Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
권호 표지

Moutan Cortex Extract Inhibits Amyloid ${\beta}$ Protein (25-35)-induced Neurotoxicity in Cultured Rat Cortical Neurons

Amyloid ${\beta}$ 2 Protein (25-35) 유도 배양신경세포 독성에 대한 목단피의 억제효과

  • Kim, Joo-Youn (College of Veterinary Medicine, Chungbuk National University) ;
  • Ju, Hyun-Soo (College of Veterinary Medicine, Chungbuk National University) ;
  • Ban, Ju-Yeon (Department of Pharmacology, College of Medicine, Kyung Hee University) ;
  • Song, Kyung-Sik (College of Agriculture and Life-Sciences, Kyungpook National University) ;
  • Seong, Yeon-Hee (College of Veterinary Medicine, Chungbuk National University)
  • 김주연 (충북대학교 수의과대학) ;
  • 주현수 (충북대학교 수의과대학) ;
  • 반주연 (경희대학교 의과대학) ;
  • 송경식 (경북대학교 농업생명과학대학) ;
  • 성연희 (충북대학교 수의과대학)
  • Published : 2008.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Moutan cortex, the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), has pharmacological effects such as anti-inflammatory, antiallergic, analgesic and antioxidant activities. We investigated a methanol extract of Moutan cortex for neuroprotective effects on neurotoxicity induced by amyloid ${\beta}$ protein ($A{\beta}$) (25-35) in cultured rat cortical neurons. Exposure of cultured cortical neurons to $10\;{\mu}M\;A{\beta}$ (25-35) for 24 h induced neuronal apoptotic death. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced neuronal cell death at 30 and $50\;{\mu}g/m{\ell}$, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) which were measured by fluorescent dyes. Moutan cortex also inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}$ (25-35), which was measured by HPLC. These results suggest that Moutan cortex prevents $A{\beta}$ (25-35)-induced neuronal cell damage by interfering with the increase of $[Ca^{2+}]_i$, and then inhibiting glutamate release and ROS generation. Moutan cortex may have a therapeutic role in preventing the progression of Alzheimer's disease.

Keywords

References

  1. Ban JY, Cho SO, Jeon SY, Song KS, Bae K and Seong YH. (2005). Protective effect of Sanguisorba officinalis L. root on amyloid $\beta$ protein (25-35)-induced neuronal cell damage in cultured rat cortical neuron. Korean Journal of Medicinal Crop Science. 13:219-226
  2. Ban JY and Seong YH. (2005). Blockade of 5-$HT_{3}$ receptor with MDL72222 and Y25130 reduces amyloid $\beta$ protein (25-35)-induced neurotoxicity in cultured rat cortical neurons. European Journal of Pharmacology. 520:12-21 https://doi.org/10.1016/j.ejphar.2005.07.021
  3. Butterfield DA, Reed T, Newman SF and Sultana R. (2007). Roles of amyloid $\beta$-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of alzheimer's disease and mild cognitive impairment. Free Radical Biology and Medicine. 43:658-677 https://doi.org/10.1016/j.freeradbiomed.2007.05.037
  4. Chan PH. (2001). Reactive oxygen radicals in signaling and damage in the ischemic brain. Journal of Cerebral Blood Flow Metabolism. 21:2-14 https://doi.org/10.1097/00004647-200101000-00002
  5. Chen G, Zhang L and Zhu Y. (2006). Determination of glycosides and sugars in Moutan cortex by capillary electrophoresis with electrochemical detection. Journal of Pharmaceutical and Biomedical Analysis. 41:129-134 https://doi.org/10.1016/j.jpba.2005.11.001
  6. Chun SC, Jee SY, Lee SG, Park SJ, Lee JR and Kim SC. (2007). Anti-inflammatory activity of the methanol extract of Moutan cortex in LPS-activated Raw264.7 cells. Evidencebased Complementary and Alternative Medicine. 4:327-333 https://doi.org/10.1093/ecam/nel093
  7. Ekinci FJ, Linsley MD and Shea TB. (2000). $\beta$-Amyloid-induced calcium influx induces apoptosis in culture by oxidative stress rather than tau phosphorylation. Molecular Brain Research. 76:389-395 https://doi.org/10.1016/S0169-328X(00)00025-5
  8. Goodman Y and Mattson MP. (1994). Secreted forms of $\beta$-amyloid precursor protein protect hippocampal neurons against amyloid $\beta$-peptide-induced oxidative injury. Experimental Neurology. 128:1-12 https://doi.org/10.1006/exnr.1994.1107
  9. Grace EA, Rabiner CA and Busciglio J. (2002). Characterization of neuronal dystrophy induced by fibrillar amyloid $\beta$: Implications for alzheimer's disease. Neuroscience. 114:265-273 https://doi.org/10.1016/S0306-4522(02)00241-5
  10. Gray CW and Patel AJ. (1995). Neurodegeneration mediated by glutamate and $\beta$-amyloid peptide: A comparison and possible interaction. Brain Research. 691:169-179 https://doi.org/10.1016/0006-8993(95)00669-H
  11. Harkany T, Hortobagyi T, Sasvari M, Konya C, Penke B, Luiten PG and Nyakas C. (1999). Neuroprotective approaches in experimental models of $\beta$-amyloid neurotoxicity: Relevance to alzheimer's disease. Progress in Neuro-psychopharmacology & Biological Psychiatry. 23:963-1008 https://doi.org/10.1016/S0278-5846(99)00058-5
  12. Hoehn BD, Palmer TD and Steinberg GK. (2005). Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin. Stroke. 36:2718-2724 https://doi.org/10.1161/01.STR.0000190020.30282.cc
  13. Hsieh CL, Cheng CY, Hsai TH, Lin I, Liu CH, Chiang SY, Lin JG, Lao CJ and Tang NY. (2006). Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats. Journal of Ethnopharmacology. 106:208-215 https://doi.org/10.1016/j.jep.2005.12.027
  14. Ivins KJ, Ivins JK, Sharp JP and Cotman CW. (1999). Multiple pathways of apoptosis in pc12 cells. Crma inhibits apoptosis induced by $\beta$-amyloid. Journal of Biological Chemistry. 274:2107-2112 https://doi.org/10.1074/jbc.274.4.2107
  15. Jang JH and Surh YJ. (2005). $\beta$-Amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation via the mitogen-activated protein kinase-NF-$\kappa\beta$ signaling pathway. Free Radical Biology and Medicine. 38:1604-1613 https://doi.org/10.1016/j.freeradbiomed.2005.02.023
  16. Jiang S, Nakano Y, Yatsuzuka R, Ono R and Kamei C. (2007). Inhibitory effects of Moutan cortex on immediate allergic reactions. Biological & Pharmaceutical Bulletin. 30:1707-710 https://doi.org/10.1248/bpb.30.1707
  17. Koh JY, Yang LL and Cotman CW. (1990). $\beta$-Amyloid protein increases the vulnerability of cultured neurons to excitotoxic damage. Brain Research. 533:315-320 https://doi.org/10.1016/0006-8993(90)91355-K
  18. Le TJ, Qiu Y, Mao JQ, Yang PY, Rui YC and Chen WS. (2007). Protective effects of Guizhi-Fuling-Capsules on rat brain ischemia/reperfusion injury. Journal of Pharmacological Sciences. 105:34-40 https://doi.org/10.1254/jphs.FP0070450
  19. Lee BY, Ban JY and Seong YH. (2005). Chronic stimulation of $GABA_{A}$ receptor with muscimol reduces amyloid $\beta$ protein (25-35)-induced neurotoxicity in cultured rat cortical cells. Neuroscience Research. 52:347-356 https://doi.org/10.1016/j.neures.2005.04.008
  20. Lee SB, Kim JY, Cho SO, Ban JY, Ju HS, Bae K and Seong YH. (2007). Extract of Cedrela sinensis leaves protects neuronal cell damage induced by hydrogen peroxide in cultured rat neurons. Korean Journal of Medicinal Crop Science. 15:444-450
  21. Matsuda H, Ohta T, Kawaguchi A and Yoshikawa M. (2001). Bioactive constituents of chinese natural medicines. VI. Moutan cortex. (2): structures and radical scavenging effects of suffruticosides A, B, C, D, and E and galloyl-oxypaeoniflorin. Chemical & Pharmaceutical Bulletin (Tokyo). 49:69-72 https://doi.org/10.1248/cpb.49.69
  22. Mattson MP and Chan SL. (2003). Neuronal and glial calcium signaling in alzheimer's disease. Cell Calcium. 34:385-397 https://doi.org/10.1016/S0143-4160(03)00128-3
  23. Parks JK, Smith TS, Trimmer PA, Bennett JP Jr and Parker WD Jr. (2001). Neurotoxic A$\beta$ peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. Journal of Neurochemistry. 76:1050-1056 https://doi.org/10.1046/j.1471-4159.2001.00112.x
  24. Pereira CF and Oliveira CR. (2000). Oxidative glutamate toxicity involves mitochondrial dysfunction and perturbation of intracellular $Ca^{2+}$ homeostasis. Neuroscience Research. 37:227-236 https://doi.org/10.1016/S0168-0102(00)00124-3
  25. Pike CJ, Walencewicz-Wasserman AJ, Kosmoski J, Cribbs DH, Glabe CG and Cotman CW. (1995). Structure-activity analyses of $\beta$-amyloid peptides: Contributions of the $\beta$ 25-35 region to aggregation and neurotoxicity. Journal of Neuro-chemistry. 64:253-265 https://doi.org/10.1046/j.1471-4159.1995.64010253.x
  26. Pitchumoni SS and Doraiswamy PM. (1998). Current status of antioxidant therapy for alzheimer's disease. Journal of the American Geriatrics Society. 46:1566-1572 https://doi.org/10.1111/j.1532-5415.1998.tb01544.x
  27. Price DL, Tanzi RE, Borchelt DR and Sisodia SS. (1998). Alzheimer's disease: Genetic studies and transgenic models. Annual Review of Genetics. 32:461-493 https://doi.org/10.1146/annurev.genet.32.1.461
  28. Rho S, Chung HS, Kang M, Lee E, Cho C, Kim H, Park S, Kim HY, Hong M, Shin M and Bae H. (2005). Inhibition of production of reactive oxygen species and gene expression profile by treatment of ethanol extract of Moutan cortex radicis in oxidative stressed PC12 cells. Biological & Pharmaceutical Bulletin. 28:661-666 https://doi.org/10.1248/bpb.28.661
  29. Shimada Y, Yokoyama K, Goto H, Sekiya N, Mantani N, Tahara E, Hikiami H and Terasawa K. (2004). Protective effect of keishi-bukuryo-gan and its constituent medicinal plants against nitric oxide donor-induced neuronal death in cultured cerebellar grannle cells. Phytomedicine. 11:404-410 https://doi.org/10.1016/j.phymed.2003.04.002
  30. Shon YH and Nam KS. (2004). Protective effect of Moutan cortex extract on acetaminophen-induced hepatotoxicity in mice. Journal of Ethnopharmacology. 90:415-419 https://doi.org/10.1016/j.jep.2003.11.004
  31. Tatsumi S, Mabuchi T, Xu L, Minami T and Ito S. (2004). Analgesic effect of extracts of Chinese medicinal herbs Moutan cortex and Coicis semen on neuropathic pain in mice. Neuroscience Letters. 370:130-134 https://doi.org/10.1016/j.neulet.2004.08.043
  32. Tohda C, Matsumoto N, Zou K, Meselhy MR and Komatsu K. (2004). A$\beta$ (25-35)-induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, A metabolite of protopanaxadiol-type saponins. Neuropsychopharmacology. 29:860-868 https://doi.org/10.1038/sj.npp.1300388
  33. Ueda K, Fukui Y and Kageyama H. (1994). Amyloid $\beta$ proteininduced neuronal cell death: neurotoxic properties of aggregated amyloid $\beta$ protein. Brain Research. 639: 240-244 https://doi.org/10.1016/0006-8993(94)91736-1
  34. Ueda K, Shinohara S, Yagami T, Asakura K and Kawasaki K. (1997). Amyloid $\beta$ protein potentiates $Ca^{2+}$ influx through Ltype voltage-sensitive $Ca^{2+}$ channels: A possible involvement of free radicals. Journal of Neurochemistry. 68:265-271 https://doi.org/10.1046/j.1471-4159.1997.68010265.x
  35. Wu JB, Song NN, Wei XB, Guan HS and Zhang XM. (2008). Protective effects of paeonol on cultured rat hippocampal neurons against oxygen-glucose deprivation-induced injury. Journal of the Neurological Sciences. 264:50-55 https://doi.org/10.1016/j.jns.2007.06.057
  36. Wu M and Gu Z. (2007). Anti-inflammatory activity of the methanol extract of Moutan cortex in LPS-activated Raw264.7 Cells. Evidence-based Complementary and Alternative Medicine. eCAM 1-7
  37. Yan XZ, Qiao JT, Dou Y and Qiao ZD. (1999). $\beta$-Amyloid peptide fragment 31-35 induces apoptosis in cultured cortical neurons. Neuroscience. 92:177-184 https://doi.org/10.1016/S0306-4522(98)00727-1
  38. Yatin SM, Varadarajan S, Link CD and Butterfield DA. (1999). In vitro and in vivo oxidative stress associated with Alzheimer' amyloid $\beta$ peptide (1-42). Neurobiology of Aging. 20:325-330 https://doi.org/10.1016/S0197-4580(99)00056-1
  39. Yoshikawa M, Uchida E, Kawaguchi A, Kitagawa I and Yamahara J. (1992). Galloyl-oxypaeoniflorin, suffruticosides A, B, C, and D, five new antioxidative glycosides, and suffruticoside E, A paeonol glycoside, from chinese Moutan cortex. Chemical and Pharmaceutical Bulletin (Tokyo). 40: 2248-2250 https://doi.org/10.1248/cpb.40.2248
  40. Zhang GQ, Hao XM, Zhou PA and Wu CH. (2003). Effect of paeonol on L-type calcium channel in rat ventricular myocytes. Mehods and Findings in Experimental and clinical Pharmacology. 25:281-285 https://doi.org/10.1358/mf.2003.25.4.769676