ACTA PHARMACOLOGICA SINICA
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2019
·Vol. 40
·期 8
·1106-1118
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IF 4.01
Zhao Kai-jing,Chen Yang,Hong Shi-jin,Yang Yi-ting,Xu Jiong,Yang Han-yu,Zhu Liang,Liu Ming,Xie Qiu-shi,Tang Xian-ge,Yang Ting-ting,Zhou Ya-qian,Liu Li,Liu Xiao-dong
Cinnamic acid and its analogues (pyragrel and ozagrel) undergo chain-shortened (β-oxidative) and reductive metabolism on acyl side chain. In this study, we characterized the β-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues using primary rat hepatocytes, hepatic mitochondrial, and microsomal systems. A compartmental model including parent compounds and metabolites was developed to characterize in vivo β-oxidative and reductive metabolism following an intravenous dose of parent compounds to rats. The fitted total in vivo clearance values were further compared with the in vitro values predicted by the well-stirred model. We showed that hepatic microsomal CYP450s did not catalyze β-oxidative or reductive metabolism of the three compounds. Similar to β-oxidation of fatty acids, β-oxidative metabolism on their acyl side chain occurred mainly in mitochondria, which was highly dependent on ATP, CoA and NAD + . Fatty acids and NADH inhibited the β-oxidative metabolism. Reductive metabolism occurred in both mitochondria and microsomes. Reduction in mitochondria was ATP-, CoA-, and NAD(P)H-dependent and reversible, which was suppressed by enoyl reductase inhibitor triclosan. Reduction in microsomes was ATP-, CoA-, and NADPH-dependent but little affected by triclosan. Both plasma concentrations of β-oxidative metabolites and reductive metabolites were successfully fitted using the compartmental model. The estimated total in vivo clearance values were consistent with those predicted from hepatocytes and organelles, implicating significance of in vitro kinetics. These findings demonstrate the roles of hepatic mitochondria and microsomes in β-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues along with their metabolic characteristics.
研究领域:
药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hongwei Jiang,Lei Zhou,Yue Wang,Guangxian Liu,Shengfeng Peng,Wenzhi Yu,Yuqing Tian,Junping Liu,Wei Liu
Phenolic acids are promising inhibitors of polyphenol oxidase (PPO), but the effects of carboxyl group and pH on their inhibition effects are still unclear. In this study, methyl cinnamate, cinnamic acid and 4-carboxycinnamic acid were investigated by their inhibitory effects with pH varied from 6.8 to 5.0. Results showed that 4-carboxycinnamic acid had the strongest inhibitory effect on PPO, followed by cinnamic acid and methyl cinnamate. Acidic pH enhanced the inhibitory effects of cinnamic acid and its derivatives on PPO, and the enhancement degree, IC 50 and K i declining degree were followed as 4-carboxycinnamic acid > cinnamic acid > methyl cinnamate. Methyl cinnamate exhibited competitive inhibition on PPO, while cinnamic acid and 4-carboxycinnamic acid exhibited mixed-type inhibition. Inhibitors induced slight changes in the secondary and tertiary structures of PPO, which were enhanced by acidic pH. Molecular docking results showed that 4-carboxycinnamic acid exhibited the strongest binding ability, and the main interaction forces were around carboxyl groups, and acidic pH enhanced the binding effect through more interactions and lower binding energy. This study could provide new insights into industrial application of cinnamic acid and its derivatives for the control of enzymatic browning of fruits and vegetables.
研究领域:
食品科学
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植物化学
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酶学
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产品关联
DOI
PubMed
高影响因子
FLUID PHASE EQUILIBRIA
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2018
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IF 2.197
Lintao Guo,Mingjie Qu,Junsu Jin,Hong Meng
To promote the extraction of natural cinnamic acid with supercritical and subcritical fluids, the solubility of cinnamic acid was measured respectively in supercritical carbon dioxide (SCCO 2 ) by the dynamic method and in subcritical 1,1,1,2-tetrafluoroethane (sub-R134a) by the static method. The experiments were performed at temperatures from 308 K to 328 K and pressures of 9.0, 11.0, 13.0, 15.0, and 18.0 MPa. The solubility of cinnamic acid in SCCO 2 and sub-R134a were compared by calculating the enhancement factor ( δ ), which indicated that the value of δ in sub-R134a is greater than that in SCCO 2 ; meanwhile, the entrainment factor ( ψ ), which describes the influence of co-solvent (ethanol, ethyl acetate and n -pentane) on the cinnamic acid solubility in SCCO 2 , showed that the solubility of cinnamic acid in SCCO 2 increased with the co-solvent polarity increasing. Six semi-empirical models (Chrastil, A-L, K-J, S-S, M-S-T, and Bartle) were used to correlate cinnamic acid solubility in binary system (cinnamic acid + SCCO 2 or sub-R134a) and four models (Gonzalea, Sovova, Tang and Sauceau) were used to correlate cinnamic acid solubility in ternary system (cinnamic acid + SCCO 2 +co-solvent). The enthalpy values of cinnamic acid, including Δ H total , Δ H sub. and Δ H sol. , were estimated through Chrastil and Bartle models; and the partial molar volume of cinnamic acid was calculated by K-J model. A new model was proposed on the basis of the molecular association theory and verified by 47 solid solutes solubility in SCCO 2 or sub-R134a with satisfactory correlation results.
研究领域:
化学工程
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天然产物提取
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药物化学
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DOI
高影响因子
Catalysts
·
2023
·Vol. 13
·期 6
·917
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IF 3.9
Xiaoni Zhu,Hongfei Li,Jiangang Ren,Yanbin Feng,Song Xue
Enzymatic decarboxylation and carboxylation are emerging as prospective processes to produce high-value compounds under mild conditions. Ferulic acid decarboxylase Fdc1 catalyzes broad substrate tolerance against α, β-unsaturated carboxylic acids, and provides green routes for carbon dioxide fixation with the reversible carboxylation, while the activity of the enzyme is limited by the indispensable cofactor prenylated flavin (prFMN), which is unstable and is rarely detected in nature. In this study, a prFMN efficient synthesis route was built using six exogenous enzymes introduced intoE. colicells, leading to the construction of a powerful cell catalyst named SC-6. Based on the metabolic analysis, the results indicated that the reduction of FMN to FMNH2was the bottleneck in prFMN synthesis pathway, and introducing FMN reductase increased the production of prFMN 3.8-fold compared with the common flavin prenyltransferase UbiX overexpression strain. Using SC-6 cell catalyst, the decarboxylation activity of Fdc1 increased more than 20 times with cinnamic acid and 4-acetoxycinnamic acid as substrates. Furthermore, the reversible carboxylation reaction was carried out, and the cell catalyst presented 20 times carbon dioxide fixation activity using styrene to produce cinnamic acid. Finally, the maximum yield of cinnamic acid catalyzed by SC-6 achieved 833.68 ± 34.51 mM·mg−1in two hours. The constructed prFMN pathway in vivo provides fundamentals for efficient decarboxylation and carbon fixation reactions catalyzed by prFMN-dependent enzymes.Keywords:cell catalyst;prFMN;decarboxylase;carboxylation;cinnamic acid
研究领域:
生物技术
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酶工程
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代谢工程
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可持续化学
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DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
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2014
·Vol. 37
·期 18
·2490-2498
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IF 2.594
Xiaoxue Wu,Jiao He,Huarong Xu,Kaishun Bi,Qing Li
A novel and improved method for the quality assessment of Cinnamomi Ramulus was developed and completely validated. The method was established using fingerprint technology and simultaneous quantitative determination of six main marker compounds including coumarin, cinnamic alcohol, cinnamic acid, 2-methoxy cinnamic acid, cinnamaldehyde, and 2-methoxy cinnamaldehyde in the herbal medicine for the first time. A newly developed high-performance thin-layer chromatography method, which achieved simultaneous definition of five marker components by comparing the colors and retardation factor values of the bands in high-performance thin-layer chromatography, was first used for the authentication of Cinnamomi Ramulus. The fingerprints of 26 batches of herbal samples from different regions of China showed very similar chromatographic patterns that were evaluated by similarity analysis and hierarchical clustering analysis. In addition, six marker compounds were simultaneously determined using single standard to determine multiple components by the relative response factors. Compared with the external standard method, the new quantitative method was validated to determine multiple compounds in 26 batches of Cinnamomi Ramulus samples. All results demonstrated that the simple and rapid method could be effectively utilized for the quality control of Cinnamomi Ramulus.
研究领域:
生药学
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分析化学
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中药
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
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2024
·
IF 10.7
Yukang Wang,Gaochen Jin,Shuyan Song,Yijun Jin,Xiaowen Wang,Shuaiqi Yang,Xingxing Shen,Yinbo Gan,Yuexing Wang,Ran Li,Jian-Xiang Liu,Jianping Hu,Ronghui Pan
The mechanism underlying the ability of rice to germinate underwater is a largely enigmatic but key research question highly relevant to rice cultivation. Moreover, although rice is known to accumulate salicylic acid (SA), SA biosynthesis is poorly defined, and its role in underwater germination is unknown. It is also unclear whether peroxisomes, organelles essential to oilseed germination and rice SA accumulation, play a role in rice germination. Here, we show that submerged imbibition of rice seeds induces SA accumulation to promote germination in submergence. Two submergence-induced peroxisomal Oryza sativa cinnamate:CoA ligases (OsCNLs) are required for this SA accumulation. SA exerts this germination-promoting function by inducing indole-acetic acid (IAA) catabolism through the IAA-amino acid conjugating enzyme GH3. The metabolic cascade we identified may potentially be adopted in agriculture to improve the underwater germination of submergence-intolerant rice varieties. SA pretreatment is also a promising strategy to improve submerged rice germination in the field.
研究领域:
植物生理学
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分子生物学
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农业科学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
·
IF 8
Yuling Liu,Xin Nie,Yihan Wu,Longfei Lin,Qian Liao,Jingjing Li,Simon Ming-Yuen Lee,Hui Li,Jinming Zhang
Introduction: The insufficient targeting delivery of therapeutic agents greatly impeded the treatment outcomes of rheumatoid arthritis (RA). Despite the recognized therapeutic advantages of gambogic acid (GBA) in inflammatory diseases, its high delivery efficiency to inflammatory site still limits its clinical application. Self-assembly of drug dimers into carrier-free nanoparticles (NPs) has become a straightforward and attractive approach to develop nanomedicines for RA treatment. Herein, homodimers of GBA were designed to form the carrier-free NPs by self-assembly for RA treatment.
Methods: The synthetic gambogic acid dimers (GBA2) were self-assembled into NPs using a one-step solvent evaporation method. The size distribution, morphology, drug-loading efficiency (DLE) and storage stability were evaluated. A molecular dynamic simulation was conducted to gain further insight into the self-assembly mechanisms of GBA2/NPs. Besides, we investigated the cytotoxicity, apoptosis and cellular uptake profiles of GBA2/NPs in macrophages and osteoclasts. Finally, the specific biodistribution on the ankles of adjuvant-induced arthritis (AIA) mice, and the anti-RA efficacy of the AIA rat model were assessed.
Results: GBA2/NPs exhibited the uniform spherical structure, possessing excellent colloidal stability, high self-assembly stability, high drug loading and low hemolytic activity. Comparing with GBA, GBA2/NPs showed higher cytotoxicity, cellular uptake and apoptosis rate against osteoclasts. In addition, GBA2/NPs exhibited much higher accumulation in ankle joints in vivo. As expected, the systematic administration of GBA2/NPs resulted in the greater alleviation of arthritic symptoms, cartilage protection, and inflammation, notably the reduced systemic toxicity compared to free GBA.
Conclusion: GBA2/NPs formed GBA dimers exhibited the superior accumulation in the inflamed joint and anti-RA activity, potentially attributing to the similar extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (""ELVIS"") effects in inflamed joint and the enhanced cellular uptake in macrophages and osteoclasts. Our findings provide substantial evidence that self-assembly of GBA2/NPs would be a promising therapeutic alternative for RA treatment.
研究领域:
药学
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纳米技术
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风湿病学
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药物递送系统
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炎症研究
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产品关联
DOI
PubMed
高影响因子
PHARMACOLOGY
·
2022
·
IF 3.429
Zhuo Rengong,Cheng Xiaoling,Luo Lili,Yang Luying,Zhao Yun,Zhou Yu,Peng Lu,Jin Xin,Cui Lishan,Liu Feng,Yang Lichao
Aim: Recent evidence indicates that neuroinflammation and oxidative stress play vital roles in the pathological process of major depressive disorder (MDD). Cinnamic acid (CA), a naturally occurring organic acid, has been reported to ameliorate neuroinflammation and oxidative stress for treatment of diabetes-related memory deficits. Here, we explored whether CA pretreatment ameliorated lipopolysaccharide (LPS)-induced depressive-like behaviors in mice by suppressing neuroinflammation and by improving oxidative stress status. Methods: The mice were treated with CA, vehicle, or fluoxetine as a positive control. After 14 days, LPS (1 mg/kg, i.p.) or saline was administered. The depression-like behaviors were examined by the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). Furthermore, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex of mice were assayed. Results: Our results demonstrated that CA pretreatment at the doses of 100 and 200 mg/kg significantly attenuated depressive-like behaviors in the TST, FST, and SPT. In addition, not only the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) but also oxidative stress parameters including SOD, GSH, and MDA in the hippocampus and cortex of mice treated with LPS were dramatically improved by CA pretreatment. Finally, CA pretreatment strikingly ameliorated the downregulation of BDNF induced by LPS in the hippocampus and cortex of mice. Conclusion: Our results indicated that CA may have therapeutic potential for MDD treatment through attenuating the LPS-induced inflammation and oxidative stress along with significant improvement of BDNF impairment
研究领域:
药理学
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神经科学
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精神病学
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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）