4-Hydroxyisophthalic acid from Decalepis hamiltonii rescues the neurobehavioral deficit in transgenic Drosophila model of taupathies.
Oxidative stress is one of the major etiological factors implicated in pathogenesis of neurodegenerative diseases. Since neurons are more sensitive to oxidative damage there is an increasing interest in developing novel antioxidant therapies, especially herbal preparations due to their safety profile and high efficiency. In this regard, the neuroprotective potential of a novel antioxidant compound, 4-hydroxyisophthalic acid (4-HIPA) isolated from aqueous extract of Decalepis hamiltonii roots was examined using transgenic Drosophila model of taupathy expressing wild-type and mutant forms of 2N4R isoform of human microtubule associated protein tau (MAPT). Taupathy model flies showed cognitive deficits in olfactory memory and deteriorated circadian rhythm of locomotory activities. Administration of 0.1 mg/ml 4-HIPA, markedly enhanced their olfactory memory performance and restored circadian rhythmicity of the transgenic flies locomotory behavior to the normal range. The mechanism of action that underlies 4-HIPA neuroprotection involves enhancement in efficiency of cellular antioxidant defense system by means of elevation in antioxidant enzyme activities and attenuation of oxidative stress. The molecule could positively affect the activity of neurotransmitter enzymes, which in turn enhances neuronal function and ameliorates the Tau-induced neurobehavioral deficits. Our findings showed that 4-HIPA can be considered as a suitable therapeutic candidate for drug development towards treatment of neurodegenerative disorders.
Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran.
Mohammad
M
Haddadi
Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
Samaneh Reiszadeh
SR
Jahromi
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, India.
Upendra
U
Nongthomba
Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
T
T
Shivanandappa
Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore, Karnataka, India. Electronic address: rameshuom@gmail.com.
S R
SR
Ramesh
D000818:Animals; D030801:Animals, Genetically Modified; D029062:Apocynaceae / Q000737:chemistry*; D002940:Circadian Rhythm / Q000187:drug effects*; D004331:Drosophila melanogaster; D008568:Memory / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010795:Phthalic Acids / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots
D010795:Phthalic Acids; D010936:Plant Extracts; C042941:4-hydroxyisophthalic acid
4-Hydroxyisophthalic acid; Decalepis hamiltonii; Neurobehavioral deficit; Oxidative stress; Tau protein; Transgenic Drosophila