A new triterpene glycoside from sea cucumber Holothuria leucospilota

A new triterpene glycoside, leucospilotaside A, along with a known saponin, isolated from sea cucumber Holothuria leucospilota, and its structure was elucidated as 3β-O-[4-O-sodiumsulfate-β-D-quinovopyranosyl-(1→2)-β-D-xylopyranosyl]-holosta-22-ketone-9-en-17α,25α-diol (1) by extensive spectroscopic analysis and chemical methods. Leucospilotaside A (1) has a ketone carbonyl group (22) in the aglycon side chain.

A new dammarane-type triterpene saponin from Gynostemma pentaphyllum

One new dammarane-type triterpene saponin, named (20S)-3β,20,21-trihydroxydammar-24-ene 3-O[α-L- rhamnopyranosyl-(1→2)][β-D-xylopyranosyl(l→3)]-β-D-glucopyranoside (1), was isolated from the aerial parts of Gynostemma pentaphyllum (Thunb.) Makino. Its structural elucidation was accomplished mainly on the basis of the interrelation of spectroscopic methods, such as IR, HR-TOF-MS, NMR.

A New Triterpene from Cephalomappa sinensis

A new triterpene 1, 1(, 2(, 3(-trihydroxylup-20 (29) -ene was isolated from Cepha-lomappa sinensis. The structure was elucidated mainly on the basis of 1D and 2D NMR spectral means.

Two new olean-type triterpene fatty esters from Scorzonera mongolica

Two new triterpene fatty esters, 33-tetradecanoyl moradiol 1 and 3β-dodecanoyl moradiol 2, were isolated from Scorzonera mongolica. Their structures were elucidated as 3β-tetradecanoyloxy-28-hydroxylolean-18-ene and 3β-dodecanoyl-28-hydroxyl-olean-18-ene on the basis of IR, MS, ID NMR and extensive 2D NMR spectroscopic analyses.

Symplocosionosides A-C, Three Megastigmane Glycosides, a Neolignan Glucoside, and Symplocosins A and B, Two Triterpene Glycosyl Esters from the Leaves of <i>Symplocos cochinchinensis</i>var. <i>Philippinensis</i>

From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Symplocos cochinchinensis var. philippinensis, 12 compounds were isolated. Spectroscopic analyses of compounds 1 - 3 established their structures to be megastig-mane glycosides, named symplocosionosides A-C. The absolute structure of 1 was determined by the modified Mosher’s method. Compound 4 was found to be a neolignan glucoside and named symplocosneolignan. The structures of com-pounds 5 and 6, named symplocosins A and B, were elucidated to be the saponins of hederagenin sugar esters. The structures of the remaining known compounds (7 - 12) were identified by comparison of spectroscopic data with those reported in the literature.

Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database

Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.

Two New Triterpene Esters from Daphniphyllum oldhami

Two new triterpene esters, 2-O-caffeoylalphitolic acid (1) and methyl 2-O-caffeoyl- alphitolate (2), together with two known triterpenes were isolated from the shrub Daphniphyllum oldhami. The structures of new compounds were elucidated on the basis of detailed spectroscopic analysis and compared with related compound.

Antiglycation,antioxidant,antiacne,and photoprotective activities of crude extracts and triterpene saponin fraction of Sapindus saponaria L.fruits:An in vitro study

Objective:To evaluate the photoprotective,antioxidant,antiglycation,and antiacne activities of crude extract(CESs)and triterpene saponin fraction(TSSs)of Sapindus saponaria.Methods:HPLC-MS purification was performed on a Symmetry TM C18 column.The saponins were identified by a UV detector.Antioxidant activity was evaluated by DPPH and O_(2)^(−)radicals scavenging,and FRAP and TBARS assays.Glycation activity was assessed by relative electrophoretic mobility and inhibition of advanced glycation end products(AGEs)formation.Additionally,antiacne activity was determined by inhibition of Cutibacterium acnes,and photoprotective effect was evaluated by Mansur’s method.Results:Most of the triterpene saponins detected in the fraction by HPLC-MS analysis were hederagenin as the aglycon.CESs and TSSs presented varying antioxidant activity in DPPH(CESs:75.69%and TSSs:83.65%),FRAP(CESs:425.39μM TE/g DW and TSSs:649.36μM TE/g DW),TBARS(CESs:42.96%and TSSs:52.16%)and O_(2)^(−)radicals scavenging(CESs:61.33%and TSSs:86.69%)tests.CESs and TSSs also exhibited antiglycation activity comparable to bovine serum albumin treated with aminoguanidine.In addition,CESs and TSSs showed inhibition of AGE formation(34.48%and 61.85%,respectively).Antiacne activity against Cutibacterium acnes was observed with a minimum inhibitory concentration equal to minimum bactericidal concentration(CESs:36.11µg/mL and TSSs:18.34µg/mL).In photoprotective assays,CESs and TSSs showed maximum absorbance of 1.42 to 0.20 and 2.80 to 1.30,respectively,in the wavelength range of 260 to 400 nm.Furthermore,CESs and TSSs showed sun protection factors of 8.89 and 14.89,respectively.Conclusions:Sapindus saponaria fruit extracts show strong antioxidant potential and antiglycation activity against bovine serum albumin glycation and AGE formation.Besides,they presented antibacterial activity against Cutibacterium acnes and photoprotective effect against UV-A and UV-B.

New Triterpene Glycoside from Thalictrum smithii

A new triterpene glycoside. 24S-cycloartane-3β. 16β. 24. 25. 30-pentaol 3-O-(2-O-β-D-xylosyl)-β-D-xyloside was isolated from Thalictrum smithii. Its structure was determined by spectroscopic and chemical methods.

Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd.

Previous phytochemical investigation of the leaves and seeds of Pittosporum angustifolium Lodd.led to the isolation and structural elucidation of polyphenols and triterpene saponins.Evaluation for cytotoxicity of isolated saponins revealed that the predominant structural feature for a cytotoxic activity are acyl substituents at the oleanane aglycon backbone.The present work reports the results of a screening of 10 selected acylated saponins for their potential to inhibit the human DNA-topoisomerase I,giving rise to IC50 values in a range of 2.8-46.5 lM.To clarify the mode of observed cytotoxic action and,moreover,to distinguish from a pure surfactant effect which is commonly accompanied with saponins,these results indicate an involvement of the topoisomerase I and its role as a possible target structure for a cytotoxic activity.In addition,computational predictions of the fitting of saponins to the topoisomerase I-DNA complex,indicate a similar binding mode to that of clinically used topoisomerase I inhibitors.Graphical Abstract Ten acylated triterpene saponins from Pittosporum angustifolium were investigated for their potential to inhibit the human DNA-topoisomerase I and computational predictions of the fitting of saponins to the topoisomerase I-DNA complex were carried out.

Anti‑inflammatory and Cytotoxic Triterpenes from the Rot Roots of Panax notoginseng

Four new protopanaxatriol-type triterpenes(1-2)and glucosides(3-4),were isolated from the rot roots of Panax notoginseng(Burk.)Chen,along with four known ones(5-8).Their structures were elucidated on the basis of extensive spectroscopic analysis(HRESIMS,NMR,UV,IR,and OR)and acidic hydrolysis.The possible transformation pathway of these compounds were also speculated from ginsenoside Rg_(1).Compound 1,with a uniqueα,β-unsaturated ketene in its side chain,showed significant inhibitory effects against NO production on Murine macrophage cells(IC_(50)=4.12±0.20μM)and comparable cytotoxicities against five human cancer cell lines(myeloid leukemia HL-60,lung cancer A-549 cells,hepatocellular carcinoma SMMC7721,breast cancer MCF-7,and colon cancer SW480)to positive control,cisplatin(DDP).

A New Euphane-Type Triterpene from Melia Azedarach

A "ex’l Euphane-type triterpene. named azedarachic acid, was isolated from the fruits ofJab ha azedarach. Its structure was determined on the basis of NMR and MS experiments.

Ganoderma triterpenes slow cyst growth in polycystic kidney disease

OBJECTIVE Autosomal dominant polycystic kidney disease(ADPKD)is a common inherited disease with a high morbidity around 1/1000-1/400,characterized by progressive enlargement of fluid-fil ed cysts derived from renal tubular epithelial cells.Massive cysts gradually compress renal parenchyma destroying normal renal structures and compromising renal functions.Unfortunately,it will cause end-stage renal disease in most of the patients but without effective therapy now,who have to live on hemodialysis or kidney transplantation.Based on this present situation,it is of great significance to find early intervention to inhibit renal cyst development.The projective of this study was to investigate whether Ganoderma triterpenes(GT)can inhibit renal cyst development and study the related mechanism.METHODS and RESULTS First,we used MDCK cyst model,cultivated MDCK cells in vitro to form fluid-filled cysts surrounded by monolayer cells.GT inhibited MDCK cyst formation significantly,and inhibited cyst enlargement dose-dependently proving GT cyst inhibition in vitro.Then we used an embryonic kidney cyst model,wile-type mice kidneys were taken out on embryonic day 13.5 to form renal cysts stimulated with 8-Br-c AMP.GT inhibited embryonic kidney cyst development significantly in a dosedependent and reversible manner proving GT cyst inhibition at organ level.Furthermore,we used two ADPKD mouse models with severe cystic kidney disease phenotypes.GT dramatically inhibited renal cyst development,decreased ADPKD mouse kidney volume and the cyst index inside proving GT cyst inhibition in vivo.By Western blot,we proved GT down-regulated Ras/MAPK signal pathway without detectable effect on m TOR signal pathway both in MDCK cells and two ADPKD mouse kidneys.CONCLUSION GT retard renal cyst development both in vitro and in vivo significantly.The related mechanisms were involved in GT promoting renal tubular epithelial cell differentiation,down-regulating intracellular c AMP level and Ras/MAPK signal pathway.

Cucurbitane-Type Triterpene Glycosides from Momordica charantia and Their α-Glucosidase Inhibitory Activities

Ten cucurbitane-type triterpene glycosides,including five new compounds named charantosides H(1),J(2),K(3),momor-characoside A(4),goyaglycoside-l(5),and five known compounds(6-10),were isolated from the EtOAc extract of Momor-dica charantia fruits.The chemical structures of these compounds were identified by 1D and 2D NMR and HRESIMS spectroscopic analyses.Configurations of new compounds were determined by ROESY correlations and comparison of their 13C NMR data with literature reported values.All compounds were evaluated for their inhibition againstα-glucosidase,in which compounds 2,5,7,8,9 showed moderate inhibitory activities with IC50 values ranging from 28.40 to 63.26μM comparing with the positive control(acarbose,IC5087.65±6.51μM).

Functional characterization of triterpene synthases in Cibotium barometz

Cibotium barometz(Linn.)J.Sm.,a tree fern in the Dicksoniaceae family,is an economically important industrial exported plant in China and widely used in Traditional Chinese Medicine.C.barometz produces a range of bioactive triterpenes and their metabolites.However,the biosynthetic pathway of triterpenes in C.barometz remains unknown.To clarify the origin of diverse triterpenes in C.barometz,we conducted de novo transcriptome sequencing and analysis of C.barometz rhizomes and leaves to identify the candidate genes involved in C.barometz triterpene biosynthesis.Three C.barometz triterpene synthases(CbTSs)candidate genes were obtained.All of them were highly expressed in C.barometz rhizomes,consisting of the accumulation pattern of triterpenes in C.barometz.To characterize the function of these CbTSs,we constructed a squalene-and oxidosqualene-overproducing yeast chassis by overexpressing all the enzymes in the MVA pathway under the control of GAL-regulated promoter and disrupted the GAL80 gene in Saccharomyces cerevisiae simultaneously.Heterologous expressing CbTS1,CbTS2,and CbTS3 in engineering yeast strain produced cycloartenol,dammaradiene,and diploptene,respectively.Phylogenetic analysis revealed that CbTS1 belongs to oxidosqualene cyclase,while CbTS2 and CbTS3 belong to squalene cyclase.These results decipher enzymatic mechanisms underlying the origin of diverse triterpene in C.barometz.

Comparative genomics reveals the diversification of triterpenoid biosynthesis and origin of ocotilloltype triterpenes in Panax

Gene duplication is assumed to be the major force driving the evolution of metabolite biosynthesis in plants.Freed from functional burdens,duplicated genes can mutate toward novelties until fixed due to selective fitness.However,the extent to which this mechanism has driven the diversification of metabolite biosynthesis remains to be tested.Here we performed comparative genomics analysis and functional characterization to evaluate the impact of gene duplication on the evolution of triterpenoid biosynthesis using Panax species as models.Wefound that whole-genome duplications(WGDs)occurred independently in Araliaceae and Apiaceae lineages.Comparative genomics revealed the evolutionary trajectories of triterpenoid biosynthesis in plants,which was mainly promoted by WGDs and tandem duplication.Lanosterol synthase(LAS)was likely derived from a tandemduplicate of cycloartenol synthase that predated the emergence of Nymphaeales.Under episodic diversifying selection,the LAS gene duplicates produced by g whole-genome triplication have given rise to triterpene biosynthesis in core eudicots through neofunctionalization.Moreover,functional characterization revealed that oxidosqualene cyclases(OSCs)responsible for synthesizing dammarane-type triterpenes in Panax species were also capable of producing ocotilloltype triterpenes.Genomic and biochemical evidence suggested that Panax genes encoding the above OSCs originated from the specialization of one OSC gene duplicate produced from a recent WGD shared by Araliaceae(Pg-b).Our results reveal the crucial role of gene duplication in diversification of triterpenoid biosynthesis in plants and provide insight into the origin of ocotillol-type triterpenes in Panax species.

Ds-echinoside A,a new triterpene glycoside derived from sea cucumber,exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions

Ds-echinoside A (DSEA),a non-sulfated triterpene glycoside,was isolated from the sea cucumber Pearsonothuria graeffei.In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion,migration,invasion,and angiogenesis.In this study,we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2,with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L,and suppressed Hep G2 cell adhesion,migration,and invasion in a dose-dependent manner.DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo.Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9),which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis.DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1),an important regulator of MMP-9 activation.From the results of Western blotting,the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA.These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.

Protein tyrosine phosphatase 1B inhibitory activities of ursane-type triterpenes from Chinese raspberry, fruits of Rubus chingii

Protein tyrosine phosphatase 1 B(PTP1 B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii(Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1 B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1 B inhibitory ursane-type triterpenes: ursolic acid(1), 2-oxopomolic acid(2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid(3). Kinetics analyses revealed that 1 was a non-competitive PTP1 B inhibitor, and 2 and 3 were mixed type PTP1 B inhibitors. Compounds 1-3 and structurally related triterpenes(4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases(TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxyurs-12-ene-28-oic acid(5), and pomolic acid-3β-acetate(6) bound at the allosteric site including α3, α6, and α7 helix of PTP1 B.

A New Triterpene Saponin from Gynostemma pentaphyllum

Objective To study the triterpene saponins from Gynostemma pentaphyllum with antitumor activities. Methods The 75% EtOH extract of G. pentaphyllum was used for isolation by silica gel column chromatography and preparative HPLC. The structures of pure compounds isolated were identified by the spectral analysis and chemical evidence. Results Two compounds were isolated and identified as 23(S)-3β,20ξ,21ξ-trihydroxy-19-oxo-21,23-epoxydammar-24-ene 3-O-α-L-rhamnopyranosyl (1→2)-[β-D-xylopyranosyl (1→3)]-β-D-arabinopyranoside (1) and 23(S)-21(R)-O-n-butyl-3β,20ξ-dihydroxy-21,23-epoxydammar-24-ene 3-O-α-L-rhamnopyranosyl (1→2)-[β-D-xylo- pyranosyl (1→3)]-β-D-arabinopyranoside (2). Conclusion Compound 2 is a new triterpene saponin with moderate antitumor activities against the HL-60, Colon205, and Du145 cell lines.

A New Cucurbitane Triterpene in Acid-treated Ethanol Extract from Momordica charantia

Objective To study the chemical constituents in the acid-hydrolyzed ethanol extract from Momordica charantia.Methods The ethanol extract from M.charantia was hydrolyzed by 36%HCl and the hydrolysate was isolated by silica gel column chromatography and preparative HPLC.The structures of the isolated compounds were identified by spectral analyses,physical constants,and chemical evidences.Results Two cucurbitane triterpenoids were isolated and identified as 5β,19-epoxy-cucurbita-6,22E,24-trien-3β-ol(1)and cucurbita-6,22(E),24-trien-3β-ol-19,5β-olide(2).Conclusion Compound 1 is a new compound.