DocumentsDate added
Original article
Zheng Liu, Haiyun Chen, Fangcheng Luo, Baojian Guo, Xiaoyong Jing, Zaijun Zhang, Yewei Sun, Yuqiang Wang
Affiliation:
Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632 China
The name of the department(s) and institution(s) to which the work should be attributed:
Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China
Address reprint requests to
* Pei Yu, PhD,
Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632 China or at pennypeiyu@163.com. Tel.: +8620-8522-5030; Fax: +8620-8522-5030
Article citation:
Zheng L, Haiyun C, Fangcheng L, Baojian G, Xiaoyong J, Zaijun Z et al. Probe to Bifunctional Memantine Derivatives for Treatment of Alzheimer's Disease. J Pharm Biomed Sci. 2015; 05(04):276-290. Available at www.jpbms.info
ABSTRACT:
Alzheimer’ disease (AD) is a neurodegenerative disease commonly occurring in older people. Two types of drugs, the acetylcholinesterase (AChE) inhibitor and the N-methyl-D-aspartate receptor (NMDAR) antagonist, were approved to treat AD by FDA. Of them, memantine was the only one of NMDAR antagonist. Previous studies had revealed that the carbamate grouphad a better AChE inhibitor activity. Herein, a series of new memantine derivatives with a carbamate group were designed and synthesized. They were expected to haveboth NMDAR antagonism and AChE inhibition. However, the neuroprotective effect of these new compounds against the glutamate-induced neurotoxicity was not as effective as memantine. The AChE inhibition of them wasalso lower than tacrine. The combine of memantine moiety and carbamate group attenuated the activities of the two functional groups. It may be caused by the changes of the spatial structures after combination. The introduction of large spatial structures makes the functional groups difficult to orientate to the active site.
KEYWORDS: Acetylcholinesterase (AChE) inhibitor; Alzheimer’s disease (AD); Memantine derivatives; Multi-functional drugs; NMDAR antagonist..
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
ACKNOWLEDGEMENTS
This work was supported partially by The Natural Science Foundation of Guangdong Province (2014A030320174).
REFRENCES
1.Prince M, Bryce R, Ferri C. World Alzheimer Report 2011: The benefits of early diagnosis and intervention: Alzheimer's Disease International; 2011.
2.Association As. 2012 Alzheimer’s disease facts and figures. Alzheimer's & Dementia. 2012;8(2):131-68.
3.Alonso AC, Li B, Grundke-Iqbal I, Iqbal K. Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies. Curr Alzheimer Res. 2008;5(4):375-84.
4.Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends pharmaco sci. 1991;12:383-8.
5.Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends in neurosciences. 1999;22(6):273-80.
6.Pimentel C, Batista NL, Rodrigues PC, Menezes RA. Oxidative stress in Alzheimer's and Parkinson's diseases: insights from the yeast Saccharomyces cerevisiae. Oxidative medicine and cellular longevity. 2012;2012.
7.Francis PT. Glutamatergic systems in Alzheimer's disease. International journal of geriatric psychiatry. 2003;18(S1):S15-S21.
8.Maragos WF, Greenamyre JT, Penney JB, Young AB. Glutamate dysfunction in Alzheimer's disease: an hypothesis. Trends in neurosciences. 1987;10(2):65-8.
9.Tsai VW, Scott HL, Lewis RJ, Dodd PR. The role of group I metabotropic glutamate receptors in neuronal excitotoxicity in Alzheimer’s disease. Neurotoxicity research. 2005;7(1-2):125-41.
10.Wenk GL. Neuropathologic changes in Alzheimer's disease: potential targets for treatment. Journal of Clinical Psychiatry. 2006;67:3.
11.Johnson JW, Kotermanski SE. Mechanism of action of memantine. Current opinion in pharmacology. 2006;6(1):61-7.
12.Wilkinson D. A review of the effects of memantine on clinical progression in Alzheimer's disease. International journal of geriatric psychiatry. 2012;27(8):769-76.
13.Witt A, Macdonald N, Kirkpatrick P. Memantine hydrochloride. Nature Reviews Drug Discovery. 2004;3(2):109-10.
14.Chen H, Wang Y, Rayudu P, Edgecomb P, Neill J, Segal M, et al. Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience. 1998;86(4):1121-32.
15.Chen HS, Lipton SA. The chemical biology of clinically tolerated NMDA receptor antagonists. Journal of neurochemistry. 2006;97(6):1611-26.
16.Standridge JB. Pharmacotherapeutic approaches to the treatment of Alzheimer's disease. Clinical therapeutics. 2004;26(5):615-30.
17.Mahlberg R, Walther S, Eichmann U, Tracik F, Kunz D. Effects of rivastigmine on actigraphically monitored motor activity in severe agitation related to Alzheimer's disease: a placebo-controlled pilot study. Archives of gerontology and geriatrics. 2007;45(1):19-26.
18.Sterling J, Herzig Y, Goren T, Finkelstein N, Lerner D, Goldenberg W, et al. Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease. Journal of medicinal chemistry. 2002;45(24):5260-79.
19.Farrimond LE, Roberts E, McShane R. Memantine and cholinesterase inhibitor combination therapy for Alzheimer's disease: a systematic review. BMJ open. 2012;2(3):e000917.
20.Marutani E, Kosugi S, Tokuda K, Khatri A, Nguyen R, Atochin DN, et al. A novel hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonist prevents ischemic neuronal death. Journal of Biological Chemistry. 2012;287(38):32124-35.
21.Simoni E, Daniele S, Bottegoni G, Pizzirani D, Trincavelli ML, Goldoni L, et al. Combining galantamine and memantine in multitargeted, new chemical entities potentially useful in Alzheimer’s disease. Journal of medicinal chemistry. 2012;55(22):9708-21. 22.Sozio P, Cerasa LS, Laserra S, Cacciatore I, Cornacchia C, Di Filippo ES, et al. Memantine-sulfur containing antioxidant conjugates as potential prodrugs to improve the treatment of Alzheimer’s disease. European Journal of Pharmaceutical Sciences. 2013;49(2):187-98.
23.Youdim MB. Why Do We Need Multifunctional Neuroprotective and Neurorestorative Drugs for Parkinson’s and Alzheimer’s Disorders? Rambam Maimonides Medical Journal. 2010;1(2).
24.Cui W, Zhang Z, Li W, Hu S, Mak S, Zhang H, et al. The anti‐cancer agent SU4312 unexpectedly protects against MPP+‐induced neurotoxicity via selective and direct inhibition of neuronal NOS. British journal of pharmacology. 2013;168(5):1201-14.
25.Fu H, Li W, Lao Y, Luo J, Lee NT, Kan KK, et al. Bis (7)‐tacrine attenuates β amyloid‐induced neuronal apoptosis by regulating L‐type calcium channels. Journal of neurochemistry. 2006;98(5):1400-10.
26. Ellman GL, Courtney KD, Andres jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 1961;7(2):88-95.
27.Sanner MF. Python: a programming language for software integration and development. Journal of molecular graphics & modelling. 1999;17(1):57-61.
28.Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry. 2010;31(2):455-61.
29.Huang CC, Couch GS, Pettersen EF, Ferrin TE, editors. Chimera: an extensible molecular modeling application constructed using standard components. Pacific symposium on biocomputing; 1996.
30.SchuÈttelkopf AW, Van Aalten DM. PRODRG: a tool for high-throughput crystallography of protein–ligand complexes. Acta Crystallographica Section D: Biological Crystallography. 2004;60(8):1355-63.
31.Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, et al. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proceedings of the National Academy of Sciences of the United States of America. 1993;90(19):9031-5.
32.Bernstein FC, Koetzle TF, Williams GJ, Meyer EF, Brice MD, Rodgers JR, et al. The protein data bank. European Journal of Biochemistry. 1977;80(2):319-24.
33.Mehta DC, Short JL, Nicolazzo JA. Memantine Transport across the Mouse Blood–Brain Barrier Is Mediated by a Cationic Influx H+ Antiporter. Molecular pharmaceutics. 2013;10(12):4491-8.
34.Henkel JG, Hane JT, Gianutsos G. Structure-anti-Parkinson activity relationships in the aminoadamantanes. Influence of bridgehead substitution. Journal of medicinal chemistry. 1982;25(1):51-6.
35.Wang Y, Ye W, Larrick JW, Stemler JS, Lipton SA. Aminoadamantane derivatives as therapeutic agents. Google Patents; 2008.
36.Klimova N, Lavrova N, Zaitseva N, Pyatin B, Morozov I, Bykov N, et al. Hydroxyladamantanes and their biological activity. Khimiko-farmatsevticheskii Zhurnal 1986;20(7):810-5.
37.Cai X, Hu W, Yao Z. Preparation of rimantadine hydrochloride. Chinese journal of medicinal chemistry. 2002;12(3):161-3.
38.Jimenez HN, Li G, Doller D, Grenon M, White AD, Ma G, et al. Adamantyl diamide derivatives and uses of same. Google Patents; 2011.
39.Wang Y, Ye W, Larrick J, Stamler J, Lipton S. Aminoadamantane derivatives as therapeutic agents. Google Patents; 2002.
40.Luo J, Li W, Zhao Y, Fu H, Ma DL, Tang J, et al. Pathologically activated neuroprotection via uncompetitive blockade of N-methyl-D-aspartate receptors with fast off-rate by novel multifunctional dimer bis (propyl)-cognitin. Journal of Biological Chemistry. 2010;285(26):19947-58.
41.Lipton SA. Pathologically activated therapeutics for neuroprotection. Nature Reviews Neuroscience. 2007;8(10):803-8.
42.Xia P, Chen H-sV, Zhang D, Lipton SA. Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses. The Journal of Neuroscience. 2010;30(33):11246-50.
43.Farlow MR, Evans RM. Pharmacologic treatment of cognition in Alzheimer's dementia. Neurology. 1998;51(1 Suppl 1):S36-S44.
44.Whitehouse PJ. Cholinergic therapy in dementia. Acta Neurologica Scandinavica. 1993;88(S149):42-5.
45.Ma HJ, Xie RL, Zhao QF, Mei XD, Ning J. Synthesis and insecticidal activity of novel carbamate derivatives as potential dual-binding site acetylcholinesterase inhibitors. Journal of agricultural and food chemistry. 2010;58(24):12817-21.
46.Ogura H, Kosasa T, Kuriya Y, Yamanishi Y. Comparison of inhibitory activities of donepezil and other cholinesterase inhibitors on acetylcholinesterase and butyrylcholinesterase in vitro. Methods Find Exp Clin Pharmacol. 2000;22(8):609-13.
47.Bin H, Ao GZ, Shi LL, Yu J. Synthesis of Memantine Hydrochloride. Chinese Journal of Pharmaceuticals. 2009;4:008.
48.Yong Z, Xiao X, Qi M. Synthesis of Memantine Hydrochloride. Chinese Journal of Pharmaceuticals. 2003.
49.Cai XH HW, Yao ZF, Liu ZH. Preparation of rimantadine hydrochloride. Chinese Journal of Medicinal Chemistry. 2002;12:161-3.
50.Wanka L, Cabrele C, Schreiner PR, Vanejews M. γ-Aminoadamantanecarboxylic Acids Through Direct C–H Bond Amidations. European Journal of Organic Chemistry. 2007;2007(9):1474–90.
51.Samnick S, Ametamey S, Gold MR, Schubiger PA. Synthesis and preliminary in vitro evaluation of a new memantine derivative 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane: A potential ligand for mapping the N-methyl-D-aspartate receptor complex. Journal of Labelled Compounds and Radiopharmaceuticals. 1997;39(3):241–50..
Source of support: This work was supported partially by The Natural Science Foundation of Guangdong Province (2014A030320174)
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Zheng L, Haiyun C, Fangcheng L, Baojian G, Xiaoyong J, Zaijun Z et al. This is an open access article under the CCBY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/). Which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Original article
Rebecca Singh1,*, Priyanka Bisoi1, Shiv Narayan Mohanty1,¥,Purna Chandra Debata1,±
Affiliation:
1P.G Student,1¥Professor, Professor and HOD1±, Department of Anaesthesiology, Hi-Tech Medical College and Hospital, Bhubaneswar, Odisha, India
The name of the department(s) and institution(s) to which the work should be attributed:
Department of Anaesthesiology, Hi-Tech Medical College and Hospital, Bhubaneswar, Odisha, India
Address reprint requests to
* Dr. Rebecca Singh.
Seba hospital, Peyton Sahi, Buxi Bazar, Cuttack, Odisha – 753001,India
Article citation:
Singh R, Bisoi P, Mohanty SN, Debata PC. Study on effect of Dexmedetomidine when added to Bupivacaine on the onset time and duration of block in Supraclavicular brachial plexus block. J Pharm Biomed Sci. 2015;05(04):338-343. Available at www.jpbms.info
ABSTRACT:
Background: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. It is always a subjective experience. Pain has been a major concern of human kind and it has been the object of ubiquitous efforts to understand and to control it. Regional anaesthesia of the extremities and of the trunk is a useful alternative to general anaesthesia in many demanding situations. The main drawback of long acting local anaesthetic drugs such as Bupivacaine was delayed onset of action.
Methods: This is a prospective, randomized, double-blind, placebo-controlled study of 100 orthopaedic cases of upper limb surgery to study the effect of adding dexmedetomidine to bupivacaine for supraclavicular brachial plexus blocks on the onset time and duration of motor and sensory blocks
Results and conclusion: From our study, we conclude that, the addition of Dexmedetomidine (1μg/kg) as an adjuvant to bupivacaine (0.5%) has following effects: Faster onset of sensory block, Faster onset of motor block, Longer duration of sensory block, Longer duration of motor block, Less number of rescue analgesics in post-op 24 hours and no significant difference in haemodynamic variables i.e., pulse rate, systolic BP, diastolic BP and O2 saturation.
KEYWORDS: Dexmedetomidine; Bupivacaine; Supraclavicular Brachial Plexus Block.
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
REFERENCES
1. Stephen E.Abram. Chronic pain management. In: Barash PG, Cullen BF, Stoelting RK. Clinical anaesthesia, 5th ed. Lippincott Williams and Wilkins, Philadelphia. 2006:1449.
2. Michael FM. Peripheral nerve blockade. In: Barash PG, Cullen BF, Stoelt ing RK. Clinical anaesthesia, 5th ed. Lippincott Williams and Wilkins, Philadelphia. 2006:718.
3. Singelyn FJ, Gouverneur JM, Robert A. A minimum dose of clonidine added to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block. Anesth Analg 1996;83:1046–50.
4. Singelyn FJ, Dangoisse M, Bartholomee S, Gouverneur JM. Adding clonidine to mepivacaine prolongs the duration of anesthesia and analgesia after brachial plexus block. Reg Anesth 1992;17:148–50.
5. Kanazi GE, Aouad MT, Jabbour-KHoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, Bulbul M, Baraka AS. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesth Scand 2006; 50:222–7.
6. Congedo E, Sgreccia M, De Cosmo G. New drugs for epidural analgesia. Curr Drug Targets 2009; 10:696–706.
7. Kenan Kaygusuz, MD et al., Effects of Adding Dexmedetomidine to Levobupivacaine in Axillary Brachial Plexus Block, ClinicalTrials.gov identifier ISRCTN67622282.
8. Amany S. Ammar et al., Ultrasound-guided single injection infraclavicular brachial plexus block using bupivacaine alone or combined with dexmedetomidine for pain control in upper limb surgery: A prospective randomized controlled trial, Saudi J Anaesth. 2012 Apr-Jun; 6(2):109–114.
9. Swami SS, Keniya VM, Ladi SD, Rao R. Comparison of dexmedetomidine and clonidine (α2 agonist drugs) as an adjuvant to local anaesthesia in supraclavicular brachial plexus block: A randomised double-blind prospective study. Indian J Anaesth 2012;56:243-9.
10.Rachana Gandhi et al., Use of dexmedetomidine along with bupivacaine for brachial plexus block , National journal of medical research 2012;2 (1):67-69.
11. Gaumann DM, Brunet PC, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg. 1992;74:719–25.
12. Heavner J. E., de Jong R.H. Lidocaine blocking concentrations for B- and C-nerve fibers. Anesthesiology 1974;40:228–233.
13. De Jong, R.H; Local anaesthetics Mosby USA.1994
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Singh R,Bisoi P,Mohanty SN,Debata PC. This is an open access article under the CCBY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/). Which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Research article
Zuo Ling1,2,4, Zhang Bei-bei1,2, Bei Yu2, Zhang Min-jing2, Pang Ji-yan3, Zhang Qi-hao2, Su Zhi-jian2, Huang Ya-dong2, Yang Hong-tu4, Xiang Qi1,2*
Affiliation:
1Department of Pharmacy, Jinan University, Guangzhou, People’s Republic of China
2Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangdong, People’s Republic of China
3School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People’s Republic of China
4The People’s Hospital of Shenzhen City, Shenzhen, People’s Republic of China
The name of the department(s) and institution(s) to which the work should be attributed:
1. Department of Pharmacy, Jinan University, Guangzhou, People’s Republic of China
2. Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangdong, People’s Republic of China
3. The People’s Hospital of Shenzhen City, Shenzhen, People’s Republic of China
4. School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People’s Republic of China
Address reprint requests to
Xiang Qi
1. Department of Pharmacy, Jinan University, Guangzhou, People’s Republic of China
2. Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, Guangdong, People’s Republic of China or at
Tel +86 20 8556 3234
Fax +86 20 8556 5109
Article citation: Zuo L, Bie Y, Zhang BB, Zhang MJ, Pang JY, Zhang QH, et al. Serum amino acids profiling in NAFLD mice. J Pharm Biomed Sci. 2015; 05(04):355-364. Available at www.jpbms.info
ABSTRACT:
Objectives: To detect the variation of serum amino acids in control and nonalcoholic fatty liver disease (NAFLD) mice by PITC pre-column derivatization HPLC, and further explore the potential biomarkers associated with the development of NAFLD using metabolism profiling analysis. Methods: Male C57BL/6J mice were fed with high fat and high fructose diet, after 8 weeks, serum samples of control and model mice were collected. Serum biochemical parameter and liver histopathology were examined, and then metabolic profile was further analyzed using PITC pre-column derivatization HPLC. Result: Levels of serum and hepatic biochemical parameter and liver histopathology verified the NAFLD model successfully. The metabolism profile of NAFLD model mice was significantly different from that of the control mice. Conclusion: Pattern recognition method demonstrated that there were significant differences in the five amino acids markers (glutamic acid, glycine, methionine, isoleucine, valine) between the control and NAFLD mice. Amino acids metabolism profile combined with pattern recognition technology may reflect to a certain extent the metabolism changes of NAFLD mice. It also provided the potential scientific and clinic value for further study of NAFLD.
KEYWORDS: HPLC; amino acid; nonalcoholic fatty liver disease.
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
ACKNOWLEDGEMENTS:
The work was supported by grants of the National Natural Science Foundation of China (No. 21172271), Youth fund project of national natural science fund (No.81202454), Major Scientific and Technological Special Project of Administration of Ocean and Fisheries of Guangdong Province (A201301C08), and from Natural Science Foundation of Guangdong Provincial, China (No. 2011020001231).
REFERENCES
1.Han D, Hanawa N, Saberi B, Kaplowitz N. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2006;291(1):G1-G7.
2.Fakurazi S, Hairuszah I, Nanthini U. Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level. Food and chemical toxicology. 2008;46(8):2611-5.
3.Kharbanda KK, editor. Alcoholic liver disease and methionine metabolism. Seminars in liver disease; 2009.
4.Dejong CH, van de Poll MC, Soeters PB, Jalan R, Damink SWO. Aromatic amino acid metabolism during liver failure. The Journal of nutrition. 2007;137(6):1579S-85S.
5.Quan HY, Kim do Y, Kim SJ, Jo HK, Kim GW, Chung SH. Betulinic acid alleviates non-alcoholic fatty liver by inhibiting SREBP1 activity via the AMPK-mTOR-SREBP signaling pathway. Biochemical pharmacology. 2013;85(9):1330-40.
6.Zafrani ES. Non-alcoholic fatty liver disease: an emerging pathological spectrum. Virchows Archiv : an international journal of pathology. 2004;444(1):3-12.
7.Charlton M. Nonalcoholic fatty liver disease: a review of current understanding and future impact. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2004;2(12):1048-58.
8.Avalueva EB, Tkachenko EI, Skazyvaeva EV, Ivanov SV, Orishak EA, Lapinskii IV. [Efficiency of ursodeoxycholic acid therapy in non-alcoholic fatty liver disease associated with metabolic syndrome]. Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology. 2013(11):26-30.
9.Jimba S, Nakagami T, Takahashi M, et al. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabetic medicine : a journal of the British Diabetic Association. 2005;22(9):1141-5.
10.Musso G, Gambino R, Cassader M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Progress in lipid research. 2009;48(1):1-26.
11.Jacome-Sosa MM, Borthwick F, Mangat R, et al. Diets enriched in trans-11 vaccenic acid alleviate ectopic lipid accumulation in a rat model of NAFLD and metabolic syndrome. The Journal of nutritional biochemistry. 2014;25(7):692-701.
12.Alonso A, Marsal S, Julia A. Analytical methods in untargeted metabolomics: state of the art in 2015. Frontiers in bioengineering and biotechnology. 2015;3:23.
13.Antonucci R, Pilloni MD, Atzori L, Fanos V. Pharmaceutical research and metabolomics in the newborn. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2012;25(Suppl 5):22-6.
14.Cox DG, Oh J, Keasling A, Colson KL, Hamann MT. The utility of metabolomics in natural product and biomarker characterization. Biochimica et biophysica acta. 2014;1840(12):3460-74.
15.Laiakis EC, Morris GAJ, Albert J. Fornace J, Howie SRC. Metabolomic Analysis in Severe Childhood Pneumonia in The Gambia, West Africa: Findings from a Pilot Study. PloS one. 2010;5(9):: e12655.
16.Nkomo MM, Katerere DD, Vismer HH, et al. Fusarium inhibition by wild populations of the medicinal plant Salvia africana-lutea L. linked to metabolomic profiling. BMC Complementary and Alternative Medicine. 2014;14(2):377-83.
17.Schmidt MM, Dringen R. Glutathione (GSH) Synthesis and Metabolism. Advances in Neurobiology. 2012.
18.Gentric G, Maillet V, Paradis V, et al. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease. The Journal of clinical investigation. 2015;125(3):981-92.
19.Layman DK, Shiue H, Sather C, Erickson DJ, Baum J. Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss. The Journal of nutrition. 2003;133(2):405-10.
Competing interest / Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Zuo L, Bie Y, Zhang BB, Zhang MJ, Pang JY, Zhang QH, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Original article
M. Sakthibalan1,*,Maruti Sripati Sawadkar1,¥
Affiliation:
1Assistant Professor,1,¥Retired Professor, Department of Pharmacology, Sri Venkateshwara Medical College Hospital & Research Centre, Pondicherry University, Pondicherry, India
The name of the department(s) and institution(s) to which the work should be attributed:
Department of Pharmacology, Sri Venkateshwara Medical College Hospital & Research Centre, Pondicherry University, Pondicherry, India
Address reprint requests to
Dr.Murugesan Sakthibalan,
Assistant Professor,
Department of Pharmacology,
Sri Venkateshwara Medical College Hospital& Research Centre, Ariyur, Pondicherry, India - 605102
Article citation:
Sakthibalan M, Sawadkar MS. To evaluate the anti-cancer effect of Doxorubicin when given in combination with cardioprotective agents like N-acetlycysteine, Enalapril and Vitamin c in Ehrlich ascites tumor induced adult wistar rats. J Pharm Biomed Sci. 2015; 05(04):300-307. Available at www.jpbms.info
ABSTRACT:
Background: The anthracycline antibiotic, Doxorubicin has beenproved very effective in a broad range of haematogenous and solid human malignancies. Its use is limited by its irreversible degenerative cardiomyopathy. This has driven us to find novel treatment modalities to reduce its cardiac side effects without conceding its anti-cancer effect.
Objective: To evaluate the anti cancer effect of Doxorubicin when given in combination with cardioprotective agents like N-acetlycysteine, Enalapril and Vitamin c in Ehrlich ascites tumor inducedwistar rats.
Methodology: The male adult wistar rats selected for investigate, divided into six groups with six rats in each group. Rats bearing Ehrlich ascites tumor were selected for the study. The rats in the control group and toxic control were administered sterile water and Doxorubicin respectively on day 5. N-Acetylcysteine, Enalapril and Vitamin c administered orally for seven days as dual drug and triple drug combinations. On day seven, the rats were sacrificed and blood was collected for estimation of cardiac stress markers and cardiac tissue was sent for histopathological estimation. The Peritoneal fluid was aspirated and the volume and viable tumor cell count assessed, using trypan blue exclusion technique. Statistical Analysis: Student ‘t’ test and one way ANOVA followed by Bonferroni test is applied.
Result and conclusion: The tumor volume and cell count at the end of the experiment was measured and it was found out that the anti-cancer effect of doxorubicin is not compromised on instilling various cardioprotective drugs in various combinations to treat doxorubicin induced cardiotoxicity.
KEYWORDS: Doxorubicin, Ehrlich ascites tumor, Trypan blue, N-Acetylcysteine, Enalapril, Vitamin C.
A part of the Manuscript was presented at: International and Annual Conference of Indian Pharmacological Society (IPSCON),Nagpur, India, on January 6th 2013.
REFERENCES
1.Olson RD, Mushlin P. Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. FASEB J. 1990;4:3076–86.
2. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med.1996;125:47–58.
3.Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900–905.
4.Ozaslan M, Karagoz ID, Kilic IH and Guldur ME.Ehrlich ascites carcinoma. African Journal of Biotechnology. Vol. 10(13):2375-78.
5. Sakthibalan M, Sawadkar MS, Asmathulla S, Ivan EA, Muthu G. Study of cardio protective effect of NAcetylcysteine,Vitamin C and Enalapril given in combination to prevent doxorubicin induced cardio toxicity in Wistar rats. Journal of pharmaceutical and biomedical sciences (J Pharm Biomed Sci.) 2013 November 36(36):1902-1908. Accessed from www.jpbms.info.
6. Stroud AN, Brues AM, Chatterley DH, et al. Serial Transplantation of Krebs-2 and Ehrlich Ascites Tumors to Rats. Cancer Res 1957;17:1102-1107.
7.Sakthibalan M, Rameshprabu S, Nileshraj G, Rameshkannan S, Ivan EA, Sawadkar MS. To Study the Chemotherapeutic Effect of Doxorubicin When Combined With Aspirin and Clopidogrel in Ehrlich Ascites Carcinoma Induced Adult Wistar Rats. International Journal of Recent Trends in Science and Technology, Volume 9, Issue 2, 2013; 218-220.
8.Pathan RA, Singh BK, Pillai KK and Dubey K.Naproxen aggravates doxorubicin-induced cardiomyopathy in rats. Indian J Pharmacol. 2010; 42(1): 44–49.
9.Ivanovski O, Szumilak D, Khoa TN, Ruellan N, Phan O, Lacour B, Latscha BD, Drueke TB and Massy ZA. The antioxidant N-acetylcysteine prevents accelerated atherosclerosis in uremic apolipoprotein E knockout mice. Kidney International.2005; 67: 2288–94.
10.Abd El-Aziz MA, Othman AI, Amer M, El-Missiry MA. Potential protective role of angiotensin-converting enzyme inhibitors captopril and enalapril against adriamycin-induced acute cardiac and hepatic toxicity in rats. Journal of Applied Toxicology. Vol. 21(6):469–473.
11. Santos RV, Batista Jr ML, Caperuto EC, Costa Rosa LF. Chronic supplementation of creatine and vitamins C and E increases survival and improves biochemical parameters after Doxorubicin treatment in rats. Clin Exp Pharmacol Physiol. 2007;34(12):1294-99. 12. Tietz, NW, Fundamentals of clinical chemistry, W.B. Saunders co., Philadelphia,1976.
13.German society for clinical chemistry: Recommendations of the Enzyme Commision. J.Clin.Chem.Clin.Biochem.1997;15:255.
14.Anderson ME. Enzymatic and chemical methods for the determination of glutathione. In: Dolphin D, editor. Glutathione. 1st vol. New York: John Wiley and Sos; 1983.340–65.
15. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95: 351-8.
16.Davies KJ, Doroshow JH. Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J Biol Chem. 1986;261:3060–67.
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
Source of funding: None
Competing interest / Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Sakthibalan M, Sawadkar MS. This is an open access article under the CCBY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/). which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Original article
M.Johnson Gritto, *V.Nanadagopalan, A. Doss*
Affiliation:
PG & Research Department of Botany, National College (Autonomous), Tiruchirappalli, Tamilnadu – 620 001, India
The name of the department(s) and institution(s) to which the work should be attributed:
Department of Botany, National College (Autonomous), Tiruchirappalli Tamilnadu – 620 001, India
Address reprint requests to
* Dr. V. Nandagopalan.
Associate Professor, PG & Research Department of Botany, National College, Tiruchirappalii- 620 001, Tamilnadu state, India.
Article citation:
Gritto MJ, Nanadagopalan V, Doss A. GC-MS analysis of Hildegardia poplifolia (Roxb.) Schott & Endl – An Endangered Potential Medicinal Plant. J Pharm Biomed Sci. 2015; 05(04):312-316. Available at www.jpbms.info
ABSTRACT:
The present study was carried out to identify the phytocomponents present in the methanolic extract of Hildegardia poplifolia by GC-MS analysis to learn it’s usage by the traditional healers as ‘a plant possessing medicinal properties’. Eighteen compounds were identified. The major constituents are 3, 7, 11, 15-Tetramethyl-2-hexadecen-1-ol (43.96%), Olean-12-ene (11.55%) n-Hexadecanoic acid (10.56%) and 4-Pyrimidinamine, 2, 6-dimethyl- (4.34%). Many of them are used in pharmacy for various uses like antioxidant, anti-diabetic, malaria, anti-inflammatory, anti-cancer and antimicrobial.
KEYWORDS: Gas-chromatography; Ailments; Hildegardia poplifolia; Phyto components.
Statement of Originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work.
REFERENCES
1.Varaprasad B., Katikala PK., Naidu KC. and Penumajji S. Antifungal activity of selected plant extracts against pytopathogenic fungi Aspergillus niger. Ind. J. Sci. Tech. 2009; 2(4): 87-90.
2.Saradha M. and Paulsamy S. Antibacterial activity of leaf and stem bark extracts of the endangered tree species, Hildegardia populifolia (Roxb.) Schott and Endl. (Sterculiaceae). J. Res. Antimicrob., 2012; 1: 023-027.
3.Saradha M. and Paulsamy S. In vitro antioxidant activity and polyphenol estimation of methanolic extract of endangered medicinal tree species, Hildegardia populifolia (Roxb.) Schott & Endl. Int. J. Phytomed., 2012; 4: 362-368.
4.Saradha M. and Paulsamy S. Antinociceptive and antiinflammatory activities of stem bark of an endangered medicinal plant, Hildegardia populifolia (Roxb.) Schott and Endl. Int. J. Pharma Bio Sci., 2013; 4(3): 30-36.
5.Saradha, M., Paulsamy S. and Vinitha R. Antioxidant and antihemolytic activity of an endangered plant species, Hildegardia populifolia (roxb.) Schott & endl. Asian J. Pharm. Clin. Res., 2013; 6(5):135-137.
6.Nezhadali A., Nabavi M. and Akbarpour M. Chemical composition of ethanol/n-hexane extract of the leaf from Tanacetum polycephalum subsp. duderanum as a herbal plant in Iran. Der Pharmacia Sinica, 2010; 1 (3): 147-150.
7.Sathyaprabha G., Kumaravel S. and Panneerselvam A. Bioactive Compounds Identification of Pleurotus platypus and Pleurotus eous by GC-MS. Adv. Appl. Sci. Res., 2011; 2: 51.
8.Abirami P and Rajendran A. GC-MS analysis of methanol extracts of Vernonia cinerea. Eur. J. Exp. Biol., 2012; 2(1): 9-12.
9.Kale SS., Vijaya Darade, Thakur HA. Analysis of fixed oil from Sterculia foetida Linn. Int. J. Pharm. Sci. Res., 2011; 2(11): 2908-2911.
10.Grace OM., Light ME., Lindsey KL., Moholland DA., Staden JV. and Jader AK. Antibacterial activity and isolation of antibacterial compounds from fruit of the traditional African medicinal plant, Kigelia africana. S. Afr. J. Bot., 2002; 68: 220-222.
11.Sharafzadeh S., Morteza Khosh-Khui and Javidnia K. Aroma Profile of Leaf and Stem of Lemon Balm (Melissa Officinalis L.) Grown under Greenhouse Conditions. Advan. Environmental Biol., 2011; 5(4): 547-550.
12.Parasuraman S., Raveendran R. and Madhavrao C. GC-MS analysis of leaf extracts of Cleistanthus collinus Roxb. (Euphorbiaceae). Int. J. Ph. Sci., 2009; 1(2):284-286.
13.Siddiq Ibraham A., Ahmad Bustamam A., Manal Mohammed E., Syam MI., Mohamed Yousif M., Abdelbasit Adam, Alhaj NA. and Rasedee Abdullah. GC-MS determination of bioactive components and antibacterial properties of Goniothalamus umbrosus extracts. Afr. J. Biotech., 2009; 8(14): 3336-3340. 30.
14.Arunkumar S. and Muthuselvam M. Analysis of Phytochemical constituents and antimicrobial activities of Aloe vera L. against clinical pathogens. World J. Agricultural Sci., 2009; 5(5): 572-576. 31.
15.Feliciano A., Medarde M., Del Rey B., Del Corral J. and Barrero A. Eudesmane glycosides from Carthamus lanatus. Phytochem., 1990; 29: 3207-3211.
16.Balaj K., Kilimozhi D. and Parthasarathy V. GC-MS analysis of various extracts of Clerodendrum phlomidis leaf. Int. J. Pharm. Pharm. Sci., 2014; 6 (1): 226-232.
17.Grover N. and Patni, V. Phytochemical characterization using various solvent extracts and GC-MS analysis of methanolic extract of Woodfordia fruticosa leaves. Int. J. Pharm. Pharm. Sci., 2013; 5 (4): 291-295.
Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense.
Copyright © 2015 Gritto MJ, Nanadagopalan V, Doss A. This is an open access article under the CCBY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/). Which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.