Microbiome biomarkers associated with the gut contraction response elicited by the Japanese traditional medicine daikenchuto.

Objective biomarkers are crucial in the development of personalized medicines, such as Japanese traditional medicine (Kampo). To date, some objective markers to predict the response of Kampo medicines have been reported, but the information is somewhat limited. The aim of this study was to search for objective markers and combinations thereof to estimate the effect of the Japanese traditional medicine daikenchuto (DKT) on colon contraction intensity in guinea pigs. Specifically, the microbiome biomarkers were employed as candidate, using the Fisher ratio and the nearest neighbor classifier for statistical pattern recognition. The combination of the ratio between gut microbes of family Ruminococcaceae/Rikenellaceae, Ruminococcaceae/Paraprevotellaceae, and genus Ruminococcus/unknown genus in family Rikenellaceae of guinea pig gut microbes was found to influence the activity of DKT with 0.8 accuracy for test samples. These findings suggest that statistical pattern recognition can contribute to identifying target markers of multi-target drugs such as Kampo.

Population pharmacokinetic analysis of daikenchuto, a traditional Japanese medicine (Kampo) in Japanese and US health volunteers.

We constructed population pharmacokinetic (PK) models for the five constituents of daikenchuto (DKT), a traditional Japanese herbal medicine. Data were collected from two randomized PK studies conducted in Japan and the United States. Participants received single oral doses of 2.5 g, 5 g, and 10 g of DKT. The plasma concentrations of five DKT constituents--hydroxy-α-sanshool (HAS), hydroxyl-ß-sanshool (HBS), 6-shogaol (6S), 10-shogaol (10S), and ginsenoside Rb1 (GRB1)--were determined by liquid chromatography-tandem mass spectrometry. A total of 1859 samples from 55 participants (US, n = 36; Japanese, n = 19) were included in the analysis. Population PK models of HAS, HBS, 6S, and 10S were best described by a one or two-compartment model with a bolus input. On the other hand, the model of GRB1 was best described by a one-compartment model with nonlinear extravascular input. Among the covariates evaluated, body mass index (BMI) and age were found to influence oral clearance (CL/F) and volume of distribution (Vd/F) for HAS and HBS, respectively. The influence of body weight on CL/F and Vd/F for 6S was demonstrated. Marked differences were observed in mean plasma concentrations of HAS and HBS between Japanese and US participants. However, the simulation results indicated that the difference in plasma concentrations may be attributed to the difference in demographic factors such as BMI, body weight, and age, whereas ethnic difference between the Japanese and US participants was considered minimal.

Hypertensive brainstem encephalopathy without parieto-occipital lesion--two case reports.

Two patients presented with malignant hypertension associated with encephalopathy predominantly manifesting as brainstem lesion. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance (MR) imaging revealed diffuse hyperintense areas in the pons and scattered lesions in the cerebellum, basal ganglia, and cerebral subcortex without parieto-occipital lesions. Diffusion-weighted MR imaging demonstrated these lesions as normal intensity, indicating vasogenic edema. These lesions resolved rapidly once hypertension was controlled. Review of clinical findings for 14 other patients with hypertensive brainstem encephalopathy without parieto-occipital lesions suggested that anterior circulation structures supplied by the carotid artery are frequently involved in such patients.