Analytical Methods
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2014
·Vol. 6
·期 9
·2998-3008
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IF 1.938
Guanghui Liu,Wei He,Hao Cai,Xiuman Sun,Waner Hou,Manna Lin,Zhiyong Xie,Qiongfeng Liao
A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine berberine, palmatine, coptisine, epiberberine and jatrorrhizine in rat plasma, using tetrahydropalmatine as an internal standard. The separation of the five compounds was carried out on a C18 column using a mobile phase consisting of acetonitrile and water (containing 5 mmol ammonium acetate adjusted to pH 5.0 with formic acid). The detection was performed in the multiple reaction monitoring (MRM) mode via the electrospray ionization (ESI) source operating in the positive ionization mode. Linear calibration curves were obtained over the concentration range of 0.20–200.0 ng ml−1 for berberine, and 0.20–100.0 ng ml−1 for palmatine, coptisine, epiberberine and jatrorrhizine. The accuracy, precision and extraction recovery of the five analytes were all satisfactory. The validated method was successfully applied to study the pharmacokinetic differences of the five protoberberine-type alkaloids after the oral administration of Rhizoma coptidis (RC) and Jiao-Tai-Wan (JTW) extract. It was found that the Tmax values of the five ingredients in the JTW extract were significantly increased (P < 0.05) when compared with those in RC. In addition, the AUC0–t of palmatine, coptisine and epiberberine were significantly increased (P < 0.05).
研究领域:
药理学
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分析化学
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中医药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Qin Tang,Zhengcai Ma,Xiang Tang,Yan Liu,Huimin Wu,Yu Peng,Baihua Jiao,Rui Wang,Xiaoli Ye,Hang Ma,Xuegang Li
Ethnopharmacological relevance Helicobacter pylori (H. pylori) is a major pathogen colonized in the human stomach and is implicated in gastritis, peptic ulcer, and gastric carcinoma. Antibiotics are useful for eradicating H. pylori but failed for drug resistance, making it urgent to develop effective and safe drugs. Rhizoma Coptidis was reported as one of the most effective Chinese medicines to treat H. pylori -related gastrointestinal diseases, while the precise antimicrobial mechanism remains unclear. Thus, it is of great significance to study the antimicrobial ingredients and corresponding mechanisms of Rhizoma Coptidis. Aim of the study To search for the most effective alkaloid against H. pylori in Rhizoma Coptidis and illustrate the probable mechanisms . Materials and methods Five main alkaloids in Rhizoma Coptidis were isolated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were tested to determine the most effective one. Bacterial growth experiments, Annexin V-FITC/PI staining, TUNEL staining, and transmission electron microscopy (TEM) were performed to further study the anti- H. pylori activity of coptisine (Cop) . The in vivo effect of Cop on H. pylori eradication rate and H. pylori -induced inflammation was investigated in mice . Transcriptomics was used to understand the underlying mechanism of eradicating H. pylori and reducing host inflammation. Western blot, RT-PCR, and ELISA experiments were utilized and confirmed that cagA was one of the targets of Cop. Results According to the MIC and MBC, Cop was the most effective alkaloid against H. pylori , especially with no drug resistance developed . In vitro experiments showed that Cop inhibited H. pylori by inducing DNA fragmentation, phosphatidylserine exposure, and membrane damage. Cop (150 mg/kg/day) effectively eradicated H. pylori in mice and reduced the levels of IL-2 and IL-6 to relieve gastric inflammation. Transcriptomic analysis revealed that virulence factor cagA was one of the hub genes associated with the inflammation-improving effect of Cop. That is, Cop could decrease the expression of CagA and subsequently reduce the translocation of CagA to gastric epithelial cells, thereby improving the morphology of hummingbird-like phenotype induced by CagA and alleviating inflammation . Conclusions Cop is the most effective alkaloid in Rhizoma Coptidis and might act through multiple mechanisms for H. pylori eradication along with reducing the expression of CagA to alleviate inflammation.
研究领域:
药理学
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微生物学
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分子生物学
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民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Minzhen Xie,Siqi Gu,Yang Hong,Yan Liu,Xiaohui Rong,Wanying Lu,Heng Liu,Adnan Mohammed Algradi,Anam Naseem,ZunPeng Shu,Qi Wang
Ethnopharmacological relevance Coptis chinensis Franch. (CCF), as an extensively used traditional Chinese medicine , has therapeutic effects on Alzheimer's disease (AD), but its mechanism of action has not yet been elucidated. Aim of the study This study aims to reveal the mechanism of action of CCF via the gut-brain axis, and provide a new strategy for the clinical treatment of AD. Materials and methods APP swe /PS1ΔE9 mice were used as AD models, and were given CCF extract by intragastric administration. Barnes maze was used to test the therapeutic effect of CCF on the treatment of AD. To reveal the mechanism of action of CCF in the treatment of AD, Vanquish Flex UHPLC-orbitrap fusion lumos mass was chosen to detect endogenous differential metabolite; MetaboAnalyst 5.0 was applied to derive relevant metabolic pathways; similarly, to explore the effects of CCF on the gut-brain axis, Vanquish Flex UPLC-Orbitrap fusion lumos mass was utilized to detect the changes in the content of SCFAs in AD mice after CCF administration; the prototype components and metabolites in CCF were identified by UPLC/ESI/qTOF-MS, then their effects on Bifidobacterium breve were explored. Results CCF shortened the latency time of AD mice, improved the target quadrant ratio of AD mice, and made the maze roadmap simpler of AD mice; CCF regulated fifteen potential metabolites of AD mice, interestingly, ILA (indole-3-lactic acid) in SCFAs (short-chain fatty acids) was also included; CCF acted on histidine and phenylalanine metabolic pathways of AD mice; CCF increased the contents of acetic acid and ILA in AD mice; magnoflorine , jatrorrhizine , coptisine , groenlandicine, thalifendine , palmatine , berberine , epiberberine, hydroxylated jatrorrhizine, and 3-methoxydemethyleneberberine in CCF were detected in fecal samples of AD mice; magnoflorine, palmatrubine, 13-methylberberine, berberine, coptisine, and palmatine promoted the growth of Bifidobacterium breve. Conclusions: we have demonstrated that CCF acts on the gut-brain axis by regulating SCFAs to treat AD.
研究领域:
民族药理学
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神经科学
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药理学
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代谢组学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 55
·34746-34754
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IF 3.108
Ziwei Hu,Mingshan Xie,Danting Yang,Dong Chen,Jingyi Jian,Haibin Li,Kaisong Yuan,Zhengjin Jiang,Haibo Zhou
Berberine is an important anti-inflammatory drug widely used for the treatment of heart and intestinal disorders. The quantification of berberine is usually required in clinic medical assays. Herein, we report simple, fast and sensitive colorimetric visualization of berberine in human plasma using citrate-stabilized gold nanoparticles (AuNPs). Upon exposure to μg mL−1 levels of berberine, the AuNP solution exhibits a highly sensitive color change from red to blue and rapid aggregation kinetics within the initial 10 min, which can be directly seen with the naked eye and monitored by UV-vis absorbance spectroscopy. As confirmed by comparison with potential coexisting foreign substances, the presence of positively charged berberine induces the aggregation of the AuNPs owing to the electrostatic attraction and coordination interactions between the ring nitrogen atoms of berberine and the AuNPs, causing a color change of the AuNP suspension. Further evidence is that the sensitivity is significantly improved when NaHSO4 is added to promote the ligand exchange between citrate and berberine at the surface of the AuNPs. The NaHSO4-optimized AuNP system provides a simple colorimetric assay for the rapid detection of berberine in human plasma. The limit of detection (LOD) is 0.24 μg mL−1 by the naked eye and 0.06 μg mL−1 by UV-vis spectroscopy.
研究领域:
药理学
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分析化学
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纳米医学
✓ 已验证
DOI
高影响因子
ARCHIVES OF PHARMACAL RESEARCH
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2014
·Vol. 37
·期 12
·1617-1623
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IF 1.751
Shi Lei,Dang Xue-Liang,Liu Xin-You,Wei Hua-Mei,Yang Meng-Meng,Zhang Yan
Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A4 which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE). CBZE is an active and toxicity metabolite, and it is a substrate of MRP-2. Using CBZ for a long time can cause hepatic injury. Sophora flavescens (SF) is a medicinal herb used for the protected hepatic injury. This study investigated the acute and chronic effects of SF on the pharmacokinetics of CBZ in rats. The concentrations of CBZ and CBZE in plasma and tissues were determined by HPLC method. The results showed that SF which significantly decreased the AUC 0-t of CBZ, increased CBZE conversely. Tissue analysis showed that the concentrations of CBZ and CBZE in brain and liver were decreased by SF. In addition, the distribution of CBZE in kidney was reduced significantly, which influenced the CBZE excretion and increased the drug toxic potentially. Results in the current study suggest that patients using CBZ might be cautioned in the use of SF extract or Sophora -derived products. Meanwhile, patients receiving drugs which are substrates of CYP 3A4 and/or MRP-2 should be advised of the potential herb–drug interaction to reduce the risk of therapeutic failure or increased toxicity of conventional drug therapy.
研究领域:
药理学
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中药学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2018
·
IF 3.638
Cailan Li,Ping Huang,Kambo Wong,Yifei Xu,Lihua Tan,Hanbin Chen,Qiang Lu,Chaodan Luo,Chunlai Tam,Lixiang Zhu,Ziren Su,Jianhui Xie
In this study, we examined the anti-Helicobactor pylori effects of the main protoberberine-type alkaloids in Rhizoma Coptidis. Coptisine exerted varying antibacterial and bactericidal effects against three standard H. pylori strains and eleven clinical isolates, including four drug-resistant strains, with minimum inhibitory concentrations ranging from 25 to 50 μg/mL and minimal bactericidal concentrations ranging from 37.5 to 125 μg/mL. Coptisine’s anti-H. pylori effects derived from specific inhibition of urease in vivo. In vitro, coptisine inactivated urease in a concentration-dependent manner through slow-binding inhibition and involved binding to the urease active site sulfhydryl group. Coptisine inhibition of H. pylori urease (HPU) was mixed type, while inhibition of jack bean urease was non-competitive. Importantly, coptisine also inhibited HPU by binding to its nickel metallocentre. Besides, coptisine interfered with urease maturation by inhibiting activity of prototypical urease accessory protein UreG and formation of UreG dimers and by promoting dissociation of nickel from UreG dimers. These findings demonstrate that coptisine inhibits urease activity by targeting its active site and inhibiting its maturation, thereby effectively inhibiting H. pylori. Coptisine may thus be an effective anti-H. pylori agent.
研究领域:
微生物学
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药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
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2019
·
IF 3.448
Jian Liu,Zhenjing Zhu,Yueyao Liu,Linlin Wei,Bai Li,Fengxia Mao,Ju Zhang,Yingchao Wang,Yufeng Liu
Aims Berberine (BBR) is reported to induce apoptosis and inhibit migration of leukemic cells, but the underlying pharmacological mechanisms have not been fully revealed. This study aims to investigate the possible mechanisms from the perspective of autophagy. Main methods P-53-null leukemic cell lines Jurkat and U937 were used for the in vitro study. MDC staining was used for observation of autophagy in leukemic cells, and Western blot analysis was for determination of the expression levels of autophagy-associated proteins. Apoptosis of the leukemic cells was detected by flow cytometry. Cellular location of MDM2 was observed with immunofluorescence staining. Ubiquitination of MDM2 was assessed by immunoprecipitation. Male 6–8-week-old NOD/SCID mice were used for evaluating the effect of BBR on chemotherapy sensitivity in vivo . Key findings BBR induced autophagy in p53-null leukemic cells, which was inhibited by autophagy inhibitors 3-methyladenine. 3-methyladenine also inhibited BBR-induced apoptosis in leukemic cells. In addition, BBR not only decreased MDM2 mRNA expression, but also enhanced MDM2 self-ubiquitination in leukemic cells. Forced overexpression of MDM2 reversed the effect of BBR on autophagy and apoptosis. Furthermore, BBR promoted doxorubicin-induced autophagy and cell death in the leukemic cells and overexpression of MDM2 suppressed these effects. In vivo , BBR combined with doxorubicin achieved better therapeutic effect than doxorubicin alone. Significance MDM2 inhibits autophagy and apoptosis in leukemic cells in a p53-independent manner. BBR induces autophagy in p53-null leukemic cells through downregulating MDM2 expression at both transcriptional and post-transcriptional levels, which may contribute to the anti-cancer effect of BBR in leukemia.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2020
·
IF 4.225
Zhao Junli,Wang Yaqian,Gao Jie,Jing Yang,Xin Wenkuan
Previous studies showed that berberine, an alkaloid from Coptis Chinensis Franch, might exert a positive inotropic effect on the heart. However, the underlying mechanisms were unclear. Here, we reported that berberine at 10–20 µM increased the left ventricular (LV) developed pressure and the maximal rate of the pressure rising, and it increased the maximal rate of the pressure descending at 20 µM in Langendorff-perfused isolated rat hearts. These effects diminished with the concentration of berberine increasing to 50 µM. In the concentration range of 50–300 µM, berberine increased the isometric tension of isolated left ventricular muscle (LVM) strips with or without electrical stimulations, and it (30–300 µM) also increased the intracellular Ca2+ level in the isolated LV myocytes. The removal of extracellular Ca2+ hindered the berberine-induced increases in the tension of LVM strips and the intracellular Ca2+ level of LV myocytes. These suggested that berberine might exert its positive inotropic effects via enhancing Ca2+ influx. The blockade of L-type Ca2+ channels (LTCCs) with nifedipine significantly attenuated 300 μM berberine-induced tension increase in LVM strips but not the increase in the intracellular Ca2+ level. Berberine (300 μM) further increased the LVM tension following the treatment with the LTCC opener FPL-64716 (10 μM), indicating an LTCC-independent effect of berberine. Lowering extracellular Na+ attenuated the berberine-induced increases in both the tension of LVM strips and the intracellular Ca2+ level of LV myocytes. In conclusion, berberine might exert a positive inotropic effect on the isolated rat heart by enhancing the Ca2+ influx in LV myocytes; these were extracellular Na+-dependent.
研究领域:
药理学
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心血管生理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2014
·
IF 2.939
Han-Ming Cui,Qiu-Yan Zhang,Jia-Long Wang,Jian-Long Chen,Yu-Ling Zhang,Xiao-Lin Tong
Ethnopharmacological relevance Berberine (BER) and BER-original herbal medicines have a variety of pharmacological functions and have been widely used in clinical. However, its effect of enzyme induction on cytochrome P450 (CYP) in human hepatocytes is unknown. Material and method Metabolism of berberine and its effect on main metabolic enzymes in HepG2 cell in vitro was investigated. Cocktail probe drugs, mRNA expression and protein expression were used to evaluate the metabolism potency. Meanwhile, an UPLC–MS/MS method was validated for the analysis of BER and four probe drugs in HepG2 cell. Result BER significantly increased the metabolism of midazolam, phenacetin and tolbutamide by inducing the CYP1A2 and 3A4 enzyme in a dose-dependent manner, the mRNA and protein expression of CYP1A2 and 3A4 were increased by berberine at 1000 ng·mL −1 . The activity of CYP1A2 and 3A4 could be induced by BER more than 500 ng·mL −1 in HepG2 cell, which was confirmed by the increase of its mRNA and protein expression. Conclusion BER increases the metabolism of cocktail drugs such as midazolam, phenacetin and tolbutamide by increasing the mRNA and protein expression of CYP1A2 and 3A4.
研究领域:
药理学
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生物化学
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临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Shang Li,Yi Tao,Guo-Hua Dao,Hong-Ying Hu
The risk of harmful algal blooms (HABs) in the water recharged with reclaimed water is a bottleneck for water reuse . The suppression effects and mechanisms of the combination of UV-C and berberine on Microcystis aeruginosa and Scenedesmus obliquus in reclaimed water were investigated. Mono UV-C irradiation at 75 mJ cm −2 could suppress the growth of M. aeruginosa for 7 d and that at 90 mJ cm −2 could suppress the growth of S. obliquus for 5 d. UV-C irradiation combined with 0.2–2 mg L −1 berberine lengthened the inhibition period of M. aeruginosa to 10- > 22 d and that of S. obliquus to 7- > 22 d and induced more rapid lethal effects on the harmful microalgal cells, in significant synergetic patterns. The combination of UV-C and berberine suppressed total, intracellular and extracellular microcystin-LR (MC-LR) more effectively and decreased the MC-LR quota significantly, which further reduced the risks of microcystin production and release. Furthermore, synergetic mechanisms of the combined treatments were systematically investigated from the aspects of photosynthetic system (photosynthetic activity and pigments), metabolic activity (ATP and membrane potential), oxidation stress (reactive oxygen species (ROS) and glutathione (GSH)), and apoptosis-like cell death (phosphatidylserine (PS) ectropion, caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive rate). The combination treatment provided a joint attack of UV-C and berberine on photosynthetic transport chain of photosynthetic system II (PS II), and a synergetic pathway to achieve more severe disruptions in energy metabolism as well as aggravated oxidative stress . The accumulated ROS enhanced increases in programmed cell death (PCD) indicators of both microalgal species, which contributed to the enhancement effects on growth suppression. The results showed that the combination treatment achieved lower dose requirements of both UV-C irradiation and berberine for inducing the same inhibition effects on microalgal cells, which was promising to be applied in the HABs control of reclaimed water.
研究领域:
环境科学
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藻类学
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水处理工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2020
·
IF 2.971
Yucheng Li,Baoying Wang,Jiduo Shen,Ming Bai,Erping Xu
Context Berberine is an alkaloid that possesses various pharmacologic effects.Objective To explore the mechanism of berberine to improve insulin sensitivity in fructose-fed mice.Materials and methods Sixty male ICR mice were randomly divided into 6 groups (10 mice in each group): control, fructose, pioglitazone (10 mg/kg) and berberine (50, 100, and 200 mg/kg). Except for the control group, the mice received 20% fructose drinking for 10 weeks. Pioglitazone and berberine were orally administered once daily during the last 4 weeks. The insulin sensitivity was evaluated using an oral glucose tolerance test (OGTT). The serum levels of fasting glucose and insulin, blood lipids, and hormones were determined. The hepatic AMP and ATP contents were detected using high performance liquid chromatography (HPLC) analysis, and the protein expression was examined by immunoblotting.Results Berberine significantly reversed the insulin resistance induced by fructose, including lowering fasting insulin levels (from 113.9 to 67.4) and area under the curve (AUC) during OGTT (from 1310 to 1073), decreasing serum leptin (from 0.28 to 0.13) and increasing serum adiponectin levels (from 1.50 to 2.80). Moreover, berberine enhanced the phosphorylation levels of protein kinase B (PKB/AKT; 2.27-fold) and glycogen synthase kinase-3β (GSK3β; 2.56-fold), and increased hepatic glycogen content (from 0.19 to 1.65). Furthermore, berberine upregulated the protein expression of peroxisome proliferator activated receptor gamma coactivator 1α (PGC1α; 2.61-fold), phospho-AMP-activated protein kinase (p-AMPK; 1.35-fold) and phospho-liver kinase B1 (p-LKB1; 1.41-fold), whereas it decreased the AMP/ATP ratio (from 4.25 to 1.82).Conclusion The present study demonstrated the protective effects of berberine against insulin resistance induced by fructose. Our findings may provide an experimental basis for the application of berberine in the treatment of insulin resistance.
研究领域:
药理学
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代谢紊乱
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2024
·
IF 3.8
Liang Qi,Xinting Zhang,Ying Gao,Pin Gong,Jian-Wu Xie
The determination of isoquinoline alkaloids (IQAs) is crucial for maximizing the pharmacological benefits of Rhizoma coptidis (RC). In this study, the dendritic silica sphere (dSiO 2 ) was covalently modified with cyanuric chloride (CNCl) to synthesize a porous dNSiO 2 -CNCl NP. The fluorescence of berberine (Ber), palmatine (Pal), coptisine (Cop), and jatrorrhizine (Jat) was remarkably enhanced by dNSiO 2 -CNCl NP for at least 38-fold, inspiring the accurate determination of the isoquinoline total alkaloids (IQTAs) in RC using fluorometry. The method exhibited good linearity within the concentration range of 0.005 to 1 μM, with a limit of detection (LOD) and quantitation (LOQ) of 0.001 and 0.004 μM. Specially, Jat was discovered to form a stable covalent linkage with dNSiO 2 -CNCl, showing an innovative and enduring fluorescent nanoparticle derived from a natural product. Furthermore, using dNSiO 2 -CNCl as a substrate for fluorescence enhancement and a dispersive solid-phase extraction (d-SPE) sorbent, a fluorescence-mediated HPLV-UV method was developed to monitor Ber, Pal, and Cop in serum. Rapid qualitative analysis using fluorescence was initially performed. In chromatography analysis, the linear range for Cop was 0.20 to 10 μM, with LOD and LOQ at 0.035 and 0.110 μM, while Pal and Ber showed good linearity in the range of 0.05 to 10 μM, with LODs and LOQs at 0.013 and 0.040 μM. The spiked recovery rates ranged from 90.4% to 99.8% for the three IQAs, with intra-day precision below 7.9% and inter-day precision below 9.9%. The dual-functional dNSiO 2 -CNCl NP exhibited promising prospect in fluorescence sensing and separation applications for detecting drugs.
研究领域:
分析化学
·
纳米技术
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药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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