title: Opuntia ficus-indica seed attenuates hepatic steatosis and promotes M2 macrophage polarization in high-fat diet-fed mice.
abstract: Opuntia ficus-indica (L.) is a popular edible plant that possesses considerable nutritional value and exhibits diverse biological actions including anti-inflammatory and antidiabetic activities. In this study, we hypothesized that DWJ504, an extract of O ficus-indica seed, would ameliorate hepatic steatosis and inflammation by regulating hepatic de novo lipogenesis and macrophage polarization against experimental nonalcoholic steatohepatitis. Mice were fed a normal diet or a high-fat diet (HFD) for 10 weeks. DWJ504 (250, 500, and 1000 mg/kg) or vehicle (0.5% carboxymethyl cellulose) were orally administered for the last 4 weeks of the 10-week HFD feeding period. DWJ504 treatment remarkably attenuated HFD-induced increases in hepatic lipid content and hepatocellular damage. DWJ504 attenuated increases in sterol regulatory element-binding protein 1 and carbohydrate-responsive element-binding protein expression and a decrease in carnitine palmitoyltransferase 1A. Although DWJ504 augmented peroxisome proliferator-activated receptor α protein expression, it attenuated peroxisome proliferator-activated receptor γ expression. Moreover, DWJ504 promoted hepatic M2 macrophage polarization as indicated by attenuation of the M1 marker genes and enhancement of M2 marker genes. Finally, DWJ504 attenuated expression of toll-like receptor 4, nuclear factor κB, tumor necrosis factor α, interleukin 6, TIR-domain-containing adapter-inducing interferon β, and interferon β levels. Our results demonstrate that DWJ504 prevented intrahepatic lipid accumulation, induced M2 macrophage polarization, and suppressed the toll-like receptor 4-mediated inflammatory signaling pathway. Thus, DWJ504 has therapeutic potential in the prevention of nonalcoholic fatty liver disease.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Kang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Shin
authors.affiliation: Daewoong Life Science Research Institute, Daewoong Pharmaceutical Co, Ltd, Yongin-si, Gyeonggi-do 449-814, South Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Koh
authors.affiliation: Daewoong Life Science Research Institute, Daewoong Pharmaceutical Co, Ltd, Yongin-si, Gyeonggi-do 449-814, South Korea.
authors.forename: Hyojeong
authors.initials: H
authors.lastname: Ryu
authors.affiliation: Molecular Recognition Research Division, Korea Institute of Science & Technology, Seoul 130-722, South Korea.
authors.forename: Hyoung Ja
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea. Electronic address: sunmee@skku.edu.
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D059305:Diet, High-Fat; D015870:Gene Expression; D007004:Hypoglycemic Agents; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000517:prevention & control*; D029747:Opuntia; D010936:Plant Extracts / Q000008:administration & dosage*; D012639:Seeds / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D007004:Hypoglycemic Agents; D010936:Plant Extracts
keywords: High-fat diet fed mice; Lipid accumulation; Macrophage polarization; Non-alcoholic fatty liver disease; Opuntia ficus-indica seed; Toll-like receptor 4