Medicinal plant extracts and plant-derived polyphenols with anthelmintic activity against intestinal nematodes.

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.

Extract and the quassinoid ailanthone from Ailanthus altissima inhibit nematode reproduction by damaging germ cells and rachis in the model organism Caenorhabditis elegans.

Bark and leaves of Ailanthus altissima (Mill.) Swingle are widely used in European folk medicine to treat intestinal worm infections. The study aimed to rationalize a potential anthelmintic effect of A. altissima extract against the model organism Caenorhabditis elegans. A methanol-water (7:3, v/v) extract of the primary stem bark was tested on L4 larvae of C. elegans for induction of mortality and influence on reproduction. Bioactivity-guided fractionation was performed by chromatography on MCI-gel, preparative HPLC on RP18 stationary phase and fast-centrifugal-partition-chromatography. Structural elucidation of isolated quassinoids was performed by NMR and HR-ESI-MS. The sterilizing effect on C. elegans was investigated by light microscopy and atomic force microscopy of ultra-sections. Different GFP-tagged reporter strains were used to identify involved signaling pathways. A. altissima extract (1 mg/mL) irreversibly inhibited the reproduction of C. elegans L4 larvae. This effect was dependent on the larval stage since L3 larvae and adults were less affected. Bioactivity-guided fractionation revealed the quassinoid ailanthone 1 as the major active compound (IC50 2.47 µM). The extract caused severe damages to germ cells and rachis, which led to none or only poorly developed oocytes. These damages led to activation of the transcription factor DAF-16, which plays a major role in the nematode's response to stress. A regulation via the respective DAF-2/insulin-like signaling pathway was not observed. The current findings support the traditional use of A. altissma in phytotherapy to treat helminth infections and provide a base for standardization of the herbal material.

Antiadhesive phthalides from Apium graveolens fruits against uropathogenic E. coli.

ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Apium graveolens (celery) are used traditionally in Persian and European medicine for the treatment of uncomplicated urinary tract infections. AIM OF THE STUDY: The study aimed at identifying potential antiadhesive compounds from celery extracts to provide strategies for improved standardization of the herbal material. MATERIALS AND METHODS: Decoction, hydroalcoholic and acetone extracts were prepared from celery fruits. Bioassay-guided fractionation was performed by Fast Centrifugal Partition Chromatography and preparative HPLC, followed by LC-MS and NMR investigations for structure elucidation. The antiadhesive activity of extracts, fractions and purified compounds was assessed by flow cytometry, evaluating the adhesion of fluorescent-labelled uropathogenic bacteria (UPEC NU14) to T24 bladder cells; mannose served as positive control. Influence of the extract on gene expression of selected adhesins and fitness genes was monitored by qPCR. RESULTS: Concentration-dependent antiadhesive activity was found for the hydroalcoholic and even more for the acetone extract AE (IC50 85 µg/mL) from celery fruits. Bioassay-guided fractionation revealed the presence of the phthalides senkyunolide (1, inactive) and sedanenolide (2, IC50 790 µM). 2 is assessed as the main antiadhesive compound, which accounts for 4.0% in the water extract, for 18% in the hydroethanolic extract and for 71% in AE. Additionally a similar phthalide, Z-ligustilide (5), was shown to exert an IC50 of 611 µM. Furthermore, AE caused a significant upregulation of fimH and sfaG in free floating, non-attached UPEC and significantly down-regulated these genes in adherent bacteria. CONCLUSIONS: Phthalides were identified as the main active compounds in polar and semi-polar extracts, which exert strong antiadhesive activity against uropathogenic E. coli. The current findings support the traditional use in phytotherapy for urinary tract infections and provide a base for standardization of the herbal material.