Irritant phorbol derivatives from four Jatropha species

Four Jatropha species used in folk medicine were screened for irritant constituents. By chromatographic and countercurrent distribution procedures, highly irritant factors were isolated from each species. They represent new polyunsaturated esters of the tigliane-type diterpenoids 16-hydroxyphorbol (J. podagrica, J. multifida) and 12-deoxy-16-hydroxyphorbol (J. curcas, J. gossypifolia).     

Bioactive diterpenoids from Celastraceae species

Celastraceae species have a long tradition of use in folk medicine and agriculture. Intensive research into this family has resulted in the isolation of a large number of secondary metabolites with a wide range of bioactivity, with the most characteristic being the dihydro-β-agarofuran sesquiterpenes and the quinomethide triterpenoids. Despite diterpenoids not often being found in Celastraceae species, the novelty of their structures and their biological activities has stimulated their research. There are several reviews covering studies on Tripterigium wilfordii, a traditional Chinese medicine, and their metabolites, but none focusing on bioactive diterpenoids isolated from other Celastraceae species. This review focuses on diterpenes isolated from Celastraceae species, and their skeleton diversity, species sources, and tested biological activities are discussed. The literature from January 2000 to October 2016 is reviewed, and 64 references are cited. A total of 118 isolated diterpenoids possessing twelve different skeletons are included and classified by the following tested biological activity: cytotoxicity, anti-inflammatory, antitumour-promotion, anti-HIV, immunosuppressant, reversal multi-drug resistance, and antifeedant. This compliance information will be helpful in further research into diterpene Celastraceae isolation, biological activity determination and structure specific modifications.     

Bio-Guided Investigation of Sideritis cypria Methanol Extract Driven by in Vitro Antioxidant and Cytotoxic Assays

Sideritis cypria Post is an endemic and endangered species of Northern Cyprus. The overall aim of the present study was to evaluate the total phenolic content, the antioxidant, the cytotoxic and the antimicrobial activity of the methanol extract obtained from the aerial parts of cultivated S. cypria. A bio-guided approach led to the isolation of 27 chemical compounds by using various analytical techniques. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy. The crude extract exerted strong antioxidant activity (DPPH and FRAP assays) which was attributed to its high total phenolic content. Furthermore, groups rich in phenolic content showed highest antioxidant property, whereas groups with phytosterols, diterpenoids and apigenin derivatives exerted cytotoxic effects in MDA-MB231 cancer cell line by the MTT method. Moreover, the cytotoxic activity of four isolated apigenin derivatives was evaluated in the same cancer cells. The antimicrobial activity of the extract and groups were measured, demonstrating lack of activity. To the best of our knowledge, this survey is the first report on the biological activities of the methanol extract of S. cypria.     

Isolation and characterisation of selected germander diterpenoids from authenticated Teucrium chamaedrys and T. canadense by HPLC, HPLC-mS and NMR

Teucrium species, such as germander, are rich in neo-clerodane diterpenoids and have been used in traditional folk medicine for their stimulant, diuretic, antipyretic and antiseptic properties. However, the furano neo-clerodane diterpenoids present in germander have been implicated in the in vivo hepatotoxicity of this botanical. In this study, authenticated germander (Teucrium chamaedrys L. and Teucrium canadense L.) was used as the source material. Methanol extracts of powdered plant mate rial were prepared and analysed by HPLC using Synergi Max-RP columns with monitoring at 220 nm. Limited amounts of teucrin A and other diterpenoid standards were analysed on a Synergi Max-RP column in order to determine their retention times and to generate calibration curves. The same standards were subjected to concurrent mass spectral analysis. Teucrin A and diterpenoids such as dihydroteugin, teuflin, teuflidin and teucvidin were tentatively identified in the plant extracts by HPLC-MS and 1H-NMR experiments. For the isolation of teucrium diterpenoids on a semipreparative scale, a solid-phase extraction method was developed for the first time using styrene divinylbenzene and strata-X sorbents for teucrin A and teuflin, respectively. Semi-preparative HPLC of the methanol extract of the powdered aerial parts of Teucrium plants was carried out on a semipreparative Synergi Max-RP column with photodiode array detection in order to confirm the identities of some diterpenoids by HPLC-MS and NMR.     

Pharmaco-toxicological study of diterpenoids

Azorella compacta, Azorella yareta and Laretia acaulis (Apiaceae) are native species from the high Andes Mountains, northeastern Chile, and they have being traditionally used to treat asthma, colds and bronchitis, illnesses with inflammation and pain as the main symptoms. Interestingly, there are no scientific reports available on their benefits or toxicity. This study was carried out with the purpose of validating the medicinal use of these species and to discover anti-inflammatory and analgesic new molecules. As a working hypothesis, we have proposed that these medicinal species contain bioactive compounds with anti-inflammatory and analgesic effects. In this context, azorellanol, 13-hydroxy-7-oxoazorellane and 7-deacetylazorellanol, three diterpenoids previously isolated only from these plants, were subjected to farmaco-toxicological evaluation. Their topical anti-inflammatory and analgesic activities along with acute toxicities or innocuosness were also investigated. Our results indicate the absence of toxic and side effects in mice. All compounds presented dose-related inhibition of pain. 13-hydroxy-7-oxoazorellane was the most potent analgesic but it was less effective than sodium naproxen, the reference drug. Azorellanol exhibited the highest topical anti-inflammatory potency on AA (arachidonic acid) and TPA (12-deoxyphorbol 13-tetradecanoate) induced oedema, and it effect was similar to the reference drugs (nimesulide and indomethacin). Probably, its mechanism of action could be explained through the inhibition to cyclo-oxygenase activity. Our results corroborate the anti-inflammatory and analgesic effects of these species, and it justifies their use in folk medicine.     

Secondary metabolites of plants from the genus cipadessa: chemistry and biological activity

The plants of genus Cipadessa, which are distributed across India and southwest of China, have been used as natural insecticides, as well as folk medicines for the treatment of a range of maladies such as diabetes, dysentery, malaria, piles, snake poison, rheumatism, etc. This article reviews the chemical constituents that have been isolated from Cipadessa species to date, including their biological activities. The compounds listed are tetranortriterpenoids (limonoids), diterpenoids, sesquiterpenoids, flavonoids, steroids, and some others.     

唇形科香茶菜属二萜类化合物分布规律

香茶菜属（Isodon）由于富含二萜类化合物（Diterpenoids）而具有较高的药用价值,本研究根据其所含二萜的骨架和氧化状态,对该类化合物在香茶菜属植物中的分布规律进行研究。UPGMA聚类分析结果显示：含二环和三环二萜为主的植物种类聚在一支上,含四环二萜为主的植物种类聚在另一支上。进一步将二萜分为二环、三环、四环三大类绘制到分子系统树上结果显示：三环二萜主要分布在较原始的类群中,如：线纹香茶菜（I.lophanthoides）和小花线纹香茶菜（I.lophanthoides var. micranthus）;而四环二萜主要分布在较进化的类群中,如：旱生香茶菜（I.xerophilus）和腺花香茶菜（I.adenanthus）。本研究通过对二萜类化合物与香茶菜属系统发育之间存在的联系进行探讨,有助于对香茶菜属植物中的二萜类化合物活性成分进行筛选与研发。     

Chrysobalanaceae: secondary metabolites, ethnopharmacology and pharmacological potential

Many Chrysobalanaceae species, in special Licania and Parinari, are widely used in folk medicine to treat several diseases. This review describes some aspects of their ethnopharmacology potential, biological activities and the secondary metabolites reported so far for Chrysobalanaceae. The chemical constituents of this family include triterpenoids, diterpenoids, steroids and phenylpropanoids like flavonoids as well as chromones derivatives.     

Diterpenoids from the roots of Euphorbia ebracteolata and their anti-tuberculosis effects

Euphorbia ebracteolata was a natural medicine for the treatment of tuberculosis. The present work has performed the investigation of bioactive chemical substances from the roots of E. ebracteolata. Using various chromatographic techniques, 15 compounds were obtained from the roots of E. ebracteolata. On the basis of widely spectroscopic data analyses, the isolated compounds were determined to be diterpenoids, including rosane derivatives (1–12), isopimarane (13), abietane (14), and lathyrane (15), among which compounds 1–4, and 9 were undescribed previously. The inhibitory effects of isolated diterpenoids against Mycobacterium tuberculosis were evaluated using an Alamar blue cell viability assay. And two rosane-type diterpenoids 3 and 8 displayed moderate inhibitory effects on with the MIC values of 18 μg/mL and 25 μg/mL, respectively. For the potential inhibitor 3, the inhibitory effect against the target enzyme GlmU was evaluated, which displayed a moderate inhibitory effect with the IC₅₀ 12.5 μg/mL. Therefore, the diterpenoids from the roots of E. ebracteolata displayed anti-tuberculosis effects, which would be pay more attentions for the anti-tuberculosis agents.     

Origin of Macaronesian Sideritis L. (Lamioideae: Lamiaceae) inferred from nuclear and chloroplast sequence datasets

Sideritis L. (Lamiaceae) comprises approximately 150 species of annuals and perennials distributed chiefly in the Mediterranean region. The majority of the species belong to the continental subgenus Sideritis which is divided into two perennial (Sideritis and Empedoclea) and two annual (Hesiodia and Burgsdorfia) sections. Twenty-three species are woody perennials endemic to the Macaronesian archipelagos of Madeira and the Canary Islands. In an effort to determine the continental origin of the insular group, we constructed independent phylogenies comprising sequence data from both chloroplast and nuclear markers. Sampling included 7 island taxa drawn from the Macaronesian subgenus Marrubiastrum and 25 continental taxa representing all four sections of subgenus Sideritis. Subgenus Marrubiastrum and the two continental perennial sections form well-supported monophyletic groups in both individual and combined analyses. The annual sections are not monophyletic in any analysis; further sampling of annual taxa is needed to resolve these relationships. All analyses identified Sideritis cossoniana, an annual species from Morocco, as the closest continental relative of the Macaronesian group. This contrasts with the hypothesis of earlier workers who suggested that the insular taxa were most closely related to eastern Mediterranean species of the genus. The phylogenies also demonstrate a distinct increase in woodiness among the Macaronesian species relative to their continental congeners, providing further support for the secondary nature of woodiness in island plants.     

红根草中的新二萜——红根草酮内酯和新红根草酮

由红根草(Salvia prionitis Hance)中分得三个abietane类二萜成分:红根草酮内酯(prioketolactone,1)、新红根草酮(neoprionitone,2)和二氢异丹参酮1(dihydroisotanshinone1,3)。经波谱分析确定了它们的化学结构。其中,1,2为新化合物,1是鼠尾草植物中首次发现的具有七元环内酯结构的二萜醌类化合物,3为首次从红根草中发现。     

In vitro effects of compounds isolated from Sideritis brevibracteata on bovine kidney cortex glutathione reductase

Glutathione reductase (GR, E.C 1.6.4.2) is a flavoprotein that catalyzes NADPH-dependent reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH). The aim of this study was to investigate in vitro effects of phenolic compounds isolated from Sideritis brevibracteata on bovine kidney GR. The Sideritis species are widely found in nature and commonly used as medicinal plants. 7-O-glycosides of 8-OH-flavones (hypolaetin, isoscutellarein and 3'-hydroxy-4'-O-methylisoscutellarein) were isolated from aerial parts of Sideritis brevibracteata. These compounds inhibited bovine kidney cortex GR in a concentration-dependent manner. Kinetic characterization of the inhibition was also performed.     

Antioxidant and Antimelanogenic Activities of Compounds Isolated from the Aerial Parts of Achillea alpina L.

Achillea alpina is widely distributed in Korea and is often used as a folk medicine for stomach disorders. Although a previous study isolated antioxidant compounds (flavonoid O‐glucoside, sesquiterpene) from this plant, no systematic study of its chemical constituents had been reported. The present study aimed to identify the phytochemicals present in a methanol extract of A. alpina, assess their potential antioxidant activities in vitro, and determine their effects on melanogenesis in B16F10 melanoma cells. Column chromatographic separation of aqueous fractions of A. alpina led to the isolation of 17 compounds. The chemical structures of these compounds were determined using spectroscopic data from electrospray ionization‐mass spectrometry and nuclear magnetic resonance. To the best of our knowledge, the present study is the first to identify compounds 2 – 10 and 12 – 17 in A. alpina. Furthermore, compound 6 possessed powerful antioxidant activity, while compound 15 suppressed intracellular tyrosinase activity and thus reduced melanogenesis in B16F10 cells. Therefore, our research suggested that these naturally occurring compounds have the potential to reduce oxidative stress and promote skin whitening. Further investigations will be required to elucidate the mechanisms underlying the antioxidant and antityrosinase activities of these compounds.     

Recent progress in phytochemistry,pharmacology and biotechnology of Astragalus saponins

Saponins are widely distributed among plant kingdom and possess a wide range of pharmacological properties. Genus Astragalus is the largest in the Fabaceae family, comprising more than 2,200 species spread over the Globe. Astragalus species have been used in traditional medicine of many countries as well as in the modern one. The main use in the folk medicine of the species is due to their saponin content. The paper is focused on the above mentioned group of compounds. Details on their structure, distribution, recent information on the pharmacological properties and biotechnology of Astragalus saponins will be summarized and thoroughly discussed.     

Essential oil composition and total metabolite content of a chemotype of Ajuga reptans L. (Lamiaceae) collected in Central Italy

In this work, an interesting application of phytochemistry for ethnopharmacological purposes was reported. In particular, the total phytochemical analysis of a single sample of Ajuga reptans L. (Lamiaceae) collected in Central Italy was carried out in order to provide a rationale for the use of this plant in folk medicine. This analysis was conducted on the volatile oil fraction by gas chromatography–mass spectroscopy (GC-MS) and on the polar one by means of classical column chromatography and nuclear magnetic resonance and MS. Thirty-nine volatile components were identified in the essential oil whereas 32 compounds were identified in the polar fraction. All of these are known to exert several beneficial medicinal activities and no potentially toxic compounds were identified such as the neo-clerodane diterpenoids, commonly evidenced in the entire genus. This study could provide a phytochemical rationale for the possible ethnopharmacological use of this specific species.     

New labdane diterpenoids from Sideritis chamaedryfolia

From the aerial parts of Sideritis chamaedryfolia six previously known ent-kaurene diterpenoids have been isolated. In addition, seven new labdane derivatives have also been obtained from the same source. The structures of these new natural diterpenoids have been established by chemical spectroscopic means and by correlation with known products.     

Chemical Constituents of Species in the Genus Pleione (Orchidaceae) and the Implications from Molecular Phylogeny

Pleiones are popular ornamental orchids and different species of Pleione are long being used as traditional medicine in many Asian countries. However, previous chemical investigations of the genus Pleione are restricted to only a few species. In the present study, high performance liquid chromatography (HPLC) fingerprint of Pleione plants was established, which in particular, eight common peaks were confirmed in 16 species/hybrids. Three of the compounds corresponding to the chromatographic peaks were identified by electrospray ionization tandem mass spectrometry (ESI-tandem-MS). HPLC analysis confirmed the studied taxa shared most of chemical compounds but the content of chemical compounds was significantly different between species. Comparison of hierarchical clustering result with phylogenetic tree revealed that closely related species have higher similarities in chemical constituents. In consideration of low chemical similarity between spring-flowering and autumn-flowering species, we suggest a discrimination of these two groups during medicinal use of the genus Pleione. Species with a large pseudobulb and with high content of a certain compound should be given priority in future artificial cultivation and medicinal cultivar breeding. We hope our findings will contribute to the quality control and promote conservation of such endangered plant group.     

A Non-Biological Method for Screening Active Components against Influenza Virus from Traditional Chinese Medicine by Coupling a LC Column with Oseltamivir Molecularly Imprinted Polymers

To develop a non-biological method for screening active components against influenza virus from traditional Chinese medicine (TCM) extraction, a liquid chromatography (LC) column prepared with oseltamivir molecularly imprinted polymer (OSMIP) was employed with LC-mass spectrometry (LC-MS). From chloroform extracts of compound TCM liquid preparation, we observed an affinitive component m/z 249, which was identified to be matrine following analysis of phytochemical literatures, OSMIP-LC column on-line of control compounds and MS/MS off-line. The results showed that matrine had similar bioactivities with OS against avian influenza virus H9N2 in vitro for both alleviating cytopathic effect and hemagglutination inhibition and that the stereostructures of these two compounds are similar while their two-dimensional structures were different. In addition, our results suggested that the bioactivities of those affinitive compounds were correlated with their chromatographic behaviors, in which less difference of the chromatographic behaviors might have more similar bioactivities. This indicates that matrine is a potential candidate drug to prevent or cure influenza for human or animal. In conclusion, the present study showed that molecularly imprinted polymers can be used as a non-biological method for screening active components against influenza virus from TCM.     

Chemotaxonomic contribution to the Sideritis species dilemma on the Balkans

Forty-two samples of Sideritis species (Sideritis scardica, Sideritis raeseri, Sideritis syriaca, Sideritis taurica and Sideritis lanata) from the Balkan Peninsula were evaluated for their polyphenolic profiles in order to establish a correlation between the taxonomy, geographical location and nature and content of phenolic compounds.Eight compounds were detected in all analyzed Sideritis samples: 5-caffeoylquinic acid, lavandulifolioside, verbascoside, isoscutellarein 7-O-allosyl(1→2)glucoside, hypolaetin 7-O-[6‴-O-acetyl]-allosyl(1→2)glucoside, isoscutellarein 7-O-[6‴-O-acetyl]-allosyl(1→2)glucoside, 3′-O-methylhypolaetin 7-O-[6‴-O-acetyl]-allosyl(1→2)glucoside and 4′-O-methylhypolaetin 7-O-[6‴-O-acetyl]-allosyl-(1→2)-[6″-O-acetyl]-glucoside). They present from 50 to 80% of total phenolic content in S. scardica, S. raeseri, S. syriaca and S. taurica and up to 90% in S. lanata and the similarity of their polyphenolic profiles implies that they are systematically very closely related.Based on their polyphenolic patterns, very good differentiation between the samples of S. lanata (sect. Hesiodia) and S. scardica, S. syriaca and S. raeseri (sect. Empedoclia) was observed, that is mainly due to the very high content of 5-cafeoylquinic acid and very low amount of phenylethanoid glycosides and flavonoid glycosides.The obtained results demonstrate considerable degree of similarity between S. scardica, S. raeseri and Bulgarian S. syriaca that give contribution to the dilemma that Bulgarian S. syriaca is very similar to Turkish S. taurica and suggest further verification of its taxonomic status.