The Study On Antioxidation And Lipid Regulation Of Saponins From Platycodon Grandiflorum

Platycodon grandiflorum A. DC. (PG) is commonly known as Jiegeng in China. In China as well as other Asian countries, it has been widely used as a food material and for the treatment of many chronic inflammatory diseases in traditional oriental medicine for such conditions as bronchitis, asthma and pulmonary tuberculosis. Chemical analyses of PG have revealed that triterpenoid saponins are its main chemical components (PGTS). And earlier studies examining the roots of Platycodon grandiflorum A.DC have reported on the isolation and structural elucidation of these triterpenoid saponins, in which platycodins A, C, and D were determined as the primary saponins. Among the many compounds that have been isolated from PG, platycodon D has been found to possess the most potent biological activities, including immunological adjuvant, anti-inflammation and immunomodulation, protective effect on ischemia or reperfusion injury in the gerbil hippocampus, induction apoptosis through nuclear factor-κB activation in immortalized keratinocytes, cholesterol-lowering effect, antinociceptive profiles, antileukemia activity, use in cancer chemotherapy and so on.Atherosclerosis is a chronic inflammatory process as a result of increased oxidative stress. Studies have demonstrated that oxidized low-density lipoprotein (OxLDL) plays an important role in the initiation and progression of atherosclerosis. OxLDL may promote atherosclerosis by direct cytotoxicity of inhibition of NO synthesis by endothelium, transformation of macrophages to foam cells, arterial smooth muscle cell proliferation and migration. The oxidation theory of atherosclerosis implies that agents effectively inhibiting low-density lipoprotein (LDL) oxidation and lesion development are potential antiatherogenic compounds. The key stages in the development of atherosclerosis were the activation of the vascular endothelium, the increased adhesion of circulating monocytes to the injured endothelial layer, followed by their infiltration into the vessel wall and differentiation into macrophages. Endothelial cells recruit monocytes by selectively expressing cell surface adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1).To study the potential mechanisms underlying cholesterol metabolism regulation and antioxidant of PGTS derived from Platycodon grandiflorum A.DC, the male SD rats treated with hyperlipidemic emulsion diet for 14 weeks were fed with PGTS (30, 50, 100 mg/kg B.W./d) and simvastatin (25 mg/kg B.W./d) respectively by gavage for 28 days. Different doses of PGTS depressed the serum and hepatic cholesterol (TC), triglyceride(TG),low-density lipoprotein cholesterol(LDL-C), apolipoprotein B(APoB), TC/ hight-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)concentration, increasing apolipoprotein A-I(APoAI),HDL-C concentration , the liver low-density lipoprotein cholesterol receptor(LDL-r)protein content by immunohistochemical analysis and decreasing liver 3-Hydroxy-3-methyl glutaryl-CoA reductase(HMG-CoA-r)protein levels of hyperlipidemic emulsion induced rats. Cytochrome P450 7A1(CYP7A1)mRNA expression and fecal bile acid levels were significantly higher in the PGTS groups compared to hyperlipidemic emulsion only groups. Simultaneously, treating with PGTS also improved the serum and hepatic homogenate metabolic antioxidant status of hyperlipidemic emulsion induced rats. These findings suggested that metabolism regulation of PGTS on hyperlipidemic rats was caused in part by regulation of synthesis, influx and efflux of hepatic intracellular cholesterol via the key points LDL-r, HMG-CoA-r and CYP7A1, which consequently changed the organismal oxidation state. The study revealed that PGTS may offer a therapeutic potential for the treatment of hyperlipidemic via regulation of cholesterol metabolism.The other study examined the effects of platycodon D(PD), a triterpene saponin from the the root of Platycodon grandiflorum A.DC on human umbilical vein endothelial cell(sHUVEC-12)in vitro, which were pre-treated with PD (0.01mg/mL, 0.15 mg/mL, 0.25 mg/mL ) respectively and treated with 50 mg/L oxidized low-density lipoprotein(OxLDL). The levels of nitric oxid(eNO)and malonaldehyde(MAD)in the culture medium, vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1 (ICAM-1)mRNA expression in endothelium cells, the adhesion of monocytes to endothelial cells were measured. The results showed that PD increased NO concentration and MDA level induced by OxLDL in the medium of endothelial cells. Moreover, PD significantly inhibited the OxLDL-induced increase in monocyte adhesion to endothelial cells as well as decreased mRNA expression levels of VCAM-1 and ICAM-1 on endothelial cells. Based on these results, it is suggested that PD is a promising anti-atherosclerotic activity, which is least in part the result of it increaseing NO concentration, reducing the OxLDL-induced cell adhesion molecule expression in endothelial cells and endothelial adhesion to monocytes.