title: Hepatoprotection of sesquiterpenoids: a quantitative structure-activity relationship (QSAR) approach.
abstract: The relative hepatoprotection effect of fifteen sesquiterpenoids, commonly found in plants and plant-derived foods and beverages was assessed. Endogenous lipid peroxidation (assay A) and induced lipid peroxidation (assay B) were evaluated in liver homogenates from Wistar rats by the thiobarbituric acid reactive species test. Sesquiterpenoids with different chemical structures were tested: trans,trans-farnesol, cis-nerolidol, (-)-α-bisabolol, trans-β-farnesene, germacrene D, α-humulene, β-caryophyllene, isocaryophyllene, (+)-valencene, guaiazulene, (-)-α-cedrene, (+)-aromadendrene, (-)-α-neoclovene, (-)-α-copaene, and (+)-cyclosativene. Ascorbic acid was used as a positive antioxidant control. With the exception of α-humulene, all the sesquiterpenoids under study (1mM) were effective in reducing the malonaldehyde levels in both endogenous and induced lipid peroxidation up to 35% and 70%, respectively. The 3D-QSAR models developed, relating the hepatoprotection activity with molecular properties, showed good fit (Radj(2) 0.819 and 0.972 for the assays A and B, respectively) with good prediction power (Q(2)>0.950 and SDEP<2%, for both models A and B). A network of effects associated with structural and chemical features of sesquiterpenoids such as shape, branching, symmetry, and presence of electronegative fragments, can modulate the hepatoprotective activity observed for these compounds.
authors.affiliation: QOPNA, Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Juliana
authors.initials: J
authors.lastname: Vinholes
authors.forename: Alisa
authors.initials: A
authors.lastname: Rudnitskaya
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonçalves
authors.forename: Fátima
authors.initials: F
authors.lastname: Martel
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Coimbra
authors.forename: Sílvia M
authors.initials: SM
authors.lastname: Rocha
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D012717:Sesquiterpenes
keywords: Hepatoprotection; Lipid peroxidation; Quantitative structure–activity relationship; Rat hepatocytes; Sesquiterpenoids; TBARS