Majonoside-R2, a major constituent of Vietnamese ginseng, attenuates opioid-induced antinociception.

The effects of majonoside-R2 on antinociceptive responses caused by the mu-opioid receptor agonist morphine and the selective kappa-opioid receptor agonist U-50, 488H were examined by the tail-pinch test in mice. Intraperitoneal (IP) or intracerebroventricular (ICV) injection of majonoside-R2 (3.1-6.2 mg/kg, IP or 5-10 micrograms/mouse, ICV) and diazepam (0.1-0.5 mg/kg, IP or 0.5-1.0 microgram/mouse, ICV), as well as an opioid receptor antagonist naloxone (2 mg/kg, IP or 5 micrograms/mouse, ICV), dose-dependently attenuated the antinociception caused by subcutaneously administered morphine and U-50,488H. Moreover, when co-administered ICV or intrathecally (IT) with morphine (4 micrograms/mouse) or U-50,488H (60 micrograms/mouse), majonoside-R2 (5-20 micrograms/mouse) also exhibited antagonism against the antinociceptive action of these opioid receptor agonists in the tail-pinch test. The inhibitory effects of majonoside-R2 (10 micrograms/mouse, ICV) and diazepam (1 microgram/mouse, ICV) were reversed by flumazenil (2.5 micrograms/mouse, ICV), a selective benzodiazepine receptor antagonist, and picrotoxin (0.25 microgram/mouse, ICV), a GABA-gated chloride channel blocker. These results suggest that majonoside-R2 attenuates the opioid-induced antinociception by acting at the spinal and supraspinal levels, and that the GABAA receptor complex at the supraspinal level is involved in the effect of ICV administered majonoside-R2.

Effect of Vietnamese Ginseng on the phagocytosis in vitro and in vivo.

The effects of Vietnamese ginseng crude extract (VG extract), total saponin (VG saponin) and its major saponin component, majonoside-R2, on phagocytosis were examined in mice by bactericidal and carbon clearance tests. Escherichia coli (E. coli) ATCC 25922 was used to induce the acute toxicity and activate the phagocytic activity of phagocytes in both in vitro and in vivo bactericidal tests. Pretreatment with VG extract (500 mg/kg, oral administration, p.o.) and majonoside-R2 (50 mg/kg, intraperitoneal administration, i.p.) protected the animals from the acute toxicity of E. coli ATCC 25922 and significantly increased the phagocytic index in both in vitro and in vivo bactericidal tests. Moreover, VG extract (100-500 mg/kg, p.o.), VG saponin (25 mg/kg, i.p.) and majonoside-R2 (10 mg/kg, i.p.), as well as zymosan A, a non-specific phagocytic stimulant, also increased the phagocytic index evaluated by the carbon clearance test. These results indicate that Vietnamese ginseng enhances the phagocytic activity of phagocytes, and suggest that majonoside-R2 plays an important role in this effect.

Effects of vietnamese ginseng on opioid agonist - and conditioned fear stress-induced antinociception.

We investigated the effects of Vietnamese ginseng (VG) extract, VG saponin and the VG major saponin constituent majonoside-R2 on opioid receptor agonist-induced antinociception using the tail-pinch and hot-plate tests in mice and on conditioned fear stress-induced antinociception using the tail-flick test in rats. VG extract (50-100 mg/kg, p.o.), VG saponin (12.5-25 mg/kg, p.o.) and majonoside-R2 (6.2-12.5 mg/kg, p.o.), as well as Panax ginseng extract (PG extract, 50-100 mg/kg, p.o.), dose-dependently attenuated the µ-opioid agonist morphine-induced antinociception in the tail-pinch and hot-plate tests. Moreover, repeated administration of VG saponin and majonoside-R2 suppressed the development of morphine tolerance in the tail-pinch test. VG extract (100-200 mg/kg, p.o.) also dose-dependently blocked the antinociceptive effects of the selective κ-opioid agonist U-50, 488H in the tail-pinch and hot-plate tests, while PG extract (100-200 mg/kg, p.o.) dose-dependently attenuated the U-50,488H-induced antinociception in the hot-plate test but not in the tail-pinch test. VG saponin (6.2-25 mg/kg, p.o.) blocked the U-50,488H-induced antinociception in the tail-pinch test but not in the hot-plate test. Furthermore, VG saponin (25 mg/kg, i.p.) and majonoside-R2 (6.2 mg/kg, i.p.), as well as naloxone (2 mg/kg, i.p.), reversed the tail-flick latency increased by conditioned fear stress in rats. These results indicate that VG and its major saponin constituent, majonoside-R2, attenuate the antinociception caused by opioid agonists and conditioned fear stress.

Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv. collected in central Vietnam. III.

Five new dammarane saponins derived from four new aglycones were isolated from the rhizomes and roots of Panax vietnamensis Ha et Grushv. On the basis of physicochemical and spectral evidence, the structures of these compounds were established as 6-O-beta-D-glucopyranosyl 20(S),25-epoxydammarane-3 beta,6 alpha,12 beta,24 alpha-tetrol (1), 6-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl 20(S),25-epoxydammarane-3 beta,6 alpha,12 beta,24 alpha-tetrol (2), 6-O-beta-D-glucopyranosyl dammarane-3 beta,6 alpha,12 beta,20(S),24 xi,25-hexol (5), 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D- glucopyranosyl dammarane-3 beta,12 beta,20(S),24 xi,25-pentol (8) and 6-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl 20(S),24(S)-epoxydammarane-3 beta,6 alpha,12 beta,25 xi,26-pentol (10). The trivial names, vina-ginsenoside-R10, -R11, -R12, -R13 and -R14, respectively, were assigned to the new saponins.