The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation.
Plant-based whole foods provide thousands of bioactive metabolites to the human diet that reduce the risk of developing chronic diseases. β-Caryophyllene (CAR) is a common constituent of the essential oil of numerous plants, vegetables, fruits and medicinal herbs, and has been used as a flavouring agent since the 1930 s. Here, we report the antioxidant activity of CAR, its protective effect on liver fibrosis and its inhibitory capacity on hepatic stellate cell (HSC) activation. CAR was tested for the inhibition of lipid peroxidation and as a free radical scavenger. CAR had higher inhibitory capacity on lipid peroxidation than probucol, α-humulene and α-tocopherol. Also, CAR showed high scavenging activities against hydroxyl radical and superoxide anion. The activity of 5-lipoxygenase, an enzyme that actively participates in fibrogenesis, was significantly inhibited by CAR. Carbon tetrachloride-treated rats received CAR at 2, 20 and 200 mg/kg. CAR significantly improved liver structure, and reduced fibrosis and the expression of Col1a1, Tgfb1 and Timp1 genes. Oxidative stress was used to establish a model of HSC activation with overproduction of extracellular matrix proteins. CAR (1 and 10 μm) increased cell viability and significantly reduced the expression of fibrotic marker genes. CAR, a sesquiterpene present in numerous plants and foods, is as a natural antioxidant that reduces carbon tetrachloride-mediated liver fibrosis and inhibits hepatic cell activation.
UGC Farmacia, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Miguel Angel
MA
Calleja
Bioquímica de Alimentos, Instituto de Investigaciones Marinas (CSIC), Vigo, Spain.
Jose María
JM
Vieites
Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
Trinidad
T
Montero-Meléndez
Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
Trinidad
T
Montero-Meterdez
Departamento de Biología Experimental, Universidad de Jaen, Jaen, Spain.
María Isabel
MI
Torres
Departamento de Bioquímica y Biología Molecular 2, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
María José
MJ
Faus
Departamento de Bioquímica y Biología Molecular 2, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
Angel
A
Gil
Instituto de Nutrición y Tecnología de los Alimentos, Centro de Investigación Biomédica, Armilla, Spain.
Antonio
A
Suárez
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019587:Dietary Supplements; D005260:Female; D005421:Flavoring Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000081222:Monocyclic Sesquiterpenes; D018384:Oxidative Stress / Q000187:drug effects; D000081223:Polycyclic Sesquiterpenes; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000378:metabolism / Q000627:therapeutic use
D000975:Antioxidants; D005421:Flavoring Agents; D016166:Free Radical Scavengers; D016859:Lipoxygenase Inhibitors; D000081222:Monocyclic Sesquiterpenes; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C042686:humulene; C024714:caryophyllene; D001094:Arachidonate 5-Lipoxygenase; D024502:alpha-Tocopherol; D011341:Probucol