Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix / 中国天然药物

Gypenosides, structurally analogous to ginsenosides and derived from a sustainable source, are recognized as the principal active compounds found in Gynostemma pentaphyllum, a Chinese medicinal plant used in the treatment of the metabolic syndrome. By bioactive tracking isolation of the plants collected from different regions across China, we obtained four new gypenosides (1-4), together with nine known gypenosides (5-13), from the methanol extract of the plant. The structures of new gypenosides were elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, complemented by chemical degradation experiments. Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cα activity assays, we established a definitive structure-activity relationship for these dammarane-type triterpenoids, affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix (ECM) deposition within hepatic stellate cells. Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration. These results underscore the potential of dammarane-type triterpenoids as prospective anti-fibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.

Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish / 中国中药杂志

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.

A new dammarane-tye triterpenoid saponin from roots of Panax notoginseng / 中草药

Objective: To study the minor triterpenoid saponins from the roots of Panax notoginseng, which provided basis for the systematic research, quality control and safety evaluation of P. notoginseng. Methods The compounds were isolated and purified by MCI resin, ODS, along with Preparative-HPLC, and the structures were identified by spectroscopic analysis, and comparing with the pubished literature values. Results: Twelve monomeric compounds isolated from the roots of P. notoginseng, were identified as notoginsenoside P1 (1), notoginsenoside T5 (2), ginsenoside Rk3 (3), ginsenoside Rh4 (4), notoginsenoside T3 (5), 20(S)-protopanaxatriol (6), dammar 20 (21),24-diene-3β,6α,12β-triol (7), ginsenoside Rg3 (8), gypenoside XIII (9), ginsenoside Rk1 (10), ginsenoside Rg5 (11), and 20 (S)-ginsenoside Rh2 (12). Conclusion: Compound 1 is a new dammarane-type triterpenoid saponin

Research progress on chemical constituents in hydrolyzed products of gypenosides and their pharmacological activities / 药物评价研究

The biologically active constituents in Gynostemma pentaphyllum are dammarane-type glycosides,called gypenosides.They are believed to be the highest contents of this herb,easy to obtain,and mainly active in anti-tumor,controlling the blood glucose,lipid-lowering,cardiovascular protection,etc.The saponins may change into sub-glucoside after hydrolysis,for the intemal acetal glucoside structure is vulnerable to acid,alkali,and enzyme degradation.Through searching the literatures in recent years,this paper summarized the chemical constituents in the hydrolyzed products of gypenosides,for providing references to discover novel and more active lead compounds.

Cytotoxicity and Structure Activity Relationship of Dammarane-Type Triterpenoids from the Bark of Aglaia elliptica against P-388 Murine Leukemia Cells

Six dammarane-type triterpenoids, dammar-24-en-3β-ol (1), 3β-epicabraleahydroxy lactone (2), (E)-25-hydroperoxydammar-23-en-3β,20-diol (3), dammar-24-en-3β,20-diol (4), 3β-acetyl-20S,24S-epoxy-25-hydroxydammarane (5), and 3β-epiocotillol (6) were isolated from the methanolic extract of the bark of Aglaia elliptica. The chemical structure were identified on the basis of spectroscopic evidence and by comparison with those spectra previously reported. Compounds 1 – 6 were isolated first time from this plant. Compounds 1 – 6, along with a known synthetic analog, cabraleone (7) were evaluated their cytotoxic activity against P-388 murine leukimia cells in vitro. Among those compounds 3β-acetyl-20S,24S-epoxy-25-hydroxydammarane (5) showed strongest cytotoxic activity with IC₅₀ value of 8.02 ± 0.06 µM.

Chemical constituents and pharmacological activities of Cyclocarya paliurus(Batal.)Iljinskaja:research advances / 国际药学研究杂志

Cyclocarya paliurus(Batal.)Iljinskaja,a Chinese native plant,contains various components of bioactive constitu-ents in leaves. The main chemical constituents are triterpenes,flavonoids,organic acids,polysaccharides,steroids,etc. and among them,the dammarane-type triterpenoids are the main sweet components. Modern pharmacological research has demonstrated that these compounds or plant extracts show hypoglycemic,lipid-lowering,blood pressure lowering,antioxidation,and antibacterial activi-ties,and so on. The research advances in chemical constituents and pharmacological effect of C. paliurus are reviewed for a prospect reference of its further development and utilization.

20(R)-Ginsenoside-Rh19, a novel ginsenoside from alkaline hydrolysates of total saponins in stems-leaves of Panax ginseng / 中草药

Objective: To study the chemical constituents of alkaline hydrolysates of total saponins from the stems and leaves of Panax ginseng. Methods: The chemical constituents were isolated and purified by various chromatographic methods, and the chemical structures were identified by NMR and MS spectra analyses. Results: A total of 30 compounds were isolated and identified. Among them, 28 were determined as 20(S)-protopanaxadiol (1), 20(R)-protopanaxadiol (2), dammar-20(21),24-diene-3β,6α,12β-triol (3), dammar-20(22)E,24-diene-3β,6α,12β-triol (4), 20(S)-protopanaxatriol (5), 20(R)-protopanaxatriol (6), 20(S)-ginsenoside Rh2 (7), 20(R)-ginsenoside Rh2 (8), ginsenoside Rh16 (9), isoginsenoside Rh3 (10), 20(S)-dammar-3β,6α,12β,20,25-pentol (11), 20(R)-dammar-3β,6α,12β,20,25-pentol (12), ginsenoside Rk3 (13), 20(S)-ginsenoside Rh1 (14), 20(R)-ginsenoside Rh1 (15), ginsenoside F1 (16), ginsenoside Rh19 (17), 20(R)-ginsenoside Rh19 (18), dammar-20(22)E-ene-3β,6α,12β,25-tetrol (19), notoginsenoside T2 (20), ginsenoside Rg6 (21), 20(22)E-ginsenoside F4 (22), ginsenoside Rk1 (23), 20(S)-ginsenoside Rg3 (24), 20(R)-ginsenoside Rg3 (25), 20(S)-ginsenoside Rg2 (26), 20(R)-ginsenoside Rg2 (27), and 3β,6α,12β,25-tetrahydroxy-dammar-20(22)E-ene-6-O-α-L-rhamno- pyranosyl-(1→2)-β-D-glucopyranoside (28). Conclusion: Compound 18 is a new saponin. Compounds 3, 4, 11, 12, and 19 are rare dammarane-type triterpenes, and 7-10, 13-18, and 20-28 are rare ginsenosides.

Research progress in hypoglycemic effect of natural dammarane saponins / 中草药

Dammarane saponins, classified as tetracyclic triterpenoid saponins, are major components of Panax ginseng, P. notoginseng, P. quinquefolium, and Gynostemma pentaphyllum. The results of recent research have demonstrated that the dammarane saponins have a significant effect on regulating blood glucose, which provides the important value in the prevention and treatment of diabetes and its complications. In this study, we summarized the progress in the research of hypoglycemic effect of dammarane saponins in ginseng, American ginseng, notoginseng, and gynostemma pentaphyllum, providing theoretical foundation for further researching.

Identification of Dammarane-type Triterpenoid Saponins from the Root of Panax ginseng

The root of Panax ginseng, is a Korea traditional medicine, which is used in both raw and processed forms due to their different pharmacological activities. As part of a continued chemical investigation of ginseng, the focus of this research is on the isolation and identification of compounds from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, semi-preparative-high performance liquid chromatography, Fast atom bombardment mass spectrometric, and nuclear magnetic resonance. Dammarane-type triterpenoid saponins were isolated from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, and semi-preparative-high performance liquid chromatography. Their structures were identified as protopanaxadiol ginsenosides [gypenoside-V (1), ginsenosides-Rb1 (2), -Rb2 (3), -Rb3 (4), -Rc (5), and -Rd (6)], protopanaxatriol ginsenosides [20(S)-notoginsenoside-R2 (7), notoginsenoside-Rt (8), 20(S)-O-glucoginsenoside-Rf (9), 6-O-[alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D-glucopyranosyl-3beta,12beta, 20(S)-dihydroxy-dammar-25-en-24-one (10), majoroside-F6 (11), pseudoginsenoside-Rt3 (12), ginsenosides-Re (13), -Re5 (14), -Rf (15), -Rg1 (16), -Rg2 (17), and -Rh1 (18), and vinaginsenoside-R15 (19)], and oleanene ginsenosides [calenduloside-B (20) and ginsenoside-Ro (21)] through the interpretation of spectroscopic analysis. The configuration of the sugar linkages in each saponin was established on the basic of chemical and spectroscopic data. Among them, compounds 1, 8, 10, 11, 12, 19, and 20 were isolated for the first time from P. ginseng root.

A novel 12, 23-epoxy dammarane saponin from Panax notoginseng / 中国天然药物

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.

Improving effects of dammarane sapogenins on sleep interruption-induced learning and memory impairment in mice / 中国比较医学杂志

Objective To study the effects of dammarane sapogenins ( DS-1226 ) on sleep interruption-induced learning and memory impairment in mice.Methods 130 SPF healthy 5 -6-week old male ICR mice were randomly divided into control, model, DS-1226 low dose, DS-1226 medium dose and DS-1226 high dose groups.The behavioral alterations in open field (OF), Morris water maze (MWM) and step-through (ST) tests were detected at 15 days after rotating drum-induced sleep interruption ( SI) .Results The total distance, movement speed, total duration of movement were increased in OF test ( P<0.05, vs.the model group) after treatment.The latency of place navigation was increased from day 5 in the MWM test after 15 d sleep interruption, and the number of crossing in the target quadrant and the percent distance in target quadrant were decreased after 15 d sleep interruption ( P <0.05, vs.the control group), while the latency of place navigation was decreased, and the percent distance in target quadrant and percent time in target quadrant after high dose DS-1226 oral administration ( P<0.05, vs.the model group) were increased.Error times, distance in dark chamber, time in dark chamber and immobility time in dark chamber were increased in training of step through test ( P<0.05, vs.the control group);while these indexes were decreased after DS-1226 oral administration ( P<0.05, vs.the model group) .But there was no significant difference in the step through testing course.Conclusions The results show that orally administrated DS-1226 can ameliorate SI-induced learning and memory impairment, and there is a significant dosage-effect relationship.

Study on anti-tumor activities of ginsenoside structure modification HRG in vivo / 中国药学杂志

OBJECTIVE: To explore the anti-tumor activities of a new compound 3β,12β,20(S)-trihydroxy dammarane-3-O-β-D-glucopyranosyl (1-2)-β-D-glucopyranoside (HRG), which is a substance of ginsenoside structure modification, in vivo. METHODS: Liver cancer H22 tumor model on the chick chorioallantoic membrane (CAM) was established to observe the effects of HRG on tumor growth, the number of induced vessels and the growth inhibition rate. The implanted tumors were dyed by hematoxylin-eosin (HE), and the morphological properties were studied with light microscope. Immunohistochemistry (SP method) was used to detect the expressions of the implanted tumor's MVD and VEGF. RESULTS: HRG inhibited the tumor growth at 25, 50 and 100 μg · mL-1. Compared with the model control group, the inhibitory rates of the tumor growth were 27.73%, 50.02%, and 64.21%, respectively. HRG significantly reduced the number of tumor-induced vessels. At the same time, there existed different degree necrosis among the treatment groups, and the degree of necrosis had an inverse relationship with the number of tumor-induced vessels. In addition, HRG reduced the MVD of the implanted tumors, and decreased the expression of VEGF. CONCLUSION: HRG has good anti-tumor activities in vivo, and can significantly inhibit the growth of liver cancer H22-CAM tumor and the induction of angiogenesis. The mechanisms may be associated with lower tumor MVD and VEGF expression.