ZYM-201 Sodium Succinate Ameliorates Streptozotocin-Induced Hyperlipidemic Conditions

Abstract

ZYM-201 is a methyl ester of a novel triterpenoid glycoside. It is isolated from SANGUISORBA OFFICINALIS, a widely used medicinal plant in Korea, China, and Japan, that is prescribed for various diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. In this study, the antihyperlipidemic effect of the salt form (sodium succinate) of ZYM-201 was examined using streptozotocin (STZ)-treated hyperglycemic rats. Oral administration of ZYM-201 sodium succinate (3 to 10 mg/kg) resulted in recovery of the increased serum levels of triglyceride (TG) and total cholesterol (TC) back to normal levels. Elevated levels of serum lipoproteins, such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), were also significantly restored by this compound without altering 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. Finally, ZYM-201 sodium succinate displayed antioxidative properties, including suppression of lipid peroxide and hydroxyl radical generation and upregulation of superoxide dismutase (SOD) activity. Therefore, our data strongly suggest that ZYM-201 sodium succinate can be used as a remedy for the treatment of diabetes-derived hyperlipidemic disorders such as atherosclerosis and vascular diseases.

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

“…Since we found that DWP208, a water-soluble salt form of ZYM-201, is able to normalize the up-regulated levels of hyperlipidemic parameters in an animal model of streptozotocin-induced diabetes that was simultaneously fed a high fat diet [ 20 ], we examined the effects of DWP208 on alcohol-induced hyperlipidemia. Chronic alcohol addiction is more prevalent in the Korean population and causes serious effects such as liver damage, leading to the generation of fatty liver, cirrhosis, and liver cancer.…”

“…Also, DWP208 was able to ameliorate the hyperlipidemia induced by a high fat diet or streptozotocin [ 20 ]. Furthermore, DWP208 protected against the hyperlipidemia induced by chronic alcohol intake.…”

O-prenylated flavonoid, an antidiabetes constituent in Melicope lunu-ankenda

“…Moreover, these results point towards the additional utility of OPF as an antihypertriglyceridimic and anti-hyperlipedemic agent. A recent study reported an antidiabetes compound sodium succinate capable of ameliorating such diabetes derived hyperlipidemic complications (Choi et al, 2012). In diabetic subjects, the body weight tends to reduce significantly as a result of extreme protein catabolism leading to muscle wasting.…”

Immunomodulatory Effects of ZYM-201 on LPS-stimulated B Cells

“…Taken together, these data indicate that ZYM-201, which has been known to have inhibiting tissue factor activity, TNF-α production and modulating hyperlipidemic conditions ( 10 , 11 , 12 ), has another function of anti-inflammatory activities via inhibition of NF-κB activation and downregulation of costimulatory molecules in B cells. In agreement with this, previous studies showed that inhibition of NF-κB activation suppress inflammatory responses ( 23 ) and have anti-inflammation and anticancer effects ( 24 ), and suggested that it could be used to treat immune diseases ( 25 ).…”

“…ZYM-201 is a modified compound of ziyuglycoside, one of triterpene glycoside originated from the root of S. officinalis , through deglycosidation and esterification ( 10 ). Previous studies have shown that ZYM-201 plays a role in inhibiting tissue factor activity, tumor necrosis factor (TNF)-α production and modulating hyperlipidemic conditions ( 10 , 11 , 12 ).…”