Chemical constituents and anticholinesterase activity of the essential oil of Algerian Elaeoselinum thapsioides (Desf.) maire.

Elaeoselinum thapsioides (Desf.) Maire (Apiaceae) is an Algerian medicinal plant used in traditional medicine to treat different diseases. The essential oil obtained by hydrodistillation from the aerial parts of Elaeoselinum thapsioides growing wild in Algeria, was analyzed by GC-MS for the first time. Forty-five compounds were detected, accounting for 93.8% of the total oil, which was characterized by a high content of hydrocarbons derivatives of monoterpenes (75.9%). Myrcene (61.0%) was the principal constituent of the essential oil, followed by germacrene D (10.3%), α-pinene (6.5%) and ß-pinene (2.9%). In vitro anticholinesterase activity of the essential oil was investigated by the Ellman method that evidenced a low acetylcholinesterase and butyrylcholinesterase inhibitory effect.[Formula: see text].

Thapsigargin-From Traditional Medicine to Anticancer Drug.

A sesquiterpene lactone, thapsigargin, is a phytochemical found in the roots and fruits of Mediterranean plants from Thapsia L. species that have been used for centuries in folk medicine to treat rheumatic pain, lung diseases, and female infertility. More recently thapsigargin was found to be a potent cytotoxin that induces apoptosis by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump, which is necessary for cellular viability. This biological activity encouraged studies on the use of thapsigargin as a novel antineoplastic agent, which were, however, hampered due to high toxicity of this compound to normal cells. In this review, we summarized the recent knowledge on the biological activity and molecular mechanisms of thapsigargin action and advances in the synthesis of less-toxic thapsigargin derivatives that are being developed as novel anticancer drugs.

Seeds, Leaves and Roots of Thapsia garganica as a Source of New Potent Lipases Inhibitors: In vitro and In silico Studies.

BACKGROUND AND OBJECTIVE: Lipase inhibitors have gained great interest because they could help in the therapy of many diseases, however, unfortunately, only a few drugs are currently available on the market. Therefore, the aim of this work was to evaluate for the first time the lipase inhibition effect of Thapsia garganica extracts from seeds, leaves and roots. METHODS: Polyphenols and flavonoids contents were determined using spectrophotometric method. Inhibitory activity of ethyl acetate extracts from seeds, leaves and roots of T. garganica against Candida rugosa lipase was determined. To uncover the active constituents responsible for this anti-lipase activity, further investigations were performed by employing theoretical docking simulations, using AutoDock Vina program to discuss the nature of interactions and the inhibition mechanism by major bioactive compounds synthesized by this plant. RESULTS: Seeds, leaves and roots extracts of T. garganica showed appreciable contents of polyphenols and flavonoids which is most in seeds extract with 2.90±0.02mg GAE/gdw and 1.53±0.05mg QE/gdw, respectively. Hence, their inhibitory activities against Candida rugosa lipase were determined as IC50 of 1.19mg/ml, 1.96mg/ml and 1.87mg/ml, respectively. Docking simulations have shown that nortribolid and tribolid are best inhibitors for both lipases (Candida rugosa and human pancreatic lipases). CONCLUSION: Testing the anti-lipase activity of the ethyl acetate extracts of T. garganica revealed a potent lipase inhibition activity, which suggests the use of these molecules as anti-obesity drugs.

Anti-scorpion venom activity of Thapsia garganica methanolic extract: Histopathological and biochemical evidences.

ETHNOPHARMACOLOGICAL RELEVANCE: Thapsia garganica, is a herbal medicine traditionally used as diuretic, emetic and purgative. It is also used as anti-scorpion venom in Morocco; however, its protective effects against scorpion venom remain elusive. AIM OF THE STUDY: The present study was undertaken to evaluate anti-venom activity of T. garganica in vivo through histological and biochemical studies. MATERIALS AND METHODS: Methanolic leaves extract of T. garganica was evaluated for anti-venom activity against buthus. occitanus under in vivo conditions. Histopathological and biochemical changes in envenomed and treated mice were also examined. Phytochemical screening was conducted to estimate the major constituents whereas DPPH, ß -Carotene-linoleic acid and reducing power assays were performed to evaluate the anti-oxidant activity of T. garganica extract. RESULTS: Methanolic leaves extract of T. garganica (2g/kg) increased the survival time (> 18h) of mice injected with lethal doses of B. occitanus venom, with remarkable recovery of histology damage. Furthermore T. garganica induced a significant decreased of biochemical markers of kidney, liver and heart function. Phytochemistry screening revealed the presence of phenolic compounds, flavonoids, tannins and steroids/terpenoids, which might explain the bioactivity of the extract. It was also shown that the extract has an exceptionally high antioxidant activity compared to well-known antioxidants used as standards. CONCLUSION: The present study provides strong evidence that support the use of T. garganica as anti-scorpion venom in traditional medicine in Morocco. However, additional studies are required to isolate and identify the metabolites responsible for the activity.

Phytochemical composition and antioxidant activity of medicinal plants collected from the Tunisian flora.

Polyphenols, flavonoids and condensed tannins contents, as well as the antioxidant activity of the ethanolic and aqueous extracts obtained from aerial parts of 10 wild Tunisian plants, have been determined. Extracts showed appreciable levels of polyphenols and flavonoids, which reached 215.16 mg GAE g-1 DW in Lavandula stoechas ethanolic extract, and 49.12 mg RE g-1 DW in Thapsia garganica aqueous extract. The majority of tested extracts exhibited low total condensed tannins content, except for Rhus tripartitum and Periploca laevigata. The antioxidant activity tests showed great activity, especially for R. tripartitum and Lavandula multifida (IC50 = 5.16 and 5.1 µg mL-1, respectively). Canonical Correspondence Analysis revealed clear groupings of species according to the solvent used.

Chemodiversity of volatile oils in Thapsia garganica L. (Apiaceae).

The chemical composition of the volatile oils obtained from the roots, leaves, flowers, and stems of Thapsia garganica of Tunisian origin was investigated by GC-FID and GC/MS analyses. Sesquiterpene hydrocarbons and oxygenated monoterpenes were predominant in the oils of all plant parts. Bicyclogermacrene (21.59-35.09%) was the main component in the former compound class, whereas geranial (3.31-14.84%) and linalool (0.81-10.9%) were the most prominent ones in the latter compound class. Principal-component (PCA) and hierarchical-cluster (HCA) analyses revealed some common constituents, but also significant variability amongst the oils of the different plant parts. This organ-specific oil composition was discussed in relation to their biological and ecological functions. For the evaluation of the intraspecific chemical variability in T. garganica, the composition of the flower volatile oils from four wild populations was investigated. Bicyclogermacrene, linalool, and geranial were predominant in the oils of three populations, whereas epicubenol, ß-sesquiphellandrene, and cadina-1,4-diene were the most prominent components of the oil of one population. PCA and HCA allowed the separation of the flower oils into three distinct groups, however, no relationship was found between the volatile-oil composition and the geographical distribution and pedoclimatic conditions of the studied populations.

Nero and the last stalk of Silphion: collecting extinct nature in early modern Europe.

Many studies of early modern natural history focus upon observational, empirical techniques. Early moderns also contended with entities which could no longer be observed because they no longer existed. Although it is often assumed that extinction only emerged as a concept in the eighteenth century, the concept of natural loss appeared, often unproblematically, in areas outside natural philosophy. A survey of discussions of the extinct plant silphion across Europe in the sixteenth and seventeenth centuries shows that the possibility of natural loss was well aired. Paper technologies for collecting extinct nature ran parallel to investigations of newly found nature, and thus can place the latter in a new light. Although ideas of natural mutability often drew on ideas of historical or political change rather than philosophical concepts of natural constancy, techniques developed for extinct nature, such as the list of lost things, remained influential for the research agendas of naturalists.

Inhibition of thrombin-induced Ca²âº influx in platelets by R59949, an inhibitor of diacylglycerol kinase.

OBJECTIVES: The aim of this study was to determine whether diacylglycerol kinase (DGK) is involved in transplasmalemmal Ca²âº influx of platelets. METHODS: Effects of R59949, an inhibitor of diacylglycerol kinase, on intracellular Ca²âº concentration ([Ca²âº](i) ) and mRNA expression of DGK isozymes were investigated using washed human platelet suspensions. KEY FINDINGS: Thrombin-induced increase in [Ca²âº](i) was significantly inhibited by pretreatment of platelets with R59949, while thapsigargin-induced increase in [Ca²âº](i) was comparable in platelets with and without R59949 pretreatment. Thapsigargin-induced increase in [Ca²âº](i) was markedly attenuated in the presence of SKF-96365. In the presence of SKF-96365, thrombin-induced increase in [Ca²âº](i) was significantly attenuated, and additional treatment with R59949 caused a further decrease in [Ca²âº](i) . Pretreatment of platelets with 1-butanol significantly attenuated thrombin-induced increase in [Ca²âº](i) , while thrombin-induced increase in [Ca²âº](i) was augmented in the presence of propranolol. mRNA expression of DGK-α and DGK-γ, which are known to be inhibited by R59949, in platelets was confirmed by RT-PCR analysis. CONCLUSIONS: R59949 inhibited a store-depletion-insensitive component of transplasmalemmal Ca²âº entry induced by thrombin, while store-operated Ca²âº entry was not affected by R59949. The results of this study suggest that phosphatidic acid is involved in thrombin-induced Ca²âº influx of platelets.

A comparison of headspace solid-phase microextraction and classic hydrodistillation for the identification of volatile constituents from Thapsia spp. provides insights into guaianolide biosynthesis in Apiaceae.

INTRODUCTION: Thapsia spp. (Apiaceae) are the major natural source of polyoxygenated guaianolide sesquiterpene lactones known as thapsigargins, which induce apoptosis in mammalian cells via a high affinity inhibition of the sarco/endoplasmic reticulum Ca(2+) ATPase. The mechanism of biosynthesis of thapsigargins has not been elucidated, and probable biochemical precursors such as hydrocarbon or oxygenated sesquiterpenes have not been identified in previous phytochemical analyses of essential oils from this genus. OBJECTIVE: To investigate the utility of solid phase micro-extraction (SPME), when compared with classical essential oil distillates, for identifying potential precursors of guaianolide sesquiterpene lactones from Thapsia garganica L. and Thapsia villosa L. type II. METHODOLOGY: A systematic description of the volatile components of roots, flowers, stems and fruits of T. villosa and of root, flower and fruits of T. garganica was constructed via GC-MS analyses of SPME-adsorbed compounds and of essential oils obtained through hydrodistillation of the same tissues. RESULTS: The sesquiterpenoids δ-cadinene, α- and δ-guaiene, elemol and guaiols were found to be major volatile constituents of the roots of T. garganica and T. villosa trapped using SPME. In contrast, these sesquiterpenoids were not detected or were at negligible levels in essential oils, where sesquiterpenoids are potentially converted to azulenes during hydrodistillation. CONCLUSION: The new data reported in this study demonstrates that SPME is a valuable tool for the identification of volatile sesquiterpenes when compared with analysis of essential oils, and we postulate that guaiene is the likely precursor of guaianolide sesquiterpenes from Thapsia.

A phenylpropanoid, a slovenolide, two sulphur-containing germacranes and Ca2+-ATPase inhibitors from Thapsia villosa.

A phenylpropanoid 1, a slovenolide 2, and two germacranes bearing a methylthiopropenoate moiety, 3 and 4, along with twenty known metabolites have been isolated from the roots of Thapsia villosa var. villosa L. The structures of two known phenylpropanoids 5 and 6 have been corrected. Compounds 7 and 8 showed activity as potential inhibitors of the sarco- and endoplasmic Ca(2+)-dependent ATPases (SERCA) pump. Compounds 9, 10 and 11 increased significantly the cytoplasmic free calcium concentration ([Ca(2+)](c)) in human platelets in a concentration-dependent manner.

Progress toward the synthesis of the basiliolides and transtaganolides: an intramolecular pyrone Diels-Alder entry into a novel class of natural products.

Efforts directed toward the synthesis of a basiliolide/transtaganolide model system are disclosed. A highly endo-selective intramolecular pyrone Diels-Alder (IMPDA) cycloaddition rapidly constructs the tricyclic core of the basiliolides and transtaganolides.

Cytotoxic phenylpropanoids and an additional thapsigargin analogue isolated from Thapsia garganica.

Four phenylpropanoids and a thapsigargin analogue have been isolated from the fruits of Thapsia garganica. A spectroscopic method for elucidating the relative stereochemistry at the two pairs of stereogenic centers in the phenylpropanoids has been developed. The phenylpropanoids were found to be potent cytotoxins.

Sesquiterpenes from Thapsia nitida var. meridionalis and Thapsia nitida var. nitida.

Nine new eudesmanolides (1-9), two new guaianolides (12 and 13), and a new germacrane (10), along with a previously reported guaianolide (11), have been isolated from the roots of Thapsia nitida var. meridionalis. Thapsia nitida var. nitida also afforded compound 13 along with a new guaianolide (14). The structure of 13 was confirmed by X-ray crystallographic analysis. Compounds 1, 2, and 11-14 have been tested as potential inhibitors of the sarco- and endoplasmic Ca2+-dependent ATPases (SERCA) pump. None of them showed significant activities.