Isolation and quantitation of ecologically important phloroglucinols and other compounds from Eucalyptus jensenii.

INTRODUCTION: Eucalyptus jensenii has not been explored for its phytoconstituents except for its essential oil although a formylated phloroglucinol compound jensenone has been the focus of several ecological studies. OBJECTIVE: i) To optimise the extraction conditions for preparative scale isolation of jensenone and other secondary metabolites from leaves. (ii) To develop an RP-HPLC method for simultaneous determination of phloroglucinols and other compounds in Eucalyptus leaves. METHODOLOGY: Jensenone and other compounds were isolated from acetone extract using VLC over TLC grade silica. HPLC quantitation of isolated compounds was undertaken on a C18-column using acetonitrile-water (2% formic acid) gradient elution. RESULTS: Extraction conditions for isolation of jensenone were optimised and more than 99% pure jensenone was obtained in a yield of 2.1% from the dried leaves. Ten phloroglucinol compounds, including a new nuclear methylated phloroglucinol named 4-O-demethyl miniatone, and two triterpenoids were also isolated. A RP-HPLC method was developed for simultaneous quantitation of phloroglucinols and other compounds in different extracts of E. jensenii leaves. A total of 19 compounds reported from different species of Eucalyptus was separated by this method. CONCLUSION: The method described for isolation of jensenone is a simple, rapid and low-cost procedure amenable to the preparative scale. A new monomeric phloroglucinol compound was isolated and characterised from the acetone extract of E. jensenii leaves. The HPLC method developed can be applied successfully to different eucalypt matrices for precise and accurate determination of 19 secondary metabolites belonging to different chemical classes.

Terpenoidal constituents of Eucalyptus loxophleba ssp. lissophloia.

CONTEXT: Eucalyptus has been a source of a number of biologically active compounds. The anti-leishmanial activity of terpenoids from Eucalyptus loxophleba (Benth.) ssp. lissophloia (Myrtaceae) has not yet been investigated. OBJECTIVE: Isolation of the terpenoidal constituents for evaluation of in vitro anti-leishmanial activity against the Leishmania donovani (Dd8 strain) promastigotes. MATERIALS AND METHODS: The chloroform-methanol (8:2) extract of dried leaves of Eucalyptus loxophleba was used to isolate terpenoidal constituents employing solvent partitioning, column chromatography and preparative high performance liquid chromatography and characterized from spectral data. The anti-leishmanial activity of the isolated compounds was tested in vitro using an Alamar blue assay against a culture of L. donovani (Dd8 strain) promastigotes. RESULTS: Two new naturally occurring triterpenes, named loxanic acid and 3-acetyl loxanic acid together with four known ursane triterpenoids and one bis-monoterpene glycoside, cuniloside B isolated from the leaves showed anti-leishmanial activity (IC(50) 133 to 235 µM) against the promastigotes of the tested strain. CONCLUSION: The terpenes isolated from the leaves of E. loxophleba showed moderate anti-leishmanial activity.

Phloroglucinol compounds of natural origin: synthetic aspects.

This review covers the synthetic aspects of various naturally occurring phloroglucinols, describing syntheses of 42 compounds and citing 137 references.

Saponins of Agave: Chemistry and bioactivity.

The genus Agave comprises more than 400 species with geographical presence in the tropical and sub-tropical regions of the world. These plants have a rich history of folkloric use and are known for a wide spectrum of applications. Secondary metabolites of diverse chemical classes have been reported from Agave species. Owing to their pharmacological significance, the steroidal saponins of Agave have caught the attention of phytochemists, biologists and drug discovery scientists. The present review describes 141 steroidal saponins and sapogenins and covers the literature published from 1970 to 2015. It is a comprehensive and coherent presentation of the structures, methods of chemical profiling, structure elucidation and biological activities of the saponins and sapogenins reported from Agave. The article provides a perspective of the research on steroidal compounds of Agave.

Cichorium intybus: Traditional Uses, Phytochemistry, Pharmacology, and Toxicology.

The genus Cichorium (Asteraceae) is made up of six species with major geographical presence in Europe and Asia. Cichorium intybus, commonly known as chicory, is well known as a coffee substitute but is also widely used medicinally to treat various ailments ranging from wounds to diabetes. Although this plant has a rich history of use in folklore, many of its constituents have not been explored for their pharmacological potential. Toxicological data on C. intybus is currently limited. This review focuses on the economic and culturally important medicinal uses of C. intybus. Traditional uses, scientific validation, and phytochemical composition are discussed in detail.

Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells.

Berry anthocyanidins (cyanidin, malvidin, peonidin, petunidin and delphinidin) have increasingly been explored for their anticancer effects; however, their combinatorial effects as a mixture, as present in blueberry, bilberry and Indian blackberry ('Jamun') remain untested. In this study, we demonstrate for the first time that the combination of suboptimal concentrations of equimolar anthocyanidins synergistically inhibited growth of two aggressive non-small-cell lung cancer cell lines, with minimal effects on non-tumorigenic cell viability. The induction of cell-cycle arrest, apoptosis and suppression of NSCLC cell invasion and migration were also significantly greater with the mixture than individual anthocyanidins. The superior effects of the combinatorial treatment presumably resulted from its effects on the oncogenic Notch and WNT pathways and their downstream targets (ß-catenin, c-myc, cyclin D1, cyclin B1, pERK, MMP9 and VEGF proteins), enhanced cleavage of the apoptotic mediators Bcl2 and PARP and enhanced inhibition of TNFα-induced NF-kappa B activation. In vivo, both the native mixture of anthocyanidins from bilberry (0.5mg/mouse) and the most potent anthocyanidin, delphinidin (1.5mg/mouse) significantly inhibited the growth of H1299 xenografts in nude miceby ≈60%. Notably, the effective dose of delphinidin in the anthocyanidin mixture was 8-fold lower than delphinidin alone, further emphasizing synergism. Our results thus demonstrate therapeutic potential of berries rich in this mixture of diverse anthocyanidins for non-small-cell lung cancer treatment and to prevent its future recurrence and metastasis.

Quantitative analysis of euglobals in Eucalyptus loxophleba leaves by qNMR.

A simple, rapid, accurate and selective 1H NMR spectroscopic method to detect and quantify euglobals in the leaves of Eucalyptus loxophleba ssp. lissophloia has been developed. The method allows for the estimation of total concentration of diformylphloroglucinol-monoterpene adducts, as well as the quantitation of sabinene- and alpha/beta-phellandrene-adducts, separately. The method was validated for accuracy, precision and linearity using as reference standards 2-ethyl phenol and mixtures of jensenone, a monomeric formylated phloroglucinol, and 2-ethyl phenol.

Formylated phloroglucinols from Eucalyptus loxophleba foliage.

Two new naturally occurring formylated phloroglucinol compounds (FPCs), a dimer, loxophlebal B (10) and a cyclized FPC, loxophlebene (8) together with eight other formylated phloroglucinols (1-7 and 9) were isolated from the chloroform-methanol (8:2) extract of the leaves of Eucalyptus loxophleba ssp. lissophloia. The structures of new compounds were established by comprehensive spectral analysis and by comparison of their NMR data with those of related compounds in the literature. All the isolated compounds were evaluated for anti-leishmanial activity against promastigotes of Leishmania donovani.

Antibacterial sideroxylonals and loxophlebal A from Eucalyptus loxophleba foliage.

Loxophlebal A, a new antibacterial formylated phloroglucinol was isolated from the mother liquor obtained after separation of sideroxylonals from the chloroform-methanol extract of leaves of Eucalyptus loxophleba ssp lissophloia. The structure of loxophlebal A was determined to be 3-desformyl sideroxylonal A by spectroscopic methods including 1D- and 2D-NMR. The stereochemistry of loxophlebal A was determined by chemical correlation with sideroxylonal A. This article also reports an efficient, simple and economic method for large scale isolation of sideroxylonals in a purity of >90% from the leaves of Eucalyptus loxophleba ssp lissophloia.

Phloroglucinol compounds of therapeutic interest: global patent and technology status.

BACKGROUND: Phloroglucinol compounds, both synthetic as well as natural, have shown a vast array of biological activities. There are a wide range of applications of phloroglucinol compounds in pharmaceuticals, cosmetics, textiles, paints and dyeing industries. Although many of the phloroglucinols have shown promising results in various biological assays, very few have reached clinics. OBJECTIVE: To compile the patented information on various therapeutically active phloroglucinol molecules, so that technologies used in isolation and activity assessment of these compounds could be unearthed and the compiled information be utilized for further development of these molecules. METHODS: The European Patent Office database (official website: espacenet.com) was searched with a keyword "phloroglucinol". In addition, patents were searched using names of compounds listed in our previous review. CONCLUSIONS: This class holds potential for development of molecules in various therapeutic areas. There exist a number of patents on preparations that have phloroglucinol compounds as active ingredient(s). Many such preparations have been tested in vitro and/or in vivo for their efficacy and proven to be active and non-toxic. Commercialization of existing technology on phloroglucinol molecules can yield fruitful results.