title: Eucommia ulmoides Oliver extract, aucubin, and geniposide enhance lysosomal activity to regulate ER stress and hepatic lipid accumulation.
abstract: Eucommia ulmoides Oliver is a natural product widely used as a dietary supplement and medicinal plant. Here, we examined the potential regulatory effects of Eucommia ulmoides Oliver extracts (EUE) on hepatic dyslipidemia and its related mechanisms by in vitro and in vivo studies. EUE and its two active constituents, aucubin and geniposide, inhibited palmitate-induced endoplasmic reticulum (ER) stress, reducing hepatic lipid accumulation through secretion of apolipoprotein B and associated triglycerides and cholesterol in human HepG2 hepatocytes. To determine how EUE diminishes the ER stress response, lysosomal and proteasomal protein degradation activities were analyzed. Although proteasomal activity was not affected, lysosomal enzyme activities including V-ATPase were significantly increased by EUE as well as aucubin and geniposide in HepG2 cells. Treatment with the V-ATPase inhibitor, bafilomycin, reversed the inhibition of ER stress, secretion of apolipoprotein B, and hepatic lipid accumulation induced by EUE or its component, aucubin or geniposide. In addition, EUE was determined to regulate hepatic dyslipidemia by enhancing lysosomal activity and to regulate ER stress in rats fed a high-fat diet. Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemia.
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Medical School, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Medical School, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Geum-Hwa
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Medical School, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Mi-Rin
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Medical School, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea, Republic of Korea.
authors.forename: Nan-young
authors.initials: NY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, Chonbuk, Republic of Korea.
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Medical School, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
mesh_terms: D002784:Cholesterol / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D031283:Eucommiaceae / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D057888:Iridoid Glucosides / Q000494:pharmacology*; D039823:Iridoids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D057888:Iridoid Glucosides; D039823:Iridoids; D010936:Plant Extracts; D014280:Triglycerides; C007835:geniposide; C006650:aucubin; D002784:Cholesterol