Diterpene Lactone Research Articles

Variation in growth and diterpene lactones among field-cultivated Andrographis paniculata

Seed-raised Andrographis paniculata (Acanthaceae) from 28 accessions were grown in a randomized complete block design to determine morphological characteristics and diterpene contents. The average amount of dried leaves per individual was between 2.13 and 8.23 g. The average andrographolide content varied from 12.44 to 33.52 mg/g dried leaves and 14-deoxy-11,12-didehydroandrographolide content varied from 0.23 to 2.08 mg/g dried leaves. The differences in phytomass and diterpene contents among the plants from different accessions were statistically significant. Furthermore, we isolated the elite individual plants containing high amounts of andrographolide and 14-deoxy-11,12-didehydroandrographolide (up to 52.57 and 3.46 mg/g dried leaves, respectively). The results indicated those populations are potentially important sources for breeding and improvement of cultivars.

Abietane Lactones and Iridoids from Goldfussia yunnanensis

Two new abietane diterpene lactones (1--2), three new abietane diterpene lactone glycosides (3--5) and a new iridoid glycoside (6), together with five known compounds, were isolated from the aerial parts of Goldfussia yunnanensis. The new compounds were determined to be 18-hydroxyhelioscopinolide A (1), 18-oxohelioscopinolide A (2), 18-hydroxy-3-O-beta-D-glucopyranosylhelioscopinolide A (3), 3-O-beta-D-glucopyranosylhelioscopinolide A (4), 3-O-beta-D-galactopyranosylhelioscopinolide A (5), and 6-O-trans-cinnamoyl E-harpagoside (6) on the basis of spectral data and chemical evidence.

HPLC determination of active diterpene lactones from Andrographis paniculata Nees planted in various seasons and regions in Thailand

HPLC determination of active diterpene lactones from Andrographis paniculata Nees planted in various seasons and regions in Thailand

In Vivo and In Vitro Anti-inflammatory Activities of Neoandrographolide

Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees, was tested in vivo and in vitro for its anti-inflammatory activities and mechanism. Oral administration of neoandrographolide (150 mg/kg) significantly suppressed ear edema induced by dimethyl benzene in mice. Oral administration of neoandrographolide (100-150 mg/kg) also reduced the increase in vascular permeability induced by acetic acid in mice. In vitro studies were performed using the macrophage cell line RAW264.7 to study the effect of neoandrographolide on suppressing phorbol-12-myristate-13-acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Respiratory bursts were quantified by chemiluminescence (CL) measurements. Results showed that neoandrographolide suppressed PMA-stimulated respiratory bursts dose-dependently from 30 muM to 150 muM. Neoandrographolide also inhibited NO and TNF-alpha production in LPS-induced macrophages, contributing to the anti-inflammatory activity of A. paniculata. These results indicate that neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.

Atribuição dos deslocamentos químicos dos átomos de ¹H e 13C do acetato de acantoaustralida

Do extrato hidroetanólico das partes aéreas de Acanthospermum australe (Asteraceae) foram identificados uma lactona diterpênica, o acetato de acantoaustralida (1) e dois flavonoides: quercetina (2) e crisosplenol D (3). As estruturas foram identificadas através de técnicas espectroscópicas de RMN de ¹H e 13C, gHSQC, gHMBC, TOCSY, gNOESY, EM e pela comparação com dados da literatura.

Therapeutic Potentials of Andrographolide from Andrographis paniculata : a Review

Andrographolide, a bitter principle obtained from Andrographis paniculata (Family: Acanthaceae), is a diterpene lactone, responsible for various pharmacological activities. This is a well-known phytoconstituent from Indian System of Medicine, used in the management of different diseases since time immemorial. Research activities worldwide to exhibit the beneficial role of Andrographolide are continuously enriching the therapeutic arsenal of this important phytomolecule. In addition to the well known pharmacological activities like hepatoprotective, antioxidant, hypoglycemic etc., recent advances in the management of immune system and neoplastic diseases make andrographolide the phytomolecule of the hour. In this report an effort has been given to highlight the research findings related to therapeutic potentials and recent development in the pharmacological activities of andrographolide.

1H and13C NMR signal assignments of a novel Baeyer-Villiger originated diterpene lactone

A highly rearranged novel dilactone was the single product isolated from Baeyer-Villiger oxidation of a norketone prepared from grandiflorenic acid, a natural kaurane diterpene. The complete 1H and 13C NMR assignment is presented for this novel compound that showed discrete in vitro antibacterial activity.

Microbial Transformations of Gelomulide G: A Member of the Rare Class of Diterpene Lactones

Microbial transformation of gelomulide G (3beta,6beta-diacetoxy-8beta,14beta-epoxyabiet-13(15)-en-16,12-olide, 1) was carried out. Incubation of 1 with Aspergillus niger afforded two new metabolites, 3beta,6beta-diacetoxy-8beta,14beta-dihydroxyabiet-13(15)-en-16,12-olide (2) and 3beta,6beta-diacetoxy-14beta-hydroxyabieta-8(9),13(15)-dien-16,12-olide (3). While Cunninghamella elegans afforded the 14-epimer of 2, i.e., 3beta,6beta-diacetoxy-8beta,14alpha-dihydroxyabiet-13(15)-en-16,12-olide (4), along with 3beta-acetoxy-6beta-hydroxy-8beta,14beta-epoxyabiet-13(15)-en-16,12-olide (5). The structures of the transformed products 2-5 were deduced to be new on the basis of MS and NMR data.

Two Diterpenes and Three Diterpene Glucosides from Phlogacanthus curviflorus

Two new diterpene lactones, phlogacantholides B (1) and C (2), and three new diterpene lactone glucosides, phlogacanthosides A (3), B (4), and C (5), together with lupeol, beta-sitosterol, betulin, beta-daucosterol, (+)-syringaresinol, and (+)-syringaresinol-4-O-beta-D-glucopyranoside, were isolated from the roots of Phlogacanthus curviflorus. Their structures were elucidated by chemical and spectroscopic evidence. The structure, including the relative configuration of phlogacantholide B (1), was confirmed by X-ray crystallographic analysis of its diacetate (6).

Six New Diterpenoids from Suregada multiflora

Six new diterpenoids were isolated from a CH(2)Cl(2)-MeOH extract of the bark of Suregada multiflora. The structures were established on the basis of one- and two-dimensional NMR and other spectroscopic studies and chemical derivatizations. Two compounds, suregadolides C (1) and D (2), were identified as new diterpene lactones of two antipodal series, containing a cyclopropane ring bridging C-3 and C-4 of the basic abietane skeleton. Suremulide A (3) was found to be a new abietene diterpene lactone. Bannaringaolide A (4), a diterpene lactone, based on a novel carbon skeleton with a seven-membered ring, possibly formed by the rearrangement of the exocyclic C-17 in ring C of an ent-pimarane framework, has also been isolated. A kaurane triol, suremulol A (5), and a kaurane diol, suremulol B (6), were also identified as new metabolites.

Dehydrocrotonin and its derivative, dimethylamide-crotonin induce apoptosis with lipid peroxidation and activation of caspases-2, -6 and -9 in human leukemic cells HL60.

A variety of stimuli can induce cells to undergo apoptosis, with one of the most reproducible inducers being mild oxidative stress following exposure to anticancer agents. Apoptosis involves events mediated by cysteine proteases (caspases) that are classified as initiators (-8, -9 and -12) or executors (-2, -3, -6 and -7). In this study, we examined the mechanisms of apoptosis induced by dehydrocrotonin (DHC), a diterpene lactone isolated from the Amazonian plant Croton cajucara, and its synthetic derivative, dimethylamide-crotonin (DCR), in human HL60 promyelocytic leukemia cells. Flow cytometric analysis of HL60 cells after treatment for 72 h showed that DCR- and DHC-induced apoptosis, with maximum cell death at a concentration of 250 microM for both compounds. DCR and DHC were effective in triggering the activation of caspases-2, -6 and -9. The level of reduced glutathione (GSH) decreased, whereas there was an increase in thiobarbituric acid-reactive substance (TBARS) production and in mitochondrial swelling. These effects on mitochondrial swelling, GSH content and lipid peroxidation were abolished by cyclosporine A, an inhibitor of the membrane permeability transition. The cytotoxicity of DHC and DCR was prevented by a high concentration of GSH (15 mM) in the culture medium. These results indicate that DCR and DHC produced apoptosis partly by oxidative stress-induced lipid peroxidation, which triggered the caspase cascade, that lead to apoptotic cell death in HL60 cells. Based on the pattern of caspase activation, on the increase in mitochondrial swelling and on the inhibitory action of cyclosporine A, we conclude that DCR and DHC triggered apoptosis in HL60 cells probably through cytochrome c release and apoptosome formation.

Revisiting diterpene lactones of Suregada multiflora

Phytochemical investigations on the organic extracts of the leaves of Suregada multiflora have led to the isolation of ten tetracyclic diterpene lactones 1– 10 , members of a rare class of abiatene diterpene lactones. Compounds 1– 5 were found to be new. The structures of gelomulides F ( 11 ), D ( 12 ) and E ( 13 ) were revised on the basis of 2D NMR and X-ray diffraction evidences. Compounds 1 and 2 contain an epoxy linkage between C-8 and C-14, whereas compounds 3– 5 were identified as 8,14-dihydroxy analogues of diterpene lactones. The stereochemical assignments in new compound 1 are based on X-ray diffraction analysis. Compounds 6 and 7 were identified as the known gelomulides A , G . The structures of compounds 7– 9 were unambiguously confirmed by X-ray diffraction analyses.

Three New Diterpenoids from Euphorbia wallichii

AbstractThree new abietane diterpene lactones, 3α‐hydroxyjolkinolide A (1), ent‐8α, 14β‐dihydroxy‐ 13(15)‐ene‐16(12α)‐abietanolide (2) and ent‐8α, 14α‐dihydroxy‐13(15)‐ene‐16(12α)‐abietanolide (3) as well as a known abietane diterpene jolkinolide A (4) were isolated from the roots of Euphorbia wallichii. Their structures were elucidated on the basis of spectroscopic analysis.

Comparison of the gastroprotective effect of a diterpene lactone isolated from Croton cajucara with its synthetic derivatives

The effect of three new derivatives from dehydrocrotonin (DHC—compound I) on gastric damage in different animal models including gastric ulceration induced by a necrotic agent and hypothermic restrained-stress was studied: compound II (produced by reducing the cyclohexenone moiety of DHC with NaBH 4); compound III (produced by reducing the carbonyls with LiAlH 4); and compound IV (produced by transforming the lactone moiety into an amide). Their structures were confirmed on the basis of chemical and physicochemical evidence. When previously administered (p.o.) at a dose of 100 mg/kg, compound II significantly ( P<0.01) reduced gastric injury induced by HCl/ethanol (78%) and indomethacin (88%) better than did reference compound I (48 and 43%, respectively). But the anti-ulcerogenic activity of compound II was completely abolished by the stress-induced ulcer. Reduction of carbonyls with LiAlH 4 (compound III) caused decreased activity, markedly when no protective effect in any of the models was applied ( P>0.05). However, compound IV, in which the lactone moiety was changed into an amide, when administered at the same dose (100 mg/kg, p.o.), was more effective. The presence of a lactone moiety or Michael acceptor is probably essential for the anti-ulcerogenic effect of these compounds.

Comparative cytotoxicity of dimethylamide-crotonin in the promyelocytic leukemia cell line (HL60) and human peripheral blood mononuclear cells

Dehydrocrotonin (DHC) is a diterpene lactone obtained from Croton cajucara (Sacaca). Dimethylamide-crotonin (DCR), a DHC derivative, has a similar inhibitory effect on leukemic HL60 cells than its parent compound evaluated by different endpoints of cytotoxicity. No cytotoxicity or morphological alterations associated with apoptosis were detected in human peripheral blood mononuclear cells (PBMC) after treatment with up to 400 μM DCR in presence of phytohemaglutinin (5 μg/ml). Based on morphological changes and the pattern of DNA fragmentation, DHC and DCR were found to induce apoptosis and terminal differentiation (assessed by nitro blue tetrazolium reduction) in HL60 cells, but these compounds did not show any toxic effect in PBMC. Thus, DCR and DHC inhibit HL60 cell growth in vitro partly by inducing apoptosis and cell differentiation, but does not cause serious damage to immune cells according to our experimental conditions.

Influence of protein phosphatase inhibitors on HL60 cells death induction by dehydrocrotonin

Oxidative stress can be involved in several cellular responses, such as differentiation, apoptosis and necrosis. Dehydrocrotonin (DCTN, diterpene lactone) from Croton cajucara, Brazilian medicinal plant, slightly induced NBT-reducing activity. In presence of protein phosphatase inhibitors significant differentiation of HL60 cells was observed. Flow cytometry analysis demonstrated that apoptosis was induced when the cells were treated with okadaic acid (OKA) and plus trans-dehydrocrotonin ( t-DCTN) this effect was two-fold increased. Unlike, when the cells were treated only with t-DCTN, necrosis was observed. On the other hand, the necrosis induced by t-DCTN could be due to oxidative stress, revealed by increase of GSH content. Therefore, this differentiation pathway involves the modulation of protein phosphatases and this inhibition promotes the t-DCTN action on apoptosis induction.

Heat-accelerated degradation of solid-state andrographolide.

The stability of andrographolide, the major active diterpene lactone from Andrographis paniculata (BURM. f.) WALL. ex NEES., was determined to show that, while crystalline andrographolide was highly stable even at 70 degrees C (75% relative humidity) over a period of 3 months, its amorphous phase degraded promptly. Heat-accelerated conditions revealed second-order kinetics of the decomposition with the rate constant at 25 degrees C (k(25 degrees C)) predicted from the Arrhenius plot of 3.8 x 10(-6) x d(-1). The major decomposed product under elevated temperature (70 degrees C, 75% relative humidity) is 14-deoxy-11,12-didehydroandrographolide.

Antimalarial Compounds from Parinari capensis

AbstractFor Abstract see ChemInform Abstract in Full Text.

A novel diterpene lactone

A highly rearranged novel dilactone, ent-5α,15α-epoxy-9,10-friedo-10β,11β-di­hydroxy-16,11α:19,10β-diseco-17-nork­aur­an-16,19-dioic acid 16\rightarrow11:19\rightarrow10-dilactone, C19H24O5, was synthesized from ent-kaur-9(11)-en,16-nor,19-oic acid, which was obtained by oxidation of grandiflorenic acid, under Baeyer–Villiger rearrangement conditions. The structure of the final product was determined unambiguously by X-ray analysis.

DETERMINATION OF ANDROGRAPHOLIDE IN COMMERCIAL ANDROGRAPHIS ( ANDROGRAPHIS PANICULATA ) PRODUCTS USING HPLC WITH EVAPORATIVE LIGHT SCATTERING DETECTION

ABSTRACT A reverse-phase high performance liquid chromatographic method is developed for the determination of andrographolide, a characteristic diterpene lactone in commercial Andrographis (Andrographis paniculata) products. Samples are analyzed by means of a reverse-phase column (Supelco Discovery C18) using acetonitrile and water, under gradient conditions as the mobile phase, over 40 min. The evaporative light scattering detector (ELSD) used, was set at an evaporating temperature of 61°C and nebulizing gas (compressed air) pressure of 2.9 bars. The detection limit (S/N>5) of andrographolide is 50 ng on the column.