Diterpene Research Articles

High emission rates and strong temperature response make boreal wetlands a large source of isoprene and terpenes

Abstract. Wetlands cover only 3 % of the global land surface area, but boreal wetlands are experiencing an unprecedented warming of four times the global average. These wetlands emit isoprene and terpenes (including monoterpenes (MT), sesquiterpenes (SQT), and diterpenes (DT)), which are climate-relevant highly reactive biogenic volatile organic compounds (BVOCs) with an exponential dependence on temperature. In this study, we present ecosystem-scale eddy covariance (EC) fluxes of isoprene, MT, SQT, and DT (hereafter referred to together as terpenes) at Siikaneva, a boreal fen in southern Finland, from the start to the peak of the growing season of 2021 (19 May 2021 to 28 June 2021). These are the first EC fluxes reported using the novel state-of-the-art Vocus proton transfer reaction mass spectrometer (Vocus-PTR) and the first-ever fluxes reported for DTs from a wetland. Isoprene was the dominant compound emitted by the wetland, followed by MTs, SQTs, and DTs, and they all exhibited a strong exponential temperature dependence. The Q10 values, the factor by which terpene emissions increases for every 10 ∘C rise in temperature, were up to five times higher than those used in most BVOC models. During the campaign, the air temperature peaked above 31 ∘C on 21–22 June 2021, which is abnormally high for boreal environments, and the maximum flux for all terpenes coincided with this period. We observed that terpene emissions were elevated after this abnormally “high-temperature stress period”, indicating that past temperatures alter emissions significantly. The standardized emission factor (EF) of the fen for isoprene (EFiso) was 11.1 ± 0.3 nmol m−2 s−1, which is at least two times higher than in previous studies and as high as the emission factors typical for broadleaf and other forests in the lower latitudes. We observed EFMT of 2.4 ± 0.1 nmol m−2 s−1, EFSQT of 1.3 ± 0.03 nmol m−2 s−1, higher than typical for needle leaf and broadleaf tree functional types, and EFDT of 0.011 ± 0.001 nmol m−2 s−1. We also compared the landscape average emissions to the model of emissions of gases and aerosols from nature (MEGAN) v2.1 and found that the emissions were underestimated by over 9 times for isoprene, over 300 times for MTs, and 800 times for SQTs. Our results show that due to very high EFs and high sensitivity to increasing temperatures, these high-latitude ecosystems can be a large source of terpenes to the atmosphere, and anthropogenic global warming could induce much higher BVOC emissions from wetlands in the future.

Review of the antioxidant properties of wild edible plants in Ethiopia

This work aims to study the potential and importance of wild edible plants (WEPs) as antioxidants in treating different diseases caused by free radicals. A total of 67 species belonging to 50 genera under 36 families and naturally growing in Ethiopia were recorded after assessing all available documents. About 16.2% of the total (413) WEPs were recorded in the country. The plant families with more number of species known to have antioxidants are Amaranthaceae and Moraceae 7 species each. Fruits are the dominant edible parts followed by leaves. Compounds such as tannins, oxalates and phenolic acids are the major contributors to the antioxidant activity of vegetables, fruits and medicinal plants. Plants also have many phytochemicals which are a potential source of natural antioxidants such as phenolic diterpenes, flavonoids, flavonols, alkaloids, iridoids and saponins, High consumption of fruits and vegetables is associated with a lowered occurrence of cancer, heart disease, inflammation, arthritis, neurodegenerative diseases and diabetes. Antioxidant components including vitamin C, vitamin E, carotenoid, and plant polyphenols appeared to play a key role in reducing the development of such diseases. This review gives a general overview of the antioxidant properties of different parts of WEPs in a single volume and ease selection of the best species for further research. The chemical composition, antioxidant contents and energy values of wild plants consumed by Ethiopians indicated that they provide key nutrients such as carbohydrates minerals and vitamins. The plants will be lost along with their valuable nutrients and indigenous knowledge without proper management and conservation in the right places and habitats. Keywords: antioxidant, Ethiopia, health benefit, phytochemicals, wild edible plants.

Optimisation of a thermal desorption–gas chromatography–mass spectrometry method for the analysis of monoterpenes, sesquiterpenes and diterpenes

Abstract. In this study, a thermal desorption–gas chromatography–mass spectrometry (TD–GC–MS) method following sorbent tube sampling was developed for the determination of monoterpenes (MTs), sesquiterpenes (SQTs) and diterpenes (DTs) in gas-phase samples. The analytical figures of merit were determined, and the method performance was tested by conducting experiments related to, for example, sampling recovery, storage stability and ozone reactivity. The limit-of-quantification values were 13–518 pg (0.5–9.3 pptv), intermediate precision was in the range of 3 %–10 % and the expanded measurement uncertainty was in the range of 16 %–55 % for terpenes. The sampling recoveries of terpenes were approximately within 100±20 % with different inlet lines (15 m long Teflon and 1 m long heated stainless steel) and branch enclosure cuvette (6 L Teflon bag) tested. Ozone is an important factor causing losses of the studied compounds during sampling. Therefore, losses of terpenes upon ozone exposure were studied and the reaction rate coefficients were estimated. The ozone reaction rate coefficient (kO3) of ent-kaurene was experimentally estimated to be 2 orders of magnitude greater than the respective literature kO3 value, demonstrating the potential underestimation of DT contribution to atmospheric reactivity. The preliminary comparison between offline- and online-mode TD–GC–MS sampling and analysis revealed that diterpenes and oxygenated sesquiterpenes are lost in excessive amounts in online-mode sampling, hindering the online-mode applicability for the quantitative analysis of these compounds. A few applications to real samples were tested to identify DTs potentially emitted by boreal forest tree species. In dynamic headspace samples of pine needles and spruce twigs heated to 60 ∘C, five DTs and 13 DTs could be detected in emissions, respectively. The semi-quantitatively estimated emission rates of DTs were roughly 1 to 3 orders of magnitude lower than those of MTs and SQTs. Similarly, in spruce branch enclosure emissions from a living tree, six DTs were detected once the enclosure was heated to ca. 60 ∘C. In summary, the developed analytical procedure was demonstrated to be applicable for the analysis of MTs, SQTs and DTs. In addition, DTs could be detected in needles, twigs and branch enclosure emissions; however, high temperatures were required to promote the emissions and for obtaining detectable concentrations.

Liquid chromatography high-resolution mass spectrometry analysis, phytochemical and biological study of two aizoaceae plants: A new kaempferol derivative from Trianthema portulacastrum L.

Background: Natural remedies used for the treatment of liver diseases have a major concernworldwide. Objectives: Evaluation of the cytotoxic potential of successive fractions of two Aizoaceae plants; Trianthema portulacastrum L. and Aizoon canariense L. against human hepatocellular carcinoma (HepG2) cell lines. Moreover, metabolomic profiling of the successive fractions of both plants was carried out. Materials and Methods: Cytotoxic activity of successive fractions of the two plants against hepatocellular carcinoma (HCC) HepG2 cell lines were evaluated using viability assay, whereas metabolomic profiling was carried out using Liquid Chromatography High-Resolution ElectroSpray Ionization Mass Spectrometry (LC-HR-ESI-MS). Results: Significant cytotoxic activity of the n-hexane and n-butanol extracts of A. canariense (24.7 ± 3.5 and 55.3 ± 4.9 μg/mL, respectively) is recorded. On the other hand, metabolomic profiling of both plants resulted in dereplication of 27 metabolites belonging to different chemical classes; for example, sterols, flavonoids, diterpenes, triterpenes, tetraterpenes, alkaloids, lignans, hydrocarbons, and nucleosides. Phytochemical study of the biologically active fractions resulted in the isolation of one new compound; kaempferol-3-O-(2''-O-β-D-glucopyranosyl)-6''-O-E-feruloyl-β-D-glucopyranosid (T1). Biological testing of the isolated compounds indicated significant activity of T1 against HCC (IC50 =7.19 ± 0.27 μg/mL). Conclusion: Phytochemicals isolated from T. portulacastrum L and A. canariense L. may be responsible for their cytotoxic activity against HCC HepG2 cell lines.

Effects of different harvesting and processing methods on quality of Andrographis Herba

The effects of the growing periods, processing methods, nutritive organs and cut parts of the herbs on the quality of Andrographis Herba have been studied, which could provide scientific basis for producing high-quality crude materials of Andrographis Herba. A quantitative analysis of multi-components by single-marker(QAMS) method was used to simultaneously determine 4 diterpene lactones of andrographolide(AD), neoandrographolide(NAD), 14-deoxyandrographolide(14-DAD), and dehydroandrographolide(DHAD) in 78 batches of Andrographis Herba samples. Visual analysis, clustering analysis and partial least squares discrimination analysis(PLS-DA) were used for data processing and mining. The growing periods of Andrographis Herba were divide into the rapid growing stage(Ⅰ), the luxuriant foliage stage(Ⅱ), the bud stage(Ⅲ), the flower stage(Ⅳ), the fruiting stage(Ⅴ) and the later fruiting stage(Ⅵ), six ones in total. The results showed that the total contents of 4 diterpene lactones(TC) kept almost constant in growing periods of Ⅰ-Ⅲ, began to fall off in growing period Ⅳ, decreased rapidly in growing period Ⅴ and reduced to minimum in growing period Ⅵ. Therefore, the best harvesting period for Andrographis Herba was the bud stage. For the processing methods, none significant difference occurred for TC between drying by the sun and drying in the shade. However, in comparison of the samples dried by the sun, the samples dried in the shade exhibited lower content of AD, nonetheless, the higher contents of DHAD and NAD, indicating that the process of drying in the shade may lead to the decomposition and transformation of AD. Therefore, when the weather conditions permitted, the method drying by the sun should be used. The distributions of AD, DHAD and TC in the different cut parts and nutritive organs were determined as follows: upper cut parts > middle cut parts ≈ entire herbs > lower cut parts, leaves > entire herbs > stems. Furthermore, the contents of 4 diterpene lactones in leaves and herbs were much higher than those in stems. Therefore, it was suggested that the upper and middle cut parts of the herbs or the parts containing leaves should be preferred for harvesting to ensure the proportion of the leaves in Andrographis Herba.

Effects of ginkgo diterpene lactone meglumine on learning and memory in old mice and its mechanisms

Objective To study the effects of diterpene ginkgolides meglumine injection (DGMI) on memory impairment, activation of microglia and astrocytes and inflammatory cytokines in aged mice. Methods Twenty aged mice (22 months old) were randomly divided into two groups: aged mouse group(n=10) and DGMI group(n=10). Another 10 mice (2 months old) were selected as young mouse control group. The mice in DGMI group were received 5 mg/kg DGMI per day by tail vain injection for 4 weeks.The mice in the other two groups were received the same amount normal saline for 4 weeks. The Morris water maze was used to evaluate the function of spacial learning and memory after administration of drugs. The expression of CD11b, GFAP, IL-1β, IL-6, TNF-α and NFκB in mice brain hippocampus were detected by Western blot. Results (1) The escape latency time of aged mouse group was significantly longer than that of young mouse control group from the 2nd day to the 7th day(P<0.01). The times of platform crossing, time and distance in target quadrant of aged mouse group were significantly shorter than those of young mouse group (all P<0.01). Compared with aged mouse group, DGMI significantly reduced the escape latency time of DGMI group (P<0.01). DGMI increased the times of platform crossing, time and distance in target quadrant of aged mouse group (P<0.01). (2) The expressions of CD11b, GFAP in young mouse control group, aged mouse group and DGMI group were as follows respectively: CD11b: (1.036±0.023), (1.757±0.046), (1.214±0.024); GFAP: (1.022±0.071), (1.344±0.021), (1.086±0.073). DGMI reduced the expression of CD11b and GFAP in hippocampus compared with aged mouse group (t=5.556, P<0.01; t=5.484, P<0.01). (3) The expressions of IL-1β, IL-6, TNF-α and NFκB in young mouse control group, aged mouse group and DGMI group were as follows respectively: IL-1β: (1.003±0.057), (2.062±0.105), (1.182±0.084); IL-6: (1.018±0.024), (1.583±0.052), (1.152±0.031); TNF-α: (1.021±0.054), (1.449±0.053), (1.211±0.036); p-NFκB: (1.052±0.034), (1.782±0.113), (1.158±0.066). DGMI reduced the expression of p-NFκB(t=6.547, P<0.01) and pro-inflammatory cytokines including IL-1β(t=8.513, P<0.01), IL-6(t=3.421, P<0.01) and TNF-α(t=5.562, P<0.01) in hippocampus compared with aged mouse group. Conclusion DGMI can improve the ability of learning and memory in aged mice. The mechanism may be related with inhibiting activity of microgliosis, astrocytosis, NFκB and neuroinflammaton. Key words: Diterpene ginkgolides meglumine injection; Aged mice; Learning and memory; Neuroinflammation

Terpenes from Otostegia integrifolia

The essential oil and chloroform extract of air-dried leaves of Otostegia integrifolia Benth. were investigated for the first time using analytical and preparative gas chromatography (GC), GC-mass spectrometry (MS) and NMR techniques. A total of 40 constituents including monoterpenes, sesquiterpenes, diterpenes and their derivatives were identified. A prenylbisabolane type diterpene, 1-methyl-4-(5, 9-dimethyl-1-methylene-deca-4, 8- dienyl) cyclohexene was identified as a major component. The chloroform extract of the leaves yielded two new labdane type diterpenoids, 15, 16-epoxy-3a, 9a-dihydroxy-labda- 13(16), 14-diene and 9(13), 15(16)-diepoxy-3a-hydroxy-16-dihydrolabda-14-ene, a saturated hydrocarbon, pentatriacontane, and stigmasterol. The structures of the isolated compounds were established by spectroscopic methods. Keywords: Otostegia integrifolia Benth.; Lamiaceae; Essential oil, Furanolabdane diterpenes, Otostegindiol, Preotostegindiol, (+)-Axinyssene, Pentatriacontane, Stigmasterol

One-pot biosynthesis of silver nanoparticles using Iboza Riparia and Ilex Mitis for cytotoxicity on human embryonic kidney cells

Plant extracts continue gaining significant prominence in green synthesis of silver nanoparticles (AgNPs), due to their potential applications in nano-medicine and material engineering. This work reports on green synthesis of silver nanoparticles (AgNPs) from aqueous extracts of Iboza Riparia leaf and Ilex Mitis root bark with diterpenes (DTPs) and saponins (SPNs) as major components. After TEM, DLS, TGA/DSC, ATR, XRD and UV–Vis characterization, the relevant cytotoxicity studies were conducted with the MTT assay on human embryonic kidney cells (HEK293T) followed by antioxidant activity with ABTS. Overall, the AgNPs-DTPs (156nm) were found to be less toxic with 49.7% cell viability, while AgNPs-SPNs (50nm) and AgNPs-PVA (44nm) had cell viability of 40.8 and 28.0% respectively at 400μM. Based on the cytotoxicity and antioxidant activity, it is fair to report that these plant extracts have potential reducing and capping agents as they retain chemical properties on the surface of the nanoparticles.

Spermatotoxic Effect of Methanol Extract of Quassia amara L.: Impact on Expression of Specific Genes Concerned with Ubiquitination-Proteosome Degradation Pathway

Ubiquitination is believed to play a critical role in removal of dead and/or defective spermatozoa in normal and, more importantly, under circumstances when such spermatozoa are produced in large numbers due to genetic defects or toxic manifestations. Ubiquitination under such instances would involve specific gene expressions, many of which are not yet clearly understood. In an exhaustive study in Swiss mouse model to find the spermatotoxic effect of quassin, a diterpene compound isolated from Quassia amara , we found most of the spermatozoa to be abnormal in morphology and unviable. In the present study, we aimed at analysing the transcriptional profile of three selected genes, Ubb, Ube2c and Psmb8, involved in the ubiquitin proteolytic pathway in the testis and epididymal segments of Q. amara bark methanol extract treated mice adopting semi-quantitative RT-PCR and to study the level of DNA damage of the treated mouse spermatozoa. The results revealed that the treatment induced considerable damage to the sperm DNA. All the three genes studied showed marked increase in their levels of expression in the treated mice compared to the corresponding controls. Thus, this study shows that Q. amara methanol extract is causative of sperm DNA damage and defective spermatozoa and, in such cases, the expression of specific genes concerned with ubiquitination pathway is increased, implying that ubiquitination-proteosomal degradation is involved in the processing of dead/defective spermatozoa.

Diterpenes from the Genus Xylopia

A familia Annonaceae, a maior familia da ordem Magnoliales, compreende cerca de 130 generos e aproximadamente 2300 especies, distribuidas nas regioes tropicais e subtropicais da Africa, Asia, Australia, America Central e do Sul. No Brasil, esta familia e representada com aproximadamente 27 generos e 290 especies. O genero Xylopia e um dos maiores generos pertencente a familia Annonaceae, compreendendo cerca de 160 especies, que se distribuem principalmente em regioes de cerrado brasileiro. As principais classes de metabolitos secundarios encontrados nas especies do genero Xylopia sao os alcaloides, flavonoides e diterpenos, este ultimo, em especial os diterpenos do tipo traquilobanos, podem ser utilizados como marcadores quimiotaxonomicos devido a especificidade em algumas especies. Com o objetivo de contribuir para a quimiossistematica do genero, o presente trabalho traz uma revisao dos diterpenos descritos na literatura, com o registro de 72 substâncias, a partir do ano de 1953, assim como o relato do potencial de atividade biologica desempenhado pelos diterpenos do genero Xylopia .

A Review on Annona squamosa L.: Phytochemicals and Biological Activities.

Annona squamosa L. (Annonaceae) is a fruit tree with a long history of traditional uses. A. squamosa is an evergreen plant mainly located in tropical and subtropical regions. Srikayas, the fruits of A. squamosa, are extensively used to prepare candies, ice creams and beverages. A wide range of ethno-medicinal uses has been related to different portions of A. squamosa, such as tonic, apophlegmatisant, cool medicine, abortient and heart sedative. Numerous research projects on A. squamosa have found that it has anticancer, anti-oxidant, antidiabetic, antihypertensive, hepatoprotective, antiparasitic, antimalarial, insecticidal, microbicidel and molluscicidal activities. Phytochemistry investigations on A. squamosa have considered annonaceous acetogenins (ACGs), diterpenes (DITs), alkaloids (ALKs) and cyclopeptides (CPs) as the main constituents. Until 2016, 33 DITs, 19 ALKs, 88 ACGs and 13 CPs from this species were reported. On the basis of the multiple researches on A. squamosa, this review strives to integrate available information on its phytochemicals, folklore uses and bioactivities, hoping to promote a better understanding of its medicinal values.

A myrsinol diterpene isolated from Euphorbia prolifera reverses multidrug resistance in breast cancer cells.

P-glycoprotein (P-gp), a member of ATP-Binding Cassette transporter superfamily, can expel a variety of anti-cancer drugs so that it impairs the effect of cancer chemotherapy and results in multidrug resistance (MDR). The P-gp inhibitors are important to circumvent MDR and improve efficacy of cancer chemotherapy. The dried root of Euphorbia prolifera Buch.-Ham. has been used to treat cancer and inflammation in Chinese folk medicine for several hundred years. A myrsinol diterpene derived from Euphorbia prolifera Buch.-Ham. (J196-9-4) could modulate multidrug resistance. Cytotoxicity assays were performed to measure the reversal efficiency of J196-9-4. Efflux assay and ATPase assay were used to elucidate the mechanism of the chemical. J196-9-4 potentiated cytotoxicity of anti-cancer drugs in the P-gp over-expressing resistant breast cancer cell line MCF-7/Adr as compared to MCF-7 cells. Concentrations of 5 and 10 μM J196-9-4 could reverse the resistance to daunorubicin, vincristine, and topotecan significantly. Since J196-9-4 inhibited P-gp mediated efflux and stimulated ATP hydrolysis, J196-9-4 was a substrate of P-gp. Thus J196-9-4 is a competitive inhibitor of P-gp and reverses multidrug resistance induced by the transporter.

8,9-Dehydrohispanolone-15,16-lactol diterpene prevents LPS-triggered inflammatory responses by inhibiting endothelial activation.

Endothelial activation contributes to lung inflammatory disorders by inducing leucocyte recruitment to pulmonary parenchyma. Consequently, vascular-targeted therapies constitute promising strategies for the treatment of inflammatory pathologies. In the present study, we evaluated the effect of 8,9-dehydrohispanolone-15,16-lactol diterpene (DT) on lung endothelium during inflammation. Lung endothelial cells pre-treated with DT and activated with lipopolysaccharide (LPS) or tumour necrosis factor-α (TNF-α) exhibited reduced expression of the pro-inflammatory cytokines Cxcl10, Ccl5 and Cxcl1, whereas the anti-inflammatory molecules IL1r2 and IL-10 were induced. Consistent with this result, DT pre-treatment inhibited nuclear factor κB (NF-κB) nuclear translocation, by interfering with IκBα phosphorylation, and consequently NF-κB transcriptional activity in endothelium activated by LPS or TNF-α. Furthermore, DT, probably through p38 signalling, induced transcriptional activation of genes containing activator protein 1 (AP-1)-binding elements. Inhibition of p38 prevented IL1r2 mRNA expression in endothelium incubated with DT alone or in combination with LPS or TNF-α. Accordingly, conditioned medium (CM) from these cells failed to stimulate leucocytes as measured by a reduction in adhesive ability of the leucocyte cell line J774 to fibronectin (FN). Additionally, DT reduced the expression of the endothelial adhesion molecules E-selectin, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) after activation. Similarly, expression of VCAM-1 and ICAM-1 molecules on the lung endothelial layer of C57/BL6 mice pre-treated with DT and challenged with LPS were unchanged. Finally, inhibition of vascular adhesion molecule expression by DT decreased the interaction of J774 cells with lung endothelial cells in an inflammatory environment. Our findings establish DT as a novel endothelial inhibitor for the treatment of inflammatory-related diseases triggered by Gram-negative bacteria or by the associated cytokine TNF-α.

Contents of diterpenes in espresso coffee brews prepared from commercial capsules

The objective of this work was to quantify kahweol and cafestol diterpenes in coffee brews prepared from commercial capsules for espresso in the Brazilian market. Four types of brews, with five preparation replications, were evaluated. The capsules had differences in the amount and type of roasted and ground coffees used (blends of arabica and robusta coffee or 100% arabica coffee), and in the conditions of time and volume of extraction (dose) recommended by the manufacturer. The coffee brews presented 1.42 and 4.88 g of solids/100 mL. Concentration of solids decreased with the increase in time/volume extraction. Contents of 0.47 to 1.04 mg of kahweol and 0.38 to 0.92 mg of cafestol by dose (ranging from 35 to 120 mL) were observed. These contents corresponded to a range of 0.40 to 2.96 mg of kahweol/100 mL and 0.32 to 2.62 mg of cafestol/100 mL. The fraction of diterpenes extracted varied from 1.85 to 4.27 % for kahweol and 1.87 to 4.16 % for cafestol. Considering the contents of cafestol, there is no indication of a hypercholesterolemic effect due to a moderate consumption of coffee brews prepared from these commercial capsules.

ChemInform Abstract: Clerodane Diterpenes from Polyalthia longifolia var. pendula Protect SK‐N‐MC Human Neuroblastoma Cells from β‐Amyloid Insult.

AbstractThe three new diterpenes, polylongifoliaic A (I) and polylongifoliaons A (II), are isolated together with nine known diterpenes.

Chemical composition and antifungal activity of leaf powders and extracts of Byrsonima crassifolia (L.) Kunth, Ocimum basilicum L., Persea americana Miller., Psidium guajava L. and Spondias purpurea L. from Morelos, Mxico

Natural products from plants have great potential as novel fungicide sources for controlling pathogenic fungi. The aims of this study were to examine the chemical composition of the leave powders and extract (Hexane, methanol and water) of Mexican plants and to test in vitro, their efficacy as antifungal potential against Fusarium oxysporum f. sp. gladioli. All the species showed antifungal activity in the methanol extract. Chemical analysis of leave powders and extracts of Byrsonima crassifolia, Ocimum basilicum, Persea americana, Psidium guajava and Spondias purpurea by gas chromatography and spectrometry of masses (CG-MS) analysis showed that 89 volatile compounds were present. Leave powders and extracts contained the following: sesquiterpenes (46.06%), fatty acids (23.6%), diterpenes (14.6%), phenolic compound (11.23%) and monoterpenes (4.7%). Sesquiterpenes were not detected in B. crassifolia. The powders and leaf of extract, at 5% (hexane and methanol) revealed remarkable antifungal effect in the growth inhibition of Fusarium oxysporum f.sp. gladioli with a range of 15 to 67%. The high chemical diversity of the analyzed plant species results in different effects on the development of the fungus. Key words: Gladiolus, botanic extracts, pathogenic fungi, growth inhibition.

Anti-inflammatory Actions of Acanthoic Acid-Related Diterpenes Involve Activation of the PI3K p110γ/δ Subunits and Inhibition of NF-κB

The effect of acanthoic acid analogs on the response to proinflammatory challenge was investigated. Some pimarane diterpenes are known activators of the LXRαβ nuclear receptors, but we show here that they also exert a rapid, potent, and selective activation of the p110γ and p110δ subunits of PI3K. Combination of these effects results in an important attenuation of the global transcriptional response to LPS in macrophages. PI3K/Akt activation leads to inhibition of the LPS-dependent stimulation of IKK/NF-κB and p38 and ERK MAPKs. Macrophages from LXRαβ-deficient mice exhibited an inhibition of these pathways similar to the corresponding wild-type cells. Silencing or inhibition of p110γ/δ suppressed the effect of these diterpenes (DTPs) on IKK/NF-κB and MAPKs signaling. Taken together, these data show a multitarget anti-inflammatory mechanism by these DTPs including a selective activation of PI3K isoenzymes.

ChemInform Abstract: Isolation of a New Labdane‐Type Diterpene from Vitex rotundifolia

Abstractisolation and structure of new labdane‐type diterpene (I) together with five known diterpenes

Efficacy of tepronone and folic acid in the treatment of chronic atrophic gastritis evaluated by the marking targeting biopsy

Objective To explore the efficacy of tepronone and folic acid in the treatment of chronic atrophic gastritis (CAG) evaluated by the marking targeting biopsy (MTB).Methods A total of 224 H.pylori negative CAG patients were selected and divided into group A (n 96,tepronone 50 mg/time,folic acid 10 mg/time,three times/day),group B (n=23,tepronone 50 mg/time,three times/day),group C (n=74,unspecific treatment) and group D (n=31,no treatment).The treatment course lasted for one year.The clinical symptoms improvement of each group was observed before and after treatment.The pathological improvement of gastric mucosa by MTB was inspected before and after treatment.The chi square test was performed for the comparison between groups.Results The total efficacy rates of group A,B,C and D were 43.8％ (42/96),39.1％ (9/23),33.8％(25/74) and 32.3％ (10/31) respectively,there was no significant difference between groups (x2 =2.328,P =0.507).For the significant efficacy rate of gastric mucosa pathological improvement,group A was compared with group D,group A was compared with group C and group B was comparedwith group D,the differences were significant (x2 =14.520,14.628 and 8.995,all P＜0.01).In the total efficacy rate of gastric mucosa pathological improvement,group A (49.8％,131/263) was compared with group D (24.2％,16/66),group A was compared with group C (35.9％,66/184)and group B (44.7％,21/47) was compared with group D,the differences were significant (x2 =13.953,8.535 and 5.207,all P＜0.05).Conclusion Teprenone alone or teprenone and folic acid combination can obviously improve pathological changes of CAG patients. Key words: Biopsy; Gastritis, atrophic; Diterpenes; Gastrointestinal agents; Folic acid

ChemInform Abstract: Cytotoxic Alcyonolide Congeners from an Okinawan Soft Coral Cespitularia sp.

AbstractThe four new diterpenes (I)‐(IV) and a known alcyonolide are isolated from the title plant.