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

Abstract

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.

Gut microbiota-mediated tributyltin-induced metabolic disorder in rats

“…46 It has been veried that the action of PERK could affect VLDL receptors that are regulators of liver TG and fatty degeneration. [47][48][49] As shown in Fig. 2G and H, the expression of PERK and CHOP increased remarkably under TBT exposure, and thus we hypothesized that TBT-induced ER stress might be due to the enhancement COX-2 by activating the PERK and CHOP responses.…”

Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease

“…ApoB100 and microsomal TG transfer protein (MTP) mediate VLDL secretion in hepatocytes. Studies have revealed that pharmacological inhibition of MTP can be used to treat hyperlipidaemia in rats with monosodium L-glutamate-induced obesity, while increases in MPT gene or protein expression can be used to treat NAFLD [33][34][35]. Studies have also indicated that upregulating PPAR-α, carnitine palmitoyltransferase-1a (CPT-1a) and fatty TG lipase (ATGL) to enhance FA oxidation and lipolysis can improve NAFLD in micee [36,37].…”

Potential benefits of patchouli alcohol in prevention of human diseases: A mechanistic review

“…In mice fed a high-fat diet for 12 weeks, oral administration of PA (25 and 50 mg/kg body weight) decreased the weight of abdominal white adipose tissues (epididymal and retroperitoneal adipose tissue). In a fatty liver animal model using Sprague Dawley rats, oral administration of PA (10, 20 and 40 mg/kg body weight) for four weeks attenuated hepatic steatosis through not only suppressing endoplasmic reticulum (ER) stress by inactivating ER stress mediators (PERK, IRE1 and ATF6) but also regulating hepatic VLDL uptake by reducing VLDL receptor expression and elevating VLDL secretion [29] . These reports imply that PA can be used for the prevention or treatment of metabolic diseases as a dietary supplement or functional food material.…”

“…Diverse health beneficial activities have been documented for PA, including: anti-influenza virus [10] , [11] , [12] , [13] , anti-inflammatory [14] , [15] , [16] , [17] , anti-oxidative [18] , anti-ulcerogenic [19] , [20] , anti-colitis [21] , [22] , anti-mucositis [23] and protective activities against brain and lung injuries [24] , [25] . Most recently, the effects of PA on cancer and metabolic disorders including obesity, fatty liver and gut microbiota have come under investigation [26] , [27] , [28] , [29] . However, despite these diverse beneficial effects, there is a lack of preclinical and clinical studies for the use of PA in the treatment of human diseases.…”