Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of Pogostemon cablin (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.

[1]  F. Tacke,et al.  Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis , 2019, Hepatology.

[2]  A. Henkel,et al.  Unfolded Protein Response Sensors in Hepatic Lipid Metabolism and Nonalcoholic Fatty Liver Disease , 2018, Seminars in Liver Disease.

[3]  C. Hetz,et al.  Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. , 2018, Journal of hepatology.

[4]  X. Lai,et al.  Patchouli oil isolated from the leaves of Pogostemon cablin ameliorates ethanol-induced acute liver injury in rats via inhibition of oxidative stress and lipid accumulation , 2018, RSC advances.

[5]  J. Lykkesfeldt,et al.  Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease , 2018, Cellular and Molecular Life Sciences.

[6]  S. Battaglia-Hsu,et al.  Endoplasmic Reticulum Stress in Metabolic Disorders , 2018, Cells.

[7]  Reina Ikaga,et al.  Soya protein β-conglycinin ameliorates fatty liver and obesity in diet-induced obese mice through the down-regulation of PPARγ , 2018, British Journal of Nutrition.

[8]  R. Kaufman,et al.  IRE1α prevents hepatic steatosis by processing and promoting the degradation of select microRNAs , 2018, Science Signaling.

[9]  A. Lehmann,et al.  High-Throughput GLP-Capable Target Cell Visualization Assay for Measuring Cell-Mediated Cytotoxicity , 2018, Cells.

[10]  Yuhan Tang,et al.  Quercetin ameliorates HFD-induced NAFLD by promoting hepatic VLDL assembly and lipophagy via the IRE1a/XBP1s pathway. , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[11]  T. Quesada-López,et al.  Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease , 2017, Molecular metabolism.

[12]  Jianhui Xie,et al.  &bgr;‐Patchoulene from patchouli oil protects against LPS‐induced acute lung injury via suppressing NF‐&kgr;B and activating Nrf2 pathways , 2017, International immunopharmacology.

[13]  Xiangmei Zhao,et al.  Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats , 2017, PloS one.

[14]  Ziren Su,et al.  Transformation of patchouli alcohol to β-patchoulene by gastric juice: β-patchoulene is more effective in preventing ethanol-induced gastric injury , 2017, Scientific Reports.

[15]  G. Yen,et al.  The hepatoprotective effect of Phyllanthus emblica L. fruit on high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in SD rats. , 2017, Food & function.

[16]  G. Watts,et al.  Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism , 2017, Circulation.

[17]  J. Ruesink,et al.  Population genetics of the Manila clam (Ruditapes philippinarum) introduced in North America and Europe , 2017, Scientific Reports.

[18]  Z. Goodman,et al.  Epidemiology and natural history of non-alcoholic fatty liver disease. , 2016, Metabolism: clinical and experimental.

[19]  Jianhui Xie,et al.  Anti-inflammatory activity of β-patchoulene isolated from patchouli oil in mice. , 2016, European journal of pharmacology.

[20]  Victor R. Preedy,et al.  Essential oils in food preservation, flavor and safety , 2015 .

[21]  N. U. Ashraf,et al.  Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non-alcoholic fatty liver disease , 2015, Free radical research.

[22]  Rongmei Wang,et al.  Patchouli alcohol protects against lipopolysaccharide-induced acute lung injury in mice. , 2015, The Journal of surgical research.

[23]  L. F. Leandro,et al.  In Vivo Assessment of Genotoxic, Antigenotoxic and Anticarcinogenic Activities of Solanum lycocarpum Fruits Glycoalkaloidic Extract , 2014, PloS one.

[24]  Xl-L. Wu,et al.  Isolation of (-)-Patchouli Alcohol from Patchouli Oil by Fractional Distillation and Crystallization , 2014 .

[25]  Sun Yoon,et al.  Fermentation of Soy Milk via Lactobacillus plantarum Improves Dysregulated Lipid Metabolism in Rats on a High Cholesterol Diet , 2014, PloS one.

[26]  Jian-Guo Jiang,et al.  Origin and concept of medicine food homology and its application in modern functional foods. , 2013, Food & function.

[27]  D. Figeys,et al.  Microsome-associated lumenal lipid droplets in the regulation of lipoprotein secretion , 2013, Current opinion in lipidology.

[28]  J. Seong,et al.  Endoplasmic reticulum stress induces hepatic steatosis via increased expression of the hepatic very low‐density lipoprotein receptor , 2013, Hepatology.

[29]  R. Kaufman,et al.  IRE1α-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid homeostasis. , 2012, Cell metabolism.

[30]  K. Adeli,et al.  Lecithin:Cholesterol Acyltransferase Deficiency Protects against Cholesterol-induced Hepatic Endoplasmic Reticulum Stress in Mice* , 2012, The Journal of Biological Chemistry.

[31]  H. Taniguchi,et al.  Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets , 2012, Molecular biology of the cell.

[32]  A. Harada,et al.  Induction of Liver Steatosis and Lipid Droplet Formation in ATF6α-Knockout Mice Burdened with Pharmacological Endoplasmic Reticulum Stress , 2010, Molecular biology of the cell.

[33]  K. Adeli,et al.  Glucosamine-induced endoplasmic reticulum stress attenuates apolipoprotein B100 synthesis via PERK signaling , 2009, Journal of Lipid Research.

[34]  H. Ginsberg,et al.  Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. , 2008, The Journal of clinical investigation.

[35]  W. Paschen,et al.  Endoplasmic Reticulum Stress , 2007, Annals of the New York Academy of Sciences.

[36]  Dong Wang,et al.  Saturated fatty acid-mediated endoplasmic reticulum stress and apoptosis are augmented by trans-10, cis-12-conjugated linoleic acid in liver cells , 2007, Molecular and Cellular Biochemistry.

[37]  Michael C. Wendl,et al.  Argonaute—a database for gene regulation by mammalian microRNAs , 2005, BMC Bioinformatics.

[38]  G. Palade.  THE ENDOPLASMIC RETICULUM , 1956, The Journal of biophysical and biochemical cytology.