Cycloartane-type glycosides from Astragalus brachycalyx FISCHER and their effects on cytokine release and hemolysis

Two new tridesmosidic cycloartane-type triterpene glycosides (1 and 2) were isolated from the methanolic extract of the roots of Astragalus brachycalyx FISCHER (A. brachycalyx) along with ten (3–12) known cycloartane-type triterpene glycosides. Structures of the new compounds were established as 3-O-β-d-xylopyranosyl-6-O-β-d-glucopyranosyl-16-O-β-d-glucopyranosyl-3β,6α,16β,24(S)-25-pentahydroxycycloartane (1), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-16-O-β-d-glucopyranosyl-3β,6α,16β,24(S)-25-pentahydroxycycloartane (2), by using 1D and 2D-NMR techniques and mass spectrometry.In vitro immunomodulatory effects and hemolytic activities of the new saponins (1 and 2) and acetylated form of 1 (1a) were studied together with the BuOH and MeOH extracts of Astragalus brachycalyx. The results have proven that tridesmosidic Astragalus cycloartanes are noteworthy immunomodulatory compounds via induction of cytokine production, namely IL-2 and IFN-γ. The test compounds also resulted slight hemolysis at very high doses substantiating a safer profile compared to the positive control QS-21.     

Cycloartane-type glycosides from Aquilegia flabellata.

Two new cycloartane-type glycosides, named aquilegiosides A and B, were isolated from the dried aerial parts of Aquilegia flabellata Sieb.et Zucc.var flabellata (Ranunculaceae). Their chemical structures have been characterized as 22S-3beta,16alpha,29-trihydroxy-cycloart-24-en-26,22-olid e 3-O-beta-D-glucopyranosyl-(1--->6)-beta-D-glucopyranosyl-(1--->2)-alpha- L-arabinopyranoside and 3-O-beta-D-glucopyranosyl-(1--->2)-alpha-L-arabinopyranoside, by chemical and spectroscopic evidence.     

Cycloartane-type glycosides from Astragalus amblolepis

Five cycloartane-type triterpene glycosides were isolated from the methanol extract of the roots of Astragalus amblolepis Fischer along with one known saponin, 3-O-β-D-xylopyranosyl-16-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane. Structures of the compounds were established as 3-O-β-D-xylopyranosyl-25-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 3-O-[β-D-glucuronopyranosyl-(1 → 2)-β-D-xylopyranosyl]-25-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 3-O-β-D-xylopyranosyl-24,25-di-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 6-O-α-L-rhamnopyranosyl-16,24-di-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 6-O-α-L-rhamnopyranosyl-16,25-di-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane by using 1D and 2D-NMR techniques and mass spectrometry. To the best of our knowledge, the glucuronic acid moiety in cycloartanes is reported for the first time.     

Cycloartane glycosides from Astragalus aureus

Eight cycloartane-type triterpene glycosides (1-8) were isolated from Astragalus aureus Willd along with ten known cycloartane-type glycosides (9-18). Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. Compounds 1-5 are cyclocanthogenin glycosides, whereas compounds 6-8 are based on cyclocephalogenin as aglycon, more unusual in the plant kingdom, so far reported only from Astragalus spp. Moreover, for the first time monoglycosides of cyclocanthogenin (5) and cyclocephalogenin (7, 8) are reported. All of the compounds tested for their cytotoxic activities against a number of cancer cell lines. Among the compounds, only 8 exhibited activity versus human breast cancer (MCF7) at 45 μM concentration.     

Triterpene glycosides from Astragalus icmadophilus

Six cycloartane-type triterpene glycosides were isolated from Astragalus icmadophilus along with two known cycloartane-type glycosides, five known oleanane-type triterpene glycosides and one known flavonol glycoside. The structures of the six compounds were established as 3-O-[α-L-arabinopyranosyl-(1 → 2)-O-3-acetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane, 3-O-[α-L-rhamnopyranosyl-(1 → 2)-O-α-L-arabinopyranosyl-(1 → 2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy cycloartane, 3-O-[α-L-arabinopyranosyl-(1 → 2)-O-3,4-diacetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane, 3-O-[α-L-arabinopyranosyl-(1 → 2)-O-3-acetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane, 3-O-[α-L-arabinopyranosyl-(1 → 2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane, 3-O-[α-L-rhamnopyranosyl-(1 → 2)-O-α-L-arabinopyranosyl-(1 → 2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis.The first four compounds are cyclocanthogenin and cycloastragenol glycosides, whereas the last two are based on cyclocephalogenin as aglycone, more unusual in the plant kingdom, so far reported only from Astragalus spp.     

Cycloartane glycosides from Astragalus gombo

Six new cycloartane-type triterpene glycosides named 3-O-[β-d-glucopyranosyl(1 → 2)-β-d-xylopyranosyl]-3β,16β,23(R),24(R),25-pentahydroxycycloartane (1), 3-O-[β-d-glucopyranosyl(1 → 2)-β-d-xylopyranosyl]-3β,16β,23(R),24(R)-tetrahydroxy-25-dehydrocycloartane (2), 3-O-[β-d-xylopyranosyl]-6α-acetoxy-23α-methoxy-16β,23(R)-epoxy-24,25,26,27-tetranorcycloartane (3), 3-O-[β-d-xylopyranosyl]-6α-acetoxy-23α-butoxy-16β,23(R)-epoxy-24,25,26,27-tetranorcycloartane (4), 3-O-[β-d-glucopyranosyl(1 → 2)]-β-d-xylopyranosyl]-6α-acetoxy-23α-methoxy-16β,23(R)-epoxy-24,25,26,27-tetranorcycloartane (5), 3-O-[β-d-glucopyranosyl(1 → 2)]-β-d-xylopyranosyl]-23α-methoxy-16β,23(R)-epoxy-4,25,26,27-tetranorcycloartane (6), in addition to three known secondary metabolites consisting of another cycloartane triterpene glycoside and two flavonol glycosides, were isolated from the aerial parts of Astragalus gombo Coss. & Dur. (Fabaceae). The structures of the isolated compounds were established by spectroscopic methods, including 1D and 2D-NMR, mass spectrometry and comparison with literature data.     

Cycloartane glycosides from Astragalus stereocalyx Bornm

Six cycloartane-type triterpene glycosides were isolated from Astragalus stereocalyx along with six known cycloartane-type glycosides. Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analysis. Three compounds are based on an aglycon characterized by the occurrence of an unusual hydroxyl group at position 20, whereas three other compounds are based on cycloasgenin C as aglycon, so far reported from Astragalus spp. All the compounds were tested for their cytotoxic activity against a number of cancer cell lines. One compound exhibited activity versus human cervical cancer (Hela) with an IC(50) value = 10 μM.     

Antitrypanosomal cycloartane glycosides from Astragalus baibutensis

Baibutoside (5), a new cycloartane-type triterpene glycoside, has been isolated from the roots of Astragalus baibutensis along with four known glycosides, acetylastragaloside I (1), and astragalosides I, II, and IV (2-4, resp.). The structure elucidation of the compounds were achieved by a combination of one- and two-dimensional NMR techniques (DQF-COSY, HSQC, HMBC, and ROESY), and mass spectrometry (ESI-MS), where all the compounds were shown to have cycloastragenol (=(20R,24S)-3beta,6alpha,16beta,25-tetrahydroxy-20,24-epoxy-9,19-cyclolanostane) as aglycone. All compounds were tested for in vitro antiprotozoal activity. Compounds 1-4 displayed notable activity vs. Trypanosoma brucei rhodesiense, with acetylastragaloside I (1) being the most potent (IC50 9.5 microg/ml). Acetylastragaloside I (1) was also lethal to T. cruzi (IC50 5.0 microg/ml), and it is the first cycloartane-type triterpene with remarkable trypanocidal activity against both T. brucei rhodesiense and T. cruzi. However, it exhibits some cytotoxicity on mammalian cells.     

Flavonoid glycosides and saponins from Astragalus shikokianus

A new flavonol glycoside, kaempferol 3-O-alpha-L-rhamnopyranosyl -(1-->6)-[alpha-L-rhamnopyranosyl-(1-->2)]-beta-D-galactopyranosyl-7-O-a lpha-L-rhamnopyranoside, named astrasikokioside I, was isolated from aerial part of Astragalus shikokianus, together with two flavonol glycosides, kaempferol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-galactopyranosyl-7-O-alpha-L- rhamnopyranoside, robinin, and three triterpenoid glycosides, soyasaponin I, sophoraflavoside II and robinioside E.     

Leishmanicidal cycloartane-type triterpene glycosides from Astragalus oleifolius

Two new cycloartane-type glycosides oleifoliosides A (1) and B (2) were isolated from the lower stem parts of Astragalus oleifolius. Their structures were identified as 3-O-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-O-beta-xylopyranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane and 3-O-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-O-beta-glucopyranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane, respectively, by means of spectroscopic methods (IR, 1D and 2D NMR, ESI-MS). Three known cycloartane glycosides cyclocanthoside E (3), astragaloside II (4) and astragaloside IV (5) were also isolated and characterized. All five compounds were evaluated for in vitro trypanocidal, leishmanicidal and antiplasmodial activities as well as their cytotoxic potential on primary mammalian (L6) cells. Except for the compound 5, all compounds showed notable growth inhibitory activity against Leishmania donovani with IC50 values ranging from 13.2 to 21.3 microg/ml. Only weak activity against Trypanosoma brucei rhodesiense was observed with the known compounds astragaloside II (4, IC50 66.6 microg/ml) and cyclocanthoside E (3, IC50 85.2 microg/ml), while all compounds were inactive against Trypanosoma cruzi and Plasmodium falciparum. None of the compounds were toxic to mammalian cells (IC50's > 90 microg/ml). This is the first report of leishmanicidal and trypanocidal activity of cycloartane-type triterpene glycosides.     

Cycloartane glycosides from Astragalus campylosema Boiss. ssp. campylosema

Four cycloartane glycosides, 3-O-[α-l-arabinopyranosyl-(1 → 2)-β-d-xylopyranosyl]-3β,6α,16β,23α,25-pentahydroxy-20(R),24(S)-epoxycycloartane (1), 3-O-[α-l-arabinopyranosyl-(1 → 2)-β-d-xylopyranosyl]-16-O-hydroxyacetoxy-23-O-acetoxy-3β,6α,25-trihydroxy-20(R),24(S)-epoxycycloartane (2), 3-O-[α-l-arabinopyranosyl-(1 → 2)-β-d-xylopyranosyl]-3β,6α,23α,25-tetrahydroxy-20(R),24(R)-16β,24;20,24-diepoxycycloartane (3), 3-O-[α-l-arabinopyranosyl-(1 → 2)-β-d-xylopyranosyl]-25-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (4), along with three known cycloartane glycosides were isolated from the MeOH extract of the roots of Astragalus campylosema ssp. campylosema. Their structures were established by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis. The occurrence of the hydroxyl function at position 23 (1-2) and of the ketalic function at C-24 (3) are very unusual findings in the cycloartane class.     

Kahiricosides II-V, cycloartane glycosides from an Egyptian collection of Astragalus kahiricus

Four cycloartane-type saponins, kahiricosides II-V (1-4), were isolated from the aerial parts of Astragalus kahiricus of Egyptian origin. Their structures were established as 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-beta-D-glucopyranoside, 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-(2'-O-acetyl)-beta-D-glucopyranoside, 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-(6'-O-acetyl)-beta-D-glucopyranoside, and 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-beta-D-glucopyranosyl-27-O-beta-D-glucopyranoside based on chemical and spectral evidences. All compounds exhibited very weak cytotoxicity against the A2780 ovarian cancer cell line.     

仙茅中两个新的环阿尔廷醇型三萜皂苷

从仙茅(Curculigo orchioides）中分离得到2个新的环阿尔廷醉型三萜皂苷,通过波诺分析鉴定了它们的化学结构,即3β,11α,16β—三羟基环阿尔廷烷-24-酮-3-O-[β-D-吡喃葡糖(1→3)-β-D-吡喃葡糖(1→2)-β-吡喃葡糖]-16-O-α-L-阿拉伯糖苷(1)和(24S)-3β,11α,16β,24-四经基环阿尔廷烷-3-O-[β-D-吡喃葡糖(1→3)-β-D-吡喃葡糖(1→2)-β-D-吡喃葡糖]-24-O-β-D-吡喃葡糖苷(2)。     

Cycloartane-type triterpenoids and sesquiterpenoids from the resinous exudates of Commiphora opobalsamum

Cycloartane-type triterpenoids (1–3), seven sesquiterpenoids (7–13), and five previously reported secondary metabolites, including three cycloartane-type triterpenoids (4–6) and two sesquiterpenoids (14 and 15), were isolated from the resinous exudates of Commiphora opobalsamum. Their structures were elucidated by extensive spectroscopic analysis, including UV, IR, NMR, and MS, and comparison with literature data. The structures of 1, 3, and 7 were confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of 1 was interpreted by the incorporation of CHCl₃ (crystallization solvent) in the crystal and that of 10 was determined by the CD exciton chirality method. Compound 12 represents the first example of a 12-norcadinane-type sesquiterpenoid. Furthermore, compounds 1, 3, 7, and 10–14 were evaluated for cytotoxicity against HeLa and HepG2 cell lines.     

Cycloartane-type triterpenes from Euphorbia fischeriana stimulate human CYP3A4 promoter activity

A chemical study of the roots of Euphorbia fischeriana resulted in the isolation of seven triterpenes (1–7), including two new compounds: (24R,S)-3β-24,31-epoxy-24-methylcycloartane (1) and (24R,S)-3β,31-dihydroxy-24-methoxy-24-methylcycloartane (2). Their structures were elucidated through extensive spectroscopic analyses. Cycloartanes 1–4 showed significant human CYP3A4 promoter activity through a series of luciferase reporter assays. Of these compounds, 3 and 4 activated the pregnane X receptor (PXR) and induced CYP3A4 mRNA expression in human primary hepatocytes. However, despite showing the most potent human CYP3A4 promoter activity via a PXR-independent pathway, 2 did not affect CYP3A4 mRNA expression in human primary hepatocytes. This difference is correlated to substitutions in C-24 and C-25 of the cycloartane structure.     

Steryl glycosides and acyl steryl glycosides from Musa paradisiaca

From peeled fruits of Musa paradisiaca (banana, vegetable variety), two new acyl steryl glycosides, sitoindoside-III and sitoindoside-IV, and two new steryl glycosides, sitosterol gentiobioside and sitosterol myo-inosityl-β-D-glucoside, have been isolated by gradient solvent extraction and extensive chromatography (CC, prep. TLC, GC and HPLC). The compounds have been characterized by comprehensive spectroscopic analyses (IR, ¹H NMR, GC, mass spectra, [α]_D) and crucial chemical transformation. Additionally, seasonal variations of the total sterols, free sterols, steryl esters, steryl glycosides and acyl steryl glycosides in the active samples of banana have been analysed. The results provide a basis for the observed fluctuations in the anti-ulcerogenic activity of the extracts, in different seasons, and the importance of appropriate formulation of the pure principles to optimize the activity.     

Antibacterial diterpenoids from Astragalus brachystachys

Antibacterial bioassay guided fractionation of acetone extracts of Astragalus brachystachys resulted in isolation of sclareol and two related labdane-type diterpenoids, 14R-epoxysclareol and 6beta-hydroxysclareol. The antibacterial activity of the isolated compounds was measured and it was deduced that the epoxidation at the double bond of sclareol or hydroxylation at C-6 decreased the activity of the resulting compounds. Salvigenin (5-hydroxy-4',6,7-trimethoxyflavone) was also separated from this plant for the first time.     

Cysteinyl-tRNA Synthetase from Astragalus Species

l-Cysteinyl-tRNA synthetases (EC 6.1.1.16) from four Astragalus species were partially purified. The substrate specificities of the cysteinyl-tRNA synthetase from three selenium accumulator species (A. crotalariae, A bisulcatus, and A. racemosus) were compared with those from two nonaccumulator species (A. lentigenosus and Phaseolus aureus). All species had similar K(m) values for cysteine, selenocysteine, and alpha-aminobutyric acid except A. bisulcatus which failed to use selenocysteine as a substrate and which had a K(m) for cysteine four times greater than the K(m) values for other species.     

Flavonoid glycosides from fiveCyathea species

The leaves of 5 fern species of the genusCyathea, i.e.C. fauriei, C. mertensiana, C. leichhardtiana, C. podophylla andC. hancockii, have been chemically analysed. The former 3 species have kaempferol 3-sophoroside (sophoraflavonoloside) and kaempferol 7-rhamnoglucoside as glycosidic components, and the latter 2 species contain kaempferol 3-galactoside (trifolin) and kaempferol 3-rhamnoglucoside (nicotiflorin). In addition, vitexin, orientin, kaempferol 3-glucoside (astragalin), kaempferol 3-rhamnoside (afzelin) and kaempferol 7-arabinoside are detected as common constituents in all the 5 species analysed.