Highlighting the Phototherapeutical Potential of Fungal Pigments in Various Fruiting Body Extracts with Informed Feature-Based Molecular Networking.

Fungal pigments are characterized by a diverse set of chemical backbones, some of which present photosensitizer-like structures. From the genus Cortinarius, for example, several biologically active photosensitizers have been identified leading to the hypothesis that photoactivity might be a more general phenomenon in the kingdom Fungi. This paper aims at testing the hypothesis. Forty-eight fruiting body-forming species producing pigments from all four major biosynthetic pathways (i.e., shikimate-chorismate, acetate-malonate, mevalonate, and nitrogen heterocycles) were selected and submitted to a workflow combining in vitro chemical and biological experiments with state-of-the-art metabolomics. Fungal extracts were profiled by high-resolution mass spectrometry and subsequently explored by spectral organization through feature-based molecular networking (FBMN), including advanced metabolite dereplication techniques. Additionally, the photochemical properties (i.e., light-dependent production of singlet oxygen), the phenolic content, and the (photo)cytotoxic activity of the extracts were studied. Different levels of photoactivity were found in species from all four metabolic groups, indicating that light-dependent effects are common among fungal pigments. In particular, extracts containing pigments from the acetate-malonate pathway, e.g., extracts from Bulgaria inquinans, Daldinia concentrica, and Cortinarius spp., were not only efficient producers of singlet oxygen but also exhibited photocytotoxicity against three different cancer cell lines. This study explores the distribution of photobiological traits in fruiting body forming fungi and highlights new sources for phototherapeutics.

In vitro evaluation of the effects of methanolic plant extracts on the embryonation rate of Ascaridia galli eggs.

The present study aims to find efficient alternatives to synthetic anthelmintics among ethno-veterinary herbs. Ascaridia galli eggs isolated from the worm uterus were exposed in vitro to methanolic extracts (ME) of nine plant species such as Achillea millefolium (AM), Artemisia absinthium (AA), Artemisia vulgaris (AV), Cicerbita alpina (CA), Cichorium intybus (CI), Inula helenium (IH), Origanum vulgare (OV), Tanacetum vulgare (TV), Tanacetum parthenium (TP). Flubendazole (FL), 0.5% formalin with dimethylsulfoxide and Petri dishes without the addition of reagents were used as positive, negative and untreated control respectively. The effects of the different ME at concentrations 0.500, 0.325, 0.200 mg/ml were assessed on the embryonic development (ED) of the eggs in duplicate. Logit analysis was used to calculate EC50 values. A generalized linear mixed model, having plant species and concentration as fixed effect and day as repeated measure, was used to determine differences in ED. Estimated EC50 was the lowest for FL at 0.11 mg/ml. CA and TV followed with 0.27 mg/ml and 0.32 mg/ml. ED for FL was significantly lower (25%) than that of CA (47%). The analysis showed 0.5 mg/ml of the ME of CA and TV significantly affected the ED at 35% and 42% inhibitions respectively. The ED for all ME showed similar pattern i.e., relatively higher efficacy in the first experimental week compared to the rest of the experimental period. The effect from all multicomponent extracts is time and dose dependent. The plants have promising results in inhibiting ED, contributing to the identification of alternative anthelmintic treatments.

A convenient separation strategy for fungal anthraquinones by centrifugal partition chromatography.

As recently shown, some fungal pigments exhibit significant photoactivity turning them into promising agents for the photodynamic treatment of microbial infections or malignant diseases. In the present study, a separation strategy for fungal anthraquinones was developed based on centrifugal partition chromatography. A suitable method was explored employing a methanolic extract of the fruiting bodies of Cortinarius sanguineus (Agaricales, Basidiomycota). An excellent fractionation was achieved using a biphasic solvent system comprising chloroform/ethyl acetate/methanol/water/acetic acid (3:1:3:2:1, v/v/v/v/v) operating in ascending mode. Experiments on an analytical scale with extracts of closely related Cortinarius species exhibited broad applicability of the devised system. Up to six pigments could be purified directly from the crude extract. Preparative-scale fractionation of the methanol extracts of C. malicorius and C. sanguineus demonstrated that up-scaling was possible without compromising selectivity.

From bench to counter: Discovery and validation of a peony extract as tyrosinase inhibiting cosmeceutical.

The anti-melanogenic principle of peony (Paeonia officinalis subsp. officinalis) seeds was elucidated via activity-guided isolation. Resveratroloside (trans-resveratrol-4'-O-beta-d-glucopyranoside) was found to be the main metabolite of P. officinalis subsp. officinalis seeds and its tyrosinase inhibiting activity was confirmed via an enzymatic assay. Furthermore, the in vitro activity and the therapeutic window were studied employing the murine melanoma cell line B16F10. The results from the conducted stability assay and the high content of resveratroloside in the seeds (i.e. 10.4% dw) motivated us to push the extract forward to an in vivo tolerance assay. A clinical study with forty Caucasian participants proofed a good skin-tolerance with high moisture effect and reduction of pores.

The photoactivity of natural products - An overlooked potential of phytomedicines?

BACKGROUND: Photoactivity, though known for centuries, is only recently shifting back into focus as a treatment option against cancer and microbial infections. The external factor light is the ingenious key-component of this therapy: Since light activates the drug locally, a high level of selectivity is reached and side effects are avoided. The first reported photoactive medicines were plant extracts. Synthetic entities (so-called photosensitizers PSs), however, paved the route towards the clinical approval of the so-called photodynamic therapy (PDT), and thus natural PSs took a backseat in the past. HYPOTHESIS: Many isolated bioactive phytochemicals hold a hidden photoactive potential, which is overlooked due to the reduced common awareness of photoactivity. METHODS: A systematic review of reported natural PSs and their supposed medicinal application was conducted by employing PubMed, Scifinder, and Web of Science. The identified photoactive natural products were compiled including information about their natural sources, their photoyield, and their pharmacological application. Furthermore, the common chemical scaffolds of natural PS are shown to enable the reader to recognize potentially overlooked natural PSs. RESULTS: The literature review revealed over 100 natural PS, excluding porphyrins. The PSs were classified according to their scaffold. Thereby it was shown that some PS-scaffolds were analyzed in a detailed way, while other classes were only scarcely investigated, which leaves space for future discoveries. In addition, the literature revealed that many PSs are phytoalexins, thus the selection of the starting material significantly matters in order to find new PSs. CONCLUSION: Photoactive principles are ubiquitous and can be found in various plant extracts. With the increasing availability of light-irradiation setups for the identification of photoactive natural products, we anticipate the discovery of many new natural PSs in the near future. With the accumulation of chemically diverse PSs, PDT itself might finally reach its clinical breakthrough as a promising alternative treatment against multi-resistant microbes and cancer types.

ß-Nitro substituted carboxylic acids and their cytotoxicity.

ß-Nitro-substituted ethyl carboxylates are a new class of cytotoxic agents; they can be easily obtained in fair to good yields in a single-step reaction by a Pd-catalyzed asymmetric conjugate addition of aryl boronic acids to 2-nitro-acrylates. Of all the tested derivatives, 2-(4-chlorophenyl)-3-nitropropionic acid ethyl ester (6) is most cytotoxic especially against the human ovarian cancer cell line A2780 therefore making this compound an interesting candidate for further investigations.

Tormentic acid derivatives: synthesis and apoptotic activity.

Several derivatives of tormentic acid have been prepared and tested for their antitumor activity. The dichloroacetate 14 is an excellent antitumor active agent acting by an apoptose inducing pathway as demonstrated by OA/PI staining, DNA laddering experiments as well as by an annexin V binding assay.

Conversions at C-30 of glycyrrhetinic acid and their impact on antitumor activity.

The extracts of the roots of licorice have been used in traditional and folk medicine to treat a broad variety of maladies. The main ingredient of these extracts is glycyrrhicinic acid. Its aglycon, glycyrrhetinic acid, has many biological activities, among them a pronounced cytotoxicity against tumor cells. In this study we varied glycyrrhetinic acid at position C-30 to get "simple" derivatives, for example esters, amides and a nitrile. The influence of these changes on the cytotoxic activity is noteworthy and was determined by a colorimetric sulphorhodamine B test using 7 human tumor cell lines and mouse embryonic fibroblasts (NIH3T3) for comparison. A Trypan blue test as well as an acridine orange/ethidium bromide test was used to discover the ability of the compounds to induce apoptosis.