title: LC-MS/MS profiling and neuroprotective effects of Mentat® against transient global ischemia and reperfusion-induced brain injury in rats.
abstract: OBJECTIVE
  The aim of this study was to evaluate the possible beneficial effects of Mentat against transient global ischemia and reperfusion-induced brain injury in rats.
  
  
  METHODS
  The neuroprotective effects of Mentat were evaluated against transient global ischemia and reperfusion (I/R)-induced brain injury in rats. Various neurobehavioral and biochemical parameters were assessed, followed by morphologic and histopathologic evaluation of brain tissue to conclude the protective effect of Mentat. Additionally, in vitro antioxidant assays were performed to explore the antioxidant capacity of Mentat and detailed liquid chromatography-mass spectrometry (LC-MS/MS) profiling was carried out to identify the active phytoconstituents responsible for the protective effects of Mentat.
  
  
  RESULTS
  Sixty minutes of transient global ischemia followed by 24 h reperfusion (I/R) caused significant alterations in the cognitive and neurologic functions in the ischemia control group (P < 0.01) compared with the sham control. Furthermore, 2,3,5-triphenyltetrazolium chloride staining of the ischemia control group showed 20.85% ± 0.39% of cerebral infarct area (P < 0.01), increased brain volume (% edema 17.81% ± 1.576%; P < 0.01), and increased lipid peroxidation (P < 0.01) in the brain homogenate. Additionally, the histopathology of the ischemia control group showed severe brain injury compared with the sham control group. Interestingly, pretreatment with Mentat (250 and 500 mg/kg, p.o.) and quercetin (20 mg/kg, p.o.) for 7 d has alleviated all pathological changes observed due to I/R injury. Mentat also showed very good antioxidant activity in in vitro assays (2,2-diphenyl-l-picrylhydrazyl, ferric-reducing antioxidant power, and oxygen radical absorbance capacity assays). Furthermore, the detailed LC-MS/MS analysis of Mentat was performed and enclosed for identifying the actives responsible for its protective effects.
  
  
  CONCLUSIONS
  These findings suggest that Mentat is a neuroprotective agent that may be a useful adjunct in the management of ischemic stroke and its rehabilitation especially with respect to associated memory impairment and other related neurologic conditions.
authors.affiliation: Department of Pharmacology, R&D Center, The Himalaya Drug Company, Bangalore, India. Electronic address: glv_000@yahoo.com.
authors.forename: Gollapalle Lakshminarayanashastry
authors.initials: GL
authors.lastname: Viswanatha
authors.affiliation: Department of Phytochemistry, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Lakkavalli Mohan Sharath
authors.initials: LM
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, R&D Center, The Himalaya Drug Company, Bangalore, India. Electronic address: Dr.rafiq@himalayawellness.com.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rafiq
authors.affiliation: Department of Pharmacology, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Kethaganahalli Jayaramaiah
authors.initials: KJ
authors.lastname: Kavya
authors.affiliation: Department of Pharmacology, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Agadi Hiremath
authors.initials: AH
authors.lastname: Thippeswamy
authors.affiliation: Department of Pharmacology, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Huvvinamadu Chandrashekarappa
authors.initials: HC
authors.lastname: Yuvaraj
authors.affiliation: Department of Pharmacology, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Azeemuddin
authors.affiliation: Department of Pharmacology, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Suryakanth Dattatreya
authors.initials: SD
authors.lastname: Anturlikar
authors.affiliation: Medical Services and Clinical Trials, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Pralhad Sadashiv
authors.initials: PS
authors.lastname: Patki
authors.affiliation: Department of Phytochemistry, R&D Center, The Himalaya Drug Company, Bangalore, India.
authors.forename: Uddagiri Venkanna
authors.initials: UV
authors.lastname: Babu
authors.affiliation: Chief Scientific Officer, The Himalaya Drug Company, Bangalore, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Ramakrishnan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002853:Chromatography, Liquid / Q000379:methods; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; C074754:Mentat; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011794:Quercetin
keywords: Antioxidants; Cerebral ischemia; Common carotid occlusion; Mentat; Stroke