Korean J Physiol Pharmacol.  2014 Dec;18(6):469-474. 10.4196/kjpp.2014.18.6.469.

Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a Sodium Succinate Form of ZYM201

• Cho JY
• Choi J
• Park JG
• Yi YS
• Hossen MJ
• Kim H
• Ro J
• Cha BC
• Yoo ES
• Kim JH
• Lee J

• KMID: 2285548
• DOI: http://doi.org/10.4196/kjpp.2014.18.6.469

Abstract

DWP208 is a sodium succinate form of ZYM-201 which is a triterpenoid glycoside isolated from Sanguisorba officinalis, a medicinal plant prescribed for various diseases, such as duodenal ulcers and bleeding in East Asian counties. We demonstrated that this compound is able to normalize the altered lipid metabolism induced by hyperglycemia and a high fat diet. In this study, we determined whether hyperlipidemic conditions induced with chronically treated alcohol can also be restored by DWP208. Similar to our previous results, orally administered DWP208 (1 to 10 mg/kg) also ameliorated the hyperlipidemia that was induced by alcohol. This compound reversed the alcohol-induced hyperlipidemia including (i) up-regulated hyperlipidemic parameters such as low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherosclerotic index (AI), triglyceride, and total cholesterol, and (ii) down-regulated hyperlipidemic parameters such as absolute body weight, superoxide dismutase (SOD) activity, and high-density lipoprotein (HDL) in serum and liver. According to our data, the ameliorative activity of DWP208 is due to its indirect anti-oxidative activity as a result of which lipid peroxide and hydroxyl radical levels were reduced and the activity of SOD was enhanced. Therefore, our data strongly suggest that DWP208 can be used as a remedy against alcohol-induced hyperlipidemia.

Keyword

Anti-hyperlipidemic activity; Chronic alcohol treatment; DWP208; Sanguisorba officinalis; Triterpenoid glycoside

MeSH Terms

Asian Continental Ancestry Group
Body Weight
Cholesterol
Diet, High-Fat
Duodenal Ulcer
Hemorrhage
Humans
Hydroxyl Radical
Hyperglycemia
Hyperlipidemias*
Lipid Metabolism
Lipoproteins
Liver
Plants, Medicinal
Sanguisorba
Sodium*
Succinic Acid*
Superoxide Dismutase
Triglycerides
Cholesterol
Hydroxyl Radical
Lipoproteins
Sodium
Succinic Acid
Superoxide Dismutase

Figure

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  Fig. 1 Chemical structure of DWP208.

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  Fig. 2 Effect of DWP208 on serum parameters in alcohol-induced hyperlipidemic rats. (A) Alcohol-treated rats were orally administered with DWP208 or fenofibrate (Feno) for 1 week. After preparing serum from rats, levels of HDL, LDL, and VLDL were examined. (B) AI values were calculated from an equation [AI=(total cholesterol-HDL-cholesterol)/HDL-cholesterol]. Data represent mean±SEM of four independent observations performed with 10 rats. #p<0.05 and ##p<0.01 compared to normal group, *p<0.05 and **p<0.01 compared to control group.

• 

  Fig. 3 Effect of DWP208 on serum parameters in alcohol-induced hyperlipidemic rats. (A) Alcohol-treated rats were orally administered with DWP208 or fenofibrate (Feno) for 1 week. After preparing serum from rats, levels of triglyceride were examined. (B) Lipase activity in serum was determined. Data represent mean±SEM of four independent observations performed with 10 rats. #p<0.05 compared to normal group, *p<0.05 and **p<0.01 compared to control group.

• 

  Fig. 4 Effect of DWP208 on hepatic parameters in alcohol-induced hyperlipidemic rats. (A) Alcohol-treated rats were orally administered with DWP208 or fenofibrate (Feno) for 1 week. After preparing liver homogenates from rats, level of total lipid was examined. (B) Level of total cholesterol in liver was determined. (C) Level of triglyceride in liver was determined. Data represent the mean±SEM of four independent observations performed with 10 rats. ##p<0.01 compared to normal group, **p<0.01 compared to control group.

• 

  Fig. 5 Effect of DWP208 on the contents of lipid peroxide and hydroxyl radicals, and the activity of SOD in serum from alcohol-treated rats. (A) Alcohol-treated rats were orally treated with DWP208 or fenofibrate (Feno) for 1 week. After preparing serum, serum lipid peroxide contents were examined. (B) Hydroxyl radicals were examined from serum. (C) SOD activity was examined in serum. Data represent the mean±SEM of four independent observations performed with 10 rats. #p<0.05 compared to normal group, *p<0.05 compared to control group.

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