Eucommia ulmoides Oliver extract, aucubin, and geniposide enhance lysosomal activity to regulate ER stress and hepatic lipid accumulation

• Published in: PloS one 2013-12, Vol.8 (12), p.e81349-e81349
• Main Authors: Lee, Hwa-Young, Lee, Geum-Hwa, Lee, Mi-Rin, Kim, Hye-Kyung, Kim, Nan-young, Kim, Seung-Hyun, Lee, Yong-Chul, Kim, Hyung-Ryong, Chae, Han-Jung
• Format: Article
• Language: English
• Subjects: Accumulation; Adenosine triphosphatase; Apolipoprotein B; Apolipoproteins; Apoptosis; Cholesterol; Cholesterol - metabolism; Diabetes; Diet; Dietary supplements industry; Dyslipidemia; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Eucommiaceae - chemistry; Fatty acids; H+-transporting ATPase; Hep G2 Cells; Hepatocytes; High fat diet; Humans; Hypertension; In vivo methods and tests; Iridoid Glucosides - pharmacology; Iridoids - pharmacology; Kinases; Leaves; Lipids; Liver; Liver - drug effects; Liver - metabolism; Liver diseases; Lysosomes - drug effects; Medical schools; Medicinal plants; Metabolic disorders; Palmitic acid; Pharmaceutical industry; Pharmaceutical sciences; Pharmacology; Pharmacy; Physiology; Plant Extracts - pharmacology; Proteasomes; Protein folding; Proteolysis; Rats; Regulation; Rodents; Secretion; Stress; Stresses; Triglycerides; Triglycerides - metabolism; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081349

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.