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[Effect of adaptogens on the activity of the pituitary-adrenocortical system in rats].

Intraperitoneal injection of Panax ginseng C. A. Mey tincture, Polyscias filicifolia Bailey tincture, Panax ginseng tincture or Eleutherococcus Maxim extract to rats produced a rise in plasma corticosterone 1 hour after the treatment. Immobilization-induced rise in plasma corticosterone was increased by 7-day pretreatment with any agent. Thus, the adaptation effect of Panax ginseng C. A. Mey and Polyscias filicifolia Bailey is probably realized through the pituitary-adrenocortical system.

Adaptation, Physiological↗

Research and development of cancer chemopreventive agents in China.

Since the late 1970s, a comprehensive search for cancer chemopreventive agents has been established in our Institute. A series of new retinoids have been synthesized and screened on the basis of established methodologies of experimental chemoprevention in vitro as well as in vivo. Pharmacological studies demonstrated that N-4-(carboxyphenyl)retinamide (RII) induces cell differentiation of HL-60 cells and inhibits dimethylnitrosamine-induced carcinogenesis of the forestomach in mice, 7,12-dimethylbenz[a]anthracene (DMBA)-induced papilloma in mouse skin, and DMBA-induced carcinogenesis of the buccal pouch in Syrian golden hamsters. It significantly promoted lymphoblastic transformation and activated macrophages. In further studies, RII significantly inhibited ornithine decarboxylase activity. After 6 months of chronic toxicological studies in rats and dogs, RII was recommended for clinical trial. Phase II studies found that RII is effective in treating oral and vulvar leukoplakia. It is also effective in treating myelodysplastic syndrome and dysplasia of uterine cervix. The chalcone retinoidal compounds were discovered when the search for new retinoids with less toxicity and higher potency led to third-generation retinoids, which were synthesized and screened. Structure-activity relationship studies found that 3,5-di-tert-butyl-4-methoxy-4-carboxyl chalcone (R9158) is the most active inhibitor of a variety of cancer cells. It has no effect on the Colony Forming Unit-Granulocyte/Macrophage (CFU-GM) of bone marrow in mice. In in vivo studies, R9158 showed a remarkable inhibition of chondrosarcoma in rats. It had no cross-resistance to vincristine, but was cross-resistant to all-trans retinoic acid. Red ginseng, a processed Panax ginseng, is considered a typical tonic in traditional Chinese medicine. Our studies demonstrated that red ginseng extract inhibited DMBA-induced skin papilloma significantly. Experiments showed that glycyrrhetinic acid inhibited croton oil-induced ear edema in mice. It also inhibited epidermal ornithine decarboxylase as well as the rapid DNA damage induced by the carcinogen benzo[a]pyrene (B[a]P). Our pharmacological studies demonstrated that Chinese gallotannin inhibited the malignant transformation of B[a]P-induced V79 cells in vitro and B[a]P-induced pulmonary adenoma in A/J mice in vivo significantly.

Animals↗

Alleviation of Helicobacter pylori-Induced Pathogenicity and Gastric Inflammation by Majonoside-R2- and Ginsenoside Rg1-Rich Fractions From Panax vietnamensis Ha Et Grushv.: A Metabolomics-Guided Investigation.

Helicobacter pylori infection remains a major global health concern due to its association with gastric inflammation, ulceration, and gastric malignancies. This study evaluated the effects of Ngoc Linh ginseng (Panax vietnamensis Ha et Grushv.) root fractions on H. pylori virulence and host inflammatory responses. UHPLC-MS/MS-based metabolomic profiling coupled with feature-based molecular networking was employed to characterize the chemical profiles of different solvent fractions, identifying the dichloromethane (DCM) fraction as enriched in ginsenosides, particularly the ocotillol-type saponin majonoside R2 (MR2). In vitro assays showed that, despite minimal direct antibacterial activity, the DCM fraction at sub-inhibitory concentrations significantly reduced urease activity, acid tolerance, biofilm formation, and the expression of major virulence genes, including vacA and cagA. In H. pylori-infected AGS gastric epithelial cells, the DCM fraction and MR2 decreased VacA and CagA translocation, suppressed pro-inflammatory signaling and cytokine production, restored antioxidant defenses, and alleviated mitochondrial apoptosis. By contrast, ginsenoside Rg1 selectively modulated host inflammatory and oxidative stress responses without affecting bacterial virulence gene expression. These results demonstrate that Ngoc Linh ginseng root fractions mitigate H. pylori-induced pathogenic effects primarily through anti-virulence and host-directed mechanisms, highlighting their potential relevance for the development of gastric health-promoting functional products.

Helicobacter pylori↗

Epigenetic activation of NK-cell effector programs and caspase-8-dependent apoptosis mediates the antitumor activity of LGP in NSCLC.

BACKGROUND: Effective activation of natural killer (NK) cell cytotoxicity and caspase-8-dependent extrinsic apoptosis remains a major challenge in non-small cell lung cancer (NSCLC). Epigenetic mechanisms regulating NK cell function within the tumor microenvironment are poorly understood and rarely targeted therapeutically. METHODS: The antitumor activity of Li-Ginseng Powder (LGP), a specifically processed Panax ginseng formulation enriched in rare ginsenosides (Rh4, Rg3, Rg5, Rk1, and Rk3), was evaluated in human lung cancer A549 cells and A549 xenograft mouse models. NK cell infiltration and activation were assessed by flow cytometry, immunoblotting, and immunohistochemistry. Whole-genome bisulfite sequencing (WGBS) was performed to analyze DNA methylation changes. The effects of LGP ginsenosides (LGG) on tumor cell apoptosis and death receptor signaling were examined in vitro. RESULTS: LGP significantly suppressed tumor growth and enhanced systemic and intratumoral NK cell activation. Promoter demethylation of NK cell effector genes, including Ncr1, Gzmb, Nktr, and Itgal, was associated with increased NK cell infiltration and activation, elevated granule-mediated cytotoxicity, and enhanced IFN-γ signaling. In parallel, LGP treatment induced caspase-8-dependent apoptosis associated with increased expression of membrane death receptors, their ligands, FADD, and procaspase-8 in tumor tissues. In vitro, LGG upregulated these apoptosis-initiating proteins and triggered caspase-8 activation in A549 cells independent of promoter methylation changes. Collectively, these immune-associated and tumor-intrinsic responses contributed to robust tumor suppression with a favorable systemic safety profile. CONCLUSIONS: LGP exerts dual antitumor effects characterized by enhanced NK-cell activation and increased sensitivity of tumor cells to caspase-8-dependent extrinsic apoptosis. These coordinated immune-associated and apoptosis-sensitizing effects underscore the therapeutic potential of LGP for the treatment of NSCLC.

DNA methylation↗

Variations in product choices of frequently purchased herbs: caveat emptor.

BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.

Cross-Sectional Studies↗

Relationship between the antidiarrhoeal effects of Hange-Shashin-To and its active components.

This study was designed to examine the relationship between the antidiarrhoeal effects of Hange-Shashin-To (TJ-14) and its active components. Oral treatment with TJ-14 at 1000 mg/kg significantly inhibited castor oil-induced diarrhoea. Both the 50% methanol eluate fraction (fraction III) and the methanol eluate fraction (fraction IV) showed antidiarrhoeal effects at oral doses of 68 mg/kg and 63 mg/kg, respectively, corresponding to 1000 mg/kg of TJ-14. TJ-14 (1000 mg/kg, p.o.) showed a significant increase in blood corticosterone levels. Increased blood corticosterone was noted after the oral administration of 63 mg/kg of fraction IV. The inhibitory activity of TJ-14 on cyclooxygenase-2 (COX-2) was also observed in fractions III and IV. The main component of fraction III was Scutellariae Radix-derived baicalin. Fraction IV contained Glycyrrhizae Radix-derived glycyrrhizin and isoliquiritin, Coptidis Rhizoma-derived berberine, coptisine and palmitine. Ginseng Radix-derived saponins were also present in fraction IV. These compounds inhibited castor-oil induced diarrhoea at oral doses of 10 or 30 mg/kg. Thus, the present results indicate that Scutellariae Radix, Glycyrrhizae Radix, Ginseng radix and Coptidis Rhizoma-derived components are involved in the antidiarrhoeal action of TJ-14.

Animals↗

Developmental toxicity research of ginsenoside Rb1 using a whole mouse embryo culture model.

BACKGROUND: Ginseng has been widely used around the world for many years. Knowledge is limited, however, on its effects on embryonic development. METHODS: Whole embryo culture was used to explore the developmental toxicity of ginsenoside Rb1 (GRb1) on mouse embryos. All embryos were exposed to different concentrations of GRb1, and scored for their growth and differentiation at the end of the 48-hr culture period. RESULTS: Total morphological score decreased significantly at the concentration of GRb1 of 30 microg/ml and was further reduced at 50 microg/ml. Yolk sac was affected at the lower concentration of 15 microg/ml. Developments of midbrain, forebrain, and optic system were relatively sensitive to GRb1 and were affected at the concentration of 30 microg/ml. Allantois, flexion, branchial arch, and limb buds were affected at 50 microg/ml. At this concentration, the embryonic crown-rump length, head length, and somite number were also reduced significantly compared to the control group. CONCLUSIONS: These results suggest that GRb1 has teratogenic effect during the mouse organogenetic period. We suggest that before more data in humans is available, ginseng should be used with caution by pregnant women in the first trimester.

Abnormalities, Drug-Induced↗

Ginsenoside Rg1 inhibits tumor necrosis factor-alpha (TNF-alpha)-induced human arterial smooth muscle cells (HASMCs) proliferation.

In China, the ginseng root began to be used in medicine over 2000 years ago. Ginsenosides are the most important component isolated from ginseng. The aim of this study was to determine the effects of ginsenoside Rg1 on the proliferation and molecular mechanism in cultured human arterial vascular smooth muscle cell (HASMC) induced by tumor necrosis factor-alpha (TNF-alpha). It was shown that ginsenoside Rg1 significantly inhibited TNF-alpha-induced HASMC proliferation in a dose-dependent manner. Treatment with ginsenoside Rg1, which blocked the cell cycle in the G1-phase, induced a downregulation of cyclin D1 and an upregulation in the expression of p53, p21(WAF/CIP1), and p27(KIP1). MEK inhibitors PD98059, U0126, and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, but not p38-inhibitor SB203580 or JNK-inhibitor SP600125 significantly aggravated ginsenoside Rg1-inhibited HASMC proliferation. Ginsenoside Rg1 markedly inactivated the extracellular signal-regulated kinases (ERK1/2) and protein kinase B (PKB), indicating that the inhibition of ginsenoside Rg1 on HASMC proliferation was associated with ERK and PI3K/PKB pathways. The inactivation of ERK and PI3K/PKB pathways and modulation of cell-cycle proteins by ginsenoside Rg1 may be of importance in inhibition of HASMCs proliferation.

Cell Line↗

Systematic evaluation of organochlorine pesticide residues in Chinese materia medica.

A systematic evaluation on the levels of organochlorine pesticide residues (OCP) was conducted on four selected, authentic Chinese materia medica, namely: Radix Angelicae Sinensis, Radix Notoginseng, Radix Salviae Miltiorrhizae and Radix Ginseng. Altogether ten representative batches of samples were analysed for each herb. Six batches were collected in the major cultivation areas of the Mainland whilst the remaining four batches were procured in the Hong Kong herbal market. All except Radix Angelicae Sinensis have been identified as containing quintozene and hexachlorocyclohexane in various levels. Hexachlorobenzene and lindane were also reported in samples of Radix Ginseng. The banned pesticide, DDT and its derivatives, was also observed in one of the Radix Notoginseng samples. The investigation will be continued for a target list of common used herbs in Hong Kong. All the results will be gathered and analysed for setting up regulatory permissible limits of OCP residues in Chinese materia medica used in Hong Kong.

Angelica sinensis↗

The anxiolytic effect of Sho-ju-sen, a Japanese herbal medicine, assessed by an elevated plus-maze test in mice.

Sho-ju-sen (SK), a Japanese herbal medicine with a nourishing tonic action, is composed of a water extract of Kumazasa leaves (Sasa kurinensis Makino et Sibata) (SS), and ethanol extracts of Japanese red pine needles (Pinus densiflora Sieb. et Zucc) (PN) and Ginseng roots (Panax ginseng C. A. Meyer) (PX) in the ratio 8:1:1. In this study, an elevated plus-maze test in mice was carried out to assess whether SK had an anxiolytic effect. No significant change was observed in either the plus-maze or activity test following a single administration of SK (10 and 20 mL/kg p.o.). However, mice allowed a free intake of SK (10% solution) for 5 days and longer showed a significant prolongation of the time spent in the open arms (an anxiolytic effect), as long as that caused by the benzodiazepine anxiolytic diazepam (1 mg/kg p.o.). SK (1%, 3% and 30% solutions for 7 days) tended to develop the anxiolytic effect. Of the constituents of SK, SS (8% solution), but not PN (1% solution) or PX (1% solution), resulted in the anxiolytic effect. Except for a slight acceleration in the motor activity by PN (1% solution), no significant change in the motor activity was produced by any treatment with SK, SS or PX. The combined treatment of SK (10% solution) or SS (8% solution) with 1 mg/kg diazepam enhanced the anxiolytic effect. Flumazenil (0.1 mg/kg s.c.), a benzodiazepine receptor antagonist, alone did not change the time spent in the open arms. However, it completely reversed the anxiolytic effect of SK, SS and diazepam. The present results suggest that: (1) long-term treatment with SK develops an anxiolytic effect, (2) SS is the main constituent for the anxiolytic effect of SK, and (3) benzodiazepine receptors are involved in the anxiolytic effect of SK and SS.

Animals↗

Hydrophilic interaction liquid chromatography with tandem mass spectrometry for the determination of underivatized dencichine (beta-N-oxalyl-L-alpha,beta-diaminopropionic acid) in Panax medicinal plant species.

Dencichine (beta-N-oxalyl-L-alpha,beta-diaminopropionic acid) is a haemostatic agent present in important Chinese medicinal herbs such as Panax notoginseng, as well as other Panax species. It is also a reported neurotoxic agent found in Lathyrus sativus (grass pea seed). A selective analytical method incorporating hydrophilic interaction chromatography with positive electrospray ionization tandem mass spectrometry (HILIC/ESI-MS/MS), for the analysis of dencichine in Panax plant species, was developed. Using multiple reaction monitoring (MRM) mode, underivatized dencichine, a small and highly polar compound, was selectively detected and quantified. The contents of dencichine in raw and steamed Panax notoginseng roots, 11 pairs of raw and steamed P. notoginseng herbal products, Panax ginseng roots, and Panax quinquefolium roots, were analyzed and compared. Optimal sensitivity of 0.3 ppm (detection limit) and 1.5 ppm (quantification limit) was achieved. The method was rapid (< or =5 min), with the HILIC peak eluting at about 1 min. Steamed P. notoginseng samples were found to contain less dencichine than the corresponding raw samples, and there were also differences among the three Panax species; raw P. ginseng and P. quinquefolium contained less dencichine than the raw P. notoginseng species. This rapid and specific method may be applied to the quantification of dencichine in complex medicinal plants and their products.

Amino Acids, Diamino↗

Ginsan improved Th1 immune response inhibited by gamma radiation.

Gamma radiation causes suppression of the immune function, and immune properties are related to cytokine production. In the present study, the polysaccharide, Ginsan, purified from an ethanol-insoluble fraction of Ginseng (Panax ginseng C.A. Meyer, Araliaceae) water extract was studied to assess its effects on the immunosuppressive activities of gamma radiation. Ginsan was found to stimulate murine normal splenocytes by inducing the mRNA expressions of Th1 and Th2 type cytokines, and also restore the mRNA expression of IFN-gamma, Th1 cytokine, after its inhibition by whole-body gamma irradiation. Therefore, Ginsan was found to restore the T lymphocytes function that had been suppressed by gamma irradiation in allogenic MLR (mixed lymphocyte reactions). However, Ginsan exhibited no excessive stimulatory effects on the control group. The above results indicated that Ginsan may constitute a new noble agent for the improvement of gamma radiation-induced immunosuppression.

Animals↗

Effects of ginsenosides Rg3 and Rh2 on the proliferation of prostate cancer cells.

Ginseng has an anti-cancer effect in several cancer models. This study was to characterize active constituents of ginseng and their effects on proliferation of prostate cancer cell lines, LNCaP and PC3. Cell proliferation was measured by [3H]thymidine incorporation, the intracellular calcium concentration by a dual-wavelength spectrophotometer system, effects on mitogen-activated protein (MAP) kinases by Western blotting, and cell attachment and morphologic changes were observed under a microscope. Among 11 ginsenosides tested, ginsenosides Rg3 and Rh2 inhibited the proliferation of prostate cancer cells. EC50s of Rg3 and Rh2 on PC3 cells were 8.4 microM and 5.5 microM, respectively, and 14.1 microM and 4.4 microM on LNCaP cells, respectively. Both ginsenosides induced cell detachment and modulated three modules of MAP kinases activities differently in LNCaP and PC3 cells. These results suggest that ginsenosides Rg3 and Rh2-induced cell detachment and inhibition of the proliferation of prostate cancer cells may be associated with modulation of three modules of MAP kinases.

Antineoplastic Agents↗

Effects of ginsenosides on GABA(A) receptor channels expressed in Xenopus oocytes.

Ginsenosides, major active ingredients of Panax ginseng, are known to regulate excitatory ligand-gated ion channel activity such as nicotinic acetylcholine and NMDA receptor channel activity. However, it is not known whether ginsenosides affect inhibitory ligand-gated ion channel activity. We investigated the effect of ginsenosides on human recombinant GABA(A) receptor (alpha1beta1gamma2S) channel activity expressed in Xenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg2, we found that Rc most potently enhanced the GABA-induced inward peak current (I(GABA)). Ginsenoside Rc alone induced an inward membrane current in certain batches of oocytes expressing the GABA(A) receptor. The effect of ginsenoside Rc on I(GABA) was both dose-dependent and reversible. The half-stimulatory concentration (EC50) of ginsenoside Rc was 53.2 +/- 12.3 microM. Both bicuculline, a GABA(A) receptor antagonist, and picrotoxin, a GABA(A) channel blocker, blocked the stimulatory effect of ginsenoside Rc on I(GABA). Niflumic acid (NFA) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), both Cl- channel blockers, attenuated the effect of ginsenoside Rc on I(GABA). This study suggests that ginsenosides regulated GABA(A) receptor expressed in Xenopus oocytes and implies that this regulation might be one of the pharmacological actions of Panax ginseng.

Animals↗

A cel44C-man26A gene of endophytic Paenibacillus polymyxa GS01 has multi-glycosyl hydrolases in two catalytic domains.

A bacterial strain Paenibacillus polymyxa GS01 was isolated from the interior of the roots of Korean cultivars of ginseng (Panax ginseng C. A. Meyer). The cel44C-man26A gene was cloned from this endophytic strain. This 4,056-bp gene encodes for a 1,352-aa protein which, based on BLAST search homologies, contains a glycosyl hydrolase family 44 (GH44) catalytic domain, a fibronectin domain type 3, a glycosyl hydrolase family 26 (GH26) catalytic domain, and a cellulose-binding module type 3. The multifunctional enzyme domain GH44 possesses cellulase, xylanase, and lichenase activities, while the enzyme domain GH26 possesses mannanase activity. The Cel44C enzyme expressed in and purified from Escherichia coli has an optimum pH of 7.0 for cellulase and lichenase activities, but is at an optimum pH of 5.0 for xylanase and mannanase activities. The optimum temperature for enzymatic activity was 50 degrees C for all substrates. No detectable enzymatic activity was detected for the Cel44C-Man26A mutants E91A and E222A. These results suggest that the amino acid residues Glu(91) and Glu(222) may play an important role in the glycosyl hydrolases activity of Cel44C-Man26A.

Amino Acid Sequence↗

Changes of [3H]MK-801, [3H]muscimol and [3H]flunitrazepam binding in rat brain by the prolonged ventricular infusion of transformed ginsenosides.

Ameliorating effects of ginseng were observed on neuronal cell death associated with ischemia or glutamate toxicity. Ginseng saponins are transformed by intestinal microflora and the transformants would be absorbed from intestine. In the present study, we have investigated the effects of transformed ginsenoside Rg3, Rh2 and compound K on the modulation of NMDA receptor and GABAA receptor binding in rat brain. The NMDA receptor binding was analyzed by quantitative autoradiography using [3H]MK-801 binding, and GABAA receptor bindings were analyzed by using [3H]muscimol and [3H]flunitrazepam binding in rat brain slices. Ginsenoside Rg3, Rh2 and compound K were infused (10 microg/10 microl/h) into rat brain lateral ventricle for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2ML). The levels of [3H]MK-801 binding were highly decreased in almost all regions of frontal cortex and hippocampus by ginsenoside Rh2 and compound K. The levels of [3H]muscimol binding were elevated in part of frontal cortex and granule layer of cerebellum by the treatment of ginsenoside Rh2 and compound K. However, the [3H]flunitrazepam binding was not modulated by any tested ginsenosides. Ginsenoside Rh2 and compound K induced the downregulation of the [3H]MK-801 binding as well as upregulation of the and [3H]muscimol binding in a region-specific manner after prolonged infusion into lateral ventricle. However, ginsenoside Rg3 did not show the significant changes of ligand bindings. In addition, ginsenoside Rh2 decreased the expression of nNOS in the hippocampus although Rg3 decreased the expression in the cortex. These results suggest that biotransformed ginsenoside Rh2 and compound K could play an important role in the biological activities in the central nervous systems and neurodegenerative disease.

Animals↗

Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in the rat aorta.

The vasoactive effects of several ginsenosides, purified from Panax ginseng, were tested in the rat aorta. Ginsenosides from the protopanaxatriol group and its purified ginsenosides Rg1 and Re cause endothelium dependent relaxation which is associated with the formation of cyclic GMP. Both responses to these protopanaxatriol-containing ginsenosides are inhibited by methylene blue, an inhibitor of soluble guanylate cyclase and of nitric oxide synthase. In contrast, ginsenosides from the protopanaxadiol group and its purified ginsenosides Rb1 and Re do not affect vascular tone or production of cyclic GMP in the rat aorta. These findings demonstrate that ginsenosides from the protopanaxatriol group but not from the protopanaxadiol group enhance the release of nitric oxide from endothelial cells and may contribute to the beneficial effect of ginseng on the cardiovascular system.

Animals↗

Effects of majonoside-R2 on pentobarbital sleep and gastric lesion in psychologically stressed mice.

The effects of Vietnamese ginseng (VG) and its major constituent majonoside-R2 on pentobarbital-induced sleep and gastric lesion in psychologically stressed mice were examined. Psychological stress exposure for 30 min significantly decreased the duration of pentobarbital (50 mg/kg, IP)-induced sleep in mice. VG extract (50 mg/kg, PO), VG saponin (25 mg/kg, PO), and majonoside-R2 (3.1-12.5 mg/kg, PO and IP) had no effect on pentobarbital sleep in unstressed control mice, but these drugs significantly recovered pentobarbital sleep decreased by psychological stress to the level of unstressed control animals. On the other hand, Panax ginseng (PG) extract (50-100 mg/kg, PO) failed to affect pentobarbital sleep in psychologically stressed mice. The effect of majonoside-R2 on psychological stress-induced decrease in the hypnotic activity of pentobarbital was significantly blocked by flumazenil (1 mg/kg, IV), a selective benzodiazepine antagonist. Diazepam (0.1 mg/kg, IP) significantly prolonged pentobarbital sleep in unstressed and psychologically stressed groups, and the effect of diazepam was significantly attenuated by the same dose of flumazenil. Naloxone (0.5-5 mg/kg, IP), an opioid antagonist, had no effect on pentobarbital sleep in unstressed or psychologically stressed animals. Psychological stress exposure for 16 h caused gastric lesion in mice. VG extract (25-50 mg/kg, PO) and majonoside-R2 (6.2-12.5 mg/kg, PO), as well as diazepam and naloxone, produced the protective action on gastric lesion in psychologically stressed mice. These results suggest that VG and its major constituent majonoside-R2 have the protective effects on the psychological stress-induced pathophysiological changes and that benzodiazepine receptors are partly implicated in the effects of majonoside-R2.

Animals↗