PMID- 27677544
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20200225
IS  - 1744-5116 (Electronic)
IS  - 1388-0209 (Print)
IS  - 1388-0209 (Linking)
VI  - 55
IP  - 1
DP  - 2017 Dec
TI  - Hesperidin, a citrus flavonoid, protects against l-methionine-induced 
      hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction 
      and neurotoxicity in Wistar rats.
PG  - 146-155
AB  - CONTEXT: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has 
      antioxidant, anti-inflammatory and neuroprotective properties. OBJECTIVE: This 
      study evaluates the protective effect of HSP on l-methionine-induced 
      hyperhomocysteinemia (HHcy) in rats. MATERIALS AND METHODS: Male Wistar rats were 
      randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 
      100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by 
      oral administration of l-methionine (1.7 g/kg) for 32 days. From the 14(th) day 
      of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to 
      l-methionine-treated rats. Cognitive impairment induced by HHcy was determined 
      using the Morris water maze (MWM) and Y-maze on video tracking system 
      (28(th)-32(nd) day). Different biomarkers of HHcy in serum and brain and vascular 
      reactivity were evaluated and histopathology (thoracic aorta and brain) was done. 
      RESULTS: HSP (100 mg/kg) treatment in l-methionine-treated rats exhibited 
      significant (p < 0.001) dose-dependent activity and reduced behavioural deficits, 
      brain acetylcholinesterase (25.99 +/- 2.36 versus 10.73 +/- 1.26 mumoles/mg), brain 
      lipid peroxidation (15.25 +/- 1.65 versus 6.18 +/- 0.74 nM/mg), serum homocysteine 
      (Hcy) (22.37 +/- 0.30 versus 11.01 +/- 1.01 mug/mL) and serum cholesterol 
      (182.7 +/- 2.15 versus 101.5 +/- 2.76 mg/dL) and increased brain antioxidant levels. 
      HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing 
      the effect of l-methionine on acetylcholine-induced endothelial-dependent 
      relaxation and increased serum nitrite and vascular nitric oxide bioavailability 
      along with the restoration of histological aberrations. CONCLUSION: HSP exerts a 
      protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.
FAU - Hemanth Kumar, B
AU  - Hemanth Kumar B
AD  - a Department of Pharmacology, Pharmacology , Anurag Group of Institutions 
      (Formerly Lalitha College of Pharmacy) , Hyderabad , Telangana , India.
AD  - b Pharmaceutical Sciences, Research and Development cell , Jawaharlal Nehru 
      Technological University , Kukatpally, Hyderabad , Telangana , India.
FAU - Dinesh Kumar, B
AU  - Dinesh Kumar B
AD  - c Food and Drug Toxicology Research Centre (FDTRC), National Institute of 
      Nutrition (ICMR) , Hyderabad , Telangana , India.
FAU - Diwan, Prakash V
AU  - Diwan PV
AD  - a Department of Pharmacology, Pharmacology , Anurag Group of Institutions 
      (Formerly Lalitha College of Pharmacy) , Hyderabad , Telangana , India.
AD  - d Maratha Mandal Research Center , Belgaum , Karnataka , India.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20160927
PL  - England
TA  - Pharm Biol
JT  - Pharmaceutical biology
JID - 9812552
RN  - 0 (Antioxidants)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Indans)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitrites)
RN  - 0 (Piperidines)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8SSC91326P (Donepezil)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - AE28F7PNPL (Methionine)
RN  - E750O06Y6O (Hesperidin)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - EC 3.1.1.7 (Ache protein, rat)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Behavior, Animal/*drug effects
MH  - Brain/*drug effects/metabolism/physiopathology
MH  - Cholesterol/blood
MH  - Cognition/drug effects
MH  - Cytoprotection
MH  - Disease Models, Animal
MH  - Donepezil
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*drug effects/metabolism/physiopathology
MH  - GPI-Linked Proteins/metabolism
MH  - Hesperidin/*pharmacology
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/blood/chemically induced/*drug therapy/physiopathology
MH  - Indans/pharmacology
MH  - Lipid Peroxidation/drug effects
MH  - Male
MH  - Maze Learning/drug effects
MH  - *Methionine
MH  - Neuroprotective Agents/*pharmacology
MH  - Neurotoxicity Syndromes/blood/physiopathology/*prevention & control/psychology
MH  - Nitric Oxide/metabolism
MH  - Nitrites/blood
MH  - Oxidative Stress/*drug effects
MH  - Piperidines/pharmacology
MH  - Rats, Wistar
MH  - Time Factors
MH  - Vasodilation/drug effects
PMC - PMC7011910
OTO - NOTNLM
OT  - Acetylcholinesterase
OT  - L-NAME
OT  - Morris water maze
OT  - donepezil
OT  - hippocampus
OT  - thoracic aorta
OT  - video tracking system
EDAT- 2016/09/30 06:00
MHDA- 2017/03/10 06:00
PMCR- 2016/09/27
CRDT- 2016/09/29 06:00
PHST- 2016/09/30 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
PHST- 2016/09/29 06:00 [entrez]
PHST- 2016/09/27 00:00 [pmc-release]
AID - 1231695 [pii]
AID - 10.1080/13880209.2016.1231695 [doi]
PST - ppublish
SO  - Pharm Biol. 2017 Dec;55(1):146-155. doi: 10.1080/13880209.2016.1231695. Epub 2016 
      Sep 27.