOI
高影响因子
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