MOLECULES
·
2019
·Vol. 24
·期 13
·2380
·
IF 3.06
Dongshuai Shen,Ning Ma,Yajun Yang,Xiwang Liu,Zhe Qin,Shihong Li,Zenghua Jiao,Xiaojun Kong,Jianyong Li
Aspirin eugenol ester (AEE) is a novel compound that is formed from the esterification of aspirin (acetylsalicylic acid (ASA)) and eugenol. This study aimed to investigate the effects of AEE on blood stasis in rats and to characterize the underlying mechanisms using a plasma metabolomic study. The results indicate that AEE and ASA could modulate whole blood viscosity (WBV), plasma viscosity (PV), blood coagulation parameters, platelet count, platelet aggregation, lactate dehydrogenase (LDH), creatinine (CR) and the levels of thromboxane A2 (TXA2) and 6-keto prostaglandin F1α (6-keto-PGF1α). The metabolic profiles of the plasma samples from all groups were clearly separated in the score plots. Nineteen potential metabolites were selected and identified, and disordered levels of these metabolites could be regulated by AEE and ASA. Pathway analysis showed that the mechanism of action of AEE on blood stasis might be principally related to the metabolism of amino acid, fatty acid, energy and glycerophospholipid. The above results indicate that AEE protected the rats against blood stasis, and that this effect might have been caused by the anticoagulation activity of AEE and its abilities to maintain a balance between TXA2and PGI2, reduce blood viscosity, inhibit platelet aggregation and normalize the plasma metabolic profile.Keywords:blood stasis;AEE;aspirin;metabolomics;UPLC-Q-TOF/MS
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RSC Advances
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2018
·Vol. 8
·期 53
·30616-30623
·
IF 2.936
Jing Chen,Ying Yuan,Xiaoku Ran,Na Guo,Deqiang Dou
Background: Panax ginseng Meyer which has been cultivated and grown naturally in mountainous forests is formally called “Lin-Xia-Shan-Shen” (LXSS), but when cultivated it is called garden ginseng (GG), according to the Chinese Pharmacopoeia (2015 edition). The medicinal value of LXSS is significantly higher than that of GG based on the clinical experience of TCM. This study aimed to evaluate the variety of chemical constituents in LXSS and GG. Methods: 18 LXSS and 6 GG samples were investigated using a UPLC-Q-TOF-MS technique. Results: the contents of 16 metabolites, mainly involved in the biosynthesis of rare ginsenosides (ginsenosides Rg3, -Rh1, -Rh2), galactose metabolism (myo-inositol), the citric cycle (citric acid and succinic acid), GABA shunt (GABA) and amino metabolism (alanine and aspartic acid), were higher in LXSS than in GG; while 14 metabolites, mainly involved in starch and sucrose metabolism (fructose and sucrose), amino metabolism (tryptophan, proline, dencichine and pyroglutamic acid) and campesterol biosynthesis (campesterol), were lower in LXSS than in GG. For LXSS with different growing years, 5 metabolites showed a tendency to increase dependent on the number of years, and these were related mainly to galactose metabolism (melibiose), the citric cycle (malic acid), fatty acid metabolism (2-hydroxy stearic acid); while 5 metabolites showed a tendency to decrease on ascending the grades, and these were related to sucrose metabolism (fructose and sucrose), fatty acid metabolism (2-hydroxy hexadecanoic acid) and campesterol biosynthesis (campesterol). Conclusion: this proposed analytical method coupled with multivariate analysis is fast, accurate, and reliable for discriminating GG and high cultivation ages of LXSS samples.
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Arabian Journal of Chemistry
·
2024
·
IF 5.3
Dong Xie,Guangfu Lv,Yuchen Wang,Wenjing Zhang,Nian Li,Yao Duan,Qing Huang,Ge Chen,Zifeng Pi,Hao Yue
Tenghuang Jiangu Wan (THJGW) is a commonly utilized treatment for osteoarthritis (OA), yet its pharmacodynamic material basis and molecular mechanism remain inadequately understood. This study systematically characterized the in vitro and in vivo chemical components of THJGW using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The pharmacodynamic material basis of THJGW in the treatment of OA was explored through a target network pharmacology approach and molecular docking technology. Cellular experiments were subsequently employed to validate the molecular mechanisms. Consequently, a total of 134 components from THJGW were identified in vitro , comprising 45 flavonoids, 10 iridoid glycosides, 39 phenylethanoid glycosides, 9 phenylpropanoids, 11 organic acids, 4 phenolics, and 16 other compounds. Additionally, 38 prototype absorbed components in serum were characterized for the purpose of network construction. 11 key components and 10 core targets (VEGFA, STAT3, RELA/NF-κB p65, PIK3R1, PIK3CA, MMP9, MMP1, IL-6, HDAC1, and FGF2) were determined by the target network pharmacology. Through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that these intersection targets are associated with various signaling pathways such as pathways in cancer, lipid and atherosclerosis, and prostate cancer. Notably, the lipid and atherosclerosis pathway was closely linked to OA. The molecular docking results demonstrated strong binding affinities of the three core targets: IL-6, STAT3, and RELA/NF-κB p65. These results suggest that these targets may play a significant role for THJGW in treating OA. In vitro experiments showed that THJGW had notable protective effects on LPS-induced RAW264.7 macrophages by reducing levels of TNF-α and IL-6, and inhibiting phosphorylation expression of STAT3 and NF-κB p65 proteins related to the lipid and atherosclerosis pathway. This study provides insight into the pharmacodynamic material basis and mechanism of action for THJGW in the treatment of OA, which provide scientific evidence for the scientific application and improvement of quality standards for THJGW.
研究领域:
药理学
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生物化学
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分子生物学
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中医药
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PLANT CELL TISSUE AND ORGAN CULTURE
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2024
·Vol. 156
·期 2
·1-11
·
IF 2.3
Zhang Gaowei,Luo Liping,Tian Kaili,Ning Fangjian,Wu Dong,Sun Qifang,Yu Wenjie,Yi Shengxiang,Hao Yingbin
Dendrobium officinale is a perennial herb with medicinal and edible qualities. The growth and nutritional properties of this plant are significantly affected by the light quality. However, the impact of varying light quality on the phytochemical characteristics of tissue-cultured seedlings of D. officinale is still unknown. In this study, tissue-cultured seedlings of D. officinale were grown for ninety days under six LED lights, including white light (W), blue LED (B), red LED (R), and three composite light environments with varying quantities of red and blue light: 1:2 (R1B2), 1:1 (R1B1), and 2:1 (R2B1). The growth status and physiological signs of the seedlings were analyzed and we used high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), and pathway enrichment analysis to thoroughly examine the metabolomic changes, with a focus on phenolic compounds. Our results indicated that R2B1 illumination led to the best growth of D. officinale seedlings, with maximal energy absorption, and phenolic contents. In conclusion, R2B1 was considered the most profitable for tissue-culture production of D. officinale .
研究领域:
植物学
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药用植物学
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代谢组学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
·
IF 3.4
Shu Chen,Li Liu,Hong-Xia Jiang,Qun Sun,Liang Zhang,Jian-Qun Liu,Li-Fang Liu
Tripterygium wilfordii (TW), a well-known traditional Chinese medicine , was widely used in the treatment of autoimmune disorders and inflammatory diseases . However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity . Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW.
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高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Yue Zhuo,Xiaomei Fu,Qiyao Jiang,Yiyi Lai,Yong Gu,Shuhuan Fang,Huiling Chen,Chenchen Liu,Huafeng Pan,Qihui Wu,Jiansong Fang
Background Alzheimer's disease (AD) is a neurodegenerative disease , characterized by progressive cognitive dysfunction and memory loss. However, the disease-modifying treatments for AD are still lacking. Traditional Chinese herbs, have shown their potentials as novel treatments for complex diseases, such as AD. Purpose This study was aimed at investigating the mechanism of action (MOA) of Acanthopanax senticosusin (AS) for treatment of AD. Methods In this study, we firstly identified the chemical constituents in Acanthopanax senticosusin (AS) utilizing ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS), and next built the drug-target network of these compounds. We also performed the systems pharmacology-based analysis to preliminary explore the MOA of AS against AD. Moreover, we applied the network proximity approach to identify the potential anti-AD components in AS. Finally, experimental validations, including animal behavior test, ELISA and TUNEL staining , were conducted to verify our systems pharmacology-based analysis. Results 60 chemical constituents in AS were identified via the UPLC-Q-TOF-MS approach. The systems pharmacology-based analysis indicated that AS might exert its therapeutic effects on AD via acetylcholinesterase and apoptosis signaling pathway. To explore the material basis of AS against AD, we further identified 15 potential anti-AD components in AS. Consistently, in vivo experiments demonstrated that AS could protect cholinergic nervous system damage and decrease neuronal apoptosis caused by scopolamine . Conclusion Overall, this study applied systems pharmacology approach, UPLC-Q-TOF-MS, network analysis, and experimental validation to decipher the potential molecular mechanism of AS against AD.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Xia Gao,Chaojie Huang,Ting Geng,Xialin Chen,Jiajia Wang,Jingying Liu,Kun Duan,Liang Cao,Zhenzhong Wang,Wei Xiao
Ethnopharmacological relevance Reduning injection (RDN), a patented traditional Chinese medicine , has the obvious antipyretic effect and has been widely used in China. Although some previous studies proved its antipyretic effect by animal efficacy experiment or clinical observation, its holistic mechanism in vivo was still unclear. Aim of the study To comprehensively elucidate the antipyretic mechanism of RDN, the investigation of fever-related potential biomarkers and metabolic pathways in the rat fever model is described in this paper. Materials and methods Rat fever model was established by dry yeast. A large number of endogenous metabolites in serum and urine were detected by UPLC-Q-TOF/MS, and fever-related potential biomarkers were screened and identified by multivariate analysis and metabolite databases. The reliability and biological significance of the largely disturbed biomarkers was verified by the metabolic network and the correlation with pharmacodynamic indicators, which contained IL-1β, IL-6, TNF-α, PGE 2 and cAMP. Results The established UPLC-Q-TOF/MS analytical method afforded satisfactory results in terms of precision, repeatability and stability, which met the requirements of biological sample determination. A total of 32 potential biomarkers associated with fever were screened and identified, among which 22 species could be adjusted by RDN. The metabolism pathway analysis revealed that valine , leucine and isoleucine biosynthesis, and sphingolipid metabolism were greatly disturbed. Their biomarkers involved L-leucine, L-valine, sphinganine and phytosphingosine , all of which showed a callback trend after RDN was given. These 4 biomarkers had a certain correlation with some known fever-related small molecules and pharmacodynamic indicators, which indicated that the selected fever-related biomarkers had certain reliability and biological significance. Conclusions RDN has a good regulation of the metabolic disorder of endogenous components in dry yeast-induced fever rats. Its antipyretic mechanism is mainly related to the regulation of amino acid, lipid and energy metabolism. The study is useful to better understand and analyze the pharmacodynamic mechanism of complex systems, such as traditional Chinese medicine.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Meimei Cheng,Huan Wu,Hongfei Wu,Xiaochuang Liu,An Zhou
The direct cause of hepatolenticular degeneration (HLD) is copper metabolic disorder caused by autosomal recessive inheritance. Gandou decoction (GDD), a classical traditional Chinese medicine formula, exhibits unambiguous therapeutic effect on HLD in China for decades. However, the mechanism of effect on HLD is not clear. With this purpose, the effects of copper content and histopathology inspection on the HLD rat model were investigated. Then, metabolomics study based on ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS E ) analysis and multivariate statistical analysis was adopted to further reveal the mechanism of action of GDD against HLD. The results showed that the characteristics of liver tissues after GDD treatment were significantly reversed, close to the control group, suggesting that GDD has a therapeutic effect on HLD. Furthermore, HLD interferes with 2 metabolites of the metabolic pathway in rats. Among them, up-regulation of Lactic acid, Tryptophan, Phenylalanine, Triacylglycerol and down-regulation of Linoleic acid, Alpha Linolenic acid, Phosphatidylcholine, Taurine is particularly significant. Analysis of metabolic pathways by a unique pathway analysis revealed significant changes in several pathways including lipid metabolism, amino metabolism and glucose metabolism in HLD. This study showed that GDD could provide satisfactory therapeutic effects on HLD and metabolomics study can be utilized to further understand the molecular mechanisms.
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BIOMEDICAL CHROMATOGRAPHY
·
2014
·Vol. 28
·期 10
·1325-1334
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IF 1.662
Zhangxiao Peng,Yan Wang,Xue Gu,Xiaojie Guo,Chao Yan
A method based on high-performance liquid chromatography coupled with ultraviolet detection was developed for studying the pharmacokinetics of costunolide (Cos) and dehydrocostus lactone (Dehy) in rats after intravenous (i.v.) administration. Following i.v. administration, the maximum plasma concentrations of Cos and Dehy were observed to be 12.29 ± 1.47 and 5.79 ± 0.13 µg/mL, respectively. The bioavailability of Cos was larger than that of Dehy; however, the clearance and the volume of distribution of Dehy were much larger than those of Cos. An ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry system with automated MS E (E represents collision energy) data analysis software (MetaboLynx TM ) was used to analyze and identify the metabolites of Cos and Dehy in vivo . Four metabolites of Cos and six metabolites of Dehy were discovered from the plasma, urine and feces of rats. The main metabolic pathway of Cos was phase II biotransformation, but the main metabolic pathways of Dehy was phase І biotransformation. Two sequential desaturations and N -acetylcysteine conjugation were the common metabolic pathways of Cos and Dehy in rats. This information may be useful for the further development of the two drug candidates. Copyright © 2014 John Wiley & Sons, Ltd.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2015
·
IF 2.979
Yang Li,Guisheng Zhou,Ying Peng,Pengfei Tu,Xiaobo Li
Acteoside, isoacteoside, and 2′-acetylacteoside are three representative phenylethanoid glycosides (PhGs), which are widely distributed in many plants and also known as the active components of Cistanches Herba . However, the extremely low oral bioavailability of acteoside in rats implies that these structural similar components may go through multiple sequential routes of hydrolysis in gastrointestinal tract before they are absorbed into blood. Therefore, the metabolites of these three components and other PhGs from gastrointestinal tract such as echinacoside, are supposed to be the bioactive elements. In this study, we established an approach combining ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) with MS E technology and MetaboLynx™ software for the rapid metabolic profiling of acteoside, isoacteoside, and 2′-acetylacteoside by human intestinal bacteria. As a result, 11 metabolites of acteoside, 7 metabolites of isoacteoside, and 11 metabolites of 2′-acetylacteoside were identified respectively. 8 metabolic pathways including deglycosylation, de-rhamnose, de-hydroxytyrosol, de-caffeoyl, deacetylation, reduction, acetylation, and sulfate conjugation were proposed to involve in the generation of these metabolites. Furthermore, we found that the degraded metabolites hydroxytyrosol (HT) and 3-hydroxyphenylpropionic (3-HPP) were transformed from acteoside, isoacteoside, and 2′-acetylacteoside by human intestinal bacteria and demonstrated similar bioactivities to their precursors. These findings are significant for our understanding of the metabolism of PhGs and the proposed metabolic pathways of bioactive components might be crucial for further pharmacokinetic evaluations of Cistanches Herba .
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Communications Biology
·
2024
·Vol. 7
·期 1
·1-15
·
IF 5.2
Zhang Wen,Cai Shuhui,Qin Lihong,Feng Yaru,Ding Menglei,Luo Zichen,Shan Jinjun,Di Liuqing
Aconiti Lateralis Radix Praeparata ( Fuzi in Chinese) is widely used in the clinical treatment of tumors. This study aims to explore the active fractions and underlying mechanisms of Fuzi in the treatment of non-small cell lung cancer (NSCLC). Fuzi alkaloids (FZA) is prepared and found to inhibit the growth of NSCLC both in vitro and in vivo significantly. A total of 53 alkaloids are identified in FZA by UPLC-Q-TOF-MS. Proteomics experiment show that 238 differentially expressed proteins regulated by FZA are involved in amino acid anabolism, pyrimidine metabolism and PI3K/Akt-mTOR signaling pathway. Metabolomics analyses identify 32 significant differential metabolites which are mainly involved in amino acid metabolism, TCA cycle and other pathways. Multi-omics research combined with molecular biological assays suggest that FZA might regulate glycolysis through PI3K/Akt-mTOR pathway to treat NSCLC. The study lays a foundation for the anti-cancer investigation of Fuzi and provides a possible scientific basis for its clinical application.
研究领域:
肿瘤学
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药理学
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分子生物学
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生物化学
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Natural Product Communications
·
2024
·
IF 1.5
Yan Lei,Bing Wang,Guanglin Zhu,Guo Feng,Wei Li,Caiyao Han,Qian Qin,Xie-an Yu,Xueli Song,Zhengyan He,Ju Zhang,Hongmei Su,Wenjing Wang
Background: In the research of the pharmacological activity of modern Chinese medicine, a large number of traditional Chinese medicines show anti-inflammatory activity. Asparagi radix is one of the anti-inflammatory drugs. With the deepening of people's research on Asparagi radix, its anti-inflammatory pharmacological effects have been gradually explored, but its specific anti-inflammatory active ingredients are still unclear. Therefore, it is necessary to screen and identify its specific anti-inflammatory active ingredients from Asparagi radix. At present, COX-2 is an important target for the treatment of chronic inflammation, and many drugs targeting this target have been marketed. However, some drugs have serious side effects, so it is very meaningful to study new COX-2 inhibitors. Methods: In this experiment, the fractions of different time periods are separated by high performance liquid chromatography-separation-trapping system (HPLC-CAD-FC). Then, ultra-high performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) and biological activity analysis techniques are used to identify the chemical composition and in vitro anti-inflammatory activity of each fraction. Finally, the data is integrated to screen out the substances with potential anti-inflammatory activity in Asparagi radix. Results: The results showed that the method established in this experiment can successfully isolate the active components of Asparagi radix, and four saponins with potential anti-inflammatory activity are identified. Conclusion: In summary, the analysis method established in this study can quickly and effectively screen out its anti-inflammatory active substances, and its potential anti-inflammatory active ingredients are mainly steroidal saponins.
研究领域:
中药学
·
药理学
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高影响因子
危险品化学品经营许可证（带存储）