BIOMEDICAL CHROMATOGRAPHY
·
2020
·Vol. 35
·期 3
·e4991
·
IF 1.728
Li-Juan Nie,Jun Liang,Feng Shan,Ya-Yun Xu,Chun-Yu Yan,Xuan Zhou,Zhuo-Yu Cheng,Qing-Rong Xia
A simple, rapid, and selective ultra-performance liquid chromatography–tandem mass spectrometry method for determination of l -carnitine (LC) and acetyl- l- carnitine (ALC) in human serum was developed. Acetyl- l- carnitine-d 3 (ALC-d 3 ) was selected as internal standard (IS). After protein precipitation with acetonitrile–water (1 mL, 2:1, v/v), the analytes and IS were separated on a 2.5-μm XSelect HSS T3 C 18 column by gradient elution with methanol–water (containing 0.01% ammonia water) as the mobile phase at a flow rate of 0.2 mL/min. Analytes were detected with multiple reaction monitoring using a positive scan mode with electrospray ionization. Good linearity ( R 2 > 0.999) was observed in the concentration range for LC and ALC. The inter- and intra-day values of relative error were −10.4% to 10.0% with CVs less than 9.84%. The average recoveries of the two analytes were 91.29%–98.23%. Blood samples containing LC and ALC were stable under various storage conditions. Normal, haemolytic, and hyperlipidaemic serum had no significant effect on the quantification of LC and ALC. This method was successfully applied to study the concentrations of endogenous LC and ALC in the serum of patients with first-episode depression.
研究领域:
分析化学
·
医学
·
精神健康研究
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 4
·489
·
IF 4.3
Hao Wang,Chenxuan Zheng,Fanyu Tian,Ziyao Xiao,Zhixiong Sun,Liye Lu,Wenjuan Dai,Qi Zhang,Xuefeng Mei
Curcumin (CUR) is a natural polyphenolic compound with various pharmacological activities. Low water solubility and bioavailability limit its clinical application. In this work, to improve the bioavailability of CUR, we prepared a new co-crystal of curcumin and L-carnitine (CUR-L-CN) via liquid-assisted grinding. Both CUR and L-CN have high safe dosages and have a wide range of applications in liver protection and animal nutrition. The co-crystal was fully characterized and the crystal structure was disclosed. Dissolution experiments were conducted in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF). CUR-L-CN exhibited significantly faster dissolution rates than those of pure CUR. Hirshfeld surface analysis and wettability testing indicate that CUR-L-CN has a higher affinity for water and thus exhibits faster dissolution rates. Pharmacokinetic studies were performed in rats and the results showed that compared to pure CUR, CUR-L-CN exhibited 6.3-times-higher AUC0–tand 10.7-times-higher Cmax.
研究领域:
药剂学
·
生物化学
·
药物开发
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DOI
PubMed
高影响因子
GOLD BULLETIN
·
2020
·Vol. 53
·期 3
·159-165
·
IF 1.706
Wang Yanwei,Zhou Xiaojuan,Liu Qiang,Jin Yan,Xu Chunli,Li Baoxin
In this work, we proposed one simple and effective chiral-sensing method for the discrimination of carnitine enantiomers. The gold nanorods (AuNRs) were used as colorimetric probes to recognize carnitine enantiomers in this method. l -Carnitine can induce rapidly the blue-to-gray change of AuNR solution color, whereas d -carnitine cannot induce the obvious change of the color. Based on this distinct difference of color, a visual method for recognition of carnitine enantiomers was suggested. This method has been applied to detect the enantiometric excess of l -carnitine in the range of − 100~100%. The presented chiral measurement can be performed with a simple ultraviolet-visible spectrometer and even the naked eyes. In this method, AuNRs need no modification with chiral molecule, and the chiral recognition is based on the inherent chirality of AuNRs. This new method opens up possibility for fast and easy assay of carnitine enantiomers.
Graphical abstract
研究领域:
分析化学
·
生物化学
·
纳米技术
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DOI
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Tan Yang,Jianfang Feng,Qian Zhang,Wei Wu,Hailan Mo,Lanzhen Huang,Wei Zhang
A delivery system based on l-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 μg/ml. The drug-loaded micelles presented a slow and incomplete in vitro release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.
研究领域:
药剂学
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Cong Liu,Ying Zou,Manli Zhang,Chaoxian Chi,Di Zhang,Fangling Wu,Chuan-Fan Ding
This work presents a straightforward approach to the separation d / l -carnitine ( d / l -Carn) using ion mobility–mass spectrometry (IM-MS) and theoretical calculations. Natamycin (Nat) was used as separation reagent to interact with the Carn, metal ions (G) were employed as ligand, the resultant ternary complexes [ d / l -Carn + Nat + G] + were observed experimentally. IM-MS results revealed that d / l -Carn could be baseline separated via complex formation using Li + , Na + , K + , Rb + , and Cs + , with a maximum peak separation resolution (R p-p ) of 2.91; Theoretical calculations were performed to determine the optimal conformations of [ d / l -Carn + Nat + Li/K] + , and the predicted collisional cross section values were consistent with the experimental values. Conformational analysis was used to elucidate the enantiomeric separation of d / l -Carn at the molecular level via the formation of ternary complexes. Furthermore, quantitative analyses for the determination of the enantiomers were established with effective linearity and acceptable sensitivity. Finally, the proposed method was successfully applied in the determination of d / l -Carn in food samples.
研究领域:
分析化学
·
食品科学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Min Hong,Haobin Chen,Lei Li,Xiaoyan Liu,Qinghong Ji,Shuang Cheng,Chenzhong Li
A glutathione (GSH)-responsive amphiphilic camptothecin (CPT) prodrug, Lc-ss-CPT, was synthesized by conjugating hydrophobic CPT with hydrophilic L-carnitine (Lc) via a disulfide carbonate linker. The prodrug self-assembled into spherical nanoparticles (Lc-ss-CPT NPs, hydrodynamic diameter: ∼180 nm). In simulated gastrointestinal fluids and FBS-containing PBS, the NPs maintained stability over 24 h, with <10 % CPT leakage after 8 h. In vitro transcytosis studies using Caco-2 monolayers revealed an 188.5-fold higher apparent permeability coefficient for Lc-ss-CPT NPs than free CPT. The confocal fluorescence imaging studies demonstrated that the specific affinity between L-carnitine and organic cation transporter 2 (OCTN2) enhanced intestinal absorption of Lc-ss-CPT NPs and then transported into the bloodstream through transcytosis, facilitated by the Golgi apparatus and endoplasmic reticulum, enabling tumor accumulation. Pharmacokinetic analysis in rats showed oral administration of Lc-ss-CPT NPs achieved a higher bioavailability of 49.6 %. In HCT-116 cells, Lc-ss-CPT NPs reduced intracellular GSH to 5.4 % of baseline at 6 h, elevated ROS levels by 4.2-fold, and induced 71.2 % apoptosis. In MC38 tumor-bearing mice, oral Lc-ss-CPT NPs suppressed tumor growth by 86 % (vs. 12 % for free CPT). These data demonstrate the potential of Lc-ss-CPT NPs as an orally administrable platform for targeted CPT delivery.
研究领域:
药理学
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肿瘤学
·
纳米医学
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产品关联
DOI
高影响因子
Food Science & Nutrition
·
2024
·
IF 3.5
Xin Wang,Xiaoyi Hu,Weiwei He,Jun-Yi Yin
Emerging evidence suggests that gut bacteria-derived trimethylamine N-oxide (TMAO) elevates the risk of cardiovascular disease, and dietary fiber holds the potential to attenuate TMAO formation. However, the effectiveness of dietary fiber, such as inulin, in inhibiting TMAO formation remains controversial. Therefore, this study investigated the effect of inulin supplementation on TMAO formation in mice with high TMAO levels induced by a high-fat diet (HFD) combined with choline and L-carnitine. Results showed that HFD treatment significantly elevated blood TMAO concentrations and increased the abundances of TMAO formation-associated gut bacteria, as well as the abundances of functional genes responsible for TMA formation. While the supplementation of choline and L-carnitine greatly enhanced blood trimethylamine (TMA) and TMAO levels, inulin supplementation did not significantly affect TMAO levels and had limited impact on TMA-associated gut bacteria, except for Desulfitobacterium hafniense .
研究领域:
营养学
·
微生物学
·
心脏病学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Ligang Xing,Yanmei Zhao,Mingzhu Gong,Xia Liu,Yuhui Zhang,Dan Li,Zefeng He,Ping Yan,Jidong Yang
In this study, Graphene Oxide (GO) was used to screen the binding with the aptamers of L-carnitine chiral enantiomers . The ssDNA library was prepared by the method of Lambda exonuclease . In addition, a simple casing device was designed to improve the purification and recovery efficiency of the small ssDNA fragments in the process of screening. Finally, more than 160,000 aptamer sequences were obtained by high-throughput sequencing. We determined the strongest affinity aptamer sequence, CA04, by the Resonance Rayleigh scattering (RRS) technology. We also analyzed the key binding sites (in the 16th position case) of the truncated aptamer sequence CAD10. Interestingly, we found that aptamer CA10 and CA06 were both C-rich bases through sequence alignment and analysis, and the aptamer CA10 was confirmed that the CA10 and CA06 were formed under acidic conditions (pH 4.5) by CD spectrum and ESI-MS analysis. The interaction between gold nanoparticles (AuNPs) and functionalized aptamer CA10 was analyzed. We used Site-directed mutagenesis design and QGRS Mapper to optimize aptamer CA10, where an optimal aptamer CA10-03 were obtained after affinity analysis. It is also proved to be an effective method to obtain stronger affinity aptamer. Meanwhile, Native-PAGE and UV spectrum analysis were performed on the mutation sequences, and the interaction with ThT was analyzed. Finally, it is hoped that my study can provide help for later identification and detection of L-carnitine .
研究领域:
生物化学
·
分子生物学
·
分析化学
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DOI
PubMed
高影响因子
FLUID PHASE EQUILIBRIA
·
2017
·
IF 2.473
Congfei Yao,Yucui Hou,Shuhang Ren,Youan Ji,Weize Wu
Phenols are important materials for the organic chemical industry. They mainly come from coal liquefaction oil, coal tar, petroleum and biomass pyrolysis oil, making the separation of phenols from oil mixtures of great commercial value. Two zwitterionic alkaloids, betaine and L-carnitine, biodegradable and environmentally benign ionic compounds , can efficiently separate phenols from oils by forming deep eutectic solvents (DESs). In this work, the phase equilibria of two ternary systems of toluene + phenol + betaine and toluene + phenol + L-carnitine were measured at 25.0 °C, 45.0 °C and 65.0 °C under atmospheric pressure. The phase behaviors of the two ternary systems were studied, which indicated that there were three kinds of phase regions: liquid, liquid-liquid, and liquid-liquid-solid. The separation of phenol from oil mixtures occurs at the latter two phase regions. Effects of temperature, zwitterionic alkaloid type and its dosage on the phase equilibrium were investigated. With decreasing temperature, the distribution and selectivity coefficients increase. L-carnitine shows better performance in separating phenol from oils via forming DES than betaine.
研究领域:
化学工程
·
物理化学
·
环境科学
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产品关联
DOI
高影响因子
Science China-Chemistry
·
2025
·
IF 9.7
Jiang Yifan,Li Lisha,Fang Xiao,Zeng Tao,Su Lichao,Liu Yichang,Wu Ying,Li Jinyu,Lyu Peng,Lu Zhonglei,Lu Chunhua,Yang Huanghao
The development of RNA interference (RNAi) therapy offers a potential solution for Alzheimer’s disease (AD). However, the brain-blood barrier (BBB) with its selective permeability and pharmacokinetic-related challenges poses restrictions on the delivery of small interfering RNA (siRNA) to the central nervous system (CNS). In this study, we demonstrate that the incorporation of 2′-fluoro (2′-F) substitutions and L-carnitine modification facilitates the self-assembly of siRNA through triple interaction, leading to the formation of nanorings, called LCSF-NR. Based on the enhanced cellular uptake and lysosomal escape by 2′-F substitution and the transport across the BBB promoted by L-carnitine, the nanorings realized the improved brain-targeted delivery of siRNA, both in zebrafish and mice models. Moreover, our findings highlight the therapeutic potential of LCSF-NR formulation in an AD zebrafish model through a synergistic effect of downregulating the β-site APP cleavage enzyme 1 (BACE1) gene and L-carnitine-mediated neuroprotection, effectively inhibiting pathological processes. Overall, these results suggest that the chemical modification-based siRNA self-assembly strategy enables trans-BBB delivery and presents a concise approach for synergistic therapy of AD.
研究领域:
分子生物学
·
神经科学
·
药物递送系统
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产品关联
DOI
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2019
·Vol. 47
·期 6
·582-591
·
IF 3.354
Mengru Bai,Qingquan Zeng,Yingchun Chen,Mingyang Chen,Ping Li,Zhiyuan Ma,Dongli Sun,Hui Zhou,Caihong Zheng,Su Zeng,Huidi Jiang
l-Carnitine (l-Car) plays a crucial role in fatty acid β-oxidation. However, the plasma l-Car concentration in women markedly declines during pregnancy, but the underlying mechanism and its consequences on maternal hepatic β-oxidation have not yet been clarified. Our results showed that the plasma l-Car level in mice at gestation day (GD) 18 was significantly lower than that in nonpregnant mice, and the mean fetal-to-maternal plasma l-Car ratio in GD 18 mice was 3.0. Carnitine/organic cation transporter 2 (OCTN2) was highly expressed in mouse and human placenta and upregulated as gestation proceeds in human placenta, whereas expressions of carnitine transporter (CT) 1, CT2, and amino acid transporter B0,+ were extremely low. Further study revealed that renal peroxisome proliferator–activated receptor α (PPARα) and OCTN2 were downregulated and the renal l-Car level was reduced, whereas the urinary excretion of l-Car was lower in late pregnant mice than in nonpregnant mice. Meanwhile, progesterone (pregnancy-related hormone) downregulated the expression of renal OCTN2 via PPARα-mediated pathway, and inhibited the activity of OCTN2, but estradiol, corticosterone, and cortisol did not. Unexpectedly, the maternal hepatic level of l-Car and β-hydroxybutyrate (an indicator of mitochondrial β-oxidation), and mRNA levels of several enzymes involved in fatty acid β-oxidation in GD 18 mice were higher than that in nonpregnant mice. In conclusion, OCTN2 mediated l-Car transfer across the placenta played a major role in maternal plasma l-Car reduction during pregnancy, which did not subsequently result in maternal hepatic fatty acid β-oxidation decrease.
研究领域:
生理学
·
药理学
·
内分泌学
·
生殖生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2019
·
IF 3.499
Ting Jiang,Yingqiong Zhang,Mengru Bai,Ping Li,Wei Wang,Mingyang Chen,Zhiyuan Ma,Su Zeng,Hui Zhou,Huidi Jiang
Olanzapine, a representative of antipsychotics, is a first-line drug for treatment of schizophrenia. However, olanzapine-induced liver steatosis limits its clinical utilization. This study is to explore the mechanism of liver steatosis induced by olanzapine based on the regulation of transporters involved in uptake and oxidation of fatty acids. Our results revealed that 12-week oral administration of olanzapine increased hepatic triglyceride(TG), caused liver steatosis. Our further studies showed that the expression of fatty acid transporter 2(FATP2) and fatty acid binding protein 1(FABP1) were up-regulated in liver of female mice after 12-week olanzapine exposure, as well as in primary mouse hepatocytes treated with olanzapine. Olanzapine treatment also reduced hepatic β-hydroxybutyrate level (indicator of fatty acid β-oxidation), meanwhile, the L-carnitine (L-Car) concentration in liver of olanzapine group was significantly lower than that in control group. Further study demonstrated that both mRNA and protein expression of hepatic OCTN2 (carnitine/organic cation transporter 2) were obviously down-regulated in male mice after 12-week olanzapine treatment. Also, olanzapine markedly inhibited L-Car uptake in MDCK-hOCTN2 cells (1.06 μM of IC 50 ), HepG2 cells and primary mouse hepatocytes. Supplementation of L-Car attenuated hepatic TG rise and improved simple steatosis in olanzapine treatment mice. Taken together, up-regulation of FATP2/FABP1 and down-regulation/inhibition of hepatic OCTN2 probably contribute to olanzapine-induced liver steatosis. Supplementation of L-Car is a promising strategy to attenuate olanzapine-induced simple steatosis.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 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）