The ¦Á-asarone/clofibrate hybrid compound, 2-methoxy-4-(2-propenyl)phenoxyacetic acid (MPPA), is endowed with neuroprotective and anticonvulsant potentialities

详细信息    查看全文

• 作者：Nicole Pages^a ; ^b ; ^{nicole.pages4@hotmail.fr} ; Pierre Maurois^b ; Pierre Bac^b ; Jean Jacques Vanden Eynde^c ; Joaqu?n Tamariz^d ; Fernando Labarrios^d ; Germá ; n Chamorro^e ; ^{gchamcev@yahoo.com.mx} ; Joseph Vamecq^f ; ^{joseph.vamecq@inserm.fr}
• 关键词：2-Methoxy-4-(2-propenyl) phenoxyacetic acid ; Neuroprotective ; Anticonvulsant and antioxidant properties ; Chemical ; Electrical and audiogenic seizure tests ; Magnesium deficiency ; Clofibrate ; ¦Á-asarone
• 刊名：Biomedicine & Aging Pathology
• 出版年：2011
• 出版时间：October-December 2011
• 年：2011
• 卷：1
• 期：4
• 页码：210-215
• 全文大小：326 K

文摘

2-methoxy-4-(2-propenyl)phenoxy acetic acid (MPPA) is a synthetic drug previously developed to mimic hypolipidemic activity and reduce side-effects of ¦Á-asarone, a vegetal extract used in traditional medicine to treat cardiovascular, neurological and other human disorders. MPPA was here evaluated in a battery of tests previously used to characterize anticonvulsant/neuroprotective and toxic potential of ¦Á-asarone in mice. MPPA toxicity was limited and doses up to 100 mg/kg induced neither hypothermia, nor reduction of spontaneous locomotor activity nor failure in rotarod test. Dose-dependent potentiation of the pentobarbital-induced sleeping was, however, observed at doses higher than 12.5 mg/kg. Little or no protection was provided by MPPA against seizures induced by N-methyl-D-aspartate. Moderate protection against subcutaneous pentylenetetrazol- and picrotoxin-induced seizures in mice, along with potentiation of pentobarbital-induced sleep, suggested GABAergic mechanisms. In maximal electroshock-induced seizures, MPPA protected 20 % tested mice at 30 mg/kg and shortened recovery phase in convulsing mice, suggesting some action on neuronal voltage-gated sodium channels. High efficacy of MPPA was further observed in magnesium-dependent audiogenic seizures test, a murine model responsive to a variety of anticonvulsant, neuroprotective and antioxidant compounds. In this test, 50 % animals were protected by 10 mg/kg MPPA, highlighting strong brain protective potential. In vitro, MPPA exhibited a superoxide-scavenging capacity about two-fold higher than that of ¦Á-asarone. Taken as a whole, present data support that MPPA is less toxic and more brain protective than ¦Á-asarone, and represents a worthy emerging neuroprotective/anticonvulsant compound endowed with a large activity spectrum including antioxidant, neuroprotective-like, moderate pro-GABAergic and sodium blockade mechanisms.