Dammarane-type Saponin Research Articles

Application of the Analytical Procedure Lifecycle Concept to a Quantitative 1H NMR Method for Total Dammarane-Type Saponins.

Dammarane-type saponins (DTSs) exist in various medicinal plants, which are a class of active ingredients with effects on improving myocardial ischemia and immunomodulation. In this study, a quantitative 1H NMR method of total DTSs in herbal medicines was developed based on the analytical procedure lifecycle. In the first stage (analytical procedure design), the Ishikawa diagram and failure mode effects and criticality analysis were used to conduct risk identification and risk ranking. Plackett-Burman design and central composite design were used to screen and optimize critical analytical procedure parameter. Then, the method operable design region was obtained through modeling. In the second stage (analytical procedure performance qualification), the performance of methodological indexes was investigated based on analytical quality by design. As examples of continued procedure performance verification, the method was successfully applied to determine the total DTSs in herbal pharmaceutical preparations and botanical extracts. As a general analytical method to quantify total DTSs in medicinal plants or pharmaceutical preparations, the developed method provides a new quality control strategy for various products containing dammarane-type saponin.

Gypensapogenin I Ameliorates Isoproterenol (ISO)-Induced Myocardial Damage through Regulating the TLR4/NF-κB/NLRP3 Pathway.

Myocardial fibrosis (MF) is a common pathological feature of many heart diseases and seriously threatens the normal activity of the heart. Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a novel dammarane-type saponin, was obtained from the hydrolysates of total gypenosides. It has been reported to exert a beneficial anti-inflammatory effect. In our study, we attempted to investigate the efficiency and possible molecular mechanism of Gyp I in cardiac injury treatment induced by ISO. In vitro, Gyp I was found to increase the survival rate of H9c2 cells and inhibit apoptosis. Combined with molecular docking and Western blot analysis, Gyp I was confirmed to regulate the TLR4/NF-κB/NLRP3 signaling pathway. In vivo, C57BL6 mice were subcutaneously injected with 10 mg/kg ISO to induce heart failure. Mice were given a gavage of Gyp I (10, 20, or 40 mg/kg/d for three weeks). Pathological alterations, fibrosis-, inflammation-, and apoptosis-related molecules were examined. By means of cardiac function detection, biochemical index analysis, QRT-PCR monitoring, histopathological staining, immunohistochemistry, and Western blot analysis, it was elucidated that Gyp I could improve cardiac dysfunction, alleviate collagen deposition, and reduce myocardial fibrosis (MF). In summary, we reported for the first time that Gyp I showed good myocardial protective activity in vitro and in vivo, and its mechanism was related to the TLR4/NF-κB/NLRP3 signaling pathway.

Deletion and tandem duplications of biosynthetic genes drive the diversity of triterpenoids in Aralia elata

Araliaceae species produce various classes of triterpene and triterpenoid saponins, such as the oleanane-type triterpenoids in Aralia species and dammarane-type saponins in Panax, valued for their medicinal properties. The lack of genome sequences of Panax relatives has hindered mechanistic insight into the divergence of triterpene saponins in Araliaceae. Here, we report a chromosome-level genome of Aralia elata with a total length of 1.05 Gb. The loss of 12 exons in the dammarenediol synthase (DDS)-encoding gene in A. elata after divergence from Panax might have caused the lack of dammarane-type saponin production, and a complementation assay shows that overexpression of the PgDDS gene from Panax ginseng in callus of A. elata recovers the accumulation of dammarane-type saponins. Tandem duplication events of triterpene biosynthetic genes are common in the A. elata genome, especially for AeCYP72As, AeCSLMs, and AeUGT73s, which function as tailoring enzymes of oleanane-type saponins and aralosides. More than 13 aralosides are de novo synthesized in Saccharomyces cerevisiae by overexpression of these genes in combination. This study sheds light on the diversity of saponins biosynthetic pathway in Araliaceae and will facilitate heterologous bioproduction of aralosides.

A novel dammarane-type saponin from Gynostemma pentaphyllum and its neuroprotective effect

One new and two known dammarane-type saponins were isolated from the leaves of Gynostemma pentaphyllum using various chromatographic methods. Their structures were identified by HR-ESI-MS,~( 1)H-NMR, ~(13)C-NMR, 2 D-NMR spectra as 2α,3β,12β,20,24(S)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(1, a new compound, namely gypenoside J5) and 2α,3β,12β,20,24(R)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(2) and 2α,3β,12β,20-tetrahydroxy-25-hydroperoxy-dammar-23-en-3-O-[β-D-glucopyranosyl(1→2)][β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl(1→6)]-β-D-glucopy-ranoside(3), respectively. Compounds 1 and 2 were a pair of C-24 epimers. All compounds showed weak cytotoxicity agxinst H1299, HepG2, PC-3, SH-SY5 Y cancer cell lines. However, they exerted protective effect against SH-SY5 Y cellular damage induced by H_2O_2 dose-dependently, of which compound 1 displayed the strongest antioxidant effect. The present study suggested that G. pentaphyllum has antioxidative potential and the saponins from G. pentaphyllum are considered as the active compounds with neuroprotecitve effect.

Effects of a dammarane-type saponin, ginsenoside Rd, in nicotine-induced vascular endothelial injury

BackgroundPanax notoginseng (Burk.) F.H. Chen is a traditional medicinal plant widely used to prevent and treat cardiovascular diseases. Ginsenoside Rd (GRd) is a major bioactive component of P. notoginseng, but specific effects on cardiovascular disease-related pathogenic processes are rarely studied, especially vascular endothelial injury. PurposeThis study investigated the potential protective efficacy of GRd against nicotine-induced vascular endothelial cell injury, disruption of vascular nitric oxide (NO) signaling, aberrant endothelium–monocyte adhesion, platelet aggregation, and vasoconstriction. Study design/MethodsVascular endothelial injury and functional disruption were investigated in cultured human umbilical vein endothelial cells (HUVECs) by biochemical assays for nitric oxide (NO) and angiotensin II (Ang II), immunofluorescence (IF) and western blotting for expression analyses of apoptosis- related proteins, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Ang II type receptor 1 (AGTR1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). In addition, vascular protection by GRd was examined in nicotine-administered Sprague-Dawley (SD) rats by serum NO and Ang II assays, and by hematoxylin-eosin (HE) and immunostaining of aorta. We also examined effects of GRd on monocyte (THP-1 cells) adhesion assays, adenosine diphosphate (ADP)-induced platelet aggregation, and phenylephrine (PE)-induced vasoconstriction of isolated rat aortic rings. ResultsIn HUVECs, nicotine significantly suppressed NO production, enhanced Ang II production, downregulated eNOS expression, and upregulated expression levels of AGTR1, TLR4, MyD88, NF-κB, iNOS, Bax/Bcl-2 ratio, cleaved caspase-3, and cytochrome c (cyt c). All of these changes were significantly reversed by GRd. In rats, oral GRd reversed the reduction NO and enhanced Ang II production in serum induced by nicotine administration, and HE staining revealed protection of aortic endothelial cells. In addition, GRd reversed nicotine-mediated enhancement of HUVECs-monocyte adhesion, inhibited ADP-induced platelet aggregation and PE-induced vasoconstriction. ConclusionGRd may prevent nicotine-induced cardiovascular diseases by preserving normal vascular endothelial NO signaling, suppressing platelet aggregation and vasoconstriction, and by preventing endothelial cell–monocyte adhesion.

The Most Important Herbs Used in the Treatment of Sexually Transmitted Infections in Traditional Medicine

Sexually transmitted diseases (STDs) or venereal diseases are transmitted through various methods of sexual intercourse (oral, vaginal, and anal). The predisposition to this type of diseases and infections depends on the immunity system of the body, so the lower the immunity system’s strength, the greater the risk of Sexually transmitted infections (STIs). The most important pathogenic causes of STIs include bacteria, viruses, and parasites. Phytochemical investigations have shown that medicinal plants are a rich source of antioxidant compounds, biologically active compounds, phenols, etc. They can have an inhibitory effect on germs and infectious viruses and are very important for a variety of parasitic diseases, microbial infections, and STIs. Some of the most important medicinal plants that produce inhibitory effects on the growth and proliferation of pathogenic agents of the STIs were reported in the present article. Based on the results obtained from the review of numerous articles indexed in the databases the Institute for Scientific Information, Scopus, PubMed, Google Scholar, etc., a number of plants have been reported to be used in the treatment and prevention of genital tract diseases and STIs, and to produce antiviral and antimicrobial effects, including Taxillus, Aristolochia, Syzygium cumini, Albizia adianthifolia, Bidens pilosa, Carica papaya, Ranunculus, Peltophorum africanum, Vachellia karroo, Rhoicissus tridentate, Houttuynia cordata, Panax notoginseng, Nelumbo nucifera, Astragalus, Hypericum aethiopicum, Spondias mombin, Jatropha zeyheri, Ximenia caffra, Trichilia dregeana, Clematis brachiate, Tabernaemontana, Sarcophyton. Phytochemical investigations have examined the therapeutic and clinical effects of medicinal plants, and the use of their active ingredients to produce herbal drugs has been addressed. The results of phytochemical investigations have shown that the most important compounds of these plants include quercetin, isoquercitrin, Dammarane-type saponin, flavonoids, alkaloids, flavonoids, glycosides, terpenoids, steroids, astragalosides, flavonoids and polysaccharides, α-pinene, β-pinene, α-pinene, quercetin, myricetin and luteolin flavonoids, β-pinene, 1,3,8-p-menthatriene, ledene, m-menthane, linalyl acetate and 3-carene. β-sitosterol, lupeol, lupeol, sitosterol, spathulenol, β-sitostenone,

Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells.

Damulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro, human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.

A New Dammarane-Type Saponin from the Rhizomes of Panax japonicus

A new dammarane-type saponin, named yesanchinoside R3 (1), along with three known compounds, has been isolated from the rhizomes of Panax japonicus. Their structures were elucidated on the basis of spectroscopic evidence.

Isolation and identification of a new dammarane-type triterpene saponin from Panax ginseng

Isolation and identification of a new dammarane-type triterpene saponin from Panax ginseng

ChemInform Abstract: A New Dammarane‐Type Saponin from Gynostemma pentaphyllum Induces Apoptosis in A549 Human Lung Carcinoma Cells.

AbstractThe new dammarane‐type saponin gypenoside Jh1 (I) is isolated from Gynostemma pentaphyllum.

A new dammarane-type saponin from Gynostemma pentaphyllum induces apoptosis in A549 human lung carcinoma cells

Gynostemma pentaphyllum has been widely used as a traditional herb for its antioxidant and immunostimulatory activities. We have previously reported several useful dammarane-type saponins with cytotoxicity against A549 human lung cancer cells from heat-processed G. pentaphyllum. In this study, a new dammarane-type saponin, 20(S)-2α,3β,12β-tetrahydroxydammar-3-O-β-d-glucopyranoside (namely gypenoside Jh1), was isolated from the ethanol extract of heat-processed G. pentaphyllum using column chromatography and semi-preparative HPLC. Gypenoside Jh1 exhibited strong cytotoxicity against A549 cells in a concentration-dependent manner, which was associated with apoptotic cell death characterized by morphological changes, Hoechst 33258 nuclear staining, Annexin V and propidium iodide binding and mitochondrial potentials assay. Quantitative analysis using flow cytometry also showed that the proportion of apoptotic cells was increased after gypenoside Jh1 treatment. These findings indicated that gypenoside Jh1 showed antiproliferative effects on A549 cells and mitochondrial-dependent pathway is involved in gypenoside Jh1-induced apoptosis.

A novel 12, 23-epoxy dammarane saponin from PanaPanax notoginseng

The present study investigated the chemical constituents of the roots and rhizomes of Panax notoginseng. Compounds were isolated by various column chromatographic methods, and their structures were elucidated by the extensive analysis of spectroscopic data and chemical evidences. A novel 12, 23-epoxy dammarane-type saponin, named epoxynotoginsenoside A (1), together with four known compounds (2-5), was isolated and characterized.

A new triterpenoid saponin from Gynostemma pentaphyllum

A new dammarane-type triterpene saponin was isolated from the aerial parts of Gynostemma pentaphyllum (Thunb.) Makino. Its structural elucidation was accomplished mainly on the basis of the interpretation of spectroscopic data, such as IR, HR–TOF–MS and NMR. Its cytotoxic activity was evaluated against one human cancer cell line HL-60 using MTT assay.

Notoginsenoside ST-4 inhibits virus penetration of herpes simplex virus in vitro

Further study on steam-treated notoginseng, the roots of Panax notoginseng (Burk.) F.H. Chen (Araliaceae), which is a famous traditional Chinese medicine that is used both in raw and treated forms for a long time, led to the isolation of a new dammarane-type saponin, namely notoginsenoside ST-4. Its structure was elucidated to be 3β,12β,20(S)-tri-hydroxydammar-24-ene-3-O-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 2)-β-d-glu-copyranoside, based on the detailed analyses of the 1D and 2D NMR spectral data and acidic hydrolysis. Notoginsenoside ST-4 was investigated for its antiviral activity on herpes simplex type 1 (HSV-1) and type 2 (HSV-2) in vitro. The 50% effective concentration (EC50) values, determined by plaque reduction assay, were 16.47 ± 0.67 and 19.44 ± 1.16 μM for HSV-1 and HSV-2, respectively, whereas the 50% cytotoxic concentration (CC50) determined by the XTT test on Vero cells was 510.64 ± 4.56 μM. As analyzed by attachment assay and penetration assay based on plaque reduction assay, the antiviral activity of notoginsenoside ST-4 was principally due to the penetration inhibition effects, which was confirmed by fluorescence microscopy observation that notoginsenoside ST-4 blocked the penetration of virus. Therefore, notoginsenoside ST-4 might be a promising agent for herpes simplex virus infection.

Minor dammarane saponins from the hongshen extract of Shenmai injection

A new dammarane-type triterpenoid saponin, (20R)-ginsenoside ST2 (1), along with five known saponins was isolated from the hongshen extract of Shenmai injection. The structure of 1 was elucidated to be (20R)-dammar-23(E)-ene-3β,6α,12β,20,25-pentol 6-O-β-d-glucopyranoside by means of spectroscopic methods.

Ginsenoside Rg8, a New Dammarane‐Type Triterpenoid Saponin from Roots of Panax quinquefolium.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Ginsenoside Re and Notoginsenoside R1: Immunologic Adjuvants with Low Haemolytic Effect

The further purification of the total saponins from the roots of Panax notoginseng (Burk.) F. H. Chen by ordinary and reversed-phase silica-gel, as well as Sephadex LH-20 chromatography afforded two adjuvant active dammarane-type saponins, ginsenoside Re (1) and notoginsenoside R1 (2). These two saponins were evaluated for haemolytic activities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA). The concentrations inducing 50% of the maximum haemolysis (HD50), using 0.5% red blood cell suspensions, were 469.6+/-16.9 and 420.4+/-22.9 microg/ml for 1 and 2, respectively. Compounds 1 and 2 significantly increased the concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte proliferation in the OVA-immunized mice (P<0.05, P<0.01, or P<0.001). The OVA-specific IgG, IgG1, and IgG2b antibody titres in serum were also significantly enhanced by 1 and 2 compared with OVA control group (P<0.05, P<0.01, or P<0.001). The results indicate that 1 and 2 showed a slight haemolytic activity and significant adjuvant effect on specific antibody and cellular immune response against OVA in mice, and that the type of the terminal sugar of the sugar chain at C(6) of protopanaxatriol could not only affect their haemolytic activities and adjuvant potentials, but have significant effects on the nature of the immune responses. The information about this structure-function relationship might be useful for developing semisynthetic dammarane-type saponin derivatives with immunological adjuvant activity.

New dammarane-type saponin from roots of Panax notoginseng

A new ginsenoside and 22 known compounds were isolated from the roots of Panax notoginseng (Araliaceae). The structure of the new compound was elucidated from 2D-NMR and other spectral evidence.

A Novel Insulin-releasing Substance, Phanoside, from the Plant Gynostemma pentaphyllum

Extracts from Gynostemma pentaphyllum Makino (Cucurbitaceae), a Southeast Asian herb, has been reported to affect numerous activities resulting in antitumor, cholesterol-lowering, immunopotentiating, antioxidant, and hypoglycemic effects. We have isolated one active compound by ethanol extraction, distribution in n-butyl alcohol/water, solid phase extraction/separation, and several rounds of reverse phase high pressure liquid chromatography. We have shown by NMR and mass spectrometry that this active compound is a novel saponin, a gypenoside, which we have named phanoside (21-,23-epoxy-,3beta-,20-,21-trihydroxydammar-24-ene-3-O-([alpha-d-rhamnopyranosyl(1-->2)]-[beta-d-glycopyranosyl(1-->3)]-beta-d-lyxopyranoside)), with a molecular mass of 914.5 Da. Phanoside is a dammarane-type saponin, and four stereoisomers differing in configurations at positions 21 and 23 were identified, each of which were found to stimulate insulin release from isolated rat pancreatic islets. We have also found that the stereoisomers are interconvertible. Dose-dependent insulin-releasing activities at 3.3 and 16.7 mM glucose levels were determined for the racemic mixture containing all four stereoisomers. Phanoside at 500 microM stimulates insulin release in vitro 10-fold at 3.3 mM glucose and potentiates the release almost 4-fold at 16.7 mM glucose. At these glucose levels, 2 microm glibenclamide stimulates insulin release only 2-fold. Interestingly, beta-cell sensitivity to phanoside is higher at 16.7 mM than at 3.3 mM glucose, although insulin responses were significantly increased by phanoside below 125 microM only at high glucose levels. Also when given orally to rats, phanoside (40 and 80 mg/ml) improved glucose tolerance and enhanced plasma insulin levels at hyperglycemia.

Studies on Dammarane-Type Saponins in the Flower-Buds of Panax ginseng C.A. Meyer

From the dried flower-buds of Panax ginseng C.A. Meyer, a new minor dammarane-type triterpene saponin named ginsenoside III together with nine known saponins was isolated. On the basis of spectral and chemical evidence, the structure of the new saponin was elucidated as 3-O-[β-D-glucopyranosyl(1 → 2)-β-D-glucopyranosyl]-20-O-β-D-glucopyranosyl-3β,12β,20(S)-trihydroxy-dammar-25-en-24-one.