We investigated the metabolic fate of swertiamarin (1) in Wistar rats. Swertiamarin (1) is a principal component of Swertia herbs used in traditional medicine. Liquid chromatography/ion trap mass spectrometry detected new metabolites (R)-gentianol (4a) and (S)-gentianol (4b) in rat plasma, together with the known metabolite gentianine (2), all of which contained nitrogen. The structures of the metabolites were identified by comparing the retention times, as well as MS and MS/MS spectra with those of authentic compounds, which were synthesized from swertiamarin (1). We prepared (S)-gentianol (4b) by stereoselective reduction from gentianone (3) which is a new oxidation product of gentianine (2), and the absolute configuration was unequivocally determined using an improved Mosher's method.
The relaxant effects of the roots of three species of Glycyrrhiza (G. uralensis, G. glabra and G. inflata) on carbachol-induced contractions in mouse jejunum were examined. The G. inflata (EC50: 93 ± 25 μg/ml) and G. uralensis roots (EC50 of 4-year-old cultivated roots: 134 ± 21 μg/ml) had potent relaxant effects; however, G. glabra had only weak activity (EC50: 250 μg/ml or more) because it did not contain the potent relaxants glycycoumarin (GC) and licochalcone A (LA). Cultivated G. uralensis roots, obtained during our previously reported cultivation studies in eastern Inner Mongolia, China, showed similar relaxant effects to commercial Glycyrrhizae Radices prepared from wild G. uralensis roots. The relaxant effects of commercially available cultivated G. uralensis roots were also comparable to those of three commercial Glycyrrhizae Radices. Our results suggest that cultivated G. uralensis roots could be used as an acceptable source of Glycyrrhizae Radix, which would conform to the Japanese Pharmacopoeia XV. The relaxant effects of the outer periderm (cork, cortex and part of the phloem) of Glycyrrhiza roots were stronger than those of the inner residual tissues (phloem, xylem and xylem rays), probably because the active ingredients, GC and LA, were abundantly present in the outer periderm of G. uralensis and G. inflata roots, respectively.
The improving effects of 70% methanol extract (RG-ext) and its potent components obtained from Red Ginseng on the peripheral circulation disorder were investigated using various experimental models in rats. RG-ext promoted the dorsal skin blood flow of intact rat and improved the lowering of the dorsal skin blood flow induced by norepinephrine (NE), and also caused by water immersion, but was ineffective on serotonin-treated rats. RG-ext restored the increase of the blood flow induced by doxazosin (DO). Ginsenoside-Rb1 (Rb1) improved the lowering of the dorsal skin blood flow by NE and ginsenoside-Rg1 (Rg1) restored the increase of blood flow by DO. When Rb1 was administered orally to rats in combination with non-saponin fraction (RW-fr) obtained from Red Ginseng, the improving effects were more enhanced than that of Rb1 alone, but it was ineffective in RW-fr itself. Non-saponin fraction (WW-fr) from White Ginseng did not show the increasing effect such a RW-fr. Rb1 produced 20(S)- and 20(R)-ginsenoside-Rg3 [20(S)- and 20(R)-Rg3] in gastric juice, and in artificial gastric juice. Ginsenoside-Rb2, -Rc and -Rd also produced 20(S)- and 20(R)-Rg3 as well as Rb1. When 20(S)-Rg3 was administered intravenously to rats, it improved the lowering of the dorsal skin blood flow induced by NE, but only showed a tendency to improve the blood flow in case of oral administration. 20(S)-Rg3 showed relatively strong improving effect in combination with RW-fr. Consequently, it has become apparent that the improving effect of RG-ext on the peripheral circulation disorder are attributable to action of 20(S)-Rg3 which was formed from protopanaxadiol saponins of RG-ext in stomach and then absorbed into blood flow through intestinal membrane with some support of RW-fr.
Varicocelectomy is an effective treatment for chronic scrotal pain caused by varicocele, but a less invasive therapy has not been established. We planned a prospective study of the effect of keishibukuryogan for this condition, since this medicine is used for male patients with infertility due to varicocele. The clinical effect of this medicine was evaluated using a questionnaire to assess the type, extent and duration of pain. The study included 11 subjects with a mean age (±S.D.) of 40 ± 14.5 years old and a disease duration of 6.2 ± 9.4 months. The patients included 2 cases of grade I, 5 of grade II and 4 of grade III varicocele. The treatment period was 27 days and significant adverse reactions were not observed. In 72.7% of patients the pain was relieved partially or completely after treatment, with the mean VAS in all patients changing from 3.4 ± 1.2 to 1.5 ± 1.5 (p =0.0106). In the pretreatment period, 5 patients had discomfort, 5 had dull pain and 1 had sharp pain, whereas after treatment 3 patients were without pain, 7 had discomfort and 1 had dull pain. Therefore, the study shows that keishibukuryogan might be a useful option as a first line treatment for chronic scrotal pain caused by varicocele. However, this conclusion requires confirmation in a larger patient population.
Our previous report described the enhancement of intestinal bleeding and anemia associated with indomethacin (INDO)-induced enteropathy in mice by oral administration of Scutellariae Radix (SR) extract. We here demonstrate that SR extract enhanced ulceration but attenuated the elevation of expression levels of interleukin (IL)-1β, IL-6 and CCL2 gene transcripts in the small intestine during INDO-induced enteropathy. Our observations further support that INDO-induced enteropathy is aggravated by the oral administration of SR extract. This effect of SR extract may be due to the modulation of immune-inflammatory processes possibly through the suppression of proinflammatory cytokine and chemokine induction.