Ginsenoside Rf2, a new dammarane glycoside from Korean red ginseng (Panax ginseng)

A new dammarane glycoside named ginsenoside Rf₂ has been isolated from Korean red ginseng (Panax ginseng) and its chemical structure has been elucidated as 6-O-[α-L-rhamnopyranosyl (1→2) β-D-glucopyranosyl]dammarane-3β, 6α, 12β, 20(R), 25-pentol by chemical and spectral methods.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

在不同饲料下人参对大鼠四氧嘧啶糖尿病的影响

我国古医书记载:人参能止消渴,治小便濒数、淋瀝。现在中医仍用含人参的复方治疗糖尿病。近藤治三郎和斋藤系平二氏曾分别报告朝鲜人参对肾上腺素所引起的高血糖有抑制作用。指出人参与胰岛素合用以治疗糖尿病,不但可以减少胰岛素用量,而且可使血糖降低的时间延长。王振綱和雷海鹏报告人参对犬的四氧嘧啶糖尿病有一定治疗作用。左箴等报告人参对雄大鼠四氧嘧啶糖尿病有一定有利影响。     

人参对于鼠四氧嘧啶糖尿病的影响

人参降低血糖的作用已有不少文献报告。斋藤系平报告人参的乙醚、酒精或水浸膏对注射肾上腺素、葡萄糖或利尿素在兔所引起的高血糖都具有抑制作用。阿部胜马与斋藤系平、近藤治三郎、金夏植、山田昌之等亦观察到人参乙醇浸膏、甲醇浸膏或人参配糖体对兔的肾上腺素高血糖具有抑制作用。金夏植报告人参皂硷体、人参酸与人参萜(panacene)都具有降低兔正常血糖的作用。王振纲与雷海鹏的研究指出人参在正     

Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways

Panax ginseng (P. ginseng) has anti-cancer effects in several cancer models. Ginsenosides are the main bioactive components in P. ginseng. Korean red ginseng (KRG) extract can potently kill various cancer cells and ginsenosides Rg3 (GRg3) and Rh2 (GRh2) are the primary ginsenosides in KRG. This study was carried out to examine whether KRG and its primary ginsenosides (GRg3 and GRh2) affect apoptosis of human hepatocellular carcinoma cells (Hep3B). KRG, GRg3 and GRh2 have obvious cytotoxic and apoptotic effects in Hep3B cells as evidenced by a decrease in cell viability and mitochondria membrane potential, but an increase in LDH release. In the mitochondria-mediated apoptosis pathway, KRG, GRg3 and GRh2 have the ability to stimulate the release of mitochondrial cytochrome c, activation of caspase-3 and Bax protein, inhibition of Bcl-2 protein and production of intracellular reactive oxygen species in Hep3B cells. These results suggest that KRG, GRg3 and GRh2 may induce apoptosis by direct activation of the mitochondrial pathway.     

Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity

Aim:

To determine whether ginsenosides with various sugar attachments may act as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin.

Methods:

The structural similarity between ginsenosides and ouabain was analyzed. The inhibitory potency of ginsenosides and ouabain on Na⁺/K⁺-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of ginsenosides to Na⁺/K⁺-ATPase.

Results:

Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, and possessed inhibitory potency on Na⁺/K⁺-ATPase activity. However, their inhibitory potency was significantly reduced or completely abolished when a monosaccharide was linked to the C-6 or C-20 position of the steroid-like structure; replacement of the monosaccharide with a disaccharide molecule at either of these positions caused the disappearance of the inhibitory potency. Molecular modeling and docking confirmed that the difference in Na⁺/K⁺-ATPase inhibitory potency among ginsenosides was due to the steric hindrance of sugar attachment at the C-6 and C-20 positions of the steroid-like structure.

Conclusion:

The cardiac therapeutic effects of ginseng and sanqi should be at least partly attributed to the effective inhibition of Na⁺/K⁺-ATPase by their metabolized ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure.     

人参的分析——Ⅲ.人参单体皂甙的提取分离与薄层光密度法测定

本文用高效液相制备柱色谱法从我国园参根中分离出Rb₁等五种主要皂甙。以此为对照品用硅胶G薄层展开,15%硫酸—硫酸氢铵乙醇饱和溶液显色后光密度法测定。并用此法对我国白参、三七与朝鲜红参、西洋参、美国野参等亲缘生药中皂甙含量进行了分析比较。     

Novel polyacetylene derivatives and their inhibitory activities on acetylcholinesterase obtained from <Emphasis Type="Italic">Panax ginseng</Emphasis> roots

In our research program to identify cholinesterase and β-secretase inhibitors, we investigated Ginseng (root of Panax ginseng), a crude drug described as a multifunctional drug in the ancient Chinese herbal book Shennong Ben Cao Jing. Results from hexane and methanol extracts showed moderate inhibitory activities. This suggests that ginseng roots may be effective for the prevention of and therapy for dementia. We then focused on hexane extracts of raw ginseng root and dried ginseng root since the determination of hexane extract constituents has not been studied extensively. Activity-guided fractionation and purification led to the isolation of 4 polyacetylene compounds; homopanaxynol, homopanaxydol, (9Z)-heptadeca-1, 9-diene-4,6-diyn-3-one, and (8E)-octadeca-1,8-diene-4,6-diyn-3,10-diol. The chemical structures of these compounds, including stereochemistry, were determined. This is the first study to identify the structure of homopanaxynol and homopanaxydol. Moreover, the modes of action of some compounds were characterized as competitive inhibitors. This study showed, for the first time, that polyacetylene compounds possess acetylcholinesterase inhibitory activities.     

Cytotoxicities of ginseng saponins and their degradation products against some cancer cell lines

In order to elucidate the cytotoxicity-structure correlation of ginseng-derived components, several prosapogenins and sapogenins were prepared from Korean red ginseng (Panax ginseng) saponins by acid hydrolysis or alkaline cleveage, and their chemical structures were identified by a combination of spectral and physical methods. Some of these degradation products showed the cytotoxic activities against various cancer cell lines, A549, SK-OV-3, SK-Mel-2, P388, L 1210 and K562. The significant difference in cytotoxicity between stereoisomers was not found and the activity was inversely proportional to the number of sugars linked to sapogenins. Diol-type prosapogenins and sapogenins showed higher cytotoxicity than triol-type ones.     

基于网络药理学的人参治疗非酒精性脂肪肝病靶点研究

目的 基于网络药理学研究人参对非酒精性脂肪肝病（NAFLD）的治疗靶点。方法 利用网络药理学分析平台BATMAN-TCM获取人参活性成分及其对应靶点,使用Cytoscape软件对功能组-靶点基因-人参药物成分网络进行构建。对靶基因通过STRING平台构建出靶点群蛋白互作网络（protein protein interaction network,PPI）,通过在线工具metascape对靶基因进行通路富集分析。从高通量基因表达数据库（Gene Expression Omnibus,GEO）下载人NAFLD转录组表达数据GSE89632,表达量进行标准化处理,使用双侧非配对t检验来检测表达差异的显著性。结果 人参药物成分对脂肪代谢有显著影响,特别是脂肪酸降解。通过蛋白相互作用分析和通路富集分析,发现了31个人参药物成分的关键靶基因（ACADM、SCD、ACACA、ACSL1、NR1H3、LEP、PPARA、ADIPOQ、NR1H4、CEBPA、HMGCR、SREBF1、TNF、SREBF2、ESR1、ABCA1、INS、AKT1、AVP、RXRA、HSD17B6、SRD5A2、UGT1A1、CYP19A1、PTGS2、CYP2E1、HTR2A、HSD17B1、EDN1、CCL5、AGTR1）和NAFLD发病过程紧密相关。其中胰岛素（insulin,INS）的节点数量远高于其他靶基因,INS的mRNA表达量在NAFLD组织中显著上调（P<0.000 1）。结论 INS可能是人参治疗NAFLD的关键核心靶点之一。     

Stabilization of β-D-galactosidase from heat and chemical inactivation with the extract ofPanax ginseng C.A. Meyer

Staiblization effect ofPanax ginseng C. A. Meyer on β-D-galactosidase inactivation was pro ved by kinetic studies of thermal inactivation of the enzyme. The water extractPanax ginseng C.A. Meyer showed stabilization activity at minimal concentration of 10ppm. The methanolic extract was purified to obtain ginseng saponins, and two groups of the ginsenosides,i.e., protopanaxadiol and protopanaxatriol were isolated. They also showed a protective effect against the thermal and chemical inactivation of the enzyme;p-chloromercuribenzoic acid and hydroxylamine known as protein modifier greatly inactivated the enzyme but inactivation was significantly blocked by the ginseng component. Mg²⁺. known as a cofactor, stabilized the enzyme and the poor stabilization effect by it was potentiated by ginseng components.     

Potential analgesic and anti-inflammatory activities of Panax ginseng head butanolic fraction in animals

The present study reports the potential anti-rheumatoid activity of Panax ginseng head part. P. ginseng-head part BuOH fraction (PGHB) was safe in acute toxicity (LD₅₀ > 5000 mg/kg) and inhibited the partially acetic acid-induced writhes (approximately 32%, P < 0.05) in mice. PGHB (500 mg/kg) inhibited the acetic acid-induced extravasation of Evan’s blue dye in mice by approximately 20.6% (P < 0.05), and was similar to the suppressive effect of ibuprofen (27.7%) as a positive control drug. Also, PGHB reduced the carrageenan-induced paw edema at 3 h after oral administration, and suppressed the production of serum IL-6 in CIA mice. This suggests that PGHB has potential analgesic and anti-inflammatory activities, and will be the supporting evidence for the potential anti-rheumatoid activity of Korean P. ginseng-head.     

Phytochemical and analytical studies of Panax notoginseng (Burk.) F.H. Chen

Panax notoginseng (Burk.) F.H. Chen is distributed throughout the southwest of China, Burma and Nepal. The root of this plant, called notoginseng or sanchi, has a long history of use as a remedy in Oriental traditional medicine. Modern studies have found that extracts and compounds from notoginseng exert various physiological effects. The active constituents are mainly recognized as saponins. In this review, we summarized the discovery and analysis of chemical constituents in notoginseng. Fifty-six saponins from notoginseng were isolated and elucidated. All of them are dammarane saponins, 35 of which can be classified as belonging to the protopanaxadiols group, and 21 as belonging to the protopanaxatriols group. Evidence from phytochemical studies on notoginseng demonstrated that no oleanane-type saponin, which exists in Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius), was found. Other types of compounds such as non-protein amino acids, polyacetylenes, phytosterols, flavonoids, and polysaccharides, many of which have pharmacological activities, were also isolated from notoginseng. Analytical studies on notoginseng were carried out based on botanical and phytochemical advances. In the qualitative studies, identification of the herbal materials and extracts was the main objective. The utilization of high-performance liquid chromatography (HPLC) fingerprint and molecular biological methods made the identification accurate and efficient. Spectral, chromatographic and immunoassay methods were used for the quantitative analysis. HPLC methods are the main authority regarding the determination of saponins and other types of constituents. The chromatographic conditions and detectors employed in the HPLC are discussed.     

Red ginseng for treating erectile dysfunction: a systematic review

AIMS

Korean red ginseng (unskinned Panax ginseng before it is steamed or otherwise heated and subsequently dried) is one of the most widely used herbal remedies. This systematic review evaluates the current evidence for the effectiveness of red ginseng for treating erectile dysfunction.

METHODS

Systematic searches were conducted on 20 electronic databases without language restrictions. Hand-searches included conference proceedings and our files. All randomized clinical studies (RCT) of red ginseng as a treatment of erectile dysfunction were considered for inclusion. Methodological quality was assessed using the Jadad score.

RESULTS

Seven RCTs met all the inclusion criteria. Their methodological quality was low on average. Six of the included RCTs compared the therapeutic efficacy of red ginseng with placebo. The meta-analysis of these data showed a significant effect (n = 349, risk ratio, 2.40; 95% CI of 1.65, 3.51, p < 0.00001, heterogeneity: tau² = 0.05, χ² = 6.42, p = 0.27, I² = 22%). Subgroup analyses also showed beneficial effects of red ginseng in psychogenic erectile dysfunction (n = 135, risk ratio, 2.05; 95% CI of 1.33, 3.16, p = 0.001, heterogeneity: χ² = 0.08, p = 0.96, I² = 0%).

CONCLUSIONS

Collectively these RCTs provide suggestive evidence for the effectiveness of red ginseng in the treatment of erectile dysfunction. However, the total number of RCTs included in the analysis, the total sample size and the methodological quality of the primary studies were too low to draw definitive conclusions. Thus more rigorous studies are necessary.     

Therapeutic potential of Panax ginseng and its constituents,ginsenosides and gintonin,in neurological and neurodegenerative disorders: a patent review

Introduction: Ginseng, Panax ginseng, has been used for various diseases and proven its great efficacy in managing central nervous system diseases.

Area covered: This article covers the therapeutic potential of patents on ginseng and its active constituents to develop therapies for neurodegenerative and neurological disorders, since 2010. The literature review was provided using multiple search engines including Google Patent, Espacenet and US Patent in the field of neurodegenerative diseases, Alzheimer’s disease, Parkinson’s disease, cognitive, and neurological disorders.

Expert opinion: The gathered data represented outstanding merits of ginseng in treatment of neurodegenerative and neurological disorders. These effects have been mediated by neurogenesis, anti-apoptotic and antioxidant properties, inhibition of mitochondrial dysfunction, receptor-operated Ca²⁺ channels, amyloid beta aggregation, and microglial activation as well as neurotransmitters modulation. However, these compounds have limited clinical application of for the prevention or treatment of neurodegenerative and neurological disorders. This might be due to incomplete data on their clinical pharmacokinetic and toxicity properties, and limited economic investments. There is an increasing trend in use of herbal medicines instead of chemical drugs, so it is time to make more attention to the application of ginseng, the grandfather of medicinal plants, from basic sciences to patients’ bed.     

The antidiabetic effect of ginsenoside Rb2 via activation of AMPK

Ginsenosides, which are active compounds found in ginseng (Panax ginseng), are used as antidiabetic treatments. The aim of this study was to determine whether Rb2, a type of ginsenoside, regulates hepatic gluconeogenesis through AMP-activated protein kinase (AMPK) and the orphan nuclear receptor small heterodimer partner (SHP) in hyperlipidemic conditions used as an in vitro model of type 2 diabetes. Considering these results, we concluded that Rb2 may inhibit palmitate-induced gluconeogenesis via AMPK-induced SHP by relieving ER stress, a cause of gluconeogenesis.     

中国红参化学成分的研究(Ⅱ)

从中国红参(Panax ginseng C.A.Meyer)中分离出十种单体(RG 1～10),用IR.MS(FD-MS.FAB-MS)、¹³C-NMR以及化学方法等鉴定了化学结构,分别为20(R)-ginsenoside Rh,(RG-1),ginsenoside-Rg,(RG-2),20(R)-ginsenoside-Rg₂(RG-3),20(R)proto-panaxatriol(RG-4)以及人参皂甙Rg.(RG-5),—Re(RG-6)—Rd(RG-7),—RC(RG-8),—Rd₂(RG-9),—Rb,(RG-10);其中RG-1、RG-3、RG-4系首次从中国红参分离得到的人参皂甙成分。用薄层对照未炮制前的白参不含以上三种成分,这可能是红参与白参药理作用上差异的原因之一。     

Ginsenoside Rg5, a genuine dammarane glycoside from Korean red ginseng

A genuine dammarane glycoside, named ginsenoside Rg₅, has been isolated by repeated column chromatography and preparative HPLC from the MeOH extract of Korean red ginseng (Panax ginseng C.A. Meyer). The chemical structure of ginsenoside Rg₅ was determined as 3-O-[β-D-glucopyranosyl (1→2)-β-D-glucopyranosyl] dammar-20(22),24-diene-3β,12β-diol by spectral and chemical methods. The stereostructure of a double bond at C-20(22) of ginsenoside Rg₅ was characterized as (E) from the chemical shift of C-21 in the¹³C-NMR and a NOESY experiment in the¹H-NMR.     

Chemical investigation on Sijunzi decoction and its two major herbs Panax ginseng and Glycyrrhiza uralensis by LC/MS/MS

Sijunzi decoction consists of Panax ginseng, Poria cocos, Atractylodes macrocephala and Glycyrrhiza uralensis. High performance liquid chromatography coupled with tandem mass spectrometry (LC/MSⁿ) was applied to identify and characterize three types of active components, ginsenoside (from P. ginseng), flavonoid and triterpenoid (from G. uralensis) in Sijunzi decoction. Spectra of MS and MS/MS from [M + Na]⁺ ions of ginsenosides were acquired and interpreted for their identification. Fragmentations with losing masses of 194 or 176 Da were the characteristic ions of triterpenoids in the MS/MS analysis. A characteristic fragment ion of the aglycon moiety at m/z 257 from source collision-induced dissociation was observed for flavonoid. LC/MS was also applied for the comparison of relative peak area of major active components between Sijunzi decoction and the single herb extracts. The concentration ratios of major active components detected in the individual herbs of P. ginseng and G. uralensis were found different from those in Sijunzi decoction. The experimental data indicated that the decocting process could result in the difference in the amount of active components.