Natural products afford a window of opportunity to study important biology. If the natural product is used or abused by human beings, finding its biological target(s) is all the more significant. Hot pepper is eaten on a daily basis by an estimated one-quarter of the world’s population and

Vanilloid (Capsaicin) Receptors and Mechanisms

Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the composite of environmental and differentiation-dependent imprinting. Phorbol-12-myristate-13-acetate (PMA) and 1,25-dihydroxyvitamin D3 (VD3) are stimuli commonly used to induce macrophage differentiation in monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear. We have compared the phenotype of the promonocytic THP-1 cell line after various protocols of differentiation utilising VD3 and PMA in comparison to primary human monocytes or monocyte-derived macrophages (MDM). Both stimuli induced changes in cell morphology indicative of differentiation but neither showed differentiation comparable to MDM. In contrast, PMA treatment followed by 5 days resting in culture without PMA (PMAr) increased cytoplasmic to nuclear ratio, increased mitochondrial and lysosomal numbers and altered differentiation-dependent cell surface markers in a pattern similar to MDM. Moreover, PMAr cells showed relative resistance to apoptotic stimuli and maintained levels of the differentiation-dependent anti-apoptotic protein Mcl-1 similar to MDM. PMAr cells retained a high phagocytic capacity for latex beads, and expressed a cytokine profile that resembled MDM in response to TLR ligands, in particular with marked TLR2 responses. Moreover, both MDM and PMAr retained marked plasticity to stimulus-directed polarization. These findings suggest a modified PMA differentiation protocol can enhance macrophage differentiation of THP-1 cells and identify increased numbers of mitochondria and lysosomes, resistance to apoptosis and the potency of TLR2 responses as important discriminators of the level of macrophage differentiation for transformed cells.

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The Identification of Markers of Macrophage Differentiation in PMA-Stimulated THP-1 Cells and Monocyte-Derived Macrophages

Natural products to drugs: natural product derived compounds in clinical trials

An evaluation of multipurpose oil seed crop for industrial uses (Jatropha curcas L.): A review

Exploitation of the tropical oil seed plant Jatropha curcas L.

Irritant phorbol derivatives from four Jatropha species

Structure determination of the new tetracyclic diterpene ingenol-triacetate with triple product methods

From leaves of E. OPPOSITIFOLIA the irritant EXCOECARIA factor O (1) was isolated. Its structure 1 was shown to be identical with that of a factor obtained by transesterification of the cryptic EXCOECARIA factor group O (')(z) from the latex of the plant. From the non-irritant ethyl acetate fractions of the latices of E. AGALLOCHA, E. OPPOSITIFOLIA and E. BICOLOR, three TLC-homogenous non-irritant mixtures A (')(z), O (')(z) and B (')(z) were isolated and shown to represent non-separable cryptic EXCOECARIA factor groups containing 9,13,14-orthoesters of 5beta-hydroxyresiniferonol esterified in 20-position. The mixtures may be activated by mild treatment with sodium methoxide to generate mixtures of highly irritant factor groups A (z), O (z) and B (z) together with mixtures of aliphatic acid methylesters. The former may be separated partially by reversed phase TLC and yielded EXCOECARIA factors O (1), O (2), A (3), B (3) and B (4) together with residual non-separable factor groups. The structures 1-5 of the individual daphnane type irritant EXCOECARIA factors were elucidated by spectroscopic means. Their irritant activities were determined quantitatively on the mouse ear. The mixtures of methyl esters of aliphatic acids were analyzed by GC. Thus the complete structures of the cryptic factor groups from latex were deduced.

Investigations of medicinal plants of euphorbiaceae and thymelaeaceae occurring and used in Thailand; II. Cryptic irritants of the diterpene ester type from three Excoecaria species

In the extremely skin irritant and caustic latex of Excoecaria agallocha the major part of the polyfunctional diterpene esters (DTE) (group I) are aliphatic polyunsaturated 9,13,14-orthoesters of the daphnane-type parent alcohol 5 beta-hydroxyresiniferonol-6 alpha, 7 alpha-epoxide, esterified simultaneously in their 20-positions with aliphatic saturated homologous n-carboxylic acids (even numbered, C22-C30). The minor part of DTE is composed of analogous structures of 5 beta, 12 beta-dihydroxyresiniferonol-6 alpha, 7 alpha-epoxide (group II) and of aliphatic 13-polyunsaturated, 20-saturated diesters of the tigliane-type parent alcohol 12-deoxyphorbol (group III). All three groups of DTE exhibit practically no irritant activity on the mouse ear. By alkaline transesterification of groups I-III, the corresponding highly irritant multicomponent mixtures of Excoecaria factors A (OH-20 deacylated) are released. They comprise a mixture of the known Excoecaria factors A1/A2/A3 and three mixtures of hitherto unknown Excoecaria factors A4/A5, A6/A7 and A8/A9. The groups I-III are typical structures of "cryptic irritants". By an alternative, extremely mild separation procedure the highly irritant mixture A1/A2/A3 was obtained directly. It represents the "free" Excoecaria factors, the natural constituents of the latex responsible for its bioactivity.

Cryptic and Free Skin Irritants of the Daphnane and Tigliane Types in Latex of Excoecaria agallocha1

Investigations of E. antiquorum, E. helioscopia, E. palustris, E. peplus and E. quadrialata for irritant and tumor promoting constituents afforded several new ingenane type diterpene esters derived from the parent alcohols ingenol and 20-deoxyingenol and from the hitherto unknown 20- deoxy-16-hydroxyingenol and 20-deoxy-13.16-dihydroxyingenol. The irritant activities of the natural compounds are reported together with some aspects on structure activity relationships

H. J. Opferkuch

Papers

Irritant phorbol derivatives from four Jatropha species

Structure determination of the new tetracyclic diterpene ingenol-triacetate with triple product methods

Investigations of medicinal plants of euphorbiaceae and thymelaeaceae occurring and used in Thailand; II. Cryptic irritants of the diterpene ester type from three Excoecaria species

Cryptic and Free Skin Irritants of the Daphnane and Tigliane Types in Latex of Excoecaria agallocha1

On the Active Principles of the Euphorbiaceae, IXa Ingenane Type Diterpene Esters from Five Euphorbia Species