Regulation of Low‐Density Lipoprotein Receptor and 3‐Hydroxy‐3‐Methylglutaryl Coenzyme A Reductase Expression by Zingiber officinale in the Liver of High‐Fat Diet‐Fed Rats

Abstract

Zingiber officinale has been used to control lipid disorders and reported to possess remarkable cholesterol-lowering activity in experimental hyperlipidaemia. In the present study, the effect of a characterized and standardized extract of Zingiber officinale on the hepatic lipid levels as well as on the hepatic mRNA and protein expression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated in a high-fat diet-fed rat model. Rats were treated with an ethanol extract of Zingiber officinale (400 mg ⁄ kg) extract along with a high-fat diet for 6 weeks. The extract of Zingiber officinale significantly decreased hepatic triglyceride and tended to decrease hepatic cholesterol levels when administered over 6 weeks to the rats fed a high-fat diet. We found that in parallel, the extract up-regulated both LDL receptor mRNA and protein level and down-regulated HMG-CoA reductase protein expression in the liver of these rats. The metabolic control of body lipid homeostasis is in part due to enhanced cholesterol biosynthesis and reduced expression of LDL receptor sites following long-term consumption of high-fat diets. The present results show restoration of transcriptional and post-transcriptional changes in low-density lipoprotein and HMG CoA reductase by Zingiber officinale administration with a high-fat diet and provide a rational explanation for the effect of ginger in the treatment of hyperlipidaemia.Although cholesterol is an essential component of mammalian cell membranes, excess cellular and circulating cholesterol is detrimental and contributes to several life-threatening diseases, including atherosclerotic and coronary artery cardiovascular disease [1,2]. Cellular cholesterol homeostasis is maintained primarily through regulation of the low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which respectively affect the uptake and endogenous synthesis of cholesterol in the liver [3][4][5]. A large number of studies have elucidated the role of these regulatory mechanisms in vitro, in experimental animals and in humans treated with experimental diets or drugs [6][7][8]. Recent studies have also shown a regulatory effect of various phyto-ingredients on potential targets controlling in vivo cholesterol homeostasis in animal models treated with atherogenic diets [9][10][11].Zingiber officinale Roscoe (Family: Zingiberaceae) commonly known as 'ginger', is a well-known food spice which has also been used traditionally in a wide variety of ailments [12,13]. The major chemical constituents of ginger rhizome are essential volatile oils and non-volatile pungent compounds [14,15]. The volatile oil components consist mainly of various terpenoids. The non-volatile compounds include the gingerols, shogaols, paradols and zingerone. Among them, the gingerols and shogaols were identified as the major bioactive constituents of ginger, found respectively in fresh and dried ginger [16].In laboratory experiments, e...

Zingiber officinale (Ginger): A Future Outlook on Its Potential in Prevention and Treatment of Diabetes and Prediabetic States

“…In the HFD-treated rats [28] ginger extract effectively reduced the elevated levels of serum total cholesterol and LDL-cholesterol towards control levels, in addition to producing a marked reduction in elevated serum triglycerides, free fatty acids, and phospholipids. Similar results were found in another HFD study (60% fat and 10.6% carbohydrate), where Zingiber officinale extract (400 mg/kg for 6 weeks) reduced the enhanced triglyceride levels and showed a small but not significant decrease in hepatic cholesterol level [29]. Rosiglitazone as a positive control had a similar effect.…”

“…This effect was similar to that of the control rosiglitazone. [29]. Animal studies allow the testing of the effects of herbal extracts on lipid changes and key enzymes and gene and receptor expression in the chosen animal model.…”

Herbal Medicines for the Treatment of Nonalcoholic Steatohepatitis: Current Scenario and Future Prospects

“…Various pharmacological studies have reported the beneficial role of ginger against diabetes, hyperlipidemia, and obesity [165–171]. Studies from our laboratory had reported on the underlying mechanisms of ginger in regulating hepatic cholesterol and lipid metabolism in high fat diet-fed rats [172, 173]. In this study, hypercholesterolemia was mainly regulated via increased protein expression of hepatic low-density lipoprotein (LDL) receptor and reduced HMG-CoA reductase.…”

Pengaruh susu kedelai dan jahe terhadap kadar kolesterol total pada wanita hiperkolesterolemia

“…12 Senyawa oleoresin (gingerol dan shogaol) merupakan komponen utama pada jahe yang dapat menghambat peroksidasi lipid dan menghambat enzim HMG-KoA reduktase dalam biosintesis kolesterol. [13][14][15] Selain itu, penambahan jahe pada komponen susu kedelai diketahui dapat meningkatkan aktivitas antioksidan, sehingga dapat berperan dalam penurunan kadar kolesterol darah.…”

“…12 Senyawa oleoresin (gingerol dan shogaol) merupakan komponen utama pada jahe yang dapat menurunkan kolesterol dengan menghambat peroksidasi lipid dan menghambat enzim HMG-KoA reduktase dalam biosintesis kolesterol. [13][14][15] Jahe yang ditambahkan dalam susu kedelai dapat meningkatkan aktivitas antioksidan. Penelitian penambahan ekstrak jahe 3% pada pembuatan susu kedelai dengan metode spray drying menunjukkan aktivitas antioksidan 21,67% lebih tinggi bila dibandingkan susu kedelai tanpa jahe dengan aktivitas antioksidan 10,3%.…”