DOCSLIB.ORG

Apocynin Dimer Derivatives Combining A-Lipoic Acid Protected

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Apocynin Dimer Derivatives Combining A-Lipoic Acid Protected ORIGINAL ARTICLE 74 Lingchao Zhu ISSN No 2230-7885 Apocynin Dimer Derivatives CODEN JPBSCT NLM Title J Pharm Biomed Sci Combining a-Lipoic Acid DOI https://doi.org/10.20936/jpbms/08/05/02 Protected RAW 264.7 Lingchao Zhu1, Jianghong Man1, Macrophage Cells from Zhijian Zhang1, Gaofang Wang1, Oxidative Injury Induced Jie Jiang1,2* by Lipopolysaccharide 1 College of Pharmacy, Jinan University, Guangzhou, China 2 Dongguan Institute of Jinan University, ABSTRACT Dongguan, China Apocynin, a classical nicotinamide adenine dinucleotide phosphate-oxidase, has been Address reprint requests to: widely studied in various oxidative stress related diseases. a-Lipoic acid (LA) is a natural *Jie Jiang, College of Pharmacy, strong antioxidant, which has been commonly used to ameliorate oxidative injury in cell and Jinan University, Guangzhou animal models. To enhance the anti-oxidative activity, three new apocynin dimer derivatives 510632, China; Dongguan Institute combining LA, JJA-D5, D6 and D7, was designed and synthesized on the basic structure of of Jinan University, Dongguan apocynin dimer analogue JJA-D0. It has been generally believed that apocynin and its deriv- 523808, China atives exerted anti-oxidative action through inhibiting NADPH oxidase. Preliminary docking E-mail: [email protected] simulation of the three derivatives with 1K4U subsection of human neutrophil NADPH oxi- Article citation: Zhu L, Man J, Zhang dase system was performed to predict the binding capacity using GOLD 5.0.1 software. The Z, Wang G Jiang J. Apocynin dimer derivatives got higher binding score than apocynin, indicating stronger interaction between derivatives combining α-lipoic acid the derivative and NADPH oxidase, and more potential anti-oxidative action was expected. protected RAW 264.7 macrophage The anti- oxidative protection of JJA-D5, D6 and D7 was investigated in RAW 264.7 mac- cells from oxidative injury induced by rophage cells treated with lipopolysaccharide. The results demonstrated that apocynin and lipopolysaccharide. J Pharm Biomed Sci the three derivatives increased cell viability at 10 and 100 μM when compared with model 2018;08(05):74−78. group, the protective effect of JJA-D5, D6 and D7 was generally higher than apocynin at 10 Available at www.jpbms.info and 100 μM, and some groups had significant difference (P < 0.05). It indicated that com- Statement of originality of work: bining LA may obtained apocynin dimer derivatives of potential anti-oxidative protection. The manuscript has been read and approved by all the authors, the requirements for KEYWORDS apocynindimer derivative, a-lipoic acid, anti-oxidative protection authorship have been met, and that each author believes that the manuscript represents honest and original work. INTRODUCTION Source of funding: This research was supported by project of National Natural Oxidative stress was found to be involved in development of a variety of Science Foundation of China (81441128) severe diseases such as diabetes, cancer, neurodegenrative diseases, asthma, and Science and Technology Program of cardiocerebral vascular diseases1–7. More and more attention was paid to the Guangzhou, China (201704020198). studies of oxidative stress injury and treatment of antioxidant. Under most Competing interest/Conflict of interest: of the oxidative stress situation, excessive reactive oxygen species (ROS) is The author(s) have no competing interests produced, which results in tissue injury. NADPH oxidase is an important for financial support, publication of this 8 research, patents and royalties through this enzyme family regulating the production of ROS . Therefore, NADPH oxi- collaborative research. All authors were equally dase inhibition has been considered as a promising target for developing involved in discussed research work. There new therapeutic drugs for oxidative stress related diseases. is no financial conflict with the subject matter Apocynin was widely used as a classical NADPH oxidase inhibitor9–11. discussed in the manuscript. The mechanism is believed to prevent translocation of cystolic subunits of Disclaimer: Any views expressed in this paper NADPH oxidase to membrane or reduce the expression of key subunits, thus are those of the authors and do not reflect the to inhibit the activation of NADPH oxidase and reduce the excessive produc- official policy orposition of the Department of tion of ROS. It was reported that apocynin play its role of NADPH oxidase Defense. inhibition after it was converted into active dimer derivative, diapocynin, by myeloperoxidase in phagocytes12. In our previous studies, an apocynin dimer analogue, JJA-D0 was synthesized. JJA-D0 demonstrated better effi- cacy than apocynin in anti-oxidative activity and NADPH oxidase inhibi- tion13 in RAW 264.7 macrophage cells. The results indicated that JJA-D0 was a hopeful leading compound. a-Lipoic acid (LA), a naturally occurring co-factor for the mitochon- drial enzymes pyruvate dehydrogenase and a-ketoglutarate dehydrogenase, Copyright © 2018 J Pharm Biomed Sci | Vol. 08 No. 05 | 74–78 Received Date: 18 March 2018 – Accepted Date: 15 May 2018 – Published Online: 24 May 2018 Apocynin dimer derivatives combining a-lipoic acid 75 2230-7885 JPBSCT is one of the strongest natural antioxidants. LA, both Preliminary investigation of docking of liposoluble and hydrosoluble, can reach anywhere of apocynin dimer derivatives combining LA J Pharm Biomed Sci cell to exert biological function of eliminating free rad- with1K4U subsection of NADPH oxidase https://doi.org/10.20936/jpbms/08/05/02 icals that accelerate aging and cause diseases. It plays an NADPH oxidase is the crucial enzyme modulating the important role in many metabolism process by clearing production of ROS, p67phox and p47phox are two import- ROS to maintain the redox balance and is an indispen- ant cystolic subunits in NADPH oxidase activation. The sable antioxidant in human body14,15. In clinic use, LA 1K4U subsection of human neutrophil NADPH oxidase was applied in the treatment of oxidative stress related system consists of parts of the C-terminal SH3 domain diseases, such as diabetes and its complication, neurode- of p67phox complexed with the C-terminal tail region of generative diseases16–18. Using LA as a combining entity p47phox20. Apocynin and its derivatives were believed to in chemical structural modification may further pro- improve oxidative stress by inhibiting the activation of mote the anti-oxidative action of compound. NADPH oxidase. Herein, after compound design, dock- To obtain candidate chemicals of more potential ing of apocynin and JJA-D0 derivatives combining LA anti-oxidative efficacy, three new apocynin dimer deriv- with 1K4U subsection was performed to predict the atives, JJA-D5, D6 and D7, was designed and yielded by efficacy using GOLD 5.0.1 program (CCDC), and the combining LA with apocynin dimer analogue JJA-D0 in binding action was scored using Goldscore function our previous work19 (Fig. 1). In this work, docking of JJA- available in GOLD 5.0.1 program. D5, D6 and D7 with 1K4U subsection of human neutrophil NADPH oxidase system was reported, and the anti-oxida- tive activity of the derivative was confirmed in RAW 264.7 Cell culture macrophage cells treated with lipopolysaccharide (LPS). The RAW 264.7 macrophage cells were purchased from the Type Culture Collection of the Chinese Academy of MATERIALS AND METHODS Sciences, Shanghai, China. Cells were cultured in DMEM Materials containing 10% FBS, 100 units/mL penicillin and 100 mg/mL streptomycin. The cells were incubated in an Compounds JJA-D0, JJA-D5, D5 and D7 were synthe- atmosphere of air containing 5% CO2 at 37°C. sized in our laboratory as previously reported19. All reagents were obtained from commercial suppliers Anti-oxidative protection of apocynin dimer as follows. Apocynin was purchased from Beijing J&K derivatives combining LA in RAW 264.7 Scientific Co., Ltd. (China). Dulbecco’s Modified Eagle macrophage cells medium (DMEM) and fetal bovine serum (FBS) were purchased from GIBCO Inc. (USA). 3-(4,5-dimethyl- The anti-oxidative protection of apocynin dimer deri- thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), vatives combining LA, JJA-D5, D6 and D7 were inves- DMSO and LPS (Escherichia coli 055:B5) were purchased tigated in RAW 264.7 macrophage cells using MTT from Sigma-Aldrich, Inc. (USA). method. Fig. 1 Structure of JJA-D0, D5, D6 and D7. J Pharm Biomed Sci | Vol. 08 No. 05 | 74–78 Received Date: 18 March 2018 – Accepted Date: 15 May 2018 – Published Online: 24 May 2018 76 Lingchao Zhu The concentration of LPS for treating RAW 264.7 Statistical analysis was screened first. The RAW 264.7 macrophage cells were seeded (5.0 × 105/well, 100 μL) in 96-well The experimental results were represented as mean plates and then cultured at 37°C for 24 h under 5% ± standard deviation. Statistical differences between the means of different groups were compared using student CO2. After removing the supernatant, 100 μL of DMEM without FBS and containing LPS of 25, 50, 100, 200, t-test (GraphPad Prism 5.0 software). P < 0.05 was con- 400 and 800 μg/mL was added for another 24 h cul- sidered to be statistically significant. ture. MTT was then added into each well to make a final concentration of 0.5 mg/mL. After incubation for RESULTS AND DISCUSSION 4 h, the supernatant was removed and DMSO (150 μL) was added. The absorbance of each well was recorded Preliminary investigation of docking of at 570 nm using a Synergy HT Multi-Detection apocynin dimer derivatives combining LA with Microplate Reader (BioTek, USA), and the cell viabil- 1K4U subsection of NADPH oxidase ity was calculated. Normal control group was set and Docking is generally used to stimulate the binding of the cells were cultured in DMEM of same volume. Each active ingredient candidates with target proteins, for group had six replicate wells. example, receptors and enzymes. The results are com- To investigate the protective activity of JJA-D5, D6 monly used to predict the efficacy of the chemicals and D7 on oxidative injury of cells, the RAW 264.7 after compound design.
Load more

Recommended publications
  • (12) United States Patent (10) Patent No.: US 6,492,429 B1 Graus Et Al
    USOO6492429B1 (12) United States Patent (10) Patent No.: US 6,492,429 B1 Graus et al. (45) Date of Patent: Dec. 10, 2002 (54) COMPOSITION FOR THE TREATMENT OF 5,401.777 A 3/1995 Ammon et al. OSTEOARTHRITIS 5,494.668 A 2/1996 Patwardhan 5,629,351 A 5/1997 Taneja et al. (75) Inventors: Ivo Maria Franciscus Graus, Wg Ede 5,872,124. A * 2/1999 Koprowski et al. ......... 514/261 (NL); Hobbe Friso Smit, As Utrecht 5,888,514 A * 3/1999 Weisman ................. 424/195.1 (NL) FOREIGN PATENT DOCUMENTS (73) Assignee: N.V. Nutricia, Zoetermeer (NL) WO 95 22323 8/1995 WO 97 O7796 3/1997 (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. Balch et al. Prescription for Nutritional Healing; Avery Publishing 2nd Ed. pp. 138–144, Oct. 1997.* (21) Appl. No.: 09/662,123 Lafeber et al., “Apocynin, a plant-derived, cartilage-Saving drug, might be useful in the treatment of rheumatoid (22) Filed: Sep. 14, 2000 arthritis", Rheumatology, (1999), pp. 1088–1093, vol. 38, O O British Society for Rheumatology. Related U.S. Application Data * cited by examiner (63) Continuation of application No. 09/613,562, filed on Jul. 10, 2000. Primary Examiner-Christopher R. Tate 7 ASSistant Examiner Patricia A Patten (51) Int. Cl." ......................... A01N 35/00; AO1N 65/00 (74) Attorney, Agent, or Firm-Browdy and Neimark, (52) U.S. Cl. ........................................ 514/688; 424/725 PL.L.C. (58) Field of Search ..........................
    [Show full text]
  • Table S1. GC-MS Analysis of the Chloroform Soluble Fraction of Chestnut Wood Extractives
    Table S1. GC-MS analysis of the chloroform soluble fraction of chestnut wood extractives. Untreated THM (chloroform soluble (chloroform soluble fraction) fraction) Extraction technique Extraction techniques a a b W/POM ASE E/T Water ASE E/T Water E/T/M c r.t. Area [%] Area [%] Compound KI [min] Furan 4.04 492 0.23 2-Furancarboxylic Acid 4.28 836 0.36 0.36 0.12 2.18 Benzaldehyde 4.31 961 0.29 1.34 1.49 Phenol 4.47 967 0.05 0.05 Methyl 2-Furancarboxylate 5.17 985 0.10 Benzyl Alcohol 5.21 1007 0.34 0.59 Levulinic Acid 5.34 1063 0.10 0.10 9.91 p-Cresol 5.61 1077 0.02 0.07 PhenylmethylFormate 5.66 1082 0.13 Nonanal 5.80 1105 0.08 0.04 2-Methoxyphenol 5.82 1106 5.88 Methyl Benzoate 5.88 1111 0.09 0.10 Benzaldehyde Dimethyl Acetal 6.03 1200 0.11 Maltol 6.05 1140 0.11 0.11 PhenylmethylAcetate 6.54 1162 0.10 Creosol 6.84 1203 0.06 5-Hydroxymethylfurfural 7.15 1224 3.60 0.90 NonanoicAcid 7.40 1272 0.05 3.60 2,3-Dihydro-3,5-Dihydroxy-6- Methyl-4H- 7.78 1290 Pyran-4-One 5-Acetoxymethyl-2-Furaldehyde 7.94 1304 0.27 2,6-Decadienal 8.04 1317 0.04 2-Methoxy-4-Vinylphenol 8.06 1320 0.11 0.20 2,6-Dimetyhoxyphenol 8.14 1357 0.14 0.17 0.17 0.17 4.16 DecanoicAcid 8.16 1370 0.07 0.13 2-Methoxy-4-Propylphenol 8.18 1382 0.19 0.34 0.80 Eugenol 8.20 1389 0.13 0.13 0.15 (e)-2-Tetradecene 8.37 1421 0.66 2.43 0.37 2,2'-Dimethylbiphenyl 8.44 1425 (e)-Cinnamic Acid 8.67 1430 0.05 Methyl 2- 8.78 1433 0.18 Phenylcyclopropancarboxylate 1-Methyl-3-(1-Methyl-2- 8.80 1435 0.38 Propenyl)Benzene 2,3-Dihydro-5,6-Dimethyl-1H-Indene 8.82 1438 0.09 Vanillin 8.95 1440 0.34 0.16
    [Show full text]
  • BOOK of ABSTRACTS Twelfth International Undergraduate Summer Research Symposium Thursday, August 1, 2019
    BOOK OF ABSTRACTS Twelfth International Undergraduate Summer Research Symposium Thursday, August 1, 2019 Copyright © 2019 by New Jersey Institute of Technology (NJIT). All rights reserved. New Jersey Institute of Technology University Heights Newark, NJ 07102-1982 Joel S. Bloom President August 1, 2019 Welcome all – students, faculty, industry mentors, sponsors and friends of the university – to NJIT’s Twelfth International Undergraduate Summer Research Symposium. It is exciting to see so many ingenious inventions, and the bright, enterprising minds behind them, gathered in one place. That some of you have joined our innovation hub from as far away as India is a testament to the power of collaboration in the service of progress – not just in our own state or country, but across the globe. I want to especially thank the Provost’s office for making undergraduate research a high priority on our campus, the students’ advisers for their ideas and precious time over the summer, and our many sponsors for their generosity and commitment to helping forge the problem-solvers of tomorrow - today. And to the more than 130 of you exhibiting your work at the symposium, congratulations! By thinking creatively, following through with diligence and tenacity – and even retooling when the evidence requires it – you have embraced the rigors of professional science. You make us proud, and we look forward to following your successes in the years to come. Sincerely, Joel S. Bloom President Fadi P. Deek Provost and Senior Executive Vice President August 1, 2019 A message from the Provost: Welcome to NJIT’s Twelfth International Undergraduate Summer Research Symposium.
    [Show full text]
  • Efeito Dos Metóxi-Catecóis Apocinina, Curcumina E Vanilina
    i RESUMO O tamoxifeno (TAM) é um agente sintético, anti-estrogênico e não esteroidal, que comumente é prescrito no tratamento de pacientes com câncer de mama. Vários efeitos colaterais estão associados ao seu uso, como alterações vaginais, irregularidade menstrual, formação de pólipos no endométrio, cistos ovarianos, tromboembolismo, hepatocarcinoma, entre outros. Alguns produtos naturais são uma excelente estratégia na busca de novas drogas antitumorais, devido ao conhecimento popular de seu uso. A associacão de produtos naturais às drogas quimioterápicas clássicas tem mostrado um efeito sinérgico de grande interesse para a terapia antitumoral. A atividade citotóxica da curcumina é bem estabelecida em vários tipos de linhagens de células tumorais e tem sido amplamente estudada. A vanilina também tem mostrado atividade sobre as células tumorais devido aos seus efeitos citotóxicos e citostáticos. Já os efeitos da apocinina são devidos, principalmente, à sua eficiente inibição do complexo NADPH-oxidase, e consequentemente, de espécies reativas de oxigênio. O objetivo deste trabalho foi avaliar o efeito dos metóxi-catecóis apocinina, curcumina e vanilina sobre a citotoxicidade em células normais, hemácias e leucócitos polimorfonucleares, e em células de leucemia mielóide crônica humana (K562) exercida pelo TAM, como também a atividade antioxidante destes compostos. A citotoxidade foi analisada em hemácias através da liberação de hemoglobina e K+, e a curcumina foi o único composto que diminuiu a citotoxicidade do TAM sobre essas células.
    [Show full text]
  • Apocynin Exerts Dose-Dependent Cardioprotective Effects by Attenuating Reactive Oxygen Species in Ischemia/Reperfusion
    maco har log P y: r O la Chen et al., Cardiovasc Pharm Open Access 2016, 5:2 u p c e n s a A DOI: 10.4176/2329-6607.1000176 v c o c i e d r s a s Open Access C Cardiovascular Pharmacology: ISSN: 2329-6607 Research Article OpenOpen Access Access Apocynin Exerts Dose-Dependent Cardioprotective Effects by Attenuating Reactive Oxygen Species in Ischemia/Reperfusion Qian Chen, Woodworth Parker C, Issachar Devine, Regina Ondrasik, Tsion Habtamu, Kyle D Bartol, Brendan Casey, Harsh Patel, William Chau, Tarah Kuhn, Robert Barsotti and Lindon Young* Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, USA Abstract Ischemia/reperfusion results in cardiac contractile dysfunction and cell death partly due to increased reactive oxygen species and decreased endothelial-derived nitric oxide bioavailability. NADPH oxidase normally produces reactive oxygen species to facilitate cell signalling and differentiation; however, excessive release of such species following ischemia exacerbates cell death. Thus, administration of an NADPH oxidase inhibitor, apocynin, may preserve cardiac function and reduce infarct size following ischemia. Apocynin dose-dependently (40 μM, 400 μM and 1 mM) attenuated leukocyte superoxide release by 87 ± 7%. Apocynin was also given to isolated perfused hearts after ischemia, with infarct size decreasing to 39 ± 7% (40 μM), 28 ± 4% (400 μM; p < 0.01) and 29 ± 6% (1 mM; p < 0.01), versus the control’s 46 ± 2%. This decrease correlated with improved final post-reperfusion left ventricular end-diastolic pressure, which decreased from 60 ± 5% in control hearts to 56 ± 5% (40 µM), 43 ± 4% (400 μM; p < 0.01) and 48 ± 5% (1 mM; p < 0.05), compared to baseline.
    [Show full text]
  • Chapter 6: Effects of Apocynin and Analogs on the Cytokine
    Chapter 6 Effects of apocynin and analogs on the cytokine production by mononuclear cells E. van den Worm#, M.E. Vianen*, C.J. Beukelman#, A.J.J. van den Berg#, R.P. Labadie#, H. van Dijk#,†, F.P.J.G. Lafeber*and J.W.J. Bijlsma*. # Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Faculty of Pharmacy, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. * Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, PO BOX 85500, 3508 GA Utrecht, The Netherlands. † Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, University Medical Center Utrecht, AZU G04.614, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. - Je moet een vraag wel stellen zoals die gesteld hoort te worden - (Johan Cruijff, 1993) Chapter 6 Abstract Apocynin is a promising, plant-derived, nonsteroidal, anti-inflammatory compound that has been studied in different in vitro systems as well as in in vivo models for chronic inflammatory diseases. So far, apocynin is known as a specific inhibitor of NADPH-oxidase activity in stimulated neutrophils. This paper is dealing with possible other aspects of apocynin action, including inhibition of cytokine (IL-1, TNFα, IFNγ) production by cultured monocytes/macrophages and T cells, as well as inhibition of the proliferative response of T cells. Our findings implicate that not only apocynin itself, but also combinations of apocynin with one or more of its major in vivo metabolites may be involved in its net in vivo effect. This putative synergistic activity will be subject of further in vitro studies. 90 Effects of apocynin on cytokine production Introduction Apocynin has proven its potential value in the treatment of several experimental inflammatory diseases such as colitis (1), atherosclerosis (2), and rheumatoid arthritis (3).
    [Show full text]
  • Effects of Apocynin on Oxidative Stress and Expression of Apoptosis-Related Genes in Testes of Diabetic Rats
    MOLECULAR MEDICINE REPORTS 7: 47-52, 2013 Effects of apocynin on oxidative stress and expression of apoptosis-related genes in testes of diabetic rats MINGCHAO LI, ZHUO LIU, LI ZHUAN, TAO WANG, SHUIMING GUO, SHAOGANG WANG, JIHONG LIU and ZHANGQUN YE Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, P.R. China Received March 15, 2012; Accepted July 13, 2012 DOI: 10.3892/mmr.2012.1132 Abstract. Reactive oxygen species (ROS) are important in the associated with male reproductive dysfunction. Compared development of diabetic testicular dysfunction. Overproduction with non-diabetic individuals, male diabetic patients showed of ROS promotes the process of apoptosis, which shows that an increased incidence of hypogonadism and infertility (2). there is a crosstalk between oxidative stress and apoptosis. Recent Oxidative stress damage is regarded as the most influential harm- research has suggested that NADPH oxidase is the main source of causing factor affecting testicular function (2-4). The increase ROS. In this study, we investigated whether the NADPH oxidase in reactive oxygen species (ROS) causes non-specific changes inhibitor, apocynin, can improve diabetes-induced testicular in nucleic acid, protein and phospholipid levels, resulting in dysfunction by suppressing oxidative stress. The streptozocin DNA, RNA and protein damage and alterations in antioxidant (STZ)-induced diabetic rats were administered apocynin, and the enzyme levels, which lead to cellular and tissue damage (1). mRNA and protein expression of Bax, Bcl-2, p47phox and p67phox Diabetes inhibits reproductive activity in experimental animals; was examined by real-time PCR (RT-PCR) and western blot for instance, the testicular function of diabetic rats is impaired, analysis.
    [Show full text]
  • Apocynin: a Lead-Compound for New Respiratory Burst Inhibitors ?
    Chapter 3 Apocynin: a lead-compound for new respiratory burst inhibitors ? E. van den Worm*, C. J. Beukelman*, A.J.J. van den Berg*, B.H. Kroes*, D. van der Wal*, H. van Dijk#* and R.P. Labadie*. * Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Faculty of Pharmacy, Utrecht University, PO Box 80082, 3508 TB, Utrecht, The Netherlands # Eijkman-Winkler Institute for Microbiology, Infectious diseases and Inflammation, University Medical Center Utrecht, AZU G04.614, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands - Vaak wordt een uitslag verward met de situatie - (Johan Cruijff, 1996) Chapter 3 Abstract Due to their multiple side effects, the use of steroidal drugs is becoming more and more controversial, resulting in an increasing need for new and safer anti- inflammatory agents. In the inflammatory process, reactive oxygen species (ROS) produced by phagocytic cells are considered to play an important role. We showed that apocynin (4'-hydroxy-3'-methoxy-acetophenone or acetovanillone), a non-toxic compound isolated from the medicinal plant Picrorhiza kurroa, selectively inhibits ROS production by activated human neutrophils. Apocynin proved to be effective in the experimental treatment of several inflammatory diseases like arthritis, colitis and atherosclerosis. These features suggest that apocynin could be a prototype of a novel series of non-steroidal anti-inflammatory drugs (NSAIDs). So far, apocynin is mainly used in vitro to block NADPH oxidase-dependent ROS generation by neutrophils. In order to get a better insight in what chemical features play a role in the anti-inflammatory effects of apocynin, a structure-activity relationship study with apocynin analogs was performed.
    [Show full text]
  • Apocynin Ameliorates Pressure Overload-Induced Cardiac Remodeling by Inhibiting Oxidative Stress and Apoptosis
    Physiol. Res. 66: 741-752, 2017 Apocynin Ameliorates Pressure Overload-Induced Cardiac Remodeling by Inhibiting Oxidative Stress and Apoptosis J.-J. LIU1*, Y. LU2*, N.-N. PING3, X. LI1, Y.-X. LIN1, C.-F. LI4 * These authors contributed equally to this work as first authors. 1Department of Physiology and Pathophysiology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi Province, China, 2Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi Province, China, 3Shaanxi Blood Center, Xi'an, Shaanxi Province, China, 4Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi Province, China Received November 10, 2015 Accepted June 21, 2016 On-line October 26, 2016 Summary Key words Oxidative stress plays an important role in pressure overload- Apocynin • Cardiac remodeling • Angiotension II • NADPH induced cardiac remodeling. The purpose of this study was to oxidase • Reactive oxygen species • Apoptosis. determine whether apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, attenuates pressure Corresponding author overload-induced cardiac remodeling in rats. After abdominal C.-F. Li, Department of Obstetrics and Gynecology, The First aorta constriction, the surviving rats were randomly divided into Affiliated Hospital of Xi'an Jiaotong University Health Science four groups: sham group, abdominal aorta constriction group, Center, Xi'an 710061, Shaanxi Province, China. Fax: +86 29 apocynin group, captopril group. Left ventricular pathological 82657497. E-mail: [email protected] changes were studied using Masson’s trichrome staining. Metalloproteinase-2 (MMP-2) levels in the left ventricle were Introduction analyzed by western blot and gelatin zymography.
    [Show full text]
  • Green, Enzymatic Syntheses of Divanillin and Diapocynin for the Organic, Biochemistry, Or Advanced General Chemistry Laboratory
    In the Laboratory edited by Mary M. Kirchhoff American Chemical Society Washington, DC 20036 Green, Enzymatic Syntheses of Divanillin and Diapocynin for the Organic, Biochemistry, or Advanced General Chemistry Laboratory Rachel T. Nishimura, Chiara H. Giammanco, and David A. Vosburg* Department of Chemistry, Harvey Mudd College, Claremont, California 91711 *[email protected] Vanillin and apocynin are versatile natural products and Scheme 1. Oxidative Dimerization of Vanillin and Apocynin by Horse- have been featured in various laboratory experiments for general radish Peroxidase or organic laboratory courses in this Journal (1-5). However, few of these procedures would be considered green (6-8). Here we describe a green, enzymatic preparation of the antioxidants divanillin and diapocynin that avoids the use of toxic reagents or inorganic salts (Scheme 1). Divanillin enhances the flavor of vanillin and can be formed by peroxidases during the curing process of vanilla beans (9). Diapocynin may have an anti- inflammatory role, as it is a potent superoxide scavenger and is generated from apocynin by stimulated human polymorpho- nuclear neutrophils (5, 10). The horseradish peroxidase-cata- lyzed (11) dimerization of vanillin or apocynin could be readily incorporated into an advanced general chemistry, organic, or biochemistry laboratory course. water, 2.2 mL, 0.022 mmol) to lower the pH to 4. At 40 °Cor below, add horseradish peroxidase (Type I, 9.0 mg, 1000 units Experiment Objectives of activity) and then hydrogen peroxide (3% in water, 7.5 mL, 6.6 mmol) to the solution while stirring. Allow the reaction to If this experiment is used in advanced general chemistry, stir for 5 min and then filter the tan precipitate using a Buchner students should funnel, rinsing the solids with deionized water.
    [Show full text]
  • Neuroprotective Effect of Apocynin Nitrone in Oxygen Glucose Deprivation-Treated SH-SY5Y Cells and Rats with Ischemic Stroke
    Liu et al Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1681-1689 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v15i8.13 Original Research Article Neuroprotective effect of apocynin nitrone in oxygen glucose deprivation-treated SH-SY5Y cells and rats with ischemic stroke Wu Liu1, Guo-Shuai Feng1,2, Yang Ou1, Jun Xu3, Zai-Jun Zhang1, Gao-Xiao Zhang1, Ye-Wei Sun1, Sha Li4 and Jie Jiang1,5* 1Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, 2Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, 3College of Pharmacy, Jinan University, Guangzhou 510632, 4Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou 510632, 5Dongguan Institute of Jinan University, Dong Guan 523808, China *For correspondence: Email: [email protected]; Tel: +86-20-8522-2156; Fax: +86-20-8522-4766 Received: 12 December 2015 Revised accepted: 2 July 2016 Abstract Purpose: To investigate the neuroprotective potential of apocynin nitrone (AN-1), a nitrone analogue of apocynin, in rat brain tissue as a novel candidate for ischemic stroke treatment. Methods: In vitro neuroprotection of AN-1 was studied in SH-SY5Y cells treated with oxygen glucose deprivation (OGD). Cell viability was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide (MTT) assay, and intracellular reactive oxygen species (ROS) level was investigated using flow cytometry. The protection of AN-1 in cerebral ischemia-reperfusion (I/R) rats was evaluated by cerebral infarct area and neurological deficit score.
    [Show full text]
  • Effects of Apocynin on Heart Muscle Oxidative Stress of Rats with Experimental Diabetes: Implications for Mitochondria
    antioxidants Article Effects of Apocynin on Heart Muscle Oxidative Stress of Rats with Experimental Diabetes: Implications for Mitochondria Estefanía Bravo-Sánchez 1,† , Donovan Peña-Montes 1,†, Sarai Sánchez-Duarte 1, Alfredo Saavedra-Molina 1, Elizabeth Sánchez-Duarte 2,* and Rocío Montoya-Pérez 1,* 1 Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Francisco J. Múgica S/N, Col. Felicitas del Río, Morelia 58030, Michoacán, Mexico; [email protected] (E.B.-S.); [email protected] (D.P.-M.); [email protected] (S.S.-D.); [email protected] (A.S.-M.) 2 Departamento de Ciencias Aplicadas al Trabajo, Universidad de Guanajuato Campus León, Eugenio Garza Sada 572, Lomas del Campestre Sección 2, León 37150, Guanajuato, Mexico * Correspondence: [email protected] (E.S.-D.); [email protected] (R.M.-P.); Tel.: +521-477-2670-4900 (ext. 4833) (E.S.-D.); +521-(443)-322-3500 (ext. 4217) (R.M.-P.) † These authors contributed in the same way and amount. Abstract: Diabetes mellitus (DM) constitutes one of the public health problems today. It is character- ized by hyperglycemia through a defect in the β-cells function and/or decreased insulin sensitivity. Apocynin has been tasted acting directly as an NADPH oxidase inhibitor and reactive oxygen species (ROS) scavenger, exhibiting beneficial effects against diabetic complications. Hence, the present study’s goal was to dissect the possible mechanisms by which apocynin could mediate its cardio- Citation: Bravo-Sánchez, E.; protective effect against DM-induced oxidative stress. Male Wistar rats were assigned into 4 groups: Peña-Montes, D.; Sánchez-Duarte, S.; Control (C), control + apocynin (C+A), diabetes (D), diabetes + apocynin (D+A).
    [Show full text]