Yokukansan, a Kampo medicine, prevents the development of morphine tolerance through the inhibition of spinal glial cell activation in rats.

BACKGROUND: Animal models have shown that glial cells (microglia and astrocytes) in the spinal cord undergo activation following peripheral injury associated with chronic pain, suggesting the involvement of these cells in pain diseases. We have previously reported that Yokukansan (YKS), a Japanese traditional herbal (Kampo) medicine, is effective against chronic pain through the suppression of spinal glial cell activation. Morphine is a widely-used opioid analgesic for relieving severe pain, but its repeated administration leads to the development of antinociceptive tolerance. The development of morphine tolerance is also reported to be caused by spinal glial cells activation. In the present study, we investigated the inhibitory effects of YKS on the development of morphine tolerance and the activation of the spinal microglia and astrocytes using a rat model. METHODS: Male Wistar rats received a subcutaneous injection of morphine hydrochloride (10 mg/kg/d) for 7 days, and the withdrawal latency to thermal stimulation was measured daily using a hot plate test. Thereafter, the appearance of activated microglia and astrocyte in the spinal cord (L5) was examined by immunofluorescence staining. Ionized calcium binding adapter molecule-1 (Iba-1) staining was used to label microglia and glial fibrillary acidic protein (GFAP) staining was performed to label astrocytes. YKS was administered mixed with powdered rodent chow at a concentration of 3%. RESULTS: The preadministration of YKS (started 3 d before the morphine injection) prevented the development of morphine tolerance. The repeated administration of morphine increased Iba-1 and GFAP immune reactivities in the spinal cord; however, these activations were inhibited by the preadministration of YKS. CONCLUSION: These results suggest that the preadministration of YKS attenuates the development of antinociceptive morphine tolerance, and the suppression of spinal glial cell activation may be one mechanism underlying this phenomenon.

Evaluation of Salacia species as anti-diabetic natural resources based on quantitative analysis of eight sulphonium constituents: a new class of α-glucosidase inhibitors.

INTRODUCTION: Stems and roots of Salacia genus plants have been used in Ayurveda as a specific remedy for early stage diabetes. Previous investigations identified four sulphonium sulphates, that is, salacinol (1), kotalanol (3), ponkoranol (5) and salaprinol (7), as the compounds responsible for the anti-diabetic activity. Their desulphonates (2, 4, 6 and 8) were also isolated as active constituents. Two separate quantitative analytical protocols, that is, for 1 and 3 and for 2 and 4, have been developed recently. OBJECTIVE: To: validate the two analytical protocols with respect to all eight sulphoniums; evaluate the quality of a variety of Salacia samples collected in different geographical regions, that is, Thailand, Sri Lanka and India; and determine their distribution in each part of the plant, that is, stems/roots, leaves and fruits. METHODS: Analyses of four sulphonium sulphates in 32 Salacia extracts were carried out on an Asahipak NH2P-50 column, and those of the corresponding desulphonates were conducted on an Inertsil ODS-3 column. RESULTS: Neokotalanol (4) was the major constituent in Salacia samples from Thailand, whereas 1 was the primary constituent in extracts of the stems/roots of plants from Sri Lanka and India. These sulphoniums were only present in trace amounts in leaves and fruits of the plants. CONCLUSION: Two analytical protocols were successfully applied to analyse 32 Salacia samples, and revealed that sulphoniums (1-8) had characteristic distributions due to the plant part and/or due to geographical region.

Suppressive effect of juzentaihoto on vascularization induced by b16 melanoma cells in vitro and in vivo.

Juzentaihoto (JTT) is well known to be one of Japanese herbal medicines, and used for the supplemental therapy of cancer patients with remarkable success. The present study, therefore, was undertaken to examine the possible therapeutic mechanisms of JTT on cancer using B16 melanoma cell (B16 cell)/experimental mouse system. JTT was well mixed with rodent chow at 3.0% concentrations, and was administered orally ad libitum. Administration of JTT was started one week before tumor cell injection and continued throughout the experiment. Administration of JTT into mice significantly inhibited tumor metastasis in lungs after intravenous injection of 2 × 10(5) B16 cells in a volume of 50 µL. JTT also significantly suppressed enlargement of tumor size in hind footpad after the subcutaneous injection of 2 × 10(5) (50 µL) B16 cells. In the second part of experiments, the chamber that containing B16 cells was buried in the murine back. In JTT administrated group, vascular endothelial growth factor (VEGF) of chamber internal fluid significantly decreased, and vascularization of chamber circumference was also inhibited. These results strongly suggest that oral administration of JTT caused decrease in the generation of VEGF, which is responsible for vascularization, and results in inhibition of B16 cell metastasis.