Abstract
Turmeric, obtained from the rhizomes of Curcuma longa, is used in South Asia as a traditional medicine for the treatment of epilepsy. To
date, in vivo studies on the anticonvulsant activity of turmeric have focused on its principal
curcuminoid, curcumin. However, poor absorption and rapid metabolism have limited
the therapeutic application of curcumin in humans. To explore the therapeutic potential
of turmeric for epilepsy further, we analyzed its anticonvulsant activity in a larval
zebrafish seizure assay. Initial experiments revealed that the anticonvulsant activity
of turmeric in zebrafish larvae cannot be explained solely by the effects of curcumin.
Zebrafish bioassay-guided fractionation of turmeric identified bisabolene sesquiterpenoids
as additional anticonvulsants that inhibit PTZ-induced seizures in both zebrafish
and mice. Here, we present the first report of the anticonvulsant properties of bisabolene
sesquiterpenoids and provide evidence which warrants further investigation toward
the mechanistic understanding of their neuromodulatory activity.
Highlights
- Anticonvulsant activity of sesquiterpenoids from turmeric oil in zebrafish model.
- Confirmation of the positive activity of bisabolene sesquiterpenoids in rodent model.
- Ar-turmerone and α,β-turmerone as potential AED candidates to be further investigated.
Abbreviations:
AEDs (antiepileptic drugs), DAD (diode array detection), DMSO (dimethyl sulfoxide), dpf (days post-fertilization), ddH2O (double-distilled water), ESI-MS (electrospray ionization mass spectrometry), i.v. (intravenous), i.p. (intraperitoneal), LC–MS (liquid chromatography–mass spectroscopy), MES (maximal electroshock seizure), MTC (maximum tolerated concentration), PEG (polyethylene glycol), p.o. (“per os”, orally), PTZ (pentylenetetrazole), RP-HPLC (reverse phase-high performance liquid chromatography), s.c. (subcutaneous), TLE (temporal lobe epilepsy)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Epilepsy & BehaviorAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Atlas: epilepsy care in the world.WHO Press, Geneva, Switzerland2005 (90 p.)
- Drug treatment of epilepsy: options and limitations.Epilepsy Behav. 2009; 15: 56-65
- Life-threatening adverse events of antiepileptic drugs.Epilepsy Res. 2001; 47: 155-174
- Complaints associated with the use of antiepileptic drugs: results from a community-based study.Seizure. 2005; 14: 198-206
- Patient-reported cognitive side effects of antiepileptic drugs: predictors and comparison of all commonly used antiepileptic drugs.Epilepsy Behav. 2009; 14: 202-209
- Cognitive and memory effects of the new antiepileptic drugs.Epilepsy Res. 2006; 68: 63-67
- Botanicals and herbs: a traditional approach to treating epilepsy.Neurotherapeutics. 2009; 6: 415-420
- Review on phytotherapy in epilepsy.Seizure. 2000; 9: 96-107
- New anticonvulsant agents.Curr Top Med Chem. 2005; 5: 69-85
- Curr Opin Investig Drugs. 2001; 2: 1763-1766
- WHO monographs on selected medicinal plants.WHO library cataloguing in publication data, Geneva, Switzerland1999 (289 p.)
- Curcumin protects against electrobehavioral progression of seizures in the iron-induced experimental model of epileptogenesis.Epilepsy Behav. 2009; 14: 300-308
- Protective role of curcumin in maximal electroshock induced seizures, memory impairment and neurotransmitters in rat brain.JPCCR. 2008; 2: 35-39
- Prevention of kainic acid-induced changes in nitric oxide level and neuronal cell damage in the rat hippocampus by manganese complexes of curcumin and diacetylcurcumin.Life Sci. 2006; 78: 1884-1891
- Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model.Life Sci. 2010; 87: 596-603
- A pilot cross-over study to evaluate human oral bioavailability of BCM-95®CG (Biocurcumax™), a novel bioenhanced preparation of curcumin.Indian J Pharm Sci. 2008; 70: 445-449
- Anticonvulsant activity of the leaf essential oil of Laurus nobilis against pentylenetetrazole- and maximal electroshock-induced seizures.Phytomedicine. 2002; 9: 212-216
- Phytochemical screening and anticonvulsant activity of Cymbopogon winterianus Jowitt (Poaceae) leaf essential oil in rodents.Phytomedicine. 2008; 15: 619-624
- Curcuma oil modulates the nitric oxide system response to cerebral ischemia/reperfusion injury.Nitric Oxide. 2008; 19: 1-11
- Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic stroke model.BMC Complement Altern Med. 2008; 8: 55
- Curcuma oil: reduces early accumulation of oxidative product and is anti-apoptogenic in transient focal ischemia in rat brain.Neurochem Res. 2008; 33: 1672-1682
- Fishing for drugs from nature: zebrafish as a technology platform for natural product discovery.Planta Med. 2008; 74: 624-632
- Chemical screening in zebrafish for novel biological and therapeutic discovery.Methods Cell Biol. 2011; 105: 493-516
- Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening.Pharmacol Biochem Behav. 2004; 77: 647-654
- In vivo drug discovery in the zebrafish.Nat Rev. 2005; 4: 35-44
- Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression.Neuroscience. 2005; 131: 759-768
- Zebrafish offer the potential for a primary screen to identify a wide variety of potential anticonvulsants.Epilepsy Res. 2007; 75: 18-28
- Validation of a larval zebrafish locomotor assay for assessing the seizure liability of early-stage development drugs.J Pharmacol Toxicol Methods. 2008; 57: 176-187
- Timed pentylenetetrazol infusion test: a comparative analysis with s.c. PTZ and MES models of anticonvulsant screening in mice.Seizure. 2007; 16: 636-644
- Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and maximal electroshock seizure models.Seizure. 2004; 13: 287-295
- Belhaven Press, London, U.K.1990: 257 p Atlas of microscopy of medicinal plants, culinary herbs and spices.
- The zebrafish book.in: A guide for the laboratory use of zebrafish (Danio rerio). 4th ed. University of Oregon, Eugene, Oregon2000
- Liquid chromatography–electrospray mass spectrometric analysis of curcuminoids and sesquiterpenoids in turmeric (Curcuma longa).J Chromatogr A. 1998; 818: 127-132
- Acute seizure tests in epilepsy research: electroshock- and chemical-induced convulsions in the mouse.in: Enna S.J. Williams M. Barret J.F. Ferkany J.W. Kenakin T. Porsolt R.D. Current protocols in pharmacology. Wiley & Sons, Hoboken, NJ, USA2009: 27-30
- vGLUT2 heterozygous mice show more susceptibility to clonic seizures induced by pentylenetetrazol.Neurochem Int. 2009; 55: 41-44
- Total synthesis of (R)- and (S)-turmerone and (7S,9R)-bisacumol by an efficient chemoenzymatic approach.Tetrahedron Asymmetr. 2009; 20: 1267-1271
- New bisabolane sesquiterpenoids from the rhizomes of Curcuma xanthorrhiza (Zingiberaceae).Chem Pharm Bull. 1989; 37: 237-240
- Preparation of γ,δ‐unsaturated β‐ketophosphonates from tertiary α‐allenic alcohols. The synthesis of (+/−)‐(E)‐α‐atlantone.J Org Chem. 1996; 61: 7202-7206
- Curcumin has anticonvulsant activity on increasing current electroshock seizures in mice.Phytother Res. 2008; 22: 1660-1664
- alpha-Tocopherol protects against pentylenetetrazol- and methylmalonate-induced convulsions.Epilepsy Res. 2005; 66: 185-194
- Regional vulnerability to oxidative stress in a model of experimental epilepsy.Neurochem Res. 1998; 23: 1477-1483
- Antiepileptic drugs and neuroprotection: current status and future roles.Epilepsy Behav. 2005; 7: S25-S28
- Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma.Epilepsia. 2011; 52: 657-678
- New mechanisms and therapeutic potential of curcumin for colorectal cancer.Mol Nutr Food Res. 2008; 52: 1040-1061
- Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers.J Assoc Physicians India. 2003; 51: 1055-1060
- Toxicity prediction of compounds from turmeric (Curcuma longa L).Food Chem Toxicol. 2010; 48: 2951-2959
Article info
Publication history
Accepted:
February 21,
2012
Received in revised form:
February 16,
2012
Received:
December 20,
2011
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.