Neuroprotective Effects in Gerbils of Spiramine T from Spiraea japonica var. acuta

Abstract

The neuroprotective effects of spiramine T, an atisine-type diterpenoid alkaloid isolated from the Chinese herbal medicine Spiraea japonica var. acuta (Rosaceaee), on cerebral ischemia-reperfusion injury produced by 10-min bilateral occlusion of the common carotid arteries followed by 5-day reperfusion in gerbils were investigated. Intravenous spiramine T (0.38, 0.75, and 1.5 mg · kg^-1) markedly reduced the stroke index, enhanced the recovery of EEG amplitude during reperfusion and decreased the concentrations of cortex calcium and LPO in a dose-dependent manner. However, no significant effects on water and sodium contents were observed. These results suggested that spiramine T exhibited protective effects on cerebral ischemia-reperfusion injury in gerbils, and its mechanism might be related to reducing calcium accumulation and lipid peroxidation. This is the first report on spiramine T as a natural product with neuroprotective effects.

Abbreviations

AA:arachidonic acid

EEG:electroencephalogram

LPO:lipid peroxide

MDA:malondialdehyde

PAF:platelet activating factor

Spiraea japonica var. acuta - Rosaceae - spiramine T - cerebral ischemia-reperfusion - stroke index - electroencephalogram - calcium - lipid peroxide

References

• 1 Pelletier S W, Page S W. Diterpenoid alkaloids.  Nat. Prod. Rep.. 1986;  3 (5) 451-64
• 2 Nie J L, Hao X J. Diterpene alkaloids from Spiraea japonica var. acuta .  Acta Bot. Yunnan.. 1997;  19 429-32
• 3 Fuji K, Node M, Kaku S, Shu T, Chin S. Anti-inflammatory diterpenes from chrysanthemums.  Chem. Abstr.. 1991;  115 287166k
• 4 Shen Z Q, Chen Z H, Li L, Lei W Y, Hao X J. Antiplatelet and antithrombotic effects of the diterpene spiramine Q from Spiraea japonica var. incisa .  Planta Medica. 2000;  66 287-9
• 5 Wang B G, Hong X, Zuo G Y, Hao X J. Structural revision of four spiramine diterpenoid alkaloids from the roots of Spiraea japonica .  J. Asian Nat. Prod. Res.. 2000;  in press
• 6 Ohno K, Ito U, Inaba Y. Regional cerebral blood flow and stroke index after left carotid artery ligation in the conscious gerbil.  Brain Res.. 1984;  297 151-7
• 7 Youny W, Rappaport H, Chalif D J, Flamm E S. Regional brain sodium, potassium and water changes in the rat middle cerebral artery occlusion of ischemia.  Stroke. 1987;  18 751-9
• 8 Bradbury M WB, Kleeman C R, Bagdoyan H, Berberian A. The calcium and magnesium content of skeletal muscle, brain, and cerebrospinal fluid as determined by atomic absorption flame photometry.  J. Lab. Clin. Med.. 1968;  71 884-92
• 9 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.  Anal. Biochem.. 1979;  95 351-8
• 10 Araki T, Kato H, Kogure K, Kanai Y. Long-term changes in gerbil neurotransmitter receptors following transient cerebral ischemia.  Br. J. Pharmacol.. 1992;  107 437-42
• 11 Rami A, Kreiglstein J. Neuronal protective effects of calcium antagonists in cerebral ischemia.  Life Sci.. 1994;  55 2105-13
• 12 Pahlmark K, Folbergrova J, Smith M L, Siesjo B K. Effects of dimethylthiourea on selective neuronal vulnerability in forebrain ischemia in rats.  Stroke. 1993;  24 731-7
• 13 Feng Y P. Pathophysiology of ischemic stroke and status of drug intervention.  Acta Pharmaceut. Sin.. 1999;  34 72-8
• 14 Frerichs K U, Feuerstein G Z. Platelet-activating factor - key mediator in neuroinjury?.  Cerebrovasc Brain Metab. Rev.. 1990;  2 148-60