Majonoside R2 Research Articles

Dammarane-Type Saponins from the Leaves of Vietnamese Ginseng (Panax vietnamensis Ha & Grushv.) and Their Acetylcholinesterase Inhibition In Vitro and In Silico.

Vietnamese ginseng (Panax vietnamensis Ha & Grushv.) represents one of the famous Panax spp. for valuable applications in both traditional and modern medicine; in which, its rhizome part has mainly been used as the medicinal materials based on the bioactive ginsenosides such as ginsenoside Rb1, ginsenoside Rg1, ginsenoside Rd, and majonoside R2. In modern medicine, the development of medicinal materials and utilization of medicinal plants are crucially based on standard bioactive ingredients, so this study to evaluate the leaves of Vietnamese ginseng as source of bioactive ginsenoside led to the identification of seven ginsenosides (1-7). Of them, ginsenoside Rd (2) and pseudoginsenoside RS1 (5) showed inhibitory effects on acetylcholinesterase in vitro with the IC50 values of 47.13 and 79.58 μM and supported by molecular docking analysis, in which ginsenoside Rd (2) and pseudoginsenoside RS1 (5) could play as allosteric inhibitors with high binding affinity (-8.5 and -9.4 kcal/mol) as evidenced by hydrogen bonding and hydrophobic interactions. The findings provided the scientific evidence for using the leaves of Vietnamese ginseng as an alternative source to the roots to enhance memory in traditional medicine as well as for further research on the anti-dementia effects of 2 and 5.

Monoclonal antibody-based enzyme-linked immunosorbent assay for quantification of majonoside R2 as an authentication marker for Nngoc Linh and Lai Chau ginsengs

BackgroundRecent years have witnessed increasing interest in the high amount of ocotillol-type saponin in Panax vietnamensis, particularly in relation to majonoside R2 (MR2). This unique 3%–5% MR2 content impart Ngoc Linh and Lai Chau ginsengs with unique pharmacological activities. However, in the commercial domain, unauthentic species have infiltrated and significantly hindered access to the authentic, efficacious variety. Thus, suitable analytical techniques for distinguishing authentic Vietnamese ginseng species from others is becoming increasingly crucial. Therefore, MR2 is attracting considerable attention as a target requiring effective management measures. MethodsAn enzyme-linked immunosorbent assay (ELISA) was developed by producing monoclonal antibodies against MR2 (mAb 16E11). The method was thoroughly validated, and the potential of the immunoassay was confirmed by high-performance liquid chromatography with ultraviolet spectroscopy. Furthermore, ELISA was applied to the assessment of the MR2 concentrations of various Panax spp., including Korean, American, and Japanese ginsengs. Results and conclusionsAn icELISA using mAb 16E11 exhibited linearity between 3.91 and 250 ng/mL of MR2, with detection and quantification limits of 1.53 and 2.50 − 46.6 ng/mL, respectively. Based on this study, the developed icELISA using mAb 16E11 could be a valuable tool for analyzing MR2 level to distinguish authentic Ngoc Linh and Lai Chau ginsengs from unauthentic ones. Furthermore, the analysis of the samples demonstrated that Ngoc Linh and Lai Chau ginsengs exhibit a notably higher MR2 value than all other Panax spp. Thus, MR2 might be their ideal marker compound, and various bioactivities of this species should be explored.

Towards differentiation of Panax vietnamensis and Panax vietnamensis var. fuscidiscus by UPLC-QTOF-MS

Vietnamese ginseng (Panax vietnamensis Ha et Grusvh., Araliaceae - PV) is a high-value medicinal plant of Vietnam. Recently, a new variety of this plant P. vietnamensis var fuscidiscus (PVF), so-called Lai Chau ginseng, was discovered and circulated on the Vietnam market along with PV. PV and PVF rhizomes and roots are preliminarily reported to possess similar saponin composition. However, PV is much more expensive than PVF due to the higher regard of the consumer, which consequently leads to the inattentive misuse or intentional adulteration of PV by PVF. In this study, a UPLC-ToF-MS method was developed to distinguish PV and PVF based on their saponin profiles. The UPLC qualitative result showed that the saponin constituent of PVF is more complex than that of PV. The significant differences in the chromatogram of PV and PVF extracts are the peaks eluted from 32 - 48 min. Vina-ginsenoside R2 (9), chikusetsusaponin L8 (10), and notoginsenoside R4 (12) are characterized for PVF, while notoginsenoside Fa (13), quinquenoside R1 (16), and pseudoginsenoside Rs1 (19) are specialized for PV. The preliminary quantitative determination result showed that the content of majonoside R2, ginsenoside Rg1, ginsenoside Rb1, and ginsenoside Rd in PV is higher than in PVF. In contrast, the content of majonoside R1 and vina-ginsenoside R2 in PVF is significantly higher than in PV. The developed method could be used as an effective method to distinguish PV and PVF.

Triterpenoid saponins from Panax zingiberesis and their network analysis of their chemotaxonomic significance

In a phytochemical investigation of Panax zingiberesis, a medicinal species in China, the following triterpenoid saponins were isolated and identified: notopanaxoside A (1), majonoside R2 (2), majonoside R1 (3), ginsenoside Rb1 (4), pseudoginsenoside RT4 (5), vina-ginsenoside R1 (6), ginsenoside RO (7), chikusetsusaponin IV (8), and vina-ginsenoside R2 (9). Compounds 1, 3, 5, 6, and 9 were found in P. zingiberesis for the first time. Network analysis was used to examine the chemotaxonomic significance of the compounds.

Majonoside-R2 Postconditioning Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Attenuating the Expression of HIF1α and Activating RISK Pathway.

Reoxygenation of hypoxic cardiac myocytes can paradoxically induce myocardial injury and affect the recovery processes. Pharmacological postconditioning is an efficient strategy used in clinical practice that protects cardiomyocytes from hypoxia/reoxygenation (HR) injury. Natural products or foods have been known to possess effective cardioprotective properties. Majonoside-R2 (MR2) is a dominant saponin component of Vietnamese ginseng that has several biological effects. In this study, we evaluated the protective effect of MR2 on HR-stimulated cardiomyocytes and investigated the related molecular mechanisms. H9C2 cardiomyocytes were exposed to HR conditions with or without MR2 supplementation. Samples from experimental groups were used to analyze the expression of apoptosis- and activating reperfusion injury salvage kinase (RISK)-related factors in response to HR injury by using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Post-treatment, MR2 enhanced cell viability under HR conditions. We found that MR2 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF1α) and transforming growth factor beta 1 (TGFβ1), modulated Akt/GSK3ß/cAMP response element-binding signaling, and regulated gene expression related to apoptosis (B cell lymphoma-extra-large [Bcl-xl], Bcl-2 homologous killer [Bak], Bcl-2 associated X [Bax], and connexin 43 [Cnx43]). Thus, the present findings demonstrate that MR2 protects cardiomyocytes against HR injury by suppressing the expression of HIF1α and activating the RISK pathway.

Vietnamese Ginseng (Panax vietnamensis Ha and Grushv.): Phylogenetic, Phytochemical, and Pharmacological Profiles

Vietnamese ginseng (VG) (Panax vietnamensis, Araliaceae) is indigenous in the central highlands of Vietnam and the southernmost distribution in the Panax genus. Compared to the long history of use and overall research on Korean ginseng and American ginseng, the up‑to‑date publication on VG is relatively much less extensive. The studies on VG have been reported focusing on phylogenetic analysis, phytochemistry, and pharmacological activity. To date, there is no systematic review of VG. In this review, the phytochemical profile including 52 individual saponins of VG is described, it becomes noteworthy that ocotillol‑type ginsenosides including majonoside R1 and majonoside R2 are unique and dominate in the title plant of the Panax spp. In addition, various pharmacological activities of VG extracts and components are summarized and discussed.

Majonoside-R2 extracted from Vietnamese ginseng protects H9C2 cells against hypoxia/reoxygenation injury via modulating mitochondrial function and biogenesis

Vietnamese ginseng has a therapeutic effect on various diseases; however its bioactivity against cardiac hypoxia/reoxygenation (HR) injury remains unclear. In this study, we evaluated the protective roles of total saponin extract (TSE) and majonoside-R2 (MR2) targeting mitochondria in HR-induced rat cardiomyocyte H9C2 cells. The results showed that both TSE and MR2 effectively protected the cells from HR damage. Particularly, 9 µM of MR2 significantly increased the viability of HR-induced cells (p < 0.05). Interestingly, MR2 treatment markedly prevented the loss of mitochondrial membrane potential and cardiolipin content, and an increase in reactive oxygen species production in HR-treated H9C2 cells. Moreover, MR2 treatment altered the mRNA expression of genes involved in mitochondrial biogenesis under HR conditions. The present study documented for the first time the cardioprotective effects of MR2 against HR injury by maintaining mitochondrial function and modulating mitochondrial biogenesis.

Antimelanogenic Activity of Ocotillol-Type Saponins from Panax vietnamensis.

The ocotillol (OCT)-type saponins have been known as a tetracyclic triterpenoid, possessing five- or six-membered epoxy ring in the side chain. Interestingly, this type saponin was mostly found in Panax vietnamensis Ha et Grushv., Araliaceae (VG), hence making VG unique from the other Panax spp. Five OCT-type saponins, majonoside R2, vina-ginsenoside R2, majonoside R1, pseudoginsenoside RT4, vina-ginsenoside R11, together with three protopanaxadiol (PPD)-type saponins and four protopanaxatriol (PPT)-type saponins from VG were evaluated for their antimelanogenic activity. All of isolates were found to be active. More importantly, the five OCT-type saponins inhibited melanin production in B16-F10 mouse melanoma cells, without showing any cytotoxicity. Besides ginsenoside Rd and ginsenoside Rg3 in PPD and notoginsenoside R1 in PPT-type saponins, majonoside R2 was the most potent melanogenesis inhibitory activity in OCT-type saponins. In this article, we highlighted antimelanogenic activity of OCT-type saponins and potential structure-activity relationship (SAR) of ginsenosides. Our results suggested that OCT-type saponins could be used as a depigmentation agent.

Phytoconstituents and Biological Activities of Panax vietnamensis (Vietnamese Ginseng): A Precious Ginseng and Call for Further Research-A systematic review

Panax vietnamensis Ha et Grushv., a Vietnamese ginseng, is a well-known plant, naturally distributed in the Ngoc Linh and Hoang Lien Son mountain areas in Vietnam. It is used as a tonic and medicinal food in traditional folk medicine because it possesses wondrous health benefits. To support its functional attributes, various investigations have been carried out to find out its anti-inflammatory, anti-cancer, anti-stress, anti-nociception, psychomotor and sedative-hypnotic effects and anxiolytic activities. Also similar to other ginsengs, Vietnamese ginseng is a rich source of saponins and it has higher content of protopanaxadiol-, protopanaxatrial- and ocotillol-type saponins compared to other ginsengs in the world. Majonoside R2 is a main saponin in Vietnamese ginseng but this compound does not exist in Panax ginseng. Based on this systematic review, we discussed for future prospects and suggest that thorough scientific scrutiny is necessary in future researches.

Hairy root cultures of Panax vietnamensis, a promising approach for the production of ocotillol-type ginsenosides

Panax vietnamensis Ha et Grushv. is an important source of majonoside R2, a dammarane saponin with an ocotillol side-chain, which is an interesting pharmacological active compound. Thirty-one transformed root lines were obtained after the inoculation of in vitro shoot explants of P. vietnamensis with Rhizobium rhizogenes ATCC 15834 strain. The transgenic nature of the hairy roots was confirmed by PCR amplification. The established hairy root lines displayed four morphological phenotypes when cultured on hormone-free medium. Most of the cultures showed the characteristic traits of hairy roots with primary roots, an extensive lateral branching and rapid growth. Kinetic growth of these hairy root lines was measured for 90 days and a biomass production of about 10 g L−1 fresh weight was obtained. The ginsenoside content of hairy roots was identified by LC–MS and compared with that of 6 year-old rhizomes of P. vietnamensis. Majonoside R2 was recovered in trace amounts, but other ocotillol saponins, pseudoginsenoside F11 and vinaginsenoside R1, were recovered in larger proportions. These results indicate that hairy roots of P. vietnamensis present an interesting potential to produce ginsenosides and, in particular, ocotillol saponins.

In silico studies for the interaction of tumor necrosis factor-alpha (TNF-α) with different saponins from Vietnamese ginseng (Panax vietnamesis).

Tumor necrosis factor-alpha (TNF-α) is a cytokine that plays an important role in inflammatory process and tumor development. Recent studies demonstrate that triterpene saponins from Vietnamese ginseng are efficient inhibitors of TNF-α. But the interactions between TNF-α and the saponins are still unclear. In this study, molecular docking and molecular dynamics simulations of TNF-α with three different triterpene saponins (majonoside R2, vina-ginsenoside R1 and vina-ginsenoside R2) were performed to evaluate their binding ability. Our results showed that the triterpene saponins have a good binding affinity with protein TNF-α. The saponins were docked to the pore at the top of the “bell” or “cone” shaped TNF-α trimer and the complexes were structurally stable during 100 ns molecular dynamics simulation. The predicted binding sites would help to subsequently investigate the inhibitory mechanism of triterpene saponins.

Anti-inflammatory effects of vina-ginsenoside R2 and majonoside R2 isolated from Panax vietnamensis and their metabolites in lipopolysaccharide-stimulated macrophages

Panax vietnamensis Ha et Grushv., with its main constituents vina-ginsenoside R2 (VR2) and majonoside R2 (MR2), is used in traditional folk medicine in the hill tribes of Vietnam for anti-fatigue, anti-inflammatory, and life-saving purposes. In a preliminary study, VR2 and MR2 were shown to be metabolized to pseudoginsenoside RT4 (PRT4) and ocotillol by human gut microbiota. Therefore, we measured the anti-inflammatory effects of VR2, MR2, and their metabolites in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. Among these ginsenosides, only VR2 exhibited cytotoxicity against peritoneal macrophages. MR2, PRT4, and ocotillol inhibited LPS-stimulated transcription factor (NF)-κB activation, and expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin (IL)-1. However, these ginsenosides did not inhibit peptidoglycan-induced NF-κB activation in the macrophages. These three ginsenosides also inhibited LPS-stimulated cyclooxygenase-2 and inducible NO synthase expression, and phosphorylation of NF-κB signal molecules IL-1 receptor-associated kinase 1 and tumor growth factor-β-activated kinase 1 in peritoneal macrophages. Treatment with either PRT4 or ocotillol inhibited the Alexa Fluor 488-conjugated LPS-mediated shift of macrophages, as observed by flow cytometry. They also potently inhibited the binding of LPS to TLR4 on peritoneal macrophages, both with and without transfected MyD88 siRNA. Among the tested ginsenosides, ocotillol exhibited the strongest inhibitory effect on inflammation in LPS-stimulated macrophages via the NF-κB signaling pathway. Based on these findings, orally administered VR2 and MR2 of P. vietnamensis may be metabolized to ocotillol via PRT4, and the metabolites, particularly ocotillol, may inhibit inflammation by inhibiting the binding of LPS to TLR4 on macrophages.

Quantitative estimation of ginsenosides in different ages of &lt;i&gt;Panax vietnamensis&lt;/i&gt; and their anti-proliferation effects in hela cells

Background: The objective of study was to investigate the major compounds of ginsenosides in Panax vietnamensis in its growing stages and their anti-proliferative activity in HeLa cells. Materials and Methods: The roots with different ages were analyzed by HPLC/MS. Anti-proliferation activity of P. Vietnamensis ginseng in HeLa cells was investigated using MTT assay. Results: Three main compounds of ginsenoside, Rb1, Rg1 and majonoside R2 were increased with the increasing of age. However, ginsenoside Rc, Re, Rd and Rg3 did not show any alteration with growing age. The major compound majonoside R2 was accumulated maximum in 5 years old ginseng. According to the data, the anti-proliferation activity was directly proportional to the growing ages of ginseng. The eleven years old ginseng showed maximum effect than the younger roots. This effect may be related to the concentration of ginsenosides or majonoside R2 content in P. Vietnamensis. Conclusion: The concentration of ginsenoside content in the roots of P. Vietnamensis is directly related to the growing ages. Overall, due to the higher concentration of ginsenoside in mature ginseng root, Panax vietnamensis ginseng can be used as an effective anti-proliferative drug.

Ocotillol, a Majonoside R2 Metabolite, Ameliorates 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis in Mice by Restoring the Balance of Th17/Treg Cells.

In a preliminary experiment, majonoside R2 (MR2), isolated from Vietnamese ginseng (Panax vietnamensis Ha et Grushv.), inhibited differentiation to Th17 cells and was metabolized to ocotillol via pseudoginsenoside RT4 (PRT4) by gut microbiota. Therefore, we examined the inhibitory effects of MR2 and its metabolites PRT4 and ocotillol against Th17 cell differentiation. These ginsenosides significantly suppressed interleukin (IL)-6/tumor growth factor beta-induced differentiation of splenic CD4(+) T cells into Th17 cells and expression of IL-17 in vitro. Among these ginsenosides, ocotillol showed the highest inhibitory effect. We also examined the anti-inflammatory effect of ocotillol in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Oral administration of ocotillol significantly suppressed TNBS-induced colon shortening, macroscopic score, myeloperoxidase activity, and production of nitric oxide and prostaglandin E2. Ocotillol treatment increased TNBS-suppressed expression of tight junction proteins ZO-1, occludin, and claudin-1 in the colon. Treatment with ocotillol inhibited TNBS-induced expression of tumor necrosis factor (TNF)-α and IL-1β, as well as activation of NF-κB and MAPKs. Moreover, treatment with ocotillol inhibited TNBS- induced differentiation to Th17 cells in the lamina propria of colon, as well as expression of T-bet, RORγt, IL-17, and IL-23. Ocotillol treatment also increased Treg cell differentiation and Foxp3 and IL-10 expression. These findings suggest that orally administered MR2 may be metabolized to ocotillol in the intestine by gut microbiota and the transformed ocotillol may ameliorate inflammatory diseases such as colitis by restoring the balance of Th17/Treg cells.

Transcriptome analysis of Panax vietnamensis var. fuscidicus discovers putative ocotillol-type ginsenosides biosynthesis genes and genetic markers.

BackgroundP. vietnamensis var. fuscidiscus, called “Yesanqi” in Chinese, is a new variety of P. vietnamensis, which was first found in Jinping County, the southern part of Yunnan Province, China. Compared with other Panax plants, this species contains higher content of ocotillol-type saponin, majonoside R2. Despite the pharmacological importance of ocotillol-type saponins, little is known about their biosynthesis in plants. Hence, P. vietnamensis var. fuscidiscus is a suitable medicinal herbal plant species to study biosynthesis of ocotillol-type saponins. In addition, the available genomic information of this important herbal plant is lacking.ResultsTo investigate the P. vietnamensis var. fuscidiscus transcriptome, Illumina HiSeq™ 2000 sequencing platform was employed. We produced 114,703,210 clean reads, assembled into 126,758 unigenes, with an average length of 1,304 bp and N50 of 2,108 bp. Among these 126,758 unigenes, 85,214 unigenes (67.23%) were annotated based on the information available from the public databases. The transcripts encoding the known enzymes involved in triterpenoid saponins biosynthesis were identified in our Illumina dataset. A full-length cDNA of three Squalene epoxidase (SE) genes were obtained using reverse transcription PCR (RT-PCR) and the expression patterns of ten unigenes were analyzed by reverse transcription quantitative real-time PCR (RT-qPCR). Furthermore, 15 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely to involve in triterpenoid saponins biosynthesis pathway were discovered from transcriptome sequencing of P. vietnamensis var. fuscidiscus. We further analyzed the data and found 21,320 simple sequence repeats (SSRs), 30 primer pairs for SSRs were randomly selected for validation of the amplification and polymorphism in 13 P. vietnamensis var. fuscidiscus accessions. Meanwhile, five major triterpene saponins in roots of P. vietnamensis var. fuscidicus were determined using high performance liquid chromatography (HPLC) and evaporative light scattering detector (ELSD).ConclusionsThe genomic resources generated from P. vietnamensis var. fuscidiscus provide new insights into the identification of putative genes involved in triterpenoid saponins biosynthesis pathway. This will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level. The SSR markers identified and developed in this study show genetic diversity for this important crop and will contribute to marker-assisted breeding for P. vietnamensis var. fuscidiscus.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1332-8) contains supplementary material, which is available to authorized users.

Simultaneous determination of triterpene saponins in ginseng drugs by high-performance liquid chromatography.

A HPLC method for the simultaneous determination of 11 triterpene saponins with four-type aglycones (protopanaxadiol, protopanaxatriol, ocotillol and oleanolic acid types) in Ginseng drugs was developed and validated. Using a gradient of acetonitrile and 10 mM K-phosphate buffer (pH 5.80) as the mobile phase and UV detection at 196 nm, more than 18 ginsenosides with different aglycones were separated satisfactorily within 60 min. The detection limits (signal/noise> or =3) were 0.1 microg for ginsenosides Rb1, Rc, Rd, Re and Rg1, chikusetsusaponin III, and notoginsenoside R2, 0.2 microg for gisenoside Ro and chikusetsusaponin IVa, 0.3 microg for chikusetsusaponin IV, and 3 microg for majonoside R2. The calibration curve of each saponin had a correlation coefficient close to 1. Intra- and interday precisions were less than 2.1% (n=5) and 3.3% (n=15), respectively. The recovery rates of extraction were in the range of 96.4-102.7% for all ginsenosides. By adopting this method, the determinations of 11 ginsenosides in three Ginseng drugs derived from Panax ginseng, Panax vietnamensis var. fuscidiscus and Panax japonicus (Japan) were achieved.

Hepatoprotective effect of majonoside R2, the major saponin from Vietnamese ginseng (Panax vietnamensis).

The hepatoprotective effect of majonoside R 2 (MR2), the major saponin constituent from Vietnamese ginseng ( Panax vietnamensis, Araliaceae), was evaluated in vivo on D-galactosamine ( D-GalN)/lipopolysaccharide (LPS)-induced hepatic apoptosis and subsequent liver failure in mice. Pretreatment of mice with MR2 (50 or 10 mg/kg, intraperitoneal) at 12 and 1 h before D-GalN/LPS injection significantly inhibited apoptosis and suppressed following hepatic necrosis. Importantly, the elevation of serum tumor necrosis factor-alpha (TNF-alpha) level, an important mediator for apoptosis in this model, was significantly inhibited by MR2 at a dose of 50 mg/kg. On the other hand, MR2 was found to protect primary cultured mouse hepatocytes from cell death by inhibiting apoptosis induced by D-GalN/TNF-alpha in vitro, as evidenced by DNA fragmentation analysis. These findings suggested that MR2 may have protected the hepatocytes from apoptosis via an inhibition of TNF-alpha production by activated macrophages and a direct inhibition of apoptosis induced by TNF-alpha.

Bioactive Saponins In Vietnamese Ginseng, Panax Vietnamensis

Vietnamese ginseng, Panax vietnamensis was recently found in central Vietnam, and regarded as a new botanical species. It was used in traditional folk medicine in hill tribes for the purpose of anti-fatigue and life saving. From the rhizome and root of this plant, 37 saponins including 14 new compounds were isolated. Some of them were common to other Panax spp., but the general yields in this species were very high. Among them, an ocotillol-type saponin majonoside-R2 (MR2) was remarkable in its yield (5.3%). Structural features of new saponins were briefly introduced. The biological effects of these saponins were studied in two ways, anti-stress effect and anti-tumor promoting effect; both activities were based upon the traditional usage of this crude drug. In psychologically stressed mice, the saponin fraction of Vietnamese ginseng significantly reduced stress-related disorders (reducing sleeping time, formation of gastric lesions) and MR2 was responsible for this effect. A possible mechanism for this effect was proposed. MR2 exhibited a significant inhibitory effect on Epstein-Barr virus early antigen (EBV-EA) induced by the tumor promoter phorbol acetate. MR2 also showed potent anti-tumor-promoting activity on mouse skin and hepatic tumors.

Suppressive Effects of Vietnamese Ginseng Saponin and Its Major Component Majonoside-R2 on Psychological Stress-Induced Enhancement of Lipid Peroxidation in the Mouse Brain

We investigated the in vivo effects of Vietnamese ginseng saponin (VG saponin) and its major component majonoside-R2 (MR2) on psychological stress-induced enhancement of lipid peroxidation in the mouse brain. Psychological stress exposure using a communication box system for 4 h significantly increased the content of thiobarbituric acid reactive substance (TBARS), an index of lipid peroxidation activity, in the brain. Pretreatment with VG saponin (15–25 mg/kg, PO) and MR2 (1–10 mg/kg, IP) significantly attenuated the psychological stress-induced increase in TBARS content in the brain. The aglycone of MR2 (MR2-aglycone: 1.2 mg/kg, IP), at the equivalent dose of MR2 (i.e., 3 mg/kg, IP), also produced the suppressive effect on the increase in the TBARS content. The in vivo suppressive effect of MR2 was dose dependently attenuated by flumazenil (3 and 10 mg/kg, IP), a benzodiazepine receptor antagonist, and pregnenolone sulfate (10 mg/kg, IP), a neurosteroidal negative allosteric modulator of GABA A receptors. These findings suggest that VG saponin and its major component MR2 have preventive effects on the psychological stress-induced brain cell membrane damage, and that the effect of MR2 is partly due to enhancement of GABA A-ergic systems in the brain.

Cancer chemopreventive activity of majonoside-R2 from Vietnamese ginseng, Panaxvietnamensis

In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Panax plants were screened. Consequently, the ocotillol-type saponin, majonoside-R2 (MR2), was obtained from the rhizome and root of Panax vietnamensis (Vietnamese ginseng) as an active constituent. MR2 exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse hepatic tumor using N-nitrosodiethylamine (DEN) as an initiator and phenobarbital (PB) as a promoter. Further, MR2 exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin induced by nitric oxide (NO) donor/12- O-tetradecanoylphorbol-13-acetate (TPA) or peroxynitrite/TPA.