Inhibitory Effects of Oren-Gedoku-to and its Components on Cholesteryl Ester Synthesis in Cultured Human Hepatocyte HepG2 Cells: Evidence from the Cultured Hep2G Cells andIn VitroAssay of ACAT

Abstract

The pharmacological effects of Oren-gedoku-to (OGT), a Japanese-Chinese traditional herbal medicinal mixture on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of OGT (0.5 and 4.2 mg/ml), which had no effect on cell proliferation and cellular protein content, caused a marked decrease in the cellular cholesterol content, particularly cholesteryl ester content following 24 h incubation. The incorporation of 14C-oleate into cellular cholesteryl ester fraction was also reduced remarkably during incubation for 6 and 24 h. The effects of OGT, its components and its main active chemicals on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity were studied in vitro to explore the mechanism by which OGT inhibits cholesteryl ester formation. The data confirmed that OGT, in a dose-dependent manner, and its components (Scutellaria baicalensis, Coptis japonica, Gardenia jasminoides and Phellodendron amurense) remarkably inhibit ACAT activity. Among the main active chemicals of OGT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent fashion from the level of 10(-6)M. These results strongly suggest that OGT reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT, and that baicalein may, in part, be responsible for ACAT inhibition.

Antiatherogenic Properties of Naringenin, a Citrus Flavonoid

“…Therefore, inhibition of hepatic ACAT may be the mechanism whereby naringenin exerts its hypocholesterolemic effects. Inhibition of hepatic ACAT has also been demonstrated for a flavonoid structurally different from naringenin, baicalein (IC 50 of approximately 100 M in isolated rat hepatic microsomes) (96). Whether reduced apoB secretion and inhibition of ACAT activity are general features of flavonoids remains to be determined.…”

“…While the majority of research has focused on the antioxidant roles of flavonoids, a number of reports have suggested that these compounds may also influence atherogenesis through an effect on lipid and lipoprotein metabolism (4,8,10,14,15,51,88,94,96). Investigation of naturally occurring compounds as regulators of triglyceride and cholesterol metabolism has particular therapeutic importance, as evidenced by the discovery of the first HMG-CoA reductase inhibitors derived from fungal fermentation products, which are now widely used for the treatment of hyperlipidemia.…”

High‐performance liquid chromatographic method for the determination and pharmacokinetic study of wogonoside in rat serum after oral administration of traditional Chinese medicinal preparation Huang‐Lian‐Jie‐Du decoction

“…Huang-Lian-Jie-Du (Oren-geduku-to) decoction is a well-known preparation officially listed in the Chinese Pharmacopoeia (2000 edition), which has been used in treatment of diabetes mellitus (Lu et al, 2002), hyperlipemia (Yotsumoto et al, 1997;Kim et al, 2002), atherosclerosis (Sekiya et al, 2005), gastroinrestinal disorders (Ohta et al, 1999), hepatitis (Lin et al, 1996a,b), cardiovascular diseases (Xu et al, 2000) and ischemia-reperfusion brain injury (Hwang et al, 2002), for its anti-oxidant, anti-inflammatory, hypoglycemic, hypocholesterolemic, antiviral, hepato-protective and anti-bacterial activities and protective effect against impairment of learning and memory induced by transient cerebral ischemia. This compound prescription consists of Coptis Rhizoma, Gardenia fructus, Phellodendron cortex and Scutellaria radix.…”

Beneficial effect of Polygoni Multiflori Radix in high fructose diet-induced metabolic syndrome rat model

“…혈관 내피세포의 손상은 세포 유착 분자 (cell adhesion molecules)와 같은 분자와 혈관수축인자인 endothelin-1 (ET-1)과 같은 분자들을 발현 증가를 유도하여 혈관 내피 세 포 기능 저하 및 조직손상을 불러와 혈관염증 및 고혈압을 유 발하게 된다 4) . 최근에는 이러한 대사성 질환은 치료보다 예방이 필요한 질환으로 여겨져, 고지혈증, 고혈압, 그리고 당뇨병 등을 예 방하고 저해하는 각종 생리활성 물질을 천연물로부터 찾아내 려는 연구가 활발하게 진행되고 있으며, 치료효과에 대한 관 심이 높아져 이에 대한 수요도 증가하고 있다 [5][6][7] . 적하수오 (Polygoni Multiflori Radix, PMR)는 다년생 덩굴 성 초본으로 마디풀과의 식물에 속한다.…”