The Korea Journal of Herbology (대한본초학회지)

The Korea Association of Herbology (대한본초학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Coptidis Rhizoma on the Anti-inflammation and Motor Recovery in Photothrombotic Brain Infarction Model in Rats

광화학적 뇌경색 백서 모델에서 황련의 항염증 및 운동기능 회복에 미치는 효과

  • Lee, Su-Kyung (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Lee, In (Dept. of Internal Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Shin, Sun-Ho (Dept. of Internal Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Kim, Eun-Young (Dept. of Internal Medicine, School of Medicine, Ewha Womans University) ;
  • Shin, Byung-Cheul (Dept. of Oriental Rehabilitation Medicine, School of Oriental Medicine, Pusan National University)
  • 이수경 (원광대학교 한의과대학 한방재활의학과) ;
  • 이인 (원광대학교 한의과대학 한방내과) ;
  • 신선호 (원광대학교 한의과대학 한방내과) ;
  • 김은영 (이화여자대학교 의학전문대학원 내과학교실) ;
  • 신병철 (부산대학교 한의학전문대학원 한방재활의학과)
  • Published : 2009.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Coptidis Rhizoma (Coptis japonica MAKINO; CR) is a well known crude drug as antimicrobial, antibacterial, anti-inflammatory, antioxidant activity. However, there is no study of the effect of CR on brain infarction and it's mechanism. The aim of this study was to investigate the effects on ischemic stroke induced by photothrombotic infarction by evaluating the functional & neuronal recovery after brain infarction. Materials & Methods : Male Sprague-Dawley rats (250-300 g) were induced photothrombotic brain infarction on sensorimotor cortex, and brain infarction volume by image J software (NIH, USA) after Nissl stain, also single pellet reaching task as a functional motor recovery were observed. After orally pretreated by CR (500 mg/kg) or normal saline as a sham control before 7 days from the time of photothrombotic infarction, rats were sacrificed. After then we analysed anti-inflammatory cytokines (TNF-$\alpha$, IL-6, IL-1$\beta$), by RT-PCR and ELISA method, and immunohistochemistry (GFAP, connexin-43) as a marker of neural plasticity. Results : CR (100, 250, 500 mg/kg) decreased the infarction volume dose-dependently, however the effect of 500mg/kg of CR (CR 500) showed the best (P=0.051). Also, CR 500 decreased the infarction volume time-dependently, the most effective time was 3-7 days after stroke. Photothrombosis increased inflammatory cytokines after infarction, CR 500 suppressed significantly mRNA expression of IL-1$\beta$, IL-6 and TNF-$\alpha$. In serum, CR 500 decreased the amount of IL-1$\beta$, 12h, 24h and 48h respectively (p < 0.05), also decreased that of IL-6 and TNF-$\alpha$, 12h respectively (p < 0.05) after infarction. The more astrocytes were observed and neural plasticity was facilitated in the rat brain of CR 500 than that of sham control in immunohistochemistry. Conclusions : This results suggest that CR decrease infarction volume and improve functional motor recovery in acute stage in photothrombotic ischemic infarction model in the mechanism of anti-inflammation and promoting neural plasticity.

Keywords

References

  1. 2007 사망원인통계. 통계청. 2008.
  2. Kessels HW, Malinow R. Synaptic AMPA receptor plasticity and behavior. Neuron. 2009, Feb, 12 ; 61(3) : 340-50. https://doi.org/10.1016/j.neuron.2009.01.015
  3. 한태륜, 이시욱, 김대열, 박성혜, 최덕형, 박희원, 이정은. 국소적 뇌허혈 백서 모델에서 조기재활의 운동강도가 신경학적 회복에 미치는 영향. 대한뇌졸중학회지. 2006 ; 8(1) : 106-18.
  4. Adkins-Muir DL, Jones TA. Cortical electrical stimulation combined with rehabilitative training: enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats. Neurol Res. 2003 ; 25(8) : 780-8. https://doi.org/10.1179/016164103771953853
  5. Moon SK, Yang CY, NO SE, Kim EY, Lee S, Park SA, Oh GJ, KIm HI, Song JH, Lee MC, Shin YI. Promotion of motor recovery by anodal continuous and low amplitude cortical stimulation in rat stroke model. Lab Anim Res. 2007 ; 23(1) : 25-30.
  6. 신민교 편저. 임상본초학. 서울 : 영림사. 1997 : 407-9.
  7. 김호철. 한약약리학. 서울 : 집문당. 2001 : 134-7.
  8. 한방약리학 교재편찬위원회 저. 한방약리학. 서울 : 신일북스. 2007 : 243-6.
  9. 이연아, 홍승재, 이상훈, 박은경, 김경수, 한정수, 유명철, 양형인. 황련 추출물의 항염 효과. 경희의학. 2007 ; 23(1) : 21-9.
  10. Yokozawa T, Ishida A, Kashiwada Y, Cho EJ, Kim HY, Ikeshiro Y. Coptidis Rhizoma: protective effects against peroxynitrite-induced oxidative damage and elucidation of its active components. J Pharm Pharmacol. 2004 ; 56(4) : 547-56. https://doi.org/10.1211/0022357023024
  11. 김용주, 이문조, 박진우, 김준기, 최달영, 김철호. 황련 열수추출물의 항산화 활성 효과. Korean J Life Sci. 2000 ; 10(3) : 241-6.
  12. Cho EJ, Yokozawa T, Rhee SH, Park KY. The role of Coptidis Rhizoma extract in a renal ischemia-reperfusion model. Phytomedicine. 2004 ; 11(7-8) : 576-84. https://doi.org/10.1016/j.phymed.2003.07.005
  13. Cui HS, Matsumoto K, Murakami Y, Hori H, Zhao Q, Obi R. Berberine exerts neuroprotective actions against in vitro ischemia-induced neuronal cell damage in organotypic hippocampal slice cultures: involvement of B-cell lymphoma 2 phosphorylation suppression. Biol Pharm Bull. 2009 ; 32(1) : 79-85. https://doi.org/10.1248/bpb.32.79
  14. Paxinos G, Watson C. The rat brain in stereotactic coordinates. 5th ed, Sydney. Academic press. 2004 : 9-203.
  15. Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985 ; 17 : 497-504. https://doi.org/10.1002/ana.410170513
  16. Vergara-Aragon P, Gonzalez CL, Whishaw IQ. A novel skilled-reaching impairment in paw supination on the “good” side of the hemi-Parkinson rat improved with rehabilitation. J Neurosci. 2003 ; 23 : 579-86.
  17. Faden A. Neuroprotection and traumatic brain injury. Arch Neurol. 2001 ; 58 : 1553-5. https://doi.org/10.1001/archneur.58.10.1553
  18. Kaas J. Plasticity of sensory and motor maps in adult mammals. Ann Rev Neurosci. 1991 ; 14 : 137-67. https://doi.org/10.1146/annurev.ne.14.030191.001033
  19. Nudo RJ, Plautz EJ, Frost SB. Role of adaptive plasticity in recovery of function after damage to motor cortex. Muscle Nerve. 2001 ; 24(8) : 1000-19. https://doi.org/10.1002/mus.1104
  20. Kleim JA, Hogg TM, VandenBerg PM, Cooper NR, Bruneau R, Remple M. Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning. J Neurosci. 2004 ; 24(3) : 628-33. https://doi.org/10.1523/JNEUROSCI.3440-03.2004
  21. Kleim JA, Barbay S, Cooper NR, Hogg TM, Reidel CN, Remple MS, Nudo RJ. Motor learning-dependent synaptogenesis is localized to functionally reorganized motor cortex. Neurobiol Learn Mem. 2002 ; 77(1) : 63-77. https://doi.org/10.1006/nlme.2000.4004
  22. Khairova RA, Machado-Vieira R, Du J, Manji HK. A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol. 2009 ; 19 : 1-18. [Epub ahead of print] https://doi.org/10.1016/j.euroneuro.2008.07.002
  23. Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol. 2005 ; 5 : 629-40. https://doi.org/10.1038/nri1664
  24. Hallenbeck JM. The many faces of tumour necrosis factor in stroke. Nat Med. 2002 ; 8(12) : 1363-8. https://doi.org/10.1038/nm1202-1363
  25. Tarkowski E, Rosengren L, Blomstrand C, Wikkelso C, Jensen C, Ekholm S, Tarkowski A. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke. 1995 : 26 : 1393-8. https://doi.org/10.1161/01.STR.26.8.1393
  26. Hoehn BD, Palmer TD, Steinberg GK. Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin. Stroke. 2005 ; 36(12) : 2718-24. https://doi.org/10.1161/01.STR.0000190020.30282.cc
  27. Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Illingworth K, Scarth S, Wickramasinghe V, Hoadley ME, Rothwell NJ, Tyrrell PJ, Hopkins SJ. Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC Neurol. 2007 ; 7 : 5. https://doi.org/10.1186/1471-2377-7-5
  28. 박용기, 이경열. 황련 클로로포름 분획물의 뇌신경소교세포로부터 염증매개물질 생성억제 효능연구. 대한본초학회지. 2007 ; 22(4) : 109-16.
  29. 박용기, 정효원, 김창민, 최재수, 김영식. 황련의 주성분인 Berberine의 뇌신경소교세포로부터 LPS에 의해 유도되는 염증매개물질 생성억제효과. 대한본초학회지. 2007 ; 22(4) : 117-25.
  30. 조은호, 이태희. LPS에 의해 유발된 염증 스트레스에 대한 황련과 부자의 효과. 대한본초학회지. 2006 ; 21(2) : 77-85.
  31. Chen Y, Swanson RA. Astrocytes and brain injury. J Cereb Blood Flow Metab. 2003 ; 23(2) : 137-49. https://doi.org/10.1038/sj.bmt.1701535
  32. Rouach N, Avignone E, Meme W, Koulakoff A, Venance L, Blomstrand F, Giaume C. Gap junctions and connexin expression in the normal and pathological central nervous system. Biol Cell. 2002 ; 94(7-8) : 457-75. https://doi.org/10.1016/S0248-4900(02)00016-3
  33. Haupt C, Witte OW, Frahm C. Up-regulation of Connexin43 in the glial scar following photothrombotic ischemic injury. Mol Cell Neurosci. 2007 ; 35(1) : 89-99. https://doi.org/10.1016/j.mcn.2007.02.005
  34. Haupt C, Witte OW, Frahm C. Temporal profile of connexin 43 expression after photothrombotic lesion in rat brain. Neuroscience. 2007 ; 144(2) : 562-70. https://doi.org/10.1016/j.neuroscience.2006.09.054