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Effects of Berberine and cinnamic acid on Palmitic acid-Induced Intracellular Triglyceride Accumulation in NIT-1 Pancreatic β Cells

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Chinese Journal of Integrative Medicine 2016年第7期22卷 496-502页

作者：赵莉姜淑君陆付耳徐丽君邹欣王开富董慧 Institute of Integrated Traditional Chinese and Western Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Nephrology Wuhan Integrated Traditional Chinese Medicine and Western Medicine Hospital Tongji Medical College Huazhong University of Science and Technology

Objective： To investigate the effects of berberine （BBR） and cinnamic acid （CA）, the main active components in Jiaotai Pill （交泰丸, JTP）, on palmitic acid （PA）-induced intracellular tdglyceride （TG） accumulation in NIT-1 pancreatic 13 cells. Methods： Cells were incubated in culture medium containing PA （0.25 mmol/L） for 24 h. Then treatments with BBR （10 μmol/L）, CA （100 μmol/L） and the combination of BBR and CA （BBR＋CA） were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase （AMPK） protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase （FAS）, acetyl-coA carboxylase （ACC）, phosphorylation acetyl-coA carboxylase （pACC）, carnitine acyl transferase 1 （CPT-1） and sterol regulating element binding protein lc （SREBP-lc） were determined by Western blot or real time polymerase chain reaction. Results： PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-I. Meanwhile, AMPK downstream lipogenic genes including SREBP-lc mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR＋CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic 13 cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study. Conclusion： It can be concluded that in vitro, BBR and BBR＋CA could inhibit PA-induced lipid accumulation by decreasing lipoqenesis and *** lipid oxidation in NIT-1 pancreatic B cells.

关键词： berberine cinnamic acid palmitic acid NIT-1 cells lipid Chinese medicine Jiaotai Pill

RP-HPLC Determination and Pharmacokinetic Comparison of cinnamic acid in Rat Plasma After Administration of Di-Gu-Pi Decoction and Pure cinnamic acid

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Chemical Research in Chinese Universities 2006年第1期22卷 56-60页

作者： LI Kang BI Kai-shun Department of Pharmacy Shenzhen Hospital Beijing University Shenzhen 518036 P.R. China College of Pharmacy Shenyang Pharmaceutical University Shenyang 110016 P.R. China

A sensitive, simple, and accurate method was developed for the determination and pharmacokinetic comparison of cinnamic acid in rat plasma after the administration of a Traditional Chinese Medicinal preparation, Di-Gu-Pi decoction, and pure cinnamic acid using RP-HPLC. Di-Gu-Pi was extracted with 5% aqueous sodium bicarbonate, which was followed by purification with ion exchange column chromatography. The plasma samples taken from rats were deproteinized with methanol. The reversed-phase （HPLC） system with a Diamonsil C18 column and methanol-acetonitfile-water （8： 32： 60, volume ratio）（adjusted to pH = 3.0 with glacial acetic acid） as the mobile phase was employed for the separation of cinnamic acid in the plasma samples. The detection was set at 272 nm and 3-（p-fluoro-phenyl）-2-propenoic acid was chosen as the internal standard. The calibration curve was linear in a range from 0. 10 to 25.0μg/mL （R2 = 0. 9988, n = 9）. The precision was 3.42%-10. 10%; the between-day precision was 2. 84%-8.91% ; the accuracy was - 1.51%-1.26% ; the mean recovery was 99. 9%. The method was found to be sensitive, simple, accurate and appropriate for the determination of cinnamic acid.

关键词： Di-Gu-Pi decoction cinnamic acid Pharmacokinetics RP-HPLC

Effects of cinnamic acid on Bacterial Community Diversity in Rhizosphere Soil of Cucumber Seedlings Under Salt Stress

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Agricultural Sciences in China 2010年第2期9卷 266-274页

作者： LIU Jing WU Feng-zhi YANG Yang Horticulture College Northeast Agricultural University Harbin 150030 P.R.China

To investigate the effects of a plant autotoxin, cinnamic acid, on bacterial communities in the rhizosphere soil of cucumber seedlings under salt stress, we used cucumber as the experimental material, cinnamic acid as the autotoxin, and NaCl to apply salt stress. Bacterial communities in the rhizosphere soil were analyzed using polymerase chain reaction （PCR）, denaturing gradient gel electrophoresis （DGGE）, and clone sequencing. Salt stress decreased the diversity of bacterial species in rhizosphere soil of cucumber seedlings at several growth stages. cinnamic acid exacerbated the effects of salt stress at high concentrations, but alleviated its effects at low concentrations. Cloning and sequencing results indicated that DGGE bands amplified from soil samples showed high homology to uncultured bacterial species. cinnamic acid at 50 mg kg^-1 soil improved cucumber growth and was the most effective treatment to alleviate the effects of salt stress on bacterial communities.

关键词： bacteria cinnamic acid cucumber salt stress PCR-DGGE

Characteristics of β-oxidative and reductive metabolism on the acyl side chain of cinnamic acid and its analogues in rats

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Acta Pharmacologica Sinica 2019年第8期40卷 1106-1118页

作者： Kai-jing Zhao Yang Chen Shi-jin Hong Yi-ting Yang Jiong Xu Han-yu Yang Liang Zhu Ming Liu Qiu-shi Xie Xian-ge Tang Ting-ting Yang Ya-qian Zhou Li Liu Xiao-dong Liu Center of Drug Metabolism and Pharmacokinetics School of PharmacyChina Pharmaceutical University

cinnamic acid and its analogues(pyragrel and ozagrel)undergo chain-shortened(β-oxidative)and reductive metabolism on acyl side *** 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 *** fitted total in vivo clearance values were further compared with the in vitro values predicted by the well-stirred *** showed that hepatic microsomal CYP450s did not catalyze β-oxidative or reductive metabolism of the three *** 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 occurred in both mitochondria and *** in mitochondria was ATP-,CoA-,and NAD(P)H-dependent and reversible,which was suppressed by enoyl reductase inhibitor *** in microsomes was ATP-,CoA-,and NADPH-dependent but little affected by *** plasma concentrations of β-oxidative metabolites and reductive metabolites were successfully fitted using the compartmental *** estimated total in vivo clearance values were consistent with those predicted from hepatocytes and organelles,implicating significance of in vitro *** 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.

关键词： antiplatelet drug cinnamic acid pyragrel ozagrel drug metabolism hepatocytes mitochondria microsomes pharmacokinetics in vitro-in vivo correlation

Design and Synthesis of 1,4-Dihydropyridine and cinnamic acid Esters and Their Antioxidant Properties

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Chemical Research in Chinese Universities 2016年第4期32卷 594-599页

作者： GAO Yang WANG Bowei GAO Shang ZHANG Ruhui YANG Chunying SUN Zheng LIU Zhihui School of Stomatology Capital Medical University Beijing 100050 P. R. China The Second Hospital of Jilin University Changchun 130021 P. R. China School of Stomatology Jilin University Changchun 130021 P. R. China

In this study, cinnamic acid derivatives with pyridine ring were synthesized via Hantzsch reaction in order to expand conjugation system and their antioxidant abilities were tested. According to the evaluation results of their antioxidant properties, compounds 2 and 3 have similar antioxidant activity to prevent DNA from ＊OH- and Cu2＋/GSH induced oxidation, demonstrating that 1,4-dihydropyridine and pyridine nucleus exhibit good resistance to oxidation while the substituents have little effect. In the meantime, the AAPH-induced oxidative DNA damage [AAPH=2,2＇-azobis（2-methylpropionamidine）dihydrochloride] and trapping ABTS＋＊ test show that N--H bond and large conjugation systems are the pivotal parts to improve the activities of antioxidant.

关键词： cinnamic acid 1,4-Dihydropyridine Free radical Oxidation Antioxidant DNA

cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2023年第2期14卷 4-21页

作者： Jin-Guang Jiang Qian Luo Shuang-Shuang Li Tian-Ying Tan Kai Xiong Tao Yang Tian-Bao Xiao Department of Colorectal and Anal Surgery Suqian Hospital of Traditional Chinese MedicineSuqian 223800Jiangsu ProvinceChina College of Clinical Medicine Guizhou University of Traditional Chinese MedicineGuiyang 550000Guizhou ProvinceChina Department of Colorectal and Anal Surgery The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang 550000Guizhou ProvinceChina

BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic *** acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal *** To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in *** Loperamide was applied to induce STC in *** treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit *** enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent ***-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal *** SCFAs in stool samples were quantitatively detected by gas chromatography-mass *** CA ameliorated the symptoms of STC and treated STC *** ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the *** addition,CA significantly increased the concentration of 5-HT and reduced *** significantly improved the diversity and abundance of the beneficial ***,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by *** changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and *** CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.

关键词： Slow transit constipation cinnamic acid Intestinal microbiome Short-chain fatty acids Intestinal motility

Strong Allelopathic Activities of Leaves and Cultured Cells of Spiraea thunbergiiAssayed by the Protoplast Co-Culture Method with Digital Image Analysis: Evaluation of Cis- and Trans-cinnamic acid as Allelochemicals

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American Journal of Plant Sciences 2021年第11期12卷 1673-1690页

作者： Sakae Suzuki Mari Kimura Rei Yasuda Naoya Wasano Yutaka Sasamoto Yoshiharu Fujii Hamako Sasamoto Faculty of Agriculture Tokyo University of Agriculture and Technology Fuchu Japan Institute of Biological Control Faculty of Agriculture Kyusyu University Fukuoka Japan

The inhibitory allelopathic activities of leaves and leaf-origin suspension cultured cells of Spiraea thunbergii, and putative allelochemicals, cis- and trans-cinnamic acid, were investigated by the protoplast co-culture method with digital image analysis (DIA-PP method) using lettuce as a recipient. The optimal conditions of 2,4-dichlorophenoxyacetic acid (2,4-D) and benzyladenine (BA) for the cell division of S. thunbergii protoplasts were first examined using 50 μL liquid MS basal medium containing 3% sucrose, and 0.8 M mannitol in a 96-well culture plate. The hormonal condition for co-culture, 1 μM 2,4-D plus 0.1 μM BA, which was optimal for lettuce protoplast growth, was sub-optimal for S. thunbergii protoplasts. Effects of co-culture on the three stages of lettuce protoplast growth, i.e., cell wall formation, cell division, and yellow pigment accumulation, were examined. Protoplasts of leaf and suspension cells of S. thunbergii strongly inhibited lettuce protoplast growth at the cell division stage (100% inhibition at 80 - 100 × 103 mL-1), but not so much at the other two stages. Both cis- and trans-cinnamic acid, showed the strongest inhibition at the cell wall formation stage, and 100% inhibition at the cell division stage at 100 μM. These results were compared with those obtained in a lettuce seedling growth test, using different allelopathic plants, and their allelochemicals were studied by the DIA-PP method.

关键词： Allelopathy cinnamic acid Protoplast Co-Culture Spiraea thunbergii

Study on Relationship between Metabolism of cinnamic acid and Cytochrome P450

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Study on Relationship between Metabolism of Cinnamic Acid an...

Determination of Plasma Concentration of cinnamic acid by High-Performance Liquid Chromatography and Its Pharmacokinetics in Rats after Oral Administration of Zi-Shen Pill

2008年中国药学会学术年会暨第八届中国药师周

作者： Li Wenlan1 2 YU Yingying1 2 Ji Yubin1 2 Ren Xiaolei 1 2 XU Dong1 2(1.Center of Research and Development on Life Sciences and Environmental Sciences Harbin University of Commerce Harbin 150076 China 2.Engineering Research Center of Natural Anticancer Drugs Ministry of Education Harbin University of Commerce Harbin 150076 China)

Objective:Studied the metabolism of cinnamic acid in homogenized liver of *** screen the CYP450 enzyme,which participate on metabolism of cinnamic *** then supply the evidence for rational ***:The content of cinnamic acid in homogenized liver was measured by the reversed phase *** effects of inductors and inhibitors on metabolism of cinnamic ***:The metabolic rate of β-NF group,the specific CYP1A inductor,was higher than control group ***,PB and DEX group,the main CYP2B and CYP3A inductor,respectively,had no significant difference among these and control *** more,α-NF,the CYP1A inhibitor,could inhibit metabolism of cinnamic acid ***:CYP1A is the major enzyme in metabolism of cinnamic *** medicine,which have induct and inhibit effects on CYP1A,may have interaction with cinnamic acid.

关键词： cinnamic acid Cytochrome P450 homogenized liver induct inhibit

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Journal of Chinese Pharmaceutical Sciences 2004年第2期13卷 130-133页

作者：戴荣华宋宗华鞠涛毕开顺沈阳药科大学药学院沈阳110016 沈阳科因生物技术有限公司沈阳110016

Aim To develop a simple and sensitive high-performance liquid chromatographicmethod for determination of plasma concentration of cinnamic acid and pharmacokinetic study in ratsafter a single oral dose of traditional Chinese medicinal preparation Zi-Shen pill. Method Plasmasamples were acidified with hydrochloric acid and extracted with ethyl acetate . cinnamic acid wasdetermined by HPLC using a G_(18) column. A mobile phase ofmethanbl-acetonitrile-water-triethyl-amine (7:22:73 = 0.2, V/V), with the pH adjusted to 4.0 withphosphoric acid, and with a UV detector set at 340 nm. Results The standard curve was linear overthe range of 1.92- 192.0 μg·mL^(-1). The LLOQ was 1.92 μg·mL^(-1) . The RSDs of within-day andbetween-day precision were < 8%. The mean recovery was 82.0% . Conclusion After validation, themethpd has been used to investigate the pharmacokinetic profiles of the traditional Chinesemedicinal preparation Zi-Shen pill.

关键词： cinnamic acid Zi-shen pill pharmacokinetics HPLC