Triterpenoid Lactone Research Articles

Isolation, Structural Elucidation, and α-Glucosidase Inhibitory Activities of Triterpenoid Lactones and Their Relevant Biogenetic Constituents from Ganoderma resinaceum.

Ganoderma resinaceum has been used as an ethnomedicine for lowering blood sugar. To clarify the bioactive chemical constituents contributing to lower blood sugar, chemical investigation on the fruiting bodies of Ganoderma resinaceum was conducted by chromatographic techniques, and led to the isolation of 14 compounds. Their structures were elucidated as triterpenoid lactones (1–4 and 8) and ganoderma acids (5–7 and 9–14) based on the analysis of extensive spectroscopy (mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and ultraviolet (UV)) and comparison with literature data. Compounds 3, 5, 6, and 9–14 were evaluated for α-glucosidase inhibitory activity. Compounds 1–7 are new compounds. Compounds 1–4 and 8 were characteristic of an oxaspirolactone moiety, consisting of a five-membered ether ring, a five-membered lactone ring, and a characteristic C-23 spiro carbon. It is rare for natural products that such an oxaspirolactone moiety occurred in the lanostane-type triterpenoids. Compounds 5–7 and 9–14 may be important intermediates of the biosynthetic pathways of 1–4 and 8. Compounds 1 and 2 showed more potent inhibitory activity against α-glucosidase compared with the positive control drug acarbose with IC50 value of 0.75 ± 0.018 mM and 1.64 ± 0.022 mM, respectively.

Three new 3,4-seco-cycloartane triterpenoids from the flower of Gardenia jasminoides

Three new 3,4-seco-cycloartane triterpenoids (1-3), including an unusual C-1 oxygenated 3,4-seco-cycloartane triterpenoid lactone (3), along with six known triterpenoids, were isolated from 95% ethanol extract of the flower of Gardenia jasminoides. Their structures were determined by spectroscopic methods, especially 2D NMR and HRESIMS techniques. Compounds 3, 4 (dikamaliartane D), and 7 (ursolic acid) showed promising cytotoxic activity against HepG2 human hepatocellular carcinoma cell line with IC50 values of 9.3, 27.7, and 39.3 μM, respectively.

The ancient CYP716 family is a major contributor to the diversification of eudicot triterpenoid biosynthesis

Triterpenoids are widespread bioactive plant defence compounds with potential use as pharmaceuticals, pesticides and other high-value products. Enzymes belonging to the cytochrome P450 family have an essential role in creating the immense structural diversity of triterpenoids across the plant kingdom. However, for many triterpenoid oxidation reactions, the corresponding enzyme remains unknown. Here we characterize CYP716 enzymes from different medicinal plant species by heterologous expression in engineered yeasts and report ten hitherto unreported triterpenoid oxidation activities, including a cyclization reaction, leading to a triterpenoid lactone. Kingdom-wide phylogenetic analysis of over 400 CYP716s from over 200 plant species reveals details of their evolution and suggests that in eudicots the CYP716s evolved specifically towards triterpenoid biosynthesis. Our findings underscore the great potential of CYP716s as a source for generating triterpenoid structural diversity and expand the toolbox available for synthetic biology programmes for sustainable production of bioactive plant triterpenoids.

Two new pyranoanthraquinones from the root of Rennellia elliptica Korth. (Rubiaceae)

Two new pyranoanthraquinones, rennellianone A (1) and rennelianone B (2) along with four known compounds, alizarin-1-methyl ether (3), scopoletin (4), 4-hydroxy-3,5-dimethoxybenzaldehyde (5) and 3b-acetateoleanan-13b, 28-lactone (6) were isolated and characterized from the root extract of Rennellia elliptica. The structures were established based on spectroscopic data including HR-ESI–MS, 1D and 2D NMR. Triterpenoid lactone (6) is reported for the first time from family Rubiaceae.

Abieslactone induces cell cycle arrest and apoptosis in human hepatocellular carcinomas through the mitochondrial pathway and the generation of reactive oxygen species.

Abieslactone is a triterpenoid lactone isolated from Abies plants. Previous studies have demonstrated that its derivative abiesenonic acid methyl ester possesses anti-tumor-promoting activity in vitro and in vivo. In the present study, cell viability assay demonstrated that abieslactone had selective cytotoxicity against human hepatoma cell lines. Immunostaining experiments revealed that abieslactone induced HepG2 and SMMC7721 cell apoptosis. Flow cytometry and western blot analysis showed that the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and p21, and down-regulation of CDK2 and cyclin D1. Furthermore, our results revealed that induction of apoptosis through a mitochondrial pathway led to upregulation of Bax, down-regulation of Bcl-2, mitochondrial release of cytochrome c, reduction of mitochondrial membrane potential (MMP), and activation of caspase cascades (Casp-9 and -3). Activation of caspase cascades also resulted in the cleavage of PARP fragment. Involvement of the caspase apoptosis pathway was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. Recent studies have shown that ROS is upstream of Akt signal in mitochondria-mediated hepatoma cell apoptosis. Our results showed that the accumulation of ROS was detected in HepG2 cells when treated with abieslactone, and ROS scavenger partly blocked the effects of abieslactone-induced HepG2 cell death. In addition, inactivation of total and phosphorylated Akt activities was found to be involved in abieslactone-induced HepG2 cell apoptosis. Therefore, our findings suggested that abieslactone induced G1 cell cycle arrest and caspase-dependent apoptosis via the mitochondrial pathway and the ROS/Akt pathway in HepG2 cells.

ACE and platelet aggregation inhibitors from Tamarix hohenackeri Bunge (host plant of Herba Cistanches) growing in Xinjiang.

Background:Tamarix hohenackeri Bunge is a salt cedar that grows widespread in the desert mountains in Xinjiang. T. hohenackeri has not been investigated earlier, although there are many reports of phytochemical work on other Tamarix species.Materials and Methods:To find out natural angiotensin-converting enzyme (ACE) inhibitor and platelet aggregation inhibitors, the bioactive extract (ethyl acetate [EtOAc] fraction) from the dried aerial parts of T. hohenackeri were investigated. The active fraction was purified by repeated column chromatography, including silica gel, Sephadex LH-20 column, medium-pressure liquid chromatography (MPLC) (polyamide column) and high-performance liquid chromatography (HPLC). The isolated major constituents were tested for their anti-platelet aggregation activity.Results:Bioassay-directed separation of the EtOAc fraction of the 70% ethanol extract from the air-dried aerial parts of T. hohenackeri led to the isolation of a new triterpenoid lactone (1), together with 13 known compounds (2-14). It was the first time to focus on screening bioactive constituents for this plant. The chemical structures were established on the basis of spectral data (ESI-MS and NMR). The results showed that the flavonoid compounds (7 and 8) and phenolic compounds (9, 10, 11, and 14) were potential ACE inhibitors. And the flavonoid compounds (5 and 7) showed significant anti-platelet aggregation activities.Conclusion:On the basis of the chemical and biological data, the material basis of ACE inhibitory activity for the active part was the phenolic constituents. However, the flavonoid compounds were responsible for the anti-platelet aggregation. The primary structure and activity relationship were also discussed respectively.

On the non-enzymatic liberation of limonin and C17-epilimonin from limonin-17-β-d-glucopyranoside in orange juice

Limonin is well-known to induce the so-called “delayed” bitterness which is developing during standing and/or processing of orange juice. The objective of this study was to investigate the hydrolytic liberation of limonin from its precursor limonin-17-β-d-glucopyranoside in aqueous model solutions and orange juice samples. Quantitative model studies on the degradation of limonin-17-β-d-glucopyranoside under acidic conditions as well as during storage of orange juice revealed the formation of limonin besides a second hydrolysis product of yet unknown structure. After isolation, the structure of that compound was unequivocally determined for the first time as the C17-epimer of limonin, named C17-epilimonin. In order to investigate the generation of these triterpenoid lactones during storage as well as heat-treatment of orange juice, freshly squeezed orange juice was stored for up to 4 weeks at 4 and 20 °C or was heated at 70 and 100 °C and, then, both limonoids were quantitatively determined by means of high performance liquid chromatography-mass spectrometry/mass spectrometry (multiple reaction monitoring). The data obtained showed first evidence for the use of the C17-epilimonin/limonin ratio as a suitable marker for the analytical determination of the thermal input applied during processing orange juice products.

Renchanglactone A, a new triterpenoid lactone from Kadsura renchangiana

From the stems of Kadsura rechangiana, a new triterpenoid lactone named renchanglactone A (1), was isolated together with four known triterpenoids, kadsulactone A, mawuweizic acid, ganwuweizic acid and kadsuric acid. Their structures were determined by spectroscopic methods including 2D-NMR techniques.

Tubiferal A, a Backbone‐Rearranged Triterpenoid Lactone Isolated from the Myxomycete Tubifera dimorphotheca, Possessing Reversal of Drug Resistance Activity.

Abstract Tubiferal A, a novel rearranged triterpenoid lactone, has been isolated from field-collected fruit bodies of the myxomycete, Tubifera dimorphotheca, and its structure elucidated by spectral data. Tubiferal A ( 1 ) possesses a 9,10-secocycloartan-16,21-olide skeleton, and this new compound exhibited a reversal effect of vincristine (VCR) resistance (more than 4-fold) against VCR-resistant KB cell lines. Tubiferal B ( 2 ), corresponding to the seco acid of 1 was also isolated, but showed no comparable activity.

Tubiferal A, a backbone-rearranged triterpenoid lactone isolated from the myxomycete Tubifera dimorphotheca, possessing reversal of drug resistance activity

Tubiferal A, a novel rearranged triterpenoid lactone, has been isolated from field-collected fruit bodies of the myxomycete, Tubifera dimorphotheca, and its structure elucidated by spectral data. Tubiferal A ( 1 ) possesses a 9,10-secocycloartan-16,21-olide skeleton, and this new compound exhibited a reversal effect of vincristine (VCR) resistance (more than 4-fold) against VCR-resistant KB cell lines. Tubiferal B ( 2 ), corresponding to the seco acid of 1 was also isolated, but showed no comparable activity.

A Novel Triterpenoid Lactone, Schiprolactone A, from Schisandra propinqua (Wall.) Hook. f. et Thorns

AbstractSchiprolactone A, a triterpenoid lactone with a new side chain skeleton was isolated from the stems of Schisandra propinqua together with schisanlactones A and B. Their structures were elucidated by spectral studies.

Triterpenoids fromAbies species 19. (22Z)-3?-Hydroxy-17,14-fridolanosta-7,14,22,24-tetraen-26,23-olide, a new lactone from the needles of the Siberian fir

A new triterpenoid lactone with a reported rearranged lanostane skeleton was isolated from the neutral fraction of the extract from the needles of Siberian fir. Its structure was established on the basis of chemical transformations and NMR spectra using two-dimensional (COSY, COLOC) NMR spectroscopy.

Two triterpenoid lactones from the resin of Bursera delpechiana

Two new triterpenoid lactones have been isolated from the resin of Bursera delpechiana and their structures assigned as 3β-acetoxy-11α, 12α-epoxyurs-28, 13-olide and 3β-acetoxy-12β-hydroxyurs-28, 13-olide respectively on the basis of their spectroscopic properties and chemical evidence.

Novel triterpenoids from the roots of Buxus papillosa

Three new compounds have been isolated from the roots of Buxus papillosa. (+)-Buxapentalactone ( 1) and (+)-buxaheptalactone ( 2) are the rearranged triterpenoid lactones while (+)- 3-deoxybuxandonine ( 3) is a 4,4-bisnortriterpenoidal alkaloid. The structures of thes steroidal compounds were determined by using X-ray diffraction and spectroscopic techniques.

Some constituents of the sea cucumber Cucumaria frondosa

Solvent extraction of Cucumaria frondosa, collected in Passamaquoddy Bay, has afforded a variety of natural products. Silica gel chromatography of the chloroform extract has provided an abundance of sterol glycosides, sterol sulfates and free sterols which have been examined by gas chromatography/mass spectrometry (GC/MS) and nuclear magnetic resonance spectroscopy ( 1H nmr). It appears that the free sterol and the sterol glycoside mixtures are composed mainly of Δ 7-sterols, whereas the sterol sulfate mixture is composed predominantly of cholesterol and cholestanol. By methanol extraction, a mixture of triterpenoid saponins has been obtained. Partial hydrolysis of this material has yielded several monosaccharides, aglycones and one aglycone with a xylose unit attached. A new triterpenoid lactone has been isolated and its structure is proposed on the basis of 1H nmr, infrared (IR), and MS data. From the light petroleum ether extract, a number of compounds have been obtained, including the known carotenoid canthaxanthin and a plastochromanol never previously reported from marine sources. Alkaline hydrolysis of the lipid fraction provided a mixture of sterols and the known compound batyl alcohol.

Triterpenoid sapogenols from the leaves of Careya arborea: Structure of careyagenolide

The acid hydrolysate of the ethanol extract of Careya arborea leaves afforded a new triterpenoid lactone designated careyagenolide along with maslinic acid and 2α-hydroxy ursolic acid. The structure of careyagenolide has been established as 2α, 3β-dihydroxytaraxastan- 28, 20β-olide by a variety of spectroscopic evidence, chemical transformations and correlation with ψ-taraxasterol.