AbstractAs viral infections are an increasing threat to human societies, the need for new therapeutic strategies is becoming even more obvious. As no vaccine is available for COVID-19, the development of directly acting antiviral agents and preventive strategies have to be considered. Nature provides a huge reservoir of anti-infectious compounds, from which we can deduce innovative ideas, therapies, and products. Anti-adhesive natural products interact with the receptor-mediated recognition and early interaction of viruses with the host cells, leading to a reduced internalisation of the virus and reduced infections (e.g., procyanidin-B-2-di-O-gallate against influenza and herpes virus). Lignans like podophyllotoxin and bicyclol show strong antiviral activities against different viruses, and essential oils can directly interact with viral membranes and reduce the hostʼs inflammatory responses (e.g., 1,8-cineol). Echinacea extracts stimulate the immune system, and bioavailable alkamides are key players by interacting with immunomodulating cannabinoid receptors. COVID-19 and SARS-CoV-2 infections have, in part, successfully been treated in China by preparations from traditional Chinese medicine and, while it is too early to draw conclusions, some promising data are available. There is huge potential, but intensified research is needed to develop evidence-based medicines with a clearly defined chemical profile. Intensified research and development, and therefore funding, are needed for exploiting natureʼs reservoir against viral infections. Combined action for basic research, chemistry, pharmacognosy, virology, and clinical studies, but also supply chain, sustainable sourcing, and economic aspects have to be considered. This review calls for intensified innovative science on natural products for the patients and for a healthier world!

Covering: 2001 up to the end of 2016Polyphenols comprise a structurally diverse class of natural products. As the development of new anthelmintic drugs against soil-transmitted helminthiases is an urgent need and polyphenols are widely used in the treatment of nematode infections in traditional medicine and modern science, we summarize the state of knowledge in the period of mainly 2001 up to the end of 2016 on plant extracts with known polyphenolic composition and of defined polyphenols, mainly from the classes of condensed and hydrolysable tannins, flavonoids, and phenylpropanoids. The diverse biological activity against different helminths and the underlying mechanisms are reviewed.

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Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the identification of the anthelmintic compounds by bioassay-guided fractionation. An EtOH-H2O (1:1) extract from defatted leaves was partitioned between EtOAc and H2O. Further fractionation was performed by fast centrifugal partition chromatography, RP18-MPLC and HPLC. Epicatechin (1), oligomeric proanthocyanidins (OPC) 2 to 10 (mainly procyanidins) and flavonoids 11 to 13 were identified as main components of the extract. The hydroalcoholic extract, fractions and purified compounds were tested in vitro for their anthelmintic activity using the model nematode Caenorhabditis elegans. The bioassay-guided fractionation led to the identification of OPCs as the active compounds with a dose-dependent anthelmintic activity ranging from 1 to 1000 μM. Using OPC-clusters with a defined degree of polymerization (DP) revealed that a DP ≥ 3 is necessary for an anthelmintic activity, whereas a DP > 4 does not lead to a further increased inhibitory effect against the helminths. In summary, the findings rationalize the traditional use of C. mucronatum and provide further insight into the anthelmintic activity of condensed tannins.

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Paullinia pinnata is a medicinal plant traditionally used in West Africa against a wide range of diseases including soil-transmitted helminthiases. In this study, a hydroethanolic root extract was investigated for its phytochemical composition and in vitro activity against the free-living nematode Caenorhabditis elegans as well as the larval stages of the parasitic helminths Ancylostoma caninum, Haemonchus contortus, Toxocara cati, and Trichuris vulpis.LC-MS analysis of the ethanol-water (1 : 1) extract revealed epicatechin and different A-type linked oligomeric and polymeric procyanidins as the predominant compounds.Within an in vitro mortality assay, the extract showed a lethal activity against T. cati (LC50 of 112 µg/mL), T. vulpis (LC50 of 17 µg/mL), and C. elegans (LC50 2.5 of mg/mL), but not against A. caninum. Additionally, effects on egg hatching and larval migration of H. contortus were investigated, but no inhibitory activity was observed.Overall, these findings rationalize the traditional use of the root extract from P. pinnata as an anthelmintic remedy and provide insight into the phytochemical composition of the extract.

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Extracts from the roots of Paullinia pinnata L. are used in West Africa as traditional remedies for a variety of diseases including infestations with soil-transmitted helminths. Based on the results of an ethnopharmacological survey in Ghana, an aqueous acetone (70%) extract was investigated for its anthelmintic and phytochemical properties. Partitioning of the crude extract followed by several fractionation steps of the ethyl acetate phase using Sephadex® LH-20, fast centrifugal partition chromatography, RP-18-MPLC and HPLC led to isolation of six oligomeric A-type procyanidins (1 to 6). To determine the anthelmintic activity, the crude extract, fractions and isolated compounds were tested in vitro against the model organism Caenorhabditis elegans. A significantly better activity was observed for the trimeric A-type procyanidin (1) compared to a B-type trimer. However, this effect could not be generalized for the tetrameric procyanidins, for which the type of the interflavan-linkage (4→6 vs. 4→8) had the greatest impact on the bioactivity. Besides the procyanidins, three novel compounds, isofraxidin-7-O-α-l-rhamnopyranosyl-(1″→6′)-β-d-glucopyranoside (17), 4-methoxycatechol-2-O-(5′′-O-vanilloyl-β-apiofuranosyl)-(1′′→2′)-β-glucopyranoside (18) and a 6-(3-methoxy-4-hydroxyphenyl)-hexane-2,4-diol-2-O-hexoside (19) were isolated together with further ten known compounds (7 to 16), mainly coumarins and coumarinolignans. Except for 3-β-d-glucopyranosyloxy-4-methyl-2(5H)-furanone (15), none of the isolated compounds has previously been described for P. pinnata. The anthelmintic activity was attributed to the presence of procyanidins, but not to any of the other compound classes. In summary, the findings rationalize the traditional use of P. pinnata root extracts as anthelmintic remedies.