Biomedical subjects
Publications and source records attributed to Y R Shen.
Optical activity in sum-frequency vibrational spectra has been observed for the first time in chiral liquids. The electric-dipole allowed chiral element of the nonlinear susceptibility appears to be 3 orders of magnitude smaller than typical allowed achiral elements. This is partly because the observed chirality requires a breakdown of the Born-Oppenheimer approximation.
As a second-order nonlinear optical process, sum-frequency generation is highly surface-specific and accordingly has been developed into a very powerful and versatile surface spectroscopic tool. It has found many unique applications in different disciplines and thus provided many exciting new research opportunities in surface and surface-related science. Selected examples are discussed here to illustrate the power of the technique.
We investigated the anti-atherosclerotic action shown by Shosaikoto, a Kampo medicine, using hypercholesterolemic mice. Oral administration of Shosaikoto significantly suppressed the elevation of serum cholesterol in C57BL/6 mice fed a 1.25% cholesterol-enriched diet for four weeks and improved the T cell ratio in peripheral blood, which decreased with the increase of the serum cholesterol level. In addition, Shosaikoto reduced the accumulation of cholesteryl oleate, which alters macrophages into foam cells, after the treatment of macrophages with oxidized or acetylated low density lipoprotein (LDL). Enzymatic study revealed that the treatment of macrophages with oxidized LDL enhanced acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity and markedly reduced neutral cholesteryl ester hydrolase (NCEase) activity. Shosaikoto treatment prevented a decrease in the NCEase activity, however due to the oxidized LDL treatment, although it slightly augmented ACAT activity. Thus, Shosaikoto, which is known to modulate the immune system, improves macrophage and lymphocyte functions diminished by hypercholesterolemia, resulting in an anti-atherosclerotic action.
Macrophages play important roles both in immune response and in lipid metabolism and contribute to the development of atherosclerosis. To clarify the mechanism by which Shosaikoto, a Kampo medicine, shows anti-atherosclerotic action, we studied its effect on macrophage function. The production of nitric oxide (NO), prostaglandin E2 and interleukin 1 by macrophages in mice was reduced by feeding of a cholesterol-enriched diet, and the reduced production was observed 1 week after the beginning of cholesterol feeding. Furthermore, although oxidized low density lipoprotein (LDL) and lysophosphatidylcholine (LPC) reduced NO production, macrophages prepared from mice treated with Shosaikoto at a dose of 1.2 g/kg/d restored the reduced NO production by them as well as by hypercholesterolemia. When the content of LPC was measured, no difference was observed between mice fed a cholesterol-enriched diet in the presence or absence of Shosaikoto treatment, suggesting that the restorative effect of Shosaikoto is not due to the inhibition of LPC production or accumulation. Conclusively, Shosaikoto prevents the modification of macrophage function induced by atherogenic factors, which is probably linked to its displayed anti-atherosclerotic action.
Monocytes/macrophages are known to be involved in atherogenesis, and the adherence of monocytes to the endothelium is considered an earliest characteristic of atherogenesis. Therefore, we studied the mechanism by which Shosaikoto, a Kampo medicine, shows anti-atherosclerotic action, which has been already shown in hypercholesterolemic rabbits. Hypercholesterolemia in rabbits gradually reduced the monocyte number in peripheral blood, whereas Shosaikoto treatment suppressed this decrease in circulating monocytes. Furthermore, although monocytes from hypercholesterolemic rabbits increased in adherence to endothelial cells even without lipopolysaccharide (LPS) activation, Shosaikoto treatment reduced the enhanced adherence observed in monocytes from hypercholesterolemic rabbits. These data suggested that the anti-atherosclerotic action shown by Shosaikoto resulted partly from the suppression of the enhanced adherence characteristic of hypercholesterolemia.
The feeding of cholesterol-enriched diet for 2 weeks was enough to reduce nitric oxide (NO), prostaglandin E(2) (PGE(2) and interleukin-1 (IL-1) productions in thioglycollate-elicited murine macrophages. Although not showing anti-hypercholesterolemic action against ICR mice, Shosaikoto, a Kampo medicine, partially prevented the reduction of NO and IL-1 productions induced by the feeding of cholesterol-enriched diet, and completely released the reduction of PGE(2) production. These data suggest that the malfunction of macrophage induced by hypercholesterolemia may contribute to early atherogenesis and that Shosaikoto retains macrophage function to prevent the development of atherosclerosis, even though serum cholesterol is markedly increased.