title: Attenuation of inflammatory mediators, oxidative stress and toxic risk evaluation of Aporosa lindleyana Baill bark extract.
abstract: BACKGROUND
  Traditionally, Aporosa lindleyana Baill. has been used against various ailments viz. jaundice, fever, headache, seminal loss and insanity. The present study aims to evaluate the anti-inflammatory and anti-oxidant activity of the ethanolic extract of Aporosa lindleyana Baill. bark and its fractions.
  
  
  METHODS
  The anti-inflammatory activity of ethanolic extract of Aporosa lindleyana Baill. bark and its various fractions at doses of 200mg/kg and 300mg/kg b.w. has been carried out by a carrageenan induced hind paw edema method. To establish the probable mechanism of action, TNF-α and NO levels have been estimated by an ELISA method and the effect of active fraction on COX-2 and NF-κB expressions has been evaluated. The effect on the levels of anti-oxidative enzymes (CAT, SOD & GPX) by the ethanolic extract and its fractions has also been investigated. Furthermore, peptic ulcer and hepatotoxic risk evaluation has also been carried out at three times higher dose than that used in inflammatory in vivo model.
  
  
  RESULTS
  Among the extract and its various fractions tested for anti-inflammatory activity, the methanolic fraction at a dose of 300mg/kg showed significant inhibition in paw edema by 73% as compared to Indomethacin which showed 77% inhibition after 5h. The same dose of methanolic fraction also caused significant reduction in TNF-α (59.27%) and NO concentration (57.12%) while Indomethacin showed inhibition of 63.91% and 60.12%. The active methanolic fraction was also found to inhibit the expression of NF-κB and COX-2 induced by carrageenan. Histological studies showed that the ethanolic extract and its fractions did not cause any damage to the stomach as well as to liver. Moreover, the active fractions also decreased lipid peroxidation levels and increased the antioxidant enzyme activities (SOD, CAT, GPX).
  
  
  CONCLUSIONS
  The results of present study demonstrated that significant anti-inflammatory activity of methanolic fraction of Aporosa lindleyana may be attributed to the modulation of pro-inflammatory mediators. Same fraction was also found to be effective against oxidative stress as it was found to elevate the levels of anti-oxidative enzymes. It can therefore be concluded that the methanolic fraction could be explored as a disease modifying agent against inflammation and oxidative stress.
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Yakub
authors.initials: Y
authors.lastname: Ali
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India. Electronic address: msalam@jamiahamdard.ac.in.
authors.forename: Mohammad Sarwar
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Hinna
authors.initials: H
authors.lastname: Hamid
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Asif
authors.initials: A
authors.lastname: Husain
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Chetna
authors.initials: C
authors.lastname: Kharbanda
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Sameena
authors.initials: S
authors.lastname: Bano
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Syed
authors.initials: S
authors.lastname: Nazreen
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Saqlain
authors.initials: S
authors.lastname: Haider
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan; D002374:Catalase / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010437:Peptic Ulcer; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D064028:Tracheophyta; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016328:NF-kappa B; D009573:Nitrites; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Anti-inflammatory; Anti-oxidant; Aporosa lindleyana; NO; TNF-α; Ulcerogenic