Ishola I.O., Chaturvedi J.P., Rai S., Rajasekar N., Adeyemi O.O., Shukla R., Narender T.
Medicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), Lucknow-226 001, Uttar Pradesh, India; Pharmacology Division, Central Drug Research Institute, Lucknow-226 001, Uttar Pradesh, India; Department of Pharmacology, College of
Ishola, I.O., Pharmacology Division, Central Drug Research Institute, Lucknow-226 001, Uttar Pradesh, India, Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria; Chaturvedi, J.P., Medicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), Lucknow-226 001, Uttar Pradesh, India; Rai, S., Pharmacology Division, Central Drug Research Institute, Lucknow-226 001, Uttar Pradesh, India; Rajasekar, N., Pharmacology Division, Central Drug Research Institute, Lucknow-226 001, Uttar Pradesh, India; Adeyemi, O.O., Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria; Shukla, R., Pharmacology Division, Central Drug Research Institute, Lucknow-226 001, Uttar Pradesh, India; Narender, T., Medicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), Lucknow-226 001, Uttar Pradesh, India
Ethnopharmacological relevance: Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. Aim of the study: This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-α production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. Materials and methods: Rat astrocytoma cells (C6) were stimulated with LPS (10 μg/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3 μg/ml) for 24 h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-α level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test. Results: LPS (10 μg/ml) significantly (P<0.05) stimulated C6 cells to release nitrite, ROS, MDA, and TNF-α generation while GSH was down regulated in comparison to control. However, amentoflavone significantly (P<0.05) attenuated nitrite, ROS, MDA and TNF-α generation and also up regulated the level of GSH. Amentoflavone per se did not have any significant effect on C6 and THP-1 cells. Amentoflavone (6.25-50 mg/kg) significantly (P<0.05) reduced number of writhes and also increase pain threshold in hot plate test. It produced time course significant (P<0.05) decrease in oedema formation in rodents. Discussion and conclusion: Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in neuroinflammation associated disorders. © 2012 Elsevier Ireland Ltd.
amentoflavone; carrageenan; glutathione; ibuprofen; lipopolysaccharide; malonaldehyde; morphine; nimesulide; nitrite; reactive oxygen metabolite; tumor necrosis factor alpha; analgesic activity; animal cell; animal experiment; animal model; antiinflammatory activity; antinociception; article; astrocytoma cell; cell lysate; cell stimulation; cell viability; cnestis ferruginea; concentration response; Connaraceae; controlled study; cytokine production; down regulation; drug isolation; drug screening; female; hot plate test; human; human cell; in vivo study; incubation time; leukemia cell line; male; mediator; monocytic leukemia; mouse; nervous system inflammation; nitrative stress; nonhuman; oxidative stress; pain; pain threshold; paw edema; plant root; rat; writhing test; Acetic Acid; Animals; Anti-Inflammatory Agents; Astrocytoma; Biflavonoids; Carrageenan; Cell Line; Cell Line, Tumor; Cell Survival; Connaraceae; Edema; Female; Glutathione; Hot Temperature; Inflammation Mediators; Lipopolysaccharides; Male; Malondialdehyde; Mice; Nitrites; Pain; Phytotherapy; Plant Roots; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Connaraceae; Rattus; Rodentia
