title: Inhibition of A&#946;(1-42)Oligomerization, Fibrillization and Acetylcholinesterase Activity by Some Anti-Inflammatory Drugs: An in vitro Study.
abstract: BACKGROUND
  Number of contradictory reports are available on the effects of antiinflammatory drugs on Alzheimer's disease (AD) including beneficial, adverse and stage dependent effects. We provide insights of the effects exerted by some anti-inflammatory drugs on the chemistry of AD.
  
  
  METHODS
  Three different doses of dexamethasone (0.015, 0.030, 0.060 μM), piroxicam (5, 7.5, 10 μM), indomethacin (1, 1.25, 1.50 μM), diclofenac (0.6, 0.8, 1.0 μM), aspirin (90, 120, 150 μM) and celecoxib (30, 45, 60 μM) were used. Rivastigmine, methylene blue and butylated hydroxyanisole were used as standard drug, oligomerization inhibitor and antioxidant, respectively. Oligomerization and fibrillization reactions were performed using Aβ1-42 peptides. Results-Indomethacin and aspirin mainly inhibited oligomerization, while rivastigmine and piroxicam inhibited fibrillization. Diclofenac and celecoxib inhibited both oligomerization and fibrillization almost equally. Dexamethasone showed poor efficiency on both the processes, but exert comparably more inhibition of oligomerization than fibrillization. Inhibition of acetylcholinesterase activity was also potent and was in the following order: celecoxib> piroxicam> diclofenac> aspirin> indomethacin> dexamethasone. Strong radical scavenging (More than 50%) activity was showed by indomethacin and aspirin for NO radicals.
  
  
  CONCLUSIONS
  Present study consistently revealed that anti-inflammatory drugs have potential to Modulate chemistry of AD progression. Inclusion of anti-inflammatory drugs in low doses along with routine therapies may provide therapeutically and economically more efficient therapies for AD. However, further studies are warranted, because the overall therapeutic effect seems to be the function of stage of disease, dose of drug, main underlying mechanism of action(s).
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore-452001, M.P.. India.
authors.forename: Hamendra S
authors.initials: HS
authors.lastname: Parmar
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.. India.
authors.forename: Anshul
authors.initials: A
authors.lastname: Assaiya
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.. India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Agrawal
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.. India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Tiwari
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.. India.
authors.forename: Iram
authors.initials: I
authors.lastname: Mufti
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.. India.
authors.forename: Neha
authors.initials: N
authors.lastname: Jain
authors.affiliation: School of Pharmacy, Devi Ahilya University, Indore-452001, M.P.. India.
authors.forename: Elangovan
authors.initials: E
authors.lastname: Manivannan
authors.affiliation: School of Life Sciences, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.. India.
authors.forename: Tushar
authors.initials: T
authors.lastname: Banerjee
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.. India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000975:Antioxidants / Q000737:chemistry; D001241:Aspirin / Q000737:chemistry; D002083:Butylated Hydroxyanisole / Q000737:chemistry; D000068579:Celecoxib / Q000737:chemistry; D003907:Dexamethasone / Q000737:chemistry; D004008:Diclofenac / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D008751:Methylene Blue / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D010894:Piroxicam / Q000737:chemistry; D000068836:Rivastigmine / Q000737:chemistry; D026082:Singlet Oxygen / Q000737:chemistry
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D010894:Piroxicam; D004008:Diclofenac; D026082:Singlet Oxygen; D002083:Butylated Hydroxyanisole; D009569:Nitric Oxide; D003907:Dexamethasone; D000110:Acetylcholinesterase; D000068579:Celecoxib; D000068836:Rivastigmine; D001241:Aspirin; D008751:Methylene Blue; D007213:Indomethacin
keywords: Acetylcholinesterase activity; Aβ oligomerization; anti-inflammatory drugs; fibrillization; nitric
  oxide radicals; singlet oxygen