TY - JOUR
T1 - The α-asarone/clofibrate hybrid compound, 2-methoxy-4-(2-propenyl) phenoxyacetic acid (MPPA), is endowed with neuroprotective and anticonvulsant potentialities
AU - Pages, Nicole
AU - Maurois, Pierre
AU - Bac, Pierre
AU - Vanden Eynde, Jean Jacques
AU - Tamariz, Joaquín
AU - Labarrios, Fernando
AU - Chamorro, Germán
AU - Vamecq, Joseph
PY - 2011/10
Y1 - 2011/10
N2 - 2-methoxy-4-(2-propenyl)phenoxy acetic acid (MPPA) is a synthetic drug previously developed to mimic hypolipidemic activity and reduce side-effects of α-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 α-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 α-asarone. Taken as a whole, present data support that MPPA is less toxic and more brain protective than α-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.
AB - 2-methoxy-4-(2-propenyl)phenoxy acetic acid (MPPA) is a synthetic drug previously developed to mimic hypolipidemic activity and reduce side-effects of α-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 α-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 α-asarone. Taken as a whole, present data support that MPPA is less toxic and more brain protective than α-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.
KW - 2-Methoxy-4-(2-propenyl) phenoxyacetic acid
KW - Anticonvulsant and antioxidant properties
KW - Chemical
KW - Clofibrate
KW - Electrical and audiogenic seizure tests
KW - Magnesium deficiency
KW - Neuroprotective
KW - α-asarone
UR - http://www.scopus.com/inward/record.url?scp=83555168150&partnerID=8YFLogxK
U2 - 10.1016/j.biomag.2011.09.005
DO - 10.1016/j.biomag.2011.09.005
M3 - Artículo
SN - 2210-5220
VL - 1
SP - 210
EP - 215
JO - Biomedicine and Aging Pathology
JF - Biomedicine and Aging Pathology
IS - 4
ER -