Journal of Natural Remedies

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Alleviating Potential of Zingiber officinale and Cow Urine Distillate Co-administered with Levetiracetam in Epileptic Rats: A Pharmacokinetic and Pharmacodynamics Approach


Affiliations
1 Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa – 388421, Gujarat, India
2 Department of Pharmacology, Parul Institute of Pharmacy and Research, Parul University, Vadodara – 391350, Gujarat, India
3 Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India
 

Background: Epilepsy is a severe neurological condition that affects all ages of people. Complex pathways involved in pathogenesis make it complicated to treat; selected antiepileptic drug options are available for Epilepsy. There is a need for an hour to develop novel treatment approaches for epilepsy with lesser side effects. This research aimed to evaluate the alleviating role of bio-enhancers co-administered with levetiracetam for pilocarpine-induced epilepsy. Methodology: Pilocarpine (250 mg/kg) was used to develop epilepsy in rats. Levetiracetam (LEV) (140 mg/kg) was administered with Zingiber officinale Extract (ZOE) (15 mg/kg and 30 mg/kg) and Cow Urine Distillate (CUD) (1.5 ml/kg and 3 ml/kg). HPLC was used to evaluate drug concentration in blood. Serum nitrate, catalase, CRP, calcium level and calcium level of the brain, behavioural markers in rats were assessed and compared with the Leviteracetam group only. Result and Discussion: The present study showed that combining ZOE and CUD with levetiracetam was advantageous through substantial reduction (p < 0.05) in serum nitrate, CRP and increased catalase (p < 0.05), while reduced serum calcium compared to LEV alone. Combination of ZOE and CUD with levetiracetam treatment also reduced seizure behaviour and duration in rats. The bioavailability of LEV in plasma and brain was increased when epileptic rats were treated with LEV plus ZOE and CUD compared to disease control. Conclusion: Utilization of Zingiber officinale and CUD in combination with LEV was proven therapeutically effective in the epileptic model and used to lower the dose of LEV along with reducing seizure behaviour and time with the potential for the treatment of epilepsy.

Keywords

Catalase and Nitrate, Cow Urine Distillate, Epilepsy, Levetiracetam, Zingiber officinale Extract.
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  • Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy

  • Alexander A, Qureshi A, Kumari L, Vaishnav P, Sharma M, Saraf S, et al. Role of herbal bioactives as a potential bio-availability enhancer for Active Pharmaceutical Ingredients. Fitoterapia. 2014; 97:1-14. https://doi.org/10.1016/j. fitote.2014.05.005 PMid:24862064

  • Mohanty I, Senapati MR, Jena D, Palai S. Diversified uses of cow urine. Int J Pharm Pharm Sci. 2014; 6(3):20-2.

  • Qazi G, Bedi K, Johri R, Tikoo M, Tikoo A, Sharma S, et al. Bioavailability enchancing activity of Zingiber officinale Linn and its extracts/fractions thereof. Google Patents; 2003.

  • Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus- Report of the ILAE task force on classification of status epilepticus. Epilepsia. 2015; 56:1515-23. https://doi.org/10.1111/epi.13121 PMid:26336950

  • Available from: https://tribuneonlineng.com/epilepsy-how-ginger-boosts-effectiveness-of-medicine/

  • Meghana A, Obulapathi U, Singh S. Indian cow urine as a therapeutic alternative in treatment of human diseases: A review. AYUHOM. 2021; 8(2):57.

  • Zheng Y, Moussally J, Cash SS, Karnam HB, Cole AJ. Intravenous levetiracetam in the rat pilocarpine-induced status epilepticus model: Behavioral, physiological and histological studies. Neuropharmacology. 2010; 58(4-5):793-8. https://doi.org/10.1016/j.neuropharm.2009.12.007 PMid:20026136 PMCid:PMC2834228

  • Al-Shorbagy MY, El Sayeh BM, Abdallah DM. Additional antiepileptic mechanisms of levetiracetam in lithium-pilocarpine treated rats. PloS one. 2013; 8(10):e76735. https://doi.org/10.1371/journal.pone.0076735 PMid:24098559 PMCid:PMC3789684

  • Li Y, Schellhorn HE. Rapid kinetic microassay for catalase activity. Journal of Biomolecular Techniques: JBT. 2007; 18(4):185.

  • Patsalos P. Pharmacokinetic profile of levetiracetam: Toward ideal characteristics. Pharmacology and Therapeutics. 2000; 85(2):77-85. https://doi.org/10.1016/S0163-7258(99)00052-2 PMid:10722121

  • Pucci V, Bugamelli F, Mandrioli R, Ferranti A, Kenndler E, Raggi MA. High‐performance liquid chromatographic determination of Levetiracetam in human plasma: Comparison of different sample clean‐up procedures. Biomedical Chromatography. 2004; 18(1):37-44. https://doi.org/10.1002/bmc.289 PMid:14872547

  • Racine RJ. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalography and Clinical Neurophysiology. 1972; 32(3):281-94. https://doi.org/10.1016/0013-4694(72)90177-0 PMid:4110 397

  • Waldbaum S, Patel M. Mitochondrial dysfunction and oxidative stress: A contributing link to acquired epilepsy? Journal of Bioenergetics and Biomembranes. 2010; 42(6):449-55. https://doi.org/10.1007/s10863-010-9320-9 PMid:21132357 PMCid:PMC3102435

  • Mohseni G, Ostadhadi S, Akbarian R, Chamanara M, Norouzi-Javidan A, Dehpour A-R. Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors. Epilepsy and Behavior. 2016; 65:49-55. https://doi.org/10.1016/j.yebeh.2016.08.001 PMid:27875784

  • Ogunro P, Mustapha A, Salau A. Lipid peroxidation and antioxidant status in patients with primary generalized epilepsy. Arch Appl Sci. 2013; 5:68-74.

  • Rahman S. Pathophysiology of mitochondrial disease causing epilepsy and status epilepticus. Epilepsy and Behavior. 2015; 49:71-5. https://doi.org/10.1016/j.yebeh.2015.05.003 PMid:26162691

  • Mattson MP. Excitotoxicity. Neurodegeneration. 2017:37-45. https://doi.org/10.1002/9781118661895.ch4

  • Aguiar CCT, Almeida AB, Araújo PVP, Abreu RNDCd, Chaves EMC, Vale OCd, et al. Oxidative stress and epilepsy: Literature review. Oxidative Medicine and Cellular Longevity. 2012; 2012. https://doi.org/10.1155/2012/795259 PMid:22848783 PMCid:PMC3403512

  • Santos LF, Freitas RL, Xavier SM, Saldanha GB, Freitas RM. Neuroprotective actions of vitamin C related to decreased lipid peroxidation and increased catalase activity in adult rats after pilocarpine-induced seizures. Pharmacology Biochemistry and Behavior. 2008; 89(1):1-5. https://doi.org/10.1016/j.pbb.2007.10.007 PMid:18096215

  • Liguori C, Romigi A, Izzi F, Placidi F, Nuccetelli M, Cordella A, et al. Complement system dysregulation in patients affected by idiopathic generalized epilepsy and the effect of antiepileptic treatment. Epilepsy Research. 2017; 137:107-11. https://doi.org/10.1016/j.eplepsyres.2017.09.005 PMid: 28985614

  • Woernle CM, Neidert MC, Wulf M-A, Burkhardt J-K, Grunwald T, Bernays R-L. Excessively elevated C-reactive protein after surgery for temporal lobe epilepsy. Clinical neurology and Neurosurgery. 2013; 115(8):1245-9. https://doi.org/10.1016/j.clineuro.2012.11.025 PMid:23266263


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  • Alleviating Potential of Zingiber officinale and Cow Urine Distillate Co-administered with Levetiracetam in Epileptic Rats: A Pharmacokinetic and Pharmacodynamics Approach

Abstract Views: 145  |  PDF Views: 72

Authors

Nilay Solanki
Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa – 388421, Gujarat, India
Harshal Patel
Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa – 388421, Gujarat, India
Milap Patel
Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa – 388421, Gujarat, India
Yamini Patel
Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa – 388421, Gujarat, India
Preetu Shukla
Department of Pharmacology, Parul Institute of Pharmacy and Research, Parul University, Vadodara – 391350, Gujarat, India
Jagdish Kakadiya
Department of Pharmacology, Parul Institute of Pharmacy and Research, Parul University, Vadodara – 391350, Gujarat, India
Rajesh Maheshwari
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara – 391760, Gujarat, India
Priyal Chauhan
Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa – 388421, Gujarat, India

Abstract


Background: Epilepsy is a severe neurological condition that affects all ages of people. Complex pathways involved in pathogenesis make it complicated to treat; selected antiepileptic drug options are available for Epilepsy. There is a need for an hour to develop novel treatment approaches for epilepsy with lesser side effects. This research aimed to evaluate the alleviating role of bio-enhancers co-administered with levetiracetam for pilocarpine-induced epilepsy. Methodology: Pilocarpine (250 mg/kg) was used to develop epilepsy in rats. Levetiracetam (LEV) (140 mg/kg) was administered with Zingiber officinale Extract (ZOE) (15 mg/kg and 30 mg/kg) and Cow Urine Distillate (CUD) (1.5 ml/kg and 3 ml/kg). HPLC was used to evaluate drug concentration in blood. Serum nitrate, catalase, CRP, calcium level and calcium level of the brain, behavioural markers in rats were assessed and compared with the Leviteracetam group only. Result and Discussion: The present study showed that combining ZOE and CUD with levetiracetam was advantageous through substantial reduction (p < 0.05) in serum nitrate, CRP and increased catalase (p < 0.05), while reduced serum calcium compared to LEV alone. Combination of ZOE and CUD with levetiracetam treatment also reduced seizure behaviour and duration in rats. The bioavailability of LEV in plasma and brain was increased when epileptic rats were treated with LEV plus ZOE and CUD compared to disease control. Conclusion: Utilization of Zingiber officinale and CUD in combination with LEV was proven therapeutically effective in the epileptic model and used to lower the dose of LEV along with reducing seizure behaviour and time with the potential for the treatment of epilepsy.

Keywords


Catalase and Nitrate, Cow Urine Distillate, Epilepsy, Levetiracetam, Zingiber officinale Extract.

References





DOI: https://doi.org/10.18311/jnr%2F2023%2F33217