Neuronal protective effect of Songling Xuemaikang capsules alone and in combination with carbamazepine on epilepsy in kainic acid-kindled rats.

Haiyan Yang, Rui Zhang, Chen Jia, Mengyu Chen, Wen Yin, Liming Wei, Haisheng Jiao
Author Information
  1. Haiyan Yang: a Department of Pharmacy , Lanzhou University Second Hospital , Lanzhou , China.
  2. Rui Zhang: b College of Pharmacy , Lanzhou University , Lanzhou , China.
  3. Chen Jia: a Department of Pharmacy , Lanzhou University Second Hospital , Lanzhou , China.
  4. Mengyu Chen: b College of Pharmacy , Lanzhou University , Lanzhou , China.
  5. Wen Yin: a Department of Pharmacy , Lanzhou University Second Hospital , Lanzhou , China.
  6. Liming Wei: a Department of Pharmacy , Lanzhou University Second Hospital , Lanzhou , China.
  7. Haisheng Jiao: a Department of Pharmacy , Lanzhou University Second Hospital , Lanzhou , China.

Abstract

CONTEXT: Epilepsy is a common life-threatening neurological disorder that is often drug-resistant and associated with cognitive impairment. The traditional Chinese patent medicine Songling Xuemaikang capsules (SXC) is clinically used for epilepsy therapy and alleviation of cognitive impairment.
OBJECTIVE: This study investigates the neuronal protective effect of SXC combined with carbamazepine (CBZ) on epilepsy and cognitive impairment in kainic acid-kindled SD rats.
MATERIALS AND METHODS: Kainic acid-kindled rats were established by injection of 0.45 μg kainic acid and randomly divided into 5 groups (n = 14): saline (sham-operated), control, CBZ, SXC and CBZ + SXC combined group. Rats in the treatment groups received CBZ (50 mg/kg/d), SXC (600 mg/kg/d) or combined CBZ (50 mg/kg/d) + SXC (600 mg/kg/d) via intragastric injection for 60 days. Epileptic behaviours, cognitive impairment, neuronal apoptosis and expression of p-Akt, Akt and caspase-9 were measured, and the alleviation of cognitive damage and neuronal apoptosis was analyzed.
RESULTS: The combined administration of SXC and CBZ significantly decreased the frequency of seizures (1.2 ± 0.3) and the number of episodes (1.3 ± 0.5) above stage III (p < 0.05). Neuronal apoptosis was improved (p < 0.01), and cognitive damage was ameliorated (p < 0.05).The level of p-Akt was enhanced (p < 0.01) whereas the expression of caspase-9 was evidently inhibited (p < 0.01) in the combined group.
CONCLUSIONS: The present findings confirm that the combined use of SXC with CBZ can effectively control epileptic seizures, alleviate damage to hippocampal neurons and protect against cognitive impairment. The mechanism of action might be related to the upregulation of p-Akt and inhibition of caspase-9 expression.

Keywords

References

  1. J Intellect Disabil Res. 1998 Dec;42 Suppl 1:36-40 [PMID: 10030430]
  2. Neurosci Lett. 1999 Oct 15;274(1):45-8 [PMID: 10530516]
  3. Epilepsy Res. 2000 Feb;38(2-3):115-25 [PMID: 10642039]
  4. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Sep;24(9):793-7 [PMID: 15495822]
  5. Neurochem Res. 2005 May;30(5):613-8 [PMID: 16176064]
  6. J Altern Complement Med. 2006 Sep;12(7):673-7 [PMID: 16970538]
  7. Nat Protoc. 2006;1(2):848-58 [PMID: 17406317]
  8. Phytomedicine. 2007 Oct;14(10):652-8 [PMID: 17870452]
  9. Cancer Res. 2010 Nov 15;70(22):9185-96 [PMID: 21045158]
  10. Nat Rev Neurol. 2011 Mar;7(3):154-64 [PMID: 21304484]
  11. Exp Cell Res. 2012 Jul 1;318(11):1213-20 [PMID: 22406265]
  12. Seizure. 2012 Jun;21(5):311-5 [PMID: 22475771]
  13. Seizure. 2013 Mar;22(2):109-15 [PMID: 23206433]
  14. Neuroreport. 2013 Apr 17;24(6):335-41 [PMID: 23518641]
  15. Int J Clin Exp Med. 2013 Aug 01;6(7):546-51 [PMID: 23936593]
  16. Food Chem. 2013 Dec 15;141(4):3598-605 [PMID: 23993526]
  17. Chin J Integr Med. 2015 Apr;21(4):312-20 [PMID: 24584755]
  18. Hippocampus. 2014 Sep;24(9):1129-45 [PMID: 24799359]
  19. Biochem Biophys Res Commun. 2014 Jun 13;448(4):414-7 [PMID: 24802403]
  20. Acta Neuropathol. 2014 Jul;128(1):21-37 [PMID: 24823761]
  21. Epilepsy Behav. 2014 Aug;37:59-70 [PMID: 24980390]
  22. Cell Mol Neurobiol. 2014 Nov;34(8):1175-82 [PMID: 25151533]
  23. Epileptic Disord. 2015 Mar;17(1):13-8; quiz 18 [PMID: 25635346]
  24. Rev Neurol (Paris). 2015 Mar;171(3):236-51 [PMID: 25724711]
  25. Cold Spring Harb Perspect Med. 2015 Jun 01;5(6):null [PMID: 26033084]
  26. Genet Mol Res. 2015 Aug 21;14(3):9994-10000 [PMID: 26345935]
  27. J Neurooncol. 2015 Nov;125(2):419-26 [PMID: 26362046]
  28. Epilepsy Res. 2015 Nov;117:90-6 [PMID: 26432759]
  29. Epilepsy Behav. 2015 Dec;53:58-65 [PMID: 26519667]
  30. Expert Opin Pharmacother. 2016;17(7):885-8 [PMID: 26999402]
  31. Neurosci Lett. 2016 Aug 15;628:207-12 [PMID: 27345387]
  32. Front Neurol. 2017 Oct 16;8:544 [PMID: 29085330]
  33. Pharm Biol. 2018 Dec;56(1):217-224 [PMID: 29560767]

MeSH Term

Animals
Anticonvulsants
Apoptosis
Carbamazepine
Caspase 9
Cognition
Drug Therapy, Combination
Drugs, Chinese Herbal
Epilepsy
Hippocampus
Kainic Acid
Male
Maze Learning
Proto-Oncogene Proteins c-akt
Random Allocation
Rats
Seizures

Chemicals

Anticonvulsants
Drugs, Chinese Herbal
songling xuemaikang
Carbamazepine
Proto-Oncogene Proteins c-akt
Caspase 9
Kainic Acid

Word Cloud

Created with Highcharts 10.0.0cognitiveimpairmentSXCcombinedCBZp < 0apoptosisp-Aktcaspase-9epilepsyneuronalkainicacid-kindledratsexpressiondamage01SonglingXuemaikangcapsulesalleviationprotectiveeffectcarbamazepineinjection5groupscontrolgroup50 mg/kg/d600 mg/kg/dseizures105NeuronalCONTEXT:Epilepsycommonlife-threateningneurologicaldisorderoftendrug-resistantassociatedtraditionalChinesepatentmedicineclinicallyusedtherapyOBJECTIVE:studyinvestigatesSDMATERIALSANDMETHODS:Kainicestablished045 μgacidrandomlydividedn = 14:salinesham-operatedCBZ + SXCRatstreatmentreceived + SXCviaintragastric60 daysEpilepticbehavioursAktmeasuredanalyzedRESULTS:administrationsignificantlydecreasedfrequency2 ± 03numberepisodes3 ± 0stageIIIimprovedamelioratedThelevelenhancedwhereasevidentlyinhibitedCONCLUSIONS:presentfindingsconfirmusecaneffectivelyepilepticalleviatehippocampalneuronsprotectmechanismactionmightrelatedupregulationinhibitionalonecombinationCognitiveneuron

Similar Articles

Cited By