CELLMED (셀메드)

Cellmed Orthocellular Medicine and Pharmaceutical Association (셀메드 세포교정의약학회)
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Role of fumarates in adaptogenics like efficacies of traditionally used Fumaria indica extracts

  • Shakya, Anshul (Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University)) ;
  • Chatterjee, Shyam Sunder (Stettiner Strabe) ;
  • Kumar, Vikas (Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University))
  • Received : 2014.09.14
  • Accepted : 2015.02.11
  • Published : 2015.02.28
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Abstract

Fumaria indica Linn. (Syn: Fumaria parviflora, Fumariaceae) is a wildly grown weed, mentioned and recommended in classical Ayurvedic texts for treatments of variety of ailments including dermatological diseases, topical diseases, cardiovascular complaints, circulatory disease, fever and headache etc. The present pilot study was designed to experimentally verify the possibility that fumarates are the major bioactive principles of Fumaria indica extracts involved in their stress response modulating activities, and to estimate pharmacologicallyactive dose ranges of fumarates and standardized methanolic extract of Fumaria indica (MFI). Effect of single, 5 and 10 daily oral doses of pure fumaric acid (FA), monomethyl fumarate (MMF), dimethyl fumarate (DMF) and MFI was quantified in well validated rodent models viz. apomorphine induced cage climbing, stress induced hyperthermia, and elevated plus-maze tests. Obtained results reveal high efficacy of MFI and pure fumarates possess qualitatively analogous activity profiles in all the three tests. There were no significant difference in the potencies of pure FA, MMF and DMF in the three tests, whereas efficacy of MFI in the elevated plus maze test for anxiolytics was higher than in the other two tests. Efficacies of all the four test agents in all the three tests increased with increasing number of days of oral treatments. Results of these pilot experiments should be helpful for more rational selections of pharmacologically interesting dose ranges and treatment regimens of fumarates and Fumaria indica extracts for further more holistic explorations of their diverse therapeutic potentials.

Keywords

References

  1. Adeleye IA, Omadime ME, Daniels EV. Antimicrobial activity of essential oil and extracts of Gongronema latifolium Decne on bacterial isolates from blood stream of HIV infected patients. J Pharmacol Toxicol. 2011;6:312-320. https://doi.org/10.3923/jpt.2011.312.320
  2. Alghasham A, Rasheed N. Stress-mediated modulations in dopaminergic system and their subsequent impact on behavioral and oxidative alterations: an update. Pharm Biol. 2014;52:368-377. https://doi.org/10.3109/13880209.2013.837492
  3. Araujo WL, Nunes-Nesi A, Fernie AR. Fumarate: multiple functions of a simple metabolite. Phytochemistry. 2011;72:838-843. https://doi.org/10.1016/j.phytochem.2011.02.028
  4. Baldessarini RJ, Kula NS, Walton KG. Behavioral effects of apomorphine and diisobutyrylapomorphine in the mouse. Psychopharmacology (Berl). 1977;53:45-53. https://doi.org/10.1007/BF00426693
  5. Chatterjee S, Srivastava S, Khalid A, Singh N, Sangwan RS, Sidhu OP, Roy R, Khetrapal CL, Tuli R. Comprehensive metabolic fingerprinting of Withania somnifera leaf and root extracts. Phytochemistry. 2010;71:1085-1094. https://doi.org/10.1016/j.phytochem.2010.04.001
  6. Chia DW, Yoder TJ, Reiter WD, Gibson SI. Fumaric acid: an overlooked form of fixed carbon in arabidopsis and other plant species. Planta. 2000;211:743-751. https://doi.org/10.1007/s004250000345
  7. Christmas D, Hood S, Nutt D. Potential novel anxiolytic drugs. Curr Pharm Des. 2008;14:3534-3546. https://doi.org/10.2174/138161208786848775
  8. Davis AS, Jenner P, Marsden CD. A comparison of motor behaviours in groups of rats distinguished by their climbing response to apomorphine. Br J Pharmacol. 1986;87:129-137. https://doi.org/10.1111/j.1476-5381.1986.tb10164.x
  9. Dibbert S, Clement B, Skak-Nielsen T, Mrowietz U, Rostami-Yazdi M. Detection of fumarate-glutathione adducts in the portal vein blood of rats: evidence for rapid dimethylfumarate metabolism. Arch Dermatol Res. 2013:305:447-451. https://doi.org/10.1007/s00403-013-1332-y
  10. Ellrichmann G, Petrasch-Parwez E, Lee DH, Reick C, Arning L, saft C, Gold R, Linker RA. Efficacy of fumaric acid esters in the R6/2 and YAC128 models of Huntington's disease. PLoS One. 2011:6:e16172. https://doi.org/10.1371/journal.pone.0016172
  11. Ermis U, Weis J, Schulz JB. PML in a patient treated with fumaric acid. N Engl J Med. 2013:368:1657-1658. https://doi.org/10.1056/NEJMc1211805
  12. Furmark T. Neurobiological aspects of social anxiety disorder. Isr J Psychiatry Relat Sci. 2009:46:5-12.
  13. Gelfuso EA, Rosa DS, Fachin AL, Mortari MR, Cunha AO, Bleboni RO. Anxiety : a systematic review of neurobiology, traditional pharmaceuticals and novel alternatives from medicinal plants. CNS Neurol Disord Drug Targets. 2014:13:150-165. https://doi.org/10.2174/18715273113129990102
  14. Gkalpakiotis S, Arenberger P, Gkalpakioti P, Meluzinova E, Chandran D, Arenbergerova M. Management of psoriasis vulgaris and multiple sclerosis with fumaric acid. J Am Acad Dermatol. 2014:70:e60-e61. https://doi.org/10.1016/j.jaad.2013.10.031
  15. Groenink L, Vinkers C, van Oorschot R, Olivier B. Models of anxiety: stress-induced hyperthermia (SIH) in singly housed mice. Curr Protoc Pharmacol. 2009:Chapter5: Unit5.16.
  16. Gupta PC, Sharma N, Rao CV. A review on ethnobotany, phytochemistry and pharmacology of Fumaria indica (Fumitory). Asian Pac J Trop Biomed. 2012:2:665-669. https://doi.org/10.1016/S2221-1691(12)60117-8
  17. He CL, Fu BD, Shen HQ, Jiang XL, Wei XB. Fumaric acid, an antibacterial component of Aloe vera L. Afr J Biotechnol. 2011:10:2973-2977. https://doi.org/10.5897/AJB10.1497
  18. Ickes GR, Fong HHS, Schiff PL, Perdue RE, Farnsworth NR. Antitumor activity and preliminary phytochemical examination of Tagetes minuta (Compositae). J Pharm Sci. 1973:62:1009-1011. https://doi.org/10.1002/jps.2600620635
  19. Iverach L, Menzies RG, Menzies RE. Death anxiety and its role in psychopathology: reviewing the status of a transdiagnostic construct. Clin Psychol Rev. 2014:34:580-593. https://doi.org/10.1016/j.cpr.2014.09.002
  20. Jaberian H, Piri K, Nazari J. Phytochemical composition and in vitro antimicrobial and antioxidant activities of some medicinal plants. Food Chem. 2013:136:237-244. https://doi.org/10.1016/j.foodchem.2012.07.084
  21. Jain A, Choubey S, singour PK, Rajak H, Pawar RS. Sida cordifolia (Linn)-An overview. J Appl Pharm Sci. 2011:1:23-31.
  22. Jing X, Shi H, Zhang C, Ren M, Han M, Wei X, Zhang X, Lou H. Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson's disease by enhancing Nrf2 activity. Neuroscience. 2015:286:131-140. https://doi.org/10.1016/j.neuroscience.2014.11.047
  23. Khalighi SF, Yazdani D, Taghizadeh M, Rezazadeh SA. Quantitative determination of an effective component of Fumaria parviflora Lam. J Med Plants. 2005:4:62-71.
  24. Kumar V, Jaiswal AK, Singh PN, Bhattacharya SK. Anxiolytic activity of Indian Hypericum perforatum Linn: an experimental study. Indian J Exp Biol. 2000:38:36-41.
  25. Lakhan SE, Vieira KF. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J. 2010:9:42. https://doi.org/10.1186/1475-2891-9-42
  26. Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, Zeng W, Hronowsky X, Buko A, Chollate S, Ellrichmann G, Bruck W, Dawson K, Goelz S, Wiese S, Scannevin RH, Lukashev M, Gold R. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011:134:678-692. https://doi.org/10.1093/brain/awq386
  27. Meissner M, Valesky EM, Kippenberger S, Kaufmann R. Dimethyl fumarate-only an anti-psoriatic medication?. J Dtsch Dermatol Ges. 2012:10:793-801.
  28. Moreno M. The role of ionotropic glutamate receptors in the dorsomedial hypothalamus in the increase in core body temperature evoked by interoceptive and exteroceptive stresses in rats. (Bloomington, U S A: PhD thesis of Indiana University), 2010.
  29. Nikolaus S, Antke C, Beu M, Muller HW. Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders--results from in vivo imaging studies. Rev Neurosci. 2010:21:119-139.
  30. Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav. 1986:24:525-529. https://doi.org/10.1016/0091-3057(86)90552-6
  31. Protais P, Costentin J, Schwartz JC. Climbing behavior induced by apomorphine in mice: A simple test for the study of dopamine receptors in striatum. Psychopharmacology (Berl). 1976:50:1-6. https://doi.org/10.1007/BF00634146
  32. Rajopadhye AA, Upadhye AS. Botanical and phytochemical standardization of Fumaria vaillantii Loisel. Indian J Nat Prod Resour. 2011:2:369-374.
  33. Rao KS, Mishra SH. Antihepatotoxic activity of monomethyl fumarate isolated from Fumaria indica. J Ethnopharmacol. 1998:60:207-213. https://doi.org/10.1016/S0378-8741(97)00149-9
  34. Rathi A, Srivastava AK, Shirwaikar A, Singh RAK, Mehrotra S. Hepatoprotective potential of Fumaria indica Pugsley whole plant extracts, fractions and an isolated alkaloid protopine. phytomedicine. 2008:15:470-477. https://doi.org/10.1016/j.phymed.2007.11.010
  35. Rostami-Yazdi M, Clement B, Mrowietz U. Pharmacokinetics of anti-psoriatic fumaric acid esters in psoriasis patients. Arch Dermatol Res. 2010:302:531-538. https://doi.org/10.1007/s00403-010-1061-4
  36. Schweckendiek W. Treatment of psoriasis vulgaris. Med Monatsschr. 1959:13:103-104.
  37. Seidel P, Roth M. Anti-inflammatory dimethylfumarate: a potential new therapy for asthma? Mediators Inflamm. 2013:2013:875403.
  38. Shakya A, Chatterjee SS, Kumar V. Holistic psychopharmacology of Fumaria indica (Fumitory). Chin Med. 2013:3:182-199.
  39. Shakya A, singh, G, Chatterjee SS, Kumar V. Role of fumaric acid in anti-inflammatory and analgesic activities of a Fumaria indica extracts. J Intercult Ethnopharmacol. 2014:3:173-178. https://doi.org/10.5455/jice.20140912021115
  40. Sharma A, Cardoso-Taketa A, Garca G, Villarreal ML. A systematic updated review of scientifically tested selected plants used for anxiety disorders. Botanics : Targets and Ther. 2012:2:21-39.
  41. Silhavy J, Zidek V, Mlejnek P, Landa V, Simakova M, Strnad H, Oliyarnyk O, Skop V, Kazdova L, Kurtz T, Pravenec M. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats. PLoS One. 2014:9:e101906. https://doi.org/10.1371/journal.pone.0101906
  42. Singh GK, Chauhan SK, Rai G, Chatterjee SS, Kumar V. Potential antianxiety activity of Fumaria indica: A preclinical study. Pharmacogn Mag. 2013:9:14-22. https://doi.org/10.4103/0973-1296.108129
  43. Singh GK, Kumar V. Neuropharmacological screening and lack of antidepressant activity of standardized extract of Fumaria indica: a preclinical study. Electron J Pharmacol Ther. 2010;3:19-28.
  44. Singh GK, Rai G, Chatterjee SS, Kumar V. Beneficial effects of fumaria indica on chronic stress-induced neurobehavioral and biochemical perturbations in rats. Chin Med. 2012:3:49-60. https://doi.org/10.4236/cm.2012.31009
  45. Singh GK, Rai G, Chatterjee SS, Kumar V. Anti-aggressive, brain neurotransmitters and receptor binding study of fumaria indica in rodents. Curr Psychopharmacol. 2012:1:195-202. https://doi.org/10.2174/2211556011201030195
  46. Singh GK, Rai G, Chatterjee SS, Kumar V. Effects of ethanolic extract of Fumaria indica L. on rat cognitive dysfunctions. Ayu. 2013:34:421-429. https://doi.org/10.4103/0974-8520.127727
  47. Srivastava S, Choudhary GP. Pharmacognostic and pharmacological study of Fumaria vaillantii Loisel: a review. J Pharmacog phytochem. 2014:3:194-197.
  48. Strassburger-Krogias K, Ellrichmann G, Krogias C, Altmeyer P, Chan A, Gold R. Fumarate treatment in progressive forms of multiple sclerosis: first results of a single-center observational study. Ther Adv Neurol Disord. 2014:7:232-238. https://doi.org/10.1177/1756285614544466
  49. Stratford HJ, Cooper MJ, Di Simplicio M, Blackwell SE, Holmes EA. Psychological therapy for anxiety in bipolar spectrum disorders: A systematic review. Clin Psychol Rev. 2015:35C:19-34.
  50. Van der Heyden JA, Zethof TJ, Olivier B. Stress-induced hyperthermia in singly housed mice. Physiol Behav. 1997:62:463-470. https://doi.org/10.1016/S0031-9384(97)00157-1
  51. Vinkers CH, van Bogaert MJ, Klanker M, Korte SM, Oosting R, Hanania T, Hopkins SC, Olivier B, Groenink L. Translational aspects of pharmacological research into anxiety disorders: the stress-induced hyperthermia (SIH) paradigm. Eur J Pharmacol. 2008:585:407-425. https://doi.org/10.1016/j.ejphar.2008.02.097
  52. Vrba J, Vrublova E, Modriansky M, Ulrichova J. Protopine and allocryptopine increase mRNA levels of cytochromes P450 1A in human hepatocytes and HepG2 cells independently of AhR. Toxicol Lett. 2011:203:135-141. https://doi.org/10.1016/j.toxlet.2011.03.015
  53. Xu LF, Chu WJ, Qing XY, Li S, Wang XS, Qing GW, Fei J, Guo LH. Protopine inhibits serotonin transporter and noradrenaline transporter and has the antidepressant-like effect in mice models. Neuropharmacology. 2006:50:934-940. https://doi.org/10.1016/j.neuropharm.2006.01.003
  54. Zethof TJ, Van der Heyden JA, Tolboom JT, Olivier B. Stress-induced hyperthermia in mice: Amethodological study. Physiol Behav. 1994:55:109-115. https://doi.org/10.1016/0031-9384(94)90017-5
  55. Zheng W, Wang S, Chen X, Hu Z. Analysis of Sarcandra glabra and its medicinal preparations by capillary electrophoresis. Talanta. 2003:60:955-960. https://doi.org/10.1016/S0039-9140(03)00178-4

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