RAPID COMMUNICATIONS IN MASS SPECTROMETRY
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2025
·Vol. 39
·期 10
·e10012
·
IF 1.7
Qi-Feng Zou,De-Jian Chen,Cheng-Jun Liu,Zi-Hao Chen,Xia Yang,Rong-Huang Xu,Zhen-Hui Zhou,Jian-Xin Chen,Wei Shi,Feng-Xiang Zhang
Rationale Protopine, an active alkaloid in Papaver somniferum L., was abundant in a well-known anticough traditional Chinese medicine preparation—Zhi-Ke-Bao tablets. Till now, the metabolism feature and anticough mechanism of protopine have not been fully elucidated, restricting its further development. Methods The metabolites of protopine in rats were profiled by using ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry, and its anticough targets and mechanism were predicted by network pharmacology. Results In rats, a total of 19 metabolites were identified following ingestion of protopine (21 mg/kg/day, i.g.), including 4 in plasma, 6 in urine, 5 in feces, 10 in liver, 2 in spleen, 4 in lung, 3 in kidney, 3 in heart, and 3 in brain. The main metabolic features were ring-opening, methylation, demethylation, glucuronidation, sulfation, and hydroxylation. Among them, methylation, sulfation, and hydroxylation of protopine in vivo were revealed for the first time. The network pharmacology results show that protopine and its metabolites regulate physiological activities by acting on STAT3, SRC, CASP3, MTOR, MMP9, ESR1, and other targets, involving PI3K-Akt signaling pathway, FoxO signaling pathway, and TNF signaling pathway, etc. Conclusions The metabolic features of protopine and its potential mechanisms for anticough effects were outlined, providing data for further anticough pharmacological validation of protopine.
研究领域:
中药学
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药理学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Toxins
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2021
·Vol. 13
·期 4
·259
·
IF 4.546
Petrus Siregar,Gilbert Audira,Ling-Yi Feng,Jia-Hau Lee,Fiorency Santoso,Wen-Hao Yu,Yu-Heng Lai,Jih-Heng Li,Ying-Ting Lin,Jung-Ren Chen,Chung-Der Hsiao
Arecoline is one of the nicotinic acid-based alkaloids, which is found in the betel nut. In addition to its function as a muscarinic agonist, arecoline exhibits several adverse effects, such as inducing growth retardation and causing developmental defects in animal embryos, including zebrafish, chicken, and mice. In this study, we aimed to study the potential adverse effects of waterborne arecoline exposure on zebrafish larvae locomotor activity and investigate the possible mechanism of the arecoline effects in zebrafish behavior. The zebrafish behavior analysis, together with molecular docking and the antagonist co-exposure experiment using muscarinic acetylcholine receptor antagonists were conducted. Zebrafish larvae aged 96 h post-fertilization (hpf) were exposed to different concentrations (0.001, 0.01, 0.1, and 1 ppm) of arecoline for 30 min and 24 h, respectively, to find out the effect of arecoline in different time exposures. Locomotor activities were measured and quantified at 120 hpf. The results showed that arecoline caused zebrafish larvae locomotor hyperactivities, even at a very low concentration. For the mechanistic study, we conducted a structure-based molecular docking simulation and antagonist co-exposure experiment to explore the potential interactions between arecoline and eight subtypes, namely, M1a, M2a, M2b, M3a, M3b, M4a, M5a, and M5b, of zebrafish endogenous muscarinic acetylcholine receptors (mAChRs). Arecoline was predicted to show a strong binding affinity to most of the subtypes. We also discovered that the locomotion hyperactivity phenotypes triggered by arecoline could be rescued by co-incubating it with M1 to M4 mAChR antagonists. Taken together, by a pharmacological approach, we demonstrated that arecoline functions as a highly potent hyperactivity-stimulating compound in zebrafish that is mediated by multiple muscarinic acetylcholine receptors.Keywords:arecoline;locomotion;zebrafish;betel nut;muscarinic acetylcholine receptor;molecular docking;antagonistKey Contribution:We provides in vivo and in silico evidences to support arecoline affected larvae zebrafish locomotor activity is associated with multiple muscarinic acetylcholine receptor interactions. Co-exposure with muscarinic acetylcholine antagonist receptors can restore locomotor hyperactivity trigger by arecoline exposure strengthen this hypothesis.
研究领域:
药理学
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神经科学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Qidan Cai,Jiang Meng,Yuewei Ge,Yan Gao,Yu Zeng,Haifang Li,Yue Sun
A new method for fishing antitumor ingredients by G-quadruplex recognition from Macleaya cordata seeds extracts was established using a three-phase-laminar-flow-chip (TPL chip). The TPL chip integrated the separation of drugs from the complex ingredients and organic solvent extraction, simplifying pretreatment processes and reducing reagents and time. In addition, the chip method showed a lower false negative result, owing to the gentle membrane-free filtration process based on diffusion separation in microchannel. Four ligands with high content in alkaloids of Macleaya cordata seeds were selected, those are chelerythrine (CHE), sanguinarine (SAN), protopine (PRO), and allocryptopine (ALL), which demonstrated affinity with G-quadruplex and were potential for antitumor.
研究领域:
药理学
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分子生物学
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药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
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2022
·Vol. 45
·期 24
·4469-4477
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IF 3.614
Ying Lu,Jianna Yu,Wen Liu,Guoxing Jing,Wenshan Li,Wenjie Liu
Areca nut is a popular and addictive food as well as a traditional herbal medicine in many countries. Areca nut contains alkaloids including arecoline, guvacine, and arecaidine, which are the major bioactive compounds in areca products. Areca alkaloids can be carcinogenic, and thus sensitive and specific analytical methods are urgently desired for the identification and quantification of these compounds. High-performance liquid chromatography-based methods are often preferred, but areca alkaloids do not have chromophores, and detection using a traditional UV detector can be difficult. The complexity of areca sample extracts can also lead to the co-elution of peaks leading to poor quantitative performance. We report here high-performance liquid chromatography coupled with an ion mobility spectrometer for sensitive determination of areca alkaloids in various products including areca nut, areca nut products, and herbal oral liquid. An X-Bridge reversed-phase C 18 column was used in the experiment and was combined with high-performance liquid chromatography coupled to an ion mobility spectrometer system. A custom-made adjustable post-column splitter acted as an interface between the high-performance liquid chromatography and the ion mobility spectrometer; it also acted as the electrospray ionization source. The mobile phase was methanol and 0.5% ammonium hydroxide. The results demonstrate that the splitter can afford a wide range of split ratios that match the ion mobility spectrometer ionization source while keeping the separation efficiency of high-performance liquid chromatography. Three major alkaloid compounds were then accurately determined using the resulting method without dativization steps. Many coeluted high-performance liquid chromatography peaks are effectively separated in the ion mobility spectrometer dimension, which in turn improved the quantification accuracy.
研究领域:
分析化学
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药理学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2017
·
IF 2.603
Hong Pan,Linyan Huang,Yi Li,Xumei Zhou,Yuanfu Lu,Fuguo Shi
Arecoline, a predominant alkaloid in areca nut, shows several pharmacological and toxicological effects. In present study, a sensitive and accurate liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed and fully validated for quantification of arecoline in rat plasma. Importantly, our group found that arecoline was highly unstable in rat plasma samples, which brought challenges to accurately quantify in vivo. The hydrolysis of ester moiety of arecoline by carboxylesterases was responsible for its instability, and arecoline was hydrolyzed to arecaidine. The degradation of arecoline was completely inhibited using 5% formic acid as a stabilizer, which was immediately added to freshly collected rat plasma samples. EDTA was adopted as the anticoagulant to also reduce the degradation during blood collection and plasma separation owing to its anti-esterase effect. The plasma sample was separated by a C18 analytical column with a mobile phase of 0.1% formic acid and methanol (95:5 v/v) at an isocratic flow rate of 300 μL/min. The analyte was monitored on a tandem mass spectrometer using the multiple reaction monitoring scan in a positive electrospray ionization mode. The method exhibited high sensitivity and a good linearity rang of 1–1000 ng/mL. The developed analytical method was employed in a pilot pharmacokinetic study of arecoline in rats. Arecoline was rapidly eliminated within 45 min in rats after oral treatment of 150 mg/kg arecoline.
研究领域:
药理学
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分析化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2021
·
IF 5.34
Xiaohui Zhang,Yule Wang,Kai Zhang,Hongda Sheng,Yuhan Wu,Huimin Wu,Yingchao Wang,Jianli Guan,Qingfen Meng,Huahuan Li,Zhenhao Li,Guanwei Fan,Yi Wang
Background Migraine is the third most common disease worldwide, leading to severely decreased quality of life for the patients. In spite of great efforts endeavored in pharmacological and nonpharmacological therapeutic strategies for treating migraine, the outcome is rather disappointing in terms of efficacy. Compelling evidence shows that the expression level of dopamine receptor D2 (DRD2) plays an essential role in progression of migraine. Purpose To explore potential therapeutical possibilities, the attention was paid to Yuanhu Zhitong formula (YHZTF), which is a classical traditional Chinese medicine prescription frequently applied to relieve pain. The aim of this study was to identify the promising compounds derived from YHZTF with anti-migraine effects and investigate the underlying molecular mechanism. Methods The high-resolution mass spectrometry and molecular networking were performed for comprehensive chemical profiling of YHZTF. Network pharmacology was used to generate herbal-component-target-pathway network. Based on the pathway enrichment analysis, the active substances of anti-migraine and the potential molecular mechanism were further determined by performing animal experiments combined with molecular docking strategy. Results In total, 31 substances were identified in YHZTF, including alkaloids such as tetrahydropalmatine and protopine . The analysis of herbal-component-target-pathway network suggests that the alkaloid substances (e.g. tetrahydropalmatine and protopine) from YHZTF target dopamine receptors , thus can be linked to neuroactive ligand-receptor interaction pathways. In a nitroglycerin-induced migraine animal model, pretreatment with tetrahydropalmatine or protopine substantially lessened the aberrant migraine-like symptoms. The results of molecular docking analysis showed that tetrahydropalmatine and protopine had strong affinities to dopamine receptor D2 (DRD2). Using RT-qPCR, the investigators found that DRD2 was significantly down-regulated at the mRNA level in brain tissues of tetrahydropalmatine and protopine-treated group compared to the control group. Conclusion Collectively, the results provide reliable evidence showing that the active substances tetrahydropalmatine and protopine from YHZTF lessens migraine symptoms in an in vivo mouse model suggestively via regulating expression of DRD2. These findings shed light on novel therapeutic strategies and targets to treat migraine using natural products.
研究领域:
药理学
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神经科学
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中医药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2020
·Vol. 43
·期 12
·2459-2466
·
IF 2.878
Yuanyuan Liu,Wenjuan Wang,Fenfang Che,Yanzhen Lu,Aoxin Li,Hao Li,Jiangang Liu,Yun Wei
Macleaya cordata (Willd) R. Br. is a medicinal plant. The most important bioactive compounds of M. cordata are alkaloids that have many biological activities including antifungal, anti-inflammatory, and antitumor. In this study, an ionic-liquid-modified high-speed counter-current chromatography method was established to obtain alkaloids from the fruits of M. cordata . The conditions of ionic-liquid-modified high-speed counter-current chromatography, including solvent systems, the content of ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate [C 4 mim][BF 4 ]), and the posttreatment of the ionic liquid, were investigated. Five alkaloids protopine, allocryptopine, sanguinarine, 8-O-demethylchelerythrine, and chelerythrine were separated from the extract of the fruits using a high speed counter-current chromatography with two-phase solvent system composed of dichloromethane/methanol/0.3 mol/L hydrochloric acid aqueous solution/[C 4 mim][BF 4 ] (4:2:2:0.015, v/v). Their purities were 96.33, 95.56, 97.94, 96.22, and 97.90%, respectively. The results indicated that a small amount of ionic liquids as modifier of the two-phase solvent system could shorten the separation time and improve the separation efficiency of the alkaloids from the fruits. The ionic-liquid-modified high-speed counter-current chromatography would provide a feasible way for highly effective separation of alkaloids from natural products.
研究领域:
生药学
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分析化学
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药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
·
IF 4.36
Hai-Lian Yuan,Yun-Li Zhao,Xu-Jie Qin,Ya-Ping Liu,Xing-Wei Yang,Xiao-Dong Luo
Ethnopharmacological relevance Hypecoum erectum has been used extensively in folk medicine to treat inflammation, fever, and pain. However, few investigations have been carried out on the biological activities related to its traditional use. The chemical constituents of this plant along with their anti-inflammatory and analgesic effects have yet to be revealed. Aim of the study This study aimed to support the traditional use of H. erectum by first assessing its anti-inflammatory and analgesic effects and then investigating its chemical constituents to identify any anti-inflammatory and/or analgesic compounds. Material and methods The in vivo anti-inflammatory and analgesic activities of the MeOH extract (ME), total alkaloid (AL), and non-alkaloid (Non-AL) fractions of H. erectum at doses of 200, 100, and 50 mg/kg and four major constituents ( 20 , 21 , 22 , and 27 ) at doses of 100 and 50 mg/kg delivered via intragastrical administration were evaluated using carrageenan-induced paw edema and acetic acid-stimulated writhing animal models. A phytochemical study of the bioactive (AL) fraction was conducted using various chromatographic techniques, and the structures of the obtained isoquinolines were identified by multiple spectroscopic analyses and quantum chemical computations. Moreover, the anti-inflammatory activities of all the isolates were assessed in vitro based on the suppression of lipopolysaccharide-activated inflammatory mediators (COX-2, IL-1 β , and TNF- α ) in RAW 264.7 macrophage cells. Results At the dose of 200 mg/kg, the three fractions (ME, AL, and Non-AL) of H. erectum ameliorated the paw edema by carrageenan-stimulated and reduced the number of writhing by acetic acid-induced in mice compared to the model group, with the AL fraction showing the most potent effects. Subsequent phytochemical investigation of the AL fraction led to the isolation of six new isoquinoline alkaloids ( 1 – 6 ) as well as 23 known analogues ( 7 – 29 ). However, compared to common isoquinolines, compounds 1 – 4 possess an additional nitrogen atom, while compound 5 has two additional nitrogen atoms. These additional atoms enrich the diversity of natural isoquinoline alkaloids. Further pharmacological evaluation in vivo revealed that the four major constituents ( 20 , 21 , 22 , and 27 ) significantly relieved paw edema at 100 mg/kg, while protopine ( 20 ) and oxyhydrastinin ( 27 ) remarkably decreased the number of writhing at 100 mg/kg. In addition, most of the isolates displayed anti-inflammatory effects, as indicated by the inhibition of inflammatory mediators (COX-2, IL-1 β , and/or TNF- α ) in vitro at a treatment concentration of 5 μg/mL. trans-benzindenoazepines ( 13 ), protopine ( 20 ), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahyboisoquiolin-8-one ( 25 ) showed comparable anti-inflammatory activity to dexamethasone by inhibiting the secretion of IL-1 β . Conclusions This investigation validated the traditional use of H. erectum by assessing its anti-inflammatory and analgesic effects. Phytochemical investigation revealed the diversity and novelty of the natural isoquinoline alkaloids in H. erectum . Four major isoquinolines were identified as the bioactive constituents of H. erectum . The findings provide scientific justification to support the traditional application of H. erectum for treating inflammatory and pain disorders .
研究领域:
药理学
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民族药理学
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化学
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生物化学
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药用植物
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）