Chrysin exerts neuroprotective effects against 3-Nitropropionic acid induced behavioral despair-Mitochondrial dysfunction and striatal apoptosis via upregulating Bcl-2 gene and downregulating Bax-Bad genes in male wistar rats.
3-Nitropropionic acid (3-NP) is an irreversible inhibitor of mitochondrial complex-II that causes transcriptional dysregulation, bioenergetics failure, protein aggregation and oxidative damage similar to Huntington's disease (HD) pathogenesis. Chrysin, a bioactive flavonoid reported to have anti-inflammation, antioxidant, vasorelaxant and neuroprotective property. The present study was framed to determine the neuroprotective efficiency of chrysin upon 3-NP induced oxidative stress, mitochondrial dysfunctions and neurodegeneration. 3-NP (10mg/kg b.w. i.p.) administration for 14days exhibited significant (P<0.01) behavioral alterations, mitochondrial dysfunction and oxidative damages to biomolecules, finally causes cell death. Chrysin at 50mg/kg b.w. orally for 14days improved all the behavioral performances and regulated the complex activities in mitochondria. Further, chrysin diminished the oxidative stress markers (lipid peroxidation, nitrite and protein carbonyls) by significantly (P<0.01) improving the antioxidant status (superoxide dismutase, catalase and reduced glutathione) in striatal mitochondria. Indeed, chrysin prevents apoptosis by upregulating the Bcl-2 mRNA expression and downregulating the pro-apoptotic (Bax, Bad) mRNAs in 3-NP induced condition. Furthermore, the survival of striatal neurons against 3-NP toxicity was enhanced upon chrysin treatment which was evidenced by observing histopathological studies. Hence, the present study collectively suggests that the chrysin can serve as a potential therapeutic agent on 3-NP induced mitochondrial deficits and subsequent apoptosis.
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113,Tamil Nadu, India. Electronic address: drsumathi.bioscience@gmail.com.
Sumathi
S
Thangarajan
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113,Tamil Nadu, India.
Surekha
S
Ramachandran
Department of Biotechnology, Rajalakshmi Engineering College, Rajalakshmi Nagar, Thandalam, Chennai, 602 105, Tamil Nadu, India.
Priya
P
Krishnamurthy
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology*; D006816:Huntington Disease / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D008933:Mitochondrial Swelling / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds; D018384:Oxidative Stress / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011422:Propionates; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*
C494821:Bad protein, rat; C494828:Bax protein, rat; D015415:Biomarkers; D005419:Flavonoids; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C043561:chrysin; C015392:3-nitropropionic acid
3-Nitropropionic acid; Apoptotic markers; Chrysin; Histopathology; Huntington’s disease; Mitochondrial dysfunction