Steroidal Saponins from the Genus Smilax and Their Biological Activities

The Smilax species,widely distributed in tropical region of the world and the warm areas of East Asia and North America,are extensively used as folk medicine to treat inflammatory disorders.Chemical investigation on Smilax species showed they are rich sources of steroidal saponins with diversified structure types,including spirostane,isospirostane,furostane,pregnane,and cholestane.This review mainly summarizes the steroidal saponins(1–104)reported from the genus Smilax between 1967 and 2016,and their biological activities.The relationship between structures of steroidal saponins and related biological activities were briefly discussed.

Two New Steroidal Saponins from Diuranthera inarticulata

Two new steroidal saponins, diuranthosides D and E, were isolated from the whole plant of Diuranthera inarticulata Wang et K. Y. Lang. By means of spectral and chemical analysis, the structure of the new compounds were established as neotigogenin-3-O-(-D-glucopyranosyl (1?3)-(-D-xylopyranosyl-(1?3)-[(-D-glucopyranosyl(1?2)]-(-D-glucopyranosyl(1?4)-(-D-galactopyranoside (1) and neotigogenin-3-O-(-D-glucopyranosyl(1?3)-(-D-glucopyranosyl (1?3)-(-D-xylopyranosyl(1?3)-[(-D-glucopyranosyl(1?2)]-(-D-glucopyranosyl(1?4)-(-D-galactopyranoside (2) respectively.

NEW MINOR STEROIDAL SAPONINS FROM SMILAX LEBRUNII

Two new minor steroidal saponins, (25R) spirostan-3β-ol-6-one-3-O-[α-L- arabinopyranosyl(1-4)]-β-D-glucopyranosidc (1) and (25S) spirost-5-en -3β, 17α, 27-triol-3-O- [α-L-arabinopyranosyl(1-6)]-β-D-glucopyranosidc (2) were isolated from the roots of Smilax lebrunii. Their structures were established on thc basis of chemical and spectral methods.

Steroidal saponins with anti-inflammatory activity from Tribulus terrestris L.

Objective:Tribulus terrestris L.(T.terrestris)is a highly valuable traditional Chinese medicine used to treat stroke,inflammation,pulmonary fibrosis,liver cancer,and urolithiasis.To identify the basic substance responsible for the anti-inflammatory effect of TST(total saponins of Tribulus),its chemical composition was systematically studied,and its effect of inhibiting nitric oxide generation and the expression of related inflammatory factors were determined.Methods:To separate chemical constituents from T.terrestris by column chromatography.Spectroscopic methods,including 1D and 2D nuclear magnetic resonance spectroscopy(NMR)and mass spectrometry(MS)techniques,were used to elucidate the isolated compounds.The anti-inflammatory activities of TST and several compounds were evaluated in vitro.Results:Fifteen steroidal saponins,including 9 furostanol steroidal saponins(1,2,3,4,5,6,7,8,and 15)and 6 isospirostanol steroidal saponins(9,10,11,12,13,and 14),were isolated from T.terrestris.TST significantly decreased the expression of tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6)in RAW 264.7 cells stimulated by lipopolysaccharides.Compounds 13 and 15 evidently reduced TNF-a expression.Compounds 6,10,12,13,and 15 markedly reduced IL-6 expression.Conclusions:Compounds 1 was a novel furostanol steroidal saponin,named 26-O-b-D-glucopyranosyl-(25R)-5afurostan-12-carbonyl-20(22)-en-3b,26-diol-3-O-{b-D-xylopyranosyl-(1→2)-[b-D-xylopyranosyl-(1→3)]-b-D-glucopyranosyl-(1→4)-[a-L-rhamnopyranosyl-(1→2)]-b-D-galactopyranoside}.Compounds 2 was isolated from the family Zygophyllaceae for the first time,and 5 and 6 were isolated from the Tribulus genus.TST and compounds 6,10,12,13,and 15 exerts antiinflammatory activity.

Two New Steroidal Saponins from Tacca plantaginea

Two new C27 steroidal glycosides, named taccaoside A (1) and B (2), were isolated from the traditional Chinese herb Tacca plantaginea. The spectroscopic and chemical evidences revealed their structures to be 26-O--D-glucopyranosyl-(25R)-3?26-dihydroxy furost-5,20-diene -3-O-[?L-rhamnopyranosyl(12)]-[?L-rhamnopyranosyl(13)]--D-glucopyranoside (1) and 26-O--D-glucopyranosyl-(25R)-3?26-dihydroxy furost-5,20-diene-3-O-[?L-rhamnopyranosyl- (12)]-[?D-glucopyranosyl(13)--L-rhamnopyranosyl(13)]--D-glucopyranoside (2), res- pectively.

Limonoid and Steroidal Saponin from Azadirachta indica

A new limonoid,17-(5-methoxy-2-oxofuran-3-yl)-28-deoxonimbolide(1),and a new C21 steroidal saponin,2a,4a-dihydroxy-pregn-5-en-16-one-3a-O-D-glucopyranoside(2),together with 11 known compounds were isolated from the methanol extract of the leaves of Azadirachta indica.The structures were elucidated by means of spectroscopic analysis and putative biosynthetic origins.All the compounds were evaluated for their antibacterial activities against six bacterial strains.

Unraveling the serial glycosylation in the biosynthesis of steroidal saponins in the medicinal plant Paris polyphylla and their antifungal action

Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins.Here,we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var.yunnanensis.Among them,a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides,respectively.These UDP-glycosyltransferases showed astonishing substrate promiscuity,resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds.A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments,and a mutant UGT91AH1^(Y187A)with increased catalytic efficiency was obtained.The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes,and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects.The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.

Fingerprint analysis of Zhimu-Huangbai herb pair and simultaneous determination of its alkaloids, xanthone glycosides and steroidal saponins by HPLC-DAD-ELSD

AIM: To develop and validate a high performance liquid chromatography(HPLC) coupled with diode array and evaporative light scattering detectors(DAD-ELSD) method for the quantitative determination and fingerprint analysis of ten active constituents in three chemical classes(namely, xanthone glycosides, steroidal saponins, and alkaloids) in Zhimu-Huangbai herb pair(ZB). METHOD: Chromatographic separation was performed on a Diamonsil C18 column(4.6 mm × 250 mm, 5 μm, Dikma) by gradient elution using acetic acid in acetonitrile solution at a flow rate of 1.0 mL·min–1 at 260 nm. The drift tube temperature of ELSD was set to 60 ℃ and nebulizer gas pressure was 4.0 Bar. Method validation was performed to assure its linearity, limits of detection and quantification, precision, repeatability, stability, and accuracy. RESULTS: The HPLC-DAD-ELSD method allowed the quantification of ten compounds(phellodendrine, jatrorrhizine, palmatine, berberine, neomangiferin, mangiferin, timosaponin E-I, timosaponin B-II, timosaponin B, and timosaponin A-III), and was successfully applied to fingerprint analysis for ten batches of ZB samples. CONCLUSION: This was the first time to apply the combination of DAD and ELSD for the simultaneous determination of ten active ingredients in ZB. The results showed that the combination of quantitative analysis for marker ingredients and chemical fingerprint for the TCM herb pair provides a potentially powerful, widely introduced, and internationally accepted strategy for assessment of complex TCM formulas.

Advances in the antitumor activities and mechanisms of action of steroidal saponins

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities,such as anticancer,anti-inflammatory,antiviral,antibacterial and nerves-calming properties.Cancer is a growing health problem worldwide.Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years.According to reported findings,steroidal saponins exert various antitumor activities,such as inhibiting proliferation,inducing apoptosis and autophagy,and regulating the tumor microenvironment,through multiple related signaling pathways.This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Two new steroidal saponins from the rhizomes of Dioscorea zingiberensis

AIM: To investigate the chemical constituents of Dioscorea zingiberensis C. H. Wright. METHODS: The compounds were isolated by various chromatographic techniques, and the structures of the new steroidal saponins were elucidated by extensive 1D- and 2D-NMR, MS, and IR spectral analysis. RESULTS: The 70% EtOH extract of the rhizomes of Dioscorea zingiberensis afforded two new steroidal saponins, zingiberenosides A(1) and B(2), along with eight known analogues, 3β, 26-dihydroxy-25(R)-furosta-△5, 20(22)-diene-3-O-α-Lrhamnopyranosyl-(1→2)-O-β-D-glucopyranoside(3), methyl parvifloside(4), deltoside(5), methyl deltoside(6), zingiberensis new saponin(7), deltonin(8), progenin III(9) and diosgenin-diglucoside(10). CONCLUSION: Two new steroidal saponins were isolated from Dioscorea zingiberensis and their structures determined.

Simultaneous determination of six steroidal saponins and one ecdysone in Asparagus filicinus using high performance liquid chromatography coupled with evaporative light scattering detection

A high-performance liquid chromatography coupled with an evaporative light scattering detector(HPLC-ELSD)has been developed to evaluate the quality of Asparagus filicinus through a simultaneous determination of six steroidal saponins and one ecdysone,including aspafiliosides A,B,C,E,G,filiasparoside A and 20-hydroxyecdysone.With a C_(18) analytical column,the seven analytes were separated efficiently using acetonitrile-water as the mobile phase in a gradient program.The method limits of detection ranged 0.1250.225μg,and the method limits of quantitation ranged 0.408-0.720μg,respectively.The intra-and inter-day precisions of the method were evaluated and were all less than 3%.All the recoveries for the spiked analytes ranged 95.16%-100.61%.The proposed method was succesfully applied to quantify the seven components in thirteen samples from different localities in China.

Studies on New Steroidal Saponins from Allii macrostemonis Bulbus and Their Antitumor Activities

Two new steroidal saponms（2, 3） and two known compounds（1, 4） were isolated from 75% ethanol extract ofAllii macrostemonis bulbus by various spectral methods. The two new steroidal saponins were respectively elucidated as （25S）-26-O-β-D-glucopyranosyl-5α-furostanol-2α,3β,22,26-tetrol-3-O-β-D-glucopyranosyl（1→2）-[β-D- glucopyranosyl（1→3）]-β-D-glucopyranosyl（1→4 ）-β-D-galactopyranoside（2 ） and 26-O-β-D-glucopyranosyl-5α- furostanol-25（ 27）-ene-3β,22,26-tetrol-3-O-β-D-glucopyranosyl（ 1→2 ）-[β-D-glucopyranosyl（ 1→3 ）] -β-D-glucopyranosyl- （1→4）-β-D-galactopyranoside（3）. Compound 4 was obtained from this medical plant for the first time. The activity experiments of proliferation inhibition on tumor cells were performed by cell counting kit-8（CCK-8） method for compound 2（25S-configuration） and its isomer（compound 1, 25R-configttration）. The results show that compounds 1 and 2 have weak inhibition on lung cancer A549 cells, melanoma A375 cells and breast cancer MCF-7 cells as well as certain inhibitory effect on liver cancer HepG2 cells, and the inhibitory effect of compound 1 is stronger than that of compound 2.

Two new steroidal saponins isolated from Anemarrhena asphodeloides

Two new steroidal saponins,named timosaponin P(1) and timosaponin Q(2),were isolated from the rhizome parts of Anemarrhena asphodeloides Bunge using various chromatographic methods.Their structures and absolute configurations were elucidated by a combination of spectroscopic and spectrometric data,including 1D,2D NMR,HR-ESI-MS and ECD calculations,and this is the first time the absolute configuration of C-23 of steroidal saponin was confirmed by ECD calculations.

C_(21) Steroidal Saponins from Cynanchum otophyllum

Objective To study the chemical structures of saponins in the rhizome of Cynanchum otophyllum（Asclepiadaceae）, and to find new compounds. Methods The total saponins of the rhizome were separated by silica gel column chromatography. The chemical structures of obtained compounds were determined by NMR and FAB-MS spectra. Results Three C21 steroidal saponins were separated. Their structures were determined as caudatin 3- O-β-D-glucopyranosyl-（1 →4）-β- D-digitoxopyranosyl-（1 → 4）-β-D-digino- pyranosyl-（1 -4）-α-D-oleandropyranoside （1）, caudatin 3-O-β-D-oleandropyranosyl- （1→4）-α-D-oleandropyranosyl-（1→4）-α-D-oleandropyranoside （2）, and caudatin 3-O- β-D-glucopyranosyl-（1 →4）-α-D-oleandropyranosyl-（1 -4）-β-D-diginopyranosyl-（1→4）- α-D-oleandropyranoside （3）, respectively. Conclusion Saponins 1-3 are new compounds.

Furostanol Saponins from Asparagus cochinchinensis and Their Cytotoxicity

Phytochemical investigation on the roots of Asparagus cochinchinensis led to the isolation of one new furostanol saponin,named 26-O-β-d-glucopyranosyl-22α-hydroxyl-(25R)-Δ5(6)-furost-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→4)]-β-d-glucopyranoside(1),along with three known congeners(2‒4).The structure of new saponin was elucidated via comprehensive inspection of its HRMS and NMR spectral data as well as chemical technology,whereas those of known ones were identified by comparison of their NMR and MS spectral data with those reported in literatures.All isolated saponins were evaluated for their cytotoxic effects on two human liver(MHCC97H)and lung adenocarcinoma(H1299)cancer cells in vitro.Among them,both 1 and 2 showed significant cytotoxicity against above mentioned cell lines.Further studies revealed that these two saponins could significantly inhibit their proliferation of MHCC97H and H1299 cells.

Neuroprotection of total steroid saponins from Dioscorea zingiberensis C.H.Wright against transient focal cerebral ischemia-reperfusion injury in rats via its anti-inflammatory and anti-apoptotic effects

OBJECTIVE The total steroid saponins(TSSN)isolated from Dioscorea zingiberensis C.H.Wright(D.zingiberensis)has shown a variety of beneficial bioactivities.However,there are no reports about the neuroprotective effects of the TSSN until now.Therefore,we explored the neuroprotective effects of TSSN on rats against transient focal cerebral ischemia-reperfusion(I/R)and the underlying mechanisms.METHODS The healthy adult Sprague-Dawley rats were randomly assigned into six groups.After pre-treatment with the TSSN intragastrically for six days,the rats were subjected to the ischemia injury by the surgery of middle cerebral artery occlusion(MCAO)for 90 min.Some indexes were evaluated and detected.RESULTS As compared to the I/R group,TSSN group of rats,especially given the 30 mg·kg^-1 of TSSN,not only marked reduction in the neurological deficit scores,cerebral infarct volume,and brain edema,but also an increase in neuron survival(Nissl bodies)in the hippocampal cornuammons 1(CA1)and cortex hemisphere of the ipsilateral ischemia.At the same time,the inflammatory cytokines in serum induced by MCAO were significantly alleviated by the TSSN pre-administration.What′s more,the increase of caspase-3 was evidently reduced in the CA1 and cortex of the hemisphere injured brain.Finally,the down-regulating anti-apoptotic Bcl-2 and up-regulating pro-apoptotic Bax proteins were obviously suppressed.CONCLUSION TSSN plays a potential neuroprotective role against a severe injury induced by transient focal cerebral ischemic reperfusion in a rat experimental model,and this role may be mediated by its antiinflammatory and anti-apoptotic actions.

Arbuscular mycorrhiza and plant growth promoting endophytes facilitates accumulation of saponin under moderate drought stress

Objective:Paris polyphylla var.yunnanensis,one of the important medicinal plant resources in Yunnan,China,usually takes 6–8 years to be harvested.Therefore,it is urgent to find a method that can not only shorten its growth years,but also improve its quality.In this study,we examined the effects of a combination treatment of arbuscular mycorrhizal fungi(AMF)and plant growth-promoting endophytes(PGPE)and drought stress on the accumulation of saponins in it.Methods:P.polyphylla var.yunnanensis was infected with a mixture of AMF and PGPE under drought stress.The content of saponins,as well as morphological,physiological,and biochemical indicators,were all measured.The UGTs gene related to saponin synthesis was obtained from transcriptome data by homologous comparison,which were used for RT-PCR and phylogenetic analysis.Results:Regardless of water,AMF treatment could infect the roots of P.polyphylla var.yunnanensis,however double inoculation with AMF and PGPE(AMF+PGPE)would reduce the infection rate of AMF.Plant height,aboveground and underground fresh weight did not differ significantly between the single inoculation AMF and the double inoculation treatment under different water conditions,but the inoculation treatment significantly increased the plant height of P.polyphylla var.yunnanensis compared to the noninoculation treatment.Single inoculation with AMF considerably increased the net photosynthetic rate,stomatal conductance,and transpiration rate of P.polyphylla var.yunnanensis leaves under various water conditions,but double inoculation with AMF+PGPE greatly increased the intercellular CO_(2) concentration and chlorophyll fluorescence parameter(Fv/Fm).Under diverse water treatments,single inoculation AMF had the highest proline content,whereas double inoculation AMF+PGPE may greatly improve the amount of abscisic acid(ABA)and indoleacetic acid(IAA)compared to normal water under moderate drought.Double inoculation AMF+PGPE treatment improved the proportion of N,P,and K in the rhizome of P.polyphylla var.yunnanensis under various water conditions.Under moderate drought stress,AMF+PGPE significantly enhanced the contents of P.polyphylla var.yunnanensis saponins I,II,VII,and total saponins as compared to normal water circumstances.Farnesyl diphosphate synthase(FPPS),Geranyl pyrophosphate synthase(GPPS),Cycloartenol synthase(CAS),and Squalene epoxidase(SE1)were the genes that were significantly up-regulated at the same time.The amount of saponins was favorably linked with the expression of CAS,GPPS,and SE1.Saponin VI content and glycosyl transferase(UGT)010922 gene expression were found to be substantially associated,as was saponin II content and UGT010935 gene expression.

The Genus Solanum:An Ethnopharmacological,Phytochemical and Biological Properties Review

Over the past 30 years,the genus Solanum has received considerable attention in chemical and biological studies.Solanum is the largest genus in the family Solanaceae,comprising of about 2000 species distributed in the subtropical and tropical regions of Africa,Australia,and parts of Asia,e.g.,China,India and Japan.Many of them are economically signifcant species.Previous phytochemical investigations on Solanum species led to the identifcation of steroidal saponins,steroidal alkaloids,terpenes,favonoids,lignans,sterols,phenolic comopunds,coumarins,amongst other compounds.Many species belonging to this genus present huge range of pharmacological activities such as cytotoxicity to diferent tumors as breast cancer(4T1 and EMT),colorectal cancer(HCT116,HT29,and SW480),and prostate cancer(DU145)cell lines.The biological activities have been attributed to a number of steroidal saponins,steroidal alkaloids and phenols.This review features 65 phytochemically studied species of Solanum between 1990 and 2018,fetched from SciFinder,Pubmed,ScienceDirect,Wikipedia and Baidu,using“Solanum”and the species’names as search terms(“all felds”).