We studied influences of acute administration of Korean red ginseng (RG) on cardiac autonomic nerve activities (CANA) and circulatory parameters in 38 outpatients with chronic cardiovascular diseases through orthostatic load test. Simultaneously, we examined the change that was elicited by RG administration in white blood cell count and differential white blood cell counts to estimate a relation of autonomic nerve change and cell immunity. In this study, patients were classified into two types : sympathetic dominant (S) and vagal dominant type (V). We examined and compared the efficacy of RG in each type. After RG administration, CANA of S was tending to move to V and that of V was tending to move to S. The influences of CANA change on circulatory parameters were more remarkable in S than V. By administration of RG to S, the total white blood cell and granulocytes were increased, but lymphocytes were decreased. On the other hand, in V, only lymphocytes showed significant decrease. G/L (ratio) was significantly increased in total and in each type of CANA. These effects of RG were thought to be useful to prevent infection in early phase, and also to suppress early cancer through enhancement of NK activity. Thus efficacies of RG are different in S or V in CANA type. So, we thought to examine types of CANA is one useful means to determine diathesis of the patient.
A quantification method using HPLC-MS for simultaneous determination of two major bioactive alkaloid isomers [rhynchophylline (RHY) and isorhynchophylline (ISOR)] and their 8 metabolites were established. The method provided satisfactory precision, accuracy and sensitivity in quantification of these compounds in biomedia. The quantification limit was as low as 0.01ng/ml. With this method, the pharmacokinetic profiles of these compounds were investigated after oral administration of two Kampo formulations yokukansan and chotosan, and compared with those after oral administration of pure compounds. Interestingly, the contents of RHY and ISOR in rat brain after administration of extracts of yokukansan and chotosan were higher than those in rat brain after individual administration of RHY and ISOR, respectively.
HMG-CoA reductase inhibitors (statins) are frequently used to prevent and/or treat atherosclerosis because of their ability to lower blood cholesterol levels, the most crucial factor affecting atherosclerosis. Recently, keishibukuryogan (KBG), a Kampo medicine, has been reported to prevent atherosclerosis in high cholesterol diet (HCD)-fed rabbits without affecting the blood cholesterol level. Here, we compared the effects of KBG and atorvastatin (ATS) on balloon-induced intimal thickening of the carotid artery in rats fed a normal diet (ND) or an HCD. The inside of each rat carotid artery was denuded using a balloon catheter. ATS or KBG was administered orally to rats, and intimal thickening was assessed histologically two weeks after denudation. Under the ND-fed condition, the intimal thickness of the ATS-treated group was equal to that of the control group, but that of the KBG-treated group was significantly less than that of the control group. On the other hand, both ATS and KBG significantly attenuated intimal thickening under the HCD-fed condition. The serum cholesterol levels of the ATS- and KBG-treated groups were equal to that of the control group under the ND-fed condition. The serum cholesterol level under the HCD-fed condition was not affected by KBG but was slightly lowered by ATS. The malondialdehyde (MDA) content, an index of lipid peroxidation, was significantly increased in the balloon injured-vascular tissue, compared with in non-injured tissue. ATS and KBG did not affect the balloon injury-induced increase in MDA. These results suggest that ATS prevents intimal thickening by lowering the blood cholesterol level in part under hypercholesterolemic condition, whereas KBG prevents intimal thickening regardless of the blood cholesterol level. Oxidative stress is presumed to be at least partly involved in balloon injury-induced intimal thickening. However, neither ATS nor KBG prevented intimal thickening by suppressing oxidative stress.
Generally, a drug candidate is dropped due to its lack of efficacy or unacceptable toxicity. However, the efficacy and toxicity of new drug candidates are usually evaluated in animals. When a drug candidate is used in humans, the expected effects and side effects are different from those seen in animals. Although various kinds of human-derived cells have been used to improve the potential of drug candidates, their availability is limited and reactivity is dependent on the age, sex, and medical history of the donor. Stable supply and quality control are the major problems associated with the use of human-derived cells. Thus, the use of differentiated cells produced from multipotent cells with indefinite proliferative potential is expected to be a turning point in drug discovery. Presently, basic technologies for differentiating human embryonic stem (ES) cells and inducing pluripotent stem (iPS) cells to various cells have been established for neural and myocardial cells. In the present report, we summarize the current status of research on ES and iPS cells for application as tools in drug discovery.