Journal of Traditional Medicines Vol. 30(2013) No. 5

This study examined the pharmacokinetics and pharmacological activities of 6-shoganol, a pungent ingredient of Zingiberis Rhizoma, and its metabolite, 6-paradol. The concentrations of 6-shogaol and 6-paradol in rat plasma determined by LC/MS/MS reached their maximum values (Cmax) at 5 minutes after oral administration of 6-shogaol (10 mg/kg). Both 6-shogaol and 6-paradol were eliminated from the plasma within 2 hours after injection. The plasma concentration of 6-paradol, the metabolite, was about 4 times higher than that of 6-shogaol at all points during blood sampling. Next, pharmacological activities of 6-shogaol and 6-paradol were studied. In vitro experiment revealed that the cyclooxygenase-2-inhibitory activity of 6-paradol was about 6 times stronger than that of 6-shogaol. In vivo experiments, 6-paradol demonstrated significantly stronger anti-inflammatory, analgesic, and antipyretic activities compared to 6-shogaol. These results suggest that 6-shogaol in Zingiberis Rhizoma is metabolized rapidly to 6-paradol and that 6-paradol is the main compound having anti-inflammatory activity.

In Ayurveda, practitioners use a herbal liquor called Arishta to treat patients suffering with emaciation or indigestion. Arishta is produced by decocting various herbs and then subjecting the resultant liquid to alcoholic fermentation. During the alcoholic fermentation stage, the constituents of Arishta change chemically, which would also alter the medicinal effects of Arishta. In order to characterize the components of Arishta, we investigated the differences between the compositions of Arishta and a tincture (an alcohol-soaked herbal liquor). First, we attempted to prepare Arishta in our laboratory from ginger, jujube, and long pepper and compared the piperine and [6]-gingerol contents of Arishta with those of the abovementioned tincture using HPLC. The alcohol content of the laboratory-made Arishta (LM-Arishta) was 15%, which was almost the same as that of the Arishta sold in Sri Lanka. The piperine content of the LM-Arishta was 14.6 mg/l, which was slightly higher than that of the tincture. It seems that decoction is more effective way to extract piperine than ethanol immersion. However, [6]-gingerol content of the LM-Arishta was 11.3 mg/l, which was less than 50% of that of the tincture. Subsequently, we incubated [6]-gingerol with yeast in culture medium to search [6]-gingerol metabolites. LC-MS/MS analysis suggested that [6]-gingerol is transformed to 4 metabolites such as [6]-shogaol and 3 or 5 acetoxy-[6]-gingerdiol during alcoholic fermentation. These metabolites were also detected in LM-Arishta and thus, it was suggested that [6]-gingerol was metabolized during LM-Arishta making.

Daiokanzoto (DKT), a Kampo medicine that includes the combination of two crude drugs (rhubarb and glycyrrhiza), is clinically effective for constipation. Sennoside A, the main purgative constituent of rhubarb, is a prodrug that is transformed into an active metabolite, rheinanthrone, by β-glucosidase derived from bifidobacteria. Thus far, we have presented evidence that anthraquinones in rhubarb, rhein 8-O-β-D-glucopyranoside (RG) and rhein, contribute to the purgative action of sennoside A by accelerating its metabolic activity. The aim of this study was to clarify the mechanism of action by which anthraquinones accelerate sennoside A metabolism. In pre-incubated fecal suspensions, mixed with anthraquinones, there was significant acceleration of the metabolic activity of sennoside A compared with that in the control. This finding suggested that anthraquinones induced metabolism by bacteria or their enzyme of sennoside A. The mechanism of action by RG was thus further investigated with puromycin, which is a protein synthesis inhibitor, in terms of quantitative or qualitative changes of sennoside A-metabolic enzyme. The results suggested that RG increased the synthesis of sennoside A-metabolic enzyme by bifidobacteria. Therefore, it is assumed that the anthraquinones included in DKT intensified the activation of sennoside A by increasing the synthesis of sennoside A-metabolic enzyme derived from bifidobacteria, which is the main metabolic bacteria.

A retrospective study was performed to compare the effects of sorafenib alone (as a control) and a combination of ninjin'yoeito and sorafenib on the presence of an abnormal aspartate aminotransferase (AST) level, an abnormal alanine transaminase (ALT) level, or an abnormal platelet count (PLT) in patients with advanced hepatocellular carcinoma. The numbers of patients with abnormal levels of AST, ALT, or PLT were 7, 5, and 9 in the combination group and 8, 6, and 10 in the control group, respectively. The combination of ninjin'yoeito and sorafenib tended to result in an improved AST level (P < 0.1) and a significant decrease in the ALT level (P = 0.048) after 4 weeks of treatment, compared with the results in the control group. Both the AST and ALT levels improved significantly, compared with the pre-treatment values, in the combination group. Furthermore, the change in the PLT after 12 weeks of treatment was significant (P = 0.046), though the improvements between the pre-treatment and post-treatment values were not significant. Throughout the treatment, the dosage of sorafenib was maintained and the treatment was continued in both the control and combination groups, and the levels of tumor markers were also monitored. Furthermore, to verify these findings, experimental rats treated with sorafenib and/or a combination of sorafenib and ninjin'yoeito were used to examine the effect of the combined treatment on liver function. As a result, the repeated administration of sorafenib led to an increase in the AST, total bilirubin (TBIL), and direct bilirubin (DBIL) levels, and they were significantly improved by the combined treatment with ninjin'yoeito. These results suggest that ninjin'yoeito might be useful for reducing the adverse effects of sorafenib treatment, such as liver injury and PLT reductions, possibly contributing to the survival benefit of sorafenib by maintaining its continuous administration.

We evaluated the effect of oral administration of an ethanol extract of Morus alba on hair quality in senescence-accelerated mice. In aged mice, the coefficient of friction of hair increased significantly by up to 31 %, but in mice given mulberry twig extract, it was normal. Scanning probe microscopic observation showed that the aging of hair was dramatically reversed by the mulberry twig extract. We propose mulberry twig extract as a novel dietary component to counter hair aging.

Diet-induced hypercholesterolemia is a major risk factor of adult disease. A commonly used class of drugs for the treatment of hypercholesterolemia is statins that decrease plasma cholesterol levels by inhibiting the cellular activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase, a rate-limiting enzyme of cholesterol biosynthesis. Since the use of statins result in several side effects, it is alternatively beneficial to prevent hypercholesterolemia by habitual intake of natural medicines or crude drugs. In this study, we aimed to clarify the effects of the combined extract of Sasa albo-marginata leaves (Sasa kurinensis Makino), Japanse red pine leaves (Pinus densiflora Sieb. et Zucc) and ginseng roots (Panax ginseng C. A. Meyer) (SJG) on cholesterol homeostasis by using genome-wide expression analysis in the liver of diet-induced hypercholesterolemic rats. For a period of 3 weeks, experimental animal groups were given food and water as follows: standard diet and water, standard diet and 50% (v/v) SJG, high-cholesterol diet (HCD) and water, and HCD and 50% SJG. We then performed genome-wide expression analyses using microarray to obtain a gene expression profile of the liver. Venn diagram was drawn to extract cholesterol-regulated genes whose expressions were altered by SJG. We also performed principal component analysis to visualize the microarray data. We found that the expression of genes involved in cholesterol metabolism, such as P450 7A1 and 8B1 were statistically increased by treatment of SJG in the presence of cholesterol. Although SJG upregulated the expression of P450 7A1, plasma cholesterol levels were not improved by SJG. Further studies are needed to clarify the effects of SJG on cholesterol homeostasis.