Inspired by vitamin A for anti-ageing: Searching for plant-derived functional retinoid analogues.

Background: Cosmetic treatments that inspire one's appearance to resemble their younger portrait often utilize ingredients that confer acute effects, particularly hydration by creating hydrophobic barriers or transient elevation of barrier water content. But superior therapies successfully promote morphogenesis of the dermal-epidermal junction, inspiring extracellular matrix (ECM) formation. This can be achieved by agonism of the very well-known retinoid nuclear receptors using the endogenous ligand all-trans retinoic acid (tRA), tRA precursors or plant-based functional analogues, with reduced side effects. Aims Materials and Methods: While there are already many promising cosmetic ingredients available from the world's flora, higher potency is favoured, so increasing known candidates is a worth undertaking. Functional analogues of retinoic acid can be identified by culturing fibroblasts with lipophilic candidates from the plant kingdom and assessing gene-arrays. Modern approaches to validating these findings include the coculturing of fibroblasts with keratinocytes as a measure to predict the potential effects of crosstalk. Results and Discussion: In this regard, the most promising plant-derived candidates are of terpene or meroterpene origin, including derivatives of squalene and phytol. Surprisingly pimaric or abietic acids and labdane diterpenes are also noteworthy agonists of the retinoic acid receptor, stimulating collagen expression in dermal fibroblasts. Conclusion: There are numerous derivatives of these terpenes available from the world's flora and research conducted thus far encourages further screening of these chemical candidates.

Synthesis of CDE molecular fragments related to sendanin mediated by titanocene(III).

A practical, brief, and diastereoselective synthesis of limonoid CDE fragments from a readily available starting material is described. The key step was the titanocene(III)-promoted cyclization of unsaturated epoxylactones, readily prepared from α-cyclocitral. In this way, we confirm the viability of our procedure for the synthesis of a limonoid model with different functionalization patterns. We also report the antifeedant activity of epoxylactones 18 and 19, which show significant antifeedant activity against Spodoptera littoralis and Spodoptera frugiperda, two insect species with different feeding ecologies.

Antibacterial compounds from the mushroom Ganoderma colossum from Nigeria.

Three colossolactones (colossolactone E, colossolactone B and 23-hydroxycolossolactone E) were isolated and characterized from an n-hexane:dichloromethane (2:7) extract of Ganoderma colossum using chromatographic techniques. The antimicrobial activity of the three compounds was then tested against Gram-positive and Gram-negative bacteria. The activity was evaluated by the thin-layer chromatography agar overlay method. The results showed that colossolactone E and 23-hydroxycolossolactone E were active against Bacillus subtilis and Pseudomonas syringae. Colossolactone B was not active against the bacteria. Their structures were elucidated by spectroscopic methods. Potency of the compounds against bacteria tested supports the use of this mushroom in therapeutic medicine.

Therapeutic uses of Aloe L. (Asphodelaceae) in southern Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: The African-Arabian succulent genus Aloe L. (Aloaceae/Asphodelaceae) is represented by approximately 120 infrageneric taxa in southern Africa, including A. ferox Mill., a species long used in commercial natural products. AIMS OF THE STUDY: To assess the documented ethnobotanical knowledge and biocultural value of utility in the genus in southern Africa. MATERIALS AND METHODS: A survey of over 350 multidisciplinary publications was undertaken. RESULTS: Local uses for medicine and wellbeing were identified for over half the species of Aloe occurring in the Flora of Southern Africa region. The most frequently cited medicinal uses were the treatment of infections and internal parasites, digestive ailments and injuries. Numerous species were recorded for their social uses, notably as ingredients in tobacco snuff. CONCLUSION: The exceptional infrageneric diversity of Aloe, and extensive therapeutic uses in southern Africa, indicate its cultural importance in the subcontinent. These factors highlight the need for the conservation of the species as well as their potential as a source of natural products.

Antimicrobial activity of some Ganoderma species from Nigeria.

The crude n-hexane:diethyl ether, chloroform:acetone and methanol extracts of four species of Ganoderma (Ganoderma colossum (Fr.) C. F. Baker, G. resinaceum Boud., G. lucidum (cf.) (Curtis) P. Karst. and G. boninense (cf.) Pat.), from Nigeria, were tested for antimicrobial activity. The three solvent extracts of all the species of Ganoderma were active against Pseudomonas syringae and Bacillus subtilis, whereas none of the extracts were active against Cladosporium herbarum. Preliminary thin layer chromatography chemical tests on these extracts of Ganoderma showed that they contained compounds that stained blue-violet and blue or green when sprayed with anisaldehyde-sulphuric acid or Dragendorff, respectively. The profile of compounds in the extracts showed some variation among the four species.

Two novel assays for the detection of haemin-binding properties of antimalarials evaluated with compounds isolated from medicinal plants.

Forty-two compounds isolated from nine plants used within South America for the treatment of malaria were tested for haemin binding using two novel, rapid screening methods. The data obtained were analysed with respect to IC(50) values for in vitro toxicity to Plasmodium falciparum trophozoites. One method, a multiwell assay based on the inhibition of the interaction of haemin with glutathione (GSH), is sensitive in the 10 microM range, takes c. 1 h and is suitable for either a high throughput screen or rapid assay during natural product isolation. Of 19 compounds showing antiplasmodial activity (IC(50) < 40 microM), 16 (84%) showed >40% inhibition of GSH-haemin reaction. The sensitivity and specificity of the assay were 0.85 and 0.82, respectively. The positive predictive value was 0.81 and the negative predictive value 0.86. A more sensitive assay (0.1 microM range) is based on the reversal by haemin-binding compounds of the haemin inhibition of the L-dopachrome-methyl ester tautomerase activity of human macrophage migration inhibitory factor. This assay gives a better idea of the affinity of interaction and uses very small amounts of test compound. The log[RI(50)] of eight of the compounds that tested positive in the above assays together with those of quinine and chloroquine showed a positive correlation with log[antiplasmodial IC(50)] for strain T9-96 (r = 0.824) and strain K1 (r = 0.904). Several of the antimalarial compounds that bind haemin are isoquinolines, a class not shown previously to interact with haemin.

Toxicity and behavioural effects of diet-borne alkaloids on larvae of the black blowfly, Phormia regina.

Larvae of the black blowfly, Phormia regina (Meigen) (Diptera: Calliphoridae) were exposed for 24 h to artificial diets that contained one of the following alkaloids: arecoline, caffeine, nicotine, quinine, sparteine or strychnine at either 1000 or 100 p.p.m. Each of the alkaloids caused reduced weight gain, relative to a control population in a no-choice bioassay and, with the exception of quinine, all alkaloids caused reduced larval weights in a choice bioassay. Larvae were unable to move away from diets containing arecoline (1000 and 100 p.p.m) and congregated away from diets containing 1000 p.p.m. quinine. Arecoline (1000 p.p.m) and both concentrations of nicotine caused significant mortality of larvae. Over a longer period (120 h), 10 and 1 p.p.m. nicotine resulted in significant numbers of larvae congregating away from a treated diet. Ten p.p.m. nicotine caused reduced weight gain over 120 h, although larvae provided with a choice were less affected. Exposure of larvae to dried residues of nicotine for 2 h did not affect subsequent development.

Can larvae of the pod-borer, Helicoverpa armigera (Lepidoptera: Noctuidae), select between wild and cultivated pigeonpea Cajanus sp. (Fabaceae)?

Experiments were conducted to observe the feeding and food selection-behaviour of different instars of the pod-borer Helicoverpa armigera (Hübner) in response to choices between the cultivated and a wild species of Cajanus. First and second instars fed upon a cultivated variety of Cajanus cajan in preference to a wild species, C. scarabaeoides and on flowers of C. cajan, rather than pods or leaves of C. cajan. First and second instars preferred pods of C. scarabaeoides with trichomes removed to pods with trichomes present. All instars fed upon pods of C. cajan rather than those of C. scarabaeoides. Solvent extraction of the pod surfaces affected the feeding of larvae, in some instances. They preferred the unextracted pods of C. cajan; the extracted pod of C. scarabaeoides (first and second instars) or the unextracted pod of C. scarabaeoides (fourth and fifth instars). Glass-fibre disc bioassays showed that the methanol, hexane and water extracts from the pod-surface of C. cajan stimulated the feeding of fifth instars. The experiments have shown that characteristics of C. cajan, such as either the compounds present or the type and distribution of trichomes on the plant surfaces, can determine the susceptibility of C. cajan to pod-borer larvae.

In vitro studies on the immunomodulatory effects of extracts of Osbeckia aspera.

Ayruvedic medical practitioners in Sri Lanka use aqueous extracts of the mature leaves of Osbeckia aspera to treat liver disease. The extract has been shown to have hepatoprotective effects in vitro and in vivo, and to have inhibitory effects on the complement system and on in vitro phagocytosis by polymorphonuclear cells. The aim of this study was to investigate the effect of an aqueous extract of Osbeckia on lymphocyte proliferation stimulated by mitogens and antigen. In control peripheral blood mononuclear cells (PBMC), high concentrations of the Osbeckia extract were inhibitory to proliferation stimulated by phytohaemagglutinin (PHA) and tuberculin purified protein derivative (PPD). On stimulation by phorbol myristate acetate and ionomycin (PMA+I) the extract showed stimulation of proliferation at low concentrations (<10 microg/ml) with inhibition at higher concentrations. A similar inhibitory pattern on mitogen/antigen stimulation was seen with PBMC from patients with chronic hepatitis C virus (HCV) infection. These results suggest that the inhibitory agent(s) in the aqueous extract of Osbeckia may have an effect on antigen-presenting cell function. The combined hepatoprotective and immunosuppressive effects of the extract are more likely to be beneficial in acute hepatitis rather than chronic hepatitis viral infection.

Semisynthetic derivatives of ent-kauranes and their antifeedant activity.

Chemical modification of functional groups on linearol yielded several ent-kaurane derivatives. These compounds were tested for their antifeedant activity against larvae of Spodoptera littoralis. Although linearol did not influence the feeding behaviour of larvae, some of its derivatives showed significant antifeedant activity.

Insect antifeedant activity of three new tetranortriterpenoids from Trichilia pallida.

Three new tetranortriterpenoids, methyl 6-hydroxy-11 beta-acetoxy-12 alpha-(2-methylpropanoyloxy)-3,7-dioxo-14 beta,15 beta-epoxy-1,5-meliacadien-29-oate (3), methyl 6,11 beta-dihydroxy-12 alpha-(2-methylpropanoyloxy)-3,7-dioxo-14 beta,15 beta-epoxy-1,5-meliacadien-29-oate (4), and methyl 6-hydroxy-11 beta-acetoxy-12 alpha-(2-methylbutanoyloxy)-3,7-dioxo-14 beta,15 beta-epoxy-1,5-meliacadien-29-oate (5), have been isolated from the roots of Trichilia pallida. The related compounds hirtin (1) and deacetylhirtin (2) were also obtained. Compound 4 had the greatest antifeedant activity of 1-5 when tested against larvae of four species of Lepidoptera.

Effects of isoflavonoids from Cicer on larvae of Heliocoverpa armigera.

Four recently identified isoflavonoids, isolated from wild relatives of chickpea, Cicer arietinum, were shown to deter larval feeding by Heliocoverpa armigera at 100 ppm, judaicin and maackiain retained their antifeedant activity at 50 ppm and 10 ppm, respectively. The isoflavonoids were tested in combinations and with chlorogenic acid; the combinations containing judaicin and maackiain were most active, and chlorogenic acid enhanced the antifeedant activity of all four isoflavonoids. H. armigera was the only one of four noctuids to be deterred by all four isoflavonoids. Spodoptera littoralis was deterred by judaicin alone and S. frugiperda by maackiain alone. Heliothis virescens and S. exigua were not deterred from feeding by any of the isoflavonoids. When incorporated into a diet, isoflavonoids decreased the weight gain of early stadia larvae of H. armigera more than they did later stadia, and maackiain and judaicin were most potent. We conclude that the isoflavonoids. especially maackiain and judaicin, could play a role in decreasing the susceptibility of Cicer to attack by H. armigera.

Antifeedant constituents from Fagara macrophylla.

Analysis of the polar fractions of an EtOH extract obtained from the bark of the African medicinal plant Fagara macrophylla led to the isolation and identification of the alkaloids oblongine (6), tembetarine (7) and magnoflorine (8) and the flavonoid hesperidin (9). These compounds, together with other metabolites (1--5) previously isolated from F. macrophylla, were tested for antifeedant activity in a binary-choice bioassay. The acridone alkaloid xanthoxoline (4) was found to have a potent antifeedant activity against larvae of both Spodoptera frugiperda and S. littoralis. 1-Hydroxy-3-methoxy-N-methyl-acridone (2), arborinine (3), tembetarine (7) and magnoflorine (8) were antifeedant against S. frugiperda.

Importance of flavonoids in insect--plant interactions: feeding and oviposition.

Jeffrey Harborne and colleagues have been responsible for collating the majority of data on the role of flavonoids in insect plant interactions. This article examines some of this information and assesses our knowledge about the role flavonoids play in insect feeding and oviposition behaviour. It is clear that insects can discriminate among flavonoids and that these compounds can modulate the feeding and oviposition behaviour of insects, but further work is required to understand the neural mechanisms associated with these behavioural responses. Despite the wealth of data about the diversity of flavonoids in plants, very few of these compounds have been tested against insects and their role in the evolution of host range in insect--plant interactions has yet to be determined.

Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells.

Rice is a staple diet in Asia, where the incidence of breast and colon cancer is markedly below that in the Western world. We investigated potential colon and breast tumor-suppressive properties of rice, testing the hypothesis that rice contains phenols that interfere with the proliferation or colony-forming ability of breast or colon cells. Brown rice, its white milled counterpart, and bran from brown rice were boiled and extracted with ethyl acetate. The extracts were analyzed by high pressure liquid chromatography-mass spectrometry. Eight phenols, protocatechuic acid, p-coumaric acid, caffeic acid, ferulic acid, sinapic acid, vanillic acid, methoxycinnamic acid, and tricin, were identified in the extracts of bran and intact brown rice. These extracts were separated into nine fractions by column chromatography. The effect of bran extract and its fractions at 100 microg/ml on cell viability and colony-forming ability of human-derived breast and colon cell lines was assessed. Bran extract decreased numbers of viable MDA MB 468 and HBL 100 breast cells and colon-derived SW 480 and human colonic epithelial cells as judged by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 -sulfophenyl)-2H-tetrazolium assay. It also reduced colony formation of SW 480 colon and MDA MB 468 breast cells. Of the eight phenols identified in the brown rice bran, when applied at 50 microM, caffeic acid decreased numbers of all cell types except HBL 100. Tricin, ferulic acid, and methoxycinnamic acid interfered with cell viability in one or more cell lines. Tricin (50 microM) and the other phenols (200 microM) inhibited colony formation of SW 480 cells. Clonogenicity of MDA MB 468 cells was inhibited by caffeic acid, ferulic acid, and tricin (50 microM). Tricin was the most potent anticlonogenic of the compounds with IC50s of 16 microM in the SW 480 colon cells and 0.6 microM in the MDA MB 468 breast cells. The results suggest that: (a) brown rice and bran contain compounds with putative cancer chemopreventive properties; (b) certain phenols contained in brown rice bran, e.g., tricin, may be associated with this activity; and (c) these phenols are present at much lower levels in white than in brown rice. Thus, the consumption of rice bran or brown rice instead of milled white rice may be advantageous with respect to cancer prevention.

Responses of Spodoptera littoralis larvae to Tunisian plant extracts and to neo-clerodane diterpenoids isolated from Ajuga pseudoiva leaves.

Thirteen plants growing in Tunisia were tested against Spodoptera littoralis larvae. From the acetone extract of Ajuga pseudoiva leaves, showing interesting antifeedant activity, three new (1-3) and two known (4-5) active clerodane diterpenoids were isolated following a bioassay-guided chromatography.

Isolation, characterization, and biological activity of naphthoquinones from Calceolaria andina L.

Two compounds recognized as responsible for the insecticidal activity of extracts of Calceolaria andina L. (Scrophulariaceae) have been isolated and characterized as 2-(1, 1-dimethylprop-2-enyl)-3-hydroxy-1,4-naphthoquinone and the corresponding acetate, 2-acetoxy-3-(1,1-dimethylprop-2-enyl)-1, 4-naphthoquinone. Their activities against 29 pest species and 9 beneficial species of arthropod from a total of 11 orders have been determined. Activities against homopteran and acarine species are of the same order as those of established pesticides, and, significantly, no cross-resistance is observed for strains resistant to established classes of insecticide. Mammalian toxicities are low.