A trace component of ginseng that inhibits Ca2+ channels through a pertussis toxin-sensitive G protein.

A crude extract from ginseng root inhibits high-threshold, voltage-dependent Ca2+ channels through an unknown receptor linked to a pertussis toxin-sensitive G protein. We now have found the particular compound that seems responsible for the effect: it is a saponin, called ginsenoside Rf (Rf), that is present in only trace amounts within ginseng. At saturating concentrations, Rf rapidly and reversibly inhibits N-type, and other high-threshold, Ca2+ channels in rat sensory neurons to the same degree as a maximal dose of opioids. The effect is dose-dependent (half-maximal inhibition: 40 microM) and it is virtually eliminated by pretreatment of the neurons with pertussis toxin, an inhibitor of G(o) and Gi GTP-binding proteins. Other ginseng saponins--ginsenosides Rb1, Rc, Re, and Rg1--caused relatively little inhibition of Ca2+ channels, and lipophilic components of ginseng root had no effect. Antagonists of a variety of neurotransmitter receptors that inhibit Ca2+ channels fail to alter the effect of Rf, raising the possibility that Rf acts through another G protein-linked receptor. Rf also inhibits Ca2+ channels in the hybrid F-11 cell line, which might, therefore, be useful for molecular characterization of the putative receptor for Rf. Because it is not a peptide and it shares important cellular and molecular targets with opioids, Rf might be useful in itself or as a template for designing additional modulators of neuronal Ca2+ channels.     

Ginsenoside Rf, a trace component of ginseng root, produces antinociception in mice

Ginseng root, a traditional oriental medicine, contains more than a dozen biologically active saponins called ginsenosides, including one present in only trace amounts called ginsenoside-Rf (Rf). Previously, we showed that Rf inhibits Ca²⁺ channels in mammalian sensory neurons through a mechanism requiring G-proteins, whereas a variety of other ginsenosides were relatively ineffective. Since inhibition of Ca²⁺ channels in sensory neurons contributes to antinociception by opioids, we tested for analgesic actions of Rf. We find dose-dependent antinociception by systemic administration of Rf in mice using two separate assays of tonic pain: in the acetic acid abdominal constriction test, the ED₅₀ was 56±9 mg/kg, a concentration similar to those reported for aspirin and acetaminophen in the same assay; in the tonic phase of the biphasic formalin test, the ED₅₀ was 129±32 mg/kg. Rf failed to affect nociception measured in three assays of acute pain: the acute phase of the formalin test, and the thermal (49°C) tail-flick and increasing-temperature (3°C/min) hot-plate tests. The simplest explanation is that Rf inhibits tonic pain without affecting acute pain, but other possibilities exist. Seeking a cellular explanation for the effect, we tested whether Rf suppresses Ca²⁺ channels on identified nociceptors. Inhibition was seen on large, but not small, nociceptors. This is inconsistent with a selective effect on tonic pain, so it seems unlikely that Ca²⁺ channel inhibition on primary sensory neurons can fully explain the behavioral antinociception we have demonstrated for Rf.     

A model for health: its use in an undergraduate nursing programme

A great deal has been said about the need for health professionals to move away from a disease model of care and place more emphasis on health and its promotion and maintenance. One way of introducing a health approach to the service is to emphasise it in the basic education of nurses and doctors.The curriculum for the BA Nursing Studies programme at Glasgow College of Technology is based on a health model for nursing, a model based on activities of living. Initially the emphasis is on health and then the move is towards the study of dysfunction and disease processes. However, a strand of health education is retained throughout the programme, and students are encouraged to identify opportunities for health teaching in both hospital and community settings. The $\text{4}\text{1}\text{3}\text{-}\text{year}$ nursing programme gives a framework for a health approach which looks towards the year 2000.     

槲寄生化学成分的研究——Ⅷ.2,3-丁二醇单葡萄糖甙的分离和结构

From the ethanol extract of Viscum coloratum (Kom.) Nakai , a giucoside ofaliphatic diol and three other glucosides were isolated. Based on chemical and spectroscopic analysis,the structures have been elucidated as 2-β-D- glucosyl-3- methylpropanol (Ⅷ), syringin (Ⅸ),eleatheroside E(Ⅹ) and syringenin-4'-O-D-apiosylglucoside (Ⅺ). Ⅷ is a new glucoside of aliphaticdiol and named 3-β-D-glucopyranosyloxy-butanol-2. Three other compounds (Ⅸ～-Ⅺ) were foundfor the first time in this plant.     

In Vivo radioprotective effect of Panax ginseng C.A. Meyer and identification of active ginsenosides

This study evaluated the effect of water extracts of Panax ginseng C.A. Meyer (PG), panaxadiol (PD), panaxatriol (PT), ginsenoside Rb(1), Rb(2), Rc, Rd, Re and Rg(1) on jejunal crypt survival, endogenous spleen colony formation and apoptosis in jejunal crypt cells in gamma-irradiated mice. Jejunal crypts were protected by pretreatment with PG, Rc and Rd. Administration of PG, PD, Rd and Re prior to irradiation resulted in an increase in the formation of endogenous spleen colonies. The frequency of radiation-induced apoptosis in intestinal crypt cells was also reduced by pretreatment with PG, PD, Rb(2), Rc, Rd, Re and Rg(1). In experiments on the effects of the individual ginsenosides, the rank order of activity was Rc > Rd > Rg(1) > Rb(2) > Re > Rb(1) on intestinal crypt survival assay, Re > Rb(2) > Rd > Rg(1) > Rb(1) > Rc on the spleen colony formation assay, and Rg(1) > Re > Rd > Rc > Rb(2) > Rb(1) on inhibiting the death of cells caused by apoptosis. The results indicated that Rc, Rd and Re may have a major radioprotective effect in mice irradiated with high and low doses of radiation. When the same experiments were performed using PD and PT, it was observed that most of the inhibitory effects came from PD rather than PT.     

Effect of calmodulin on ginseng saponin-induced Ca2+-Activated CI-channel activation inXenopus laevis oocytes

We previously demonstrated the ability of ginseng saponins (active ingredients of Panax ginseng) to enhance Ca2+-activated Cl- current. The mechanism for this ginseng saponin-induced enhancement was proposed to be the release of Ca2+ from IP3-sensitive intracellular stores through the activation of PTX-insensitive Galpha(q/11) proteins and PLC pathway. Recent studies have shown that calmodulin (CaM) regulates IP3 receptor-mediated Ca2+ release in both Ca2+-dependent and -independent manner. In the present study, we have investigated the effects of CaM on ginseng saponin-induced Ca2+-activated Cl- current responses in Xenopus oocytes. Intraoocyte injection of CaM inhibited ginseng saponin-induced Ca2+-activated Cl- current enhancement, whereas co-injection of calmidazolium, a CaM antagonist, with CaM blocked CaM action. The inhibitory effect of CaM on ginseng saponin-induced Ca2+-activated Cl- current enhancement was dose- and time-dependent, with an IC50 of 14.9 +/- 3.5 microM. The inhibitory effect of CaM on saponin's activity was maximal after 6 h of intraoocyte injection of CaM, and after 48 h the activity of saponin recovered to control level. The half-recovery time was calculated to be 16.7 +/- 4.3 h. Intraoocyte injection of CaM inhibited Ca2+-induced Ca2+-activated Cl- current enhancement and also attenuated IP3-induced Ca2+-activated Cl- current enhancement. Ca2+/CaM kinase II inhibitor did not inhibit CaM-caused attenuation of ginseng saponin-induced Ca2+-activated Cl- current enhancement. These results suggest that CaM regulates ginseng saponin effect on Ca2+-activated Cl current enhancement via Ca2+-independent manner.     

Effects of Korean red ginseng extract on cisplatin-induced nausea and vomiting

Ginseng, the root of Panax ginseng C.A. Meyer, is well known as a tonic medicine for restoring and enhancing human health. In traditional medicine, ginseng is utilized for the alleviation of emesis, which includes nausea and vomiting. However, it has not yet been demonstrated whether ginseng exhibits in vivo anti-nausea and anti-vomiting properties. In this study, we examined the anti-emetic effect of Korean red ginseng total extract (KRGE) on cisplatin-induced nausea and vomiting using ferrets. Intraperitoneal administration (i.p.) of cisplatin (7.5 mg/kg) induced both nausea and vomiting with one-hour latency. The episodes of nausea and vomiting reached a peak after 1.5 h and persisted for 3 h. Treatment with KRGE via oral route significantly reduced the cisplatin-induced nausea and vomiting in a dose-dependent manner. The anti-emetic effect was 12.7 +/- 8.6, 31.8 +/- 6.9, and 67.6 +/- 4.0% with doses of 0.3, 1.0, and 3.0 g/kg of KRGE, respectively. Pretreatment with KRGE via oral route 1 and 2 h before cisplatin administration also significantly attenuated the cisplatin-induced nausea and vomiting. However this did not occur with a pretreatment 4 h before cisplatin administration. These results are supportive of KRGE being utilized as an anti-emetic agent against nausea and vomiting caused by chemotherapy (i.e. cisplatin).     

Effects of ranitidine for exercise induced gastric mucosal changes and bleeding

AIM: To evaluate the effect of ranitidine on gastric mucosal changes and on GI bleeding in long distance runners. METHODS: Twenty-four long distance runners (M:16, F: 8, age: 18.2±1.5 years) participated in this study. A symptom questionnaire, stool hemoccult test, and upper gastrointestinal (GI) endoscopy were performed on the subjects prior to the study. The subjects took oral ranitidine (150 mg, b.i.d.) for two weeks. The upper GI endoscopy and stool Hemoccult tests were repeated after the treatment. RESULTS: Twenty-two of the 24 runners had at least one upper GI mucosal lesion before the medication. The Endoscopic improvements were seen in eleven of the 14 cases of erosive gastritis and four of the 5 cases of esophagitis. Six subjects were Heme occult positive prior to the study, but only one was positive after the medication. CONCLUSION: Gastric mucosal lesions and GI bleeding in long distance runners seem to be associated to acidrelated factors mediated by the high level of regular run- ning. Ranitidine seems to be and effective prophylaxis to prevent gastric mucosal lesions and GI bleeding.