3-O-Galloylated Procyanidins from Rumex acetosa L. Inhibit the Attachment of Influenza A Virus

Abstract

Infections by influenza A viruses (IAV) are a major health burden to mankind. The current antiviral arsenal against IAV is limited and novel drugs are urgently required. Medicinal plants are known as an abundant source for bioactive compounds, including antiviral agents. The aim of the present study was to characterize the anti-IAV potential of a proanthocyanidin-enriched extract derived from the aerial parts of Rumex acetosa (RA), and to identify active compounds of RA, their mode of action, and structural features conferring anti-IAV activity. In a modified MTT (MTTIAV) assay, RA was shown to inhibit growth of the IAV strain PR8 (H1N1) and a clinical isolate of IAV(H1N1)pdm09 with a half-maximal inhibitory concentration (IC50) of 2.5 µg/mL and 2.2 µg/mL, and a selectivity index (SI) (half-maximal cytotoxic concentration (CC50)/IC50)) of 32 and 36, respectively. At RA concentrations>1 µg/mL plaque formation of IAV(H1N1)pdm09 was abrogated. RA was also active against an oseltamivir-resistant isolate of IAV(H1N1)pdm09. TNF-α and EGF-induced signal transduction in A549 cells was not affected by RA. The dimeric proanthocyanidin epicatechin-3-O-gallate-(4β→8)-epicatechin-3′-O-gallate (procyanidin B2-di-gallate) was identified as the main active principle of RA (IC50 approx. 15 µM, SI≥13). RA and procyanidin B2-di-gallate blocked attachment of IAV and interfered with viral penetration at higher concentrations. Galloylation of the procyanidin core structure was shown to be a prerequisite for anti-IAV activity; o-trihydroxylation in the B-ring increased the anti-IAV activity. In silico docking studies indicated that procyanidin B2-di-gallate is able to interact with the receptor binding site of IAV(H1N1)pdm09 hemagglutinin (HA). In conclusion, the proanthocyanidin-enriched extract RA and its main active constituent procyanidin B2-di-gallate protect cells from IAV infection by inhibiting viral entry into the host cell. RA and procyanidin B2-di-gallate appear to be a promising expansion of the currently available anti-influenza agents.

Benefits of Condensed Tannins in Forage Legumes Fed to Ruminants: Importance of Structure, Concentration, and Diet Composition

“…Acacia nilotica (L.) Delile leaves, carob (Ceratonia siliqua L.) pods, grape (Vitis vinifera L.) seeds, persimmon fruits, lentisk (Pistacia lentiscus L.) leaves, shea nuts, tea leaves, and Rumex L. spp. are good sources of galloylated CTs (Self et al, 1986;Henning et al, 2003;Papagiannopoulos et al, 2004;Spencer et al, 2007;Li et al, 2010;Rodríguez-Pérez et al, 2013;Derksen et It is also essential to use CT mixtures that are specific to the plant species being investigated, because CT composition affects ultraviolet-visible absorption maxima and reaction yields that result from the hydrochloric acid (HCl)-butanol-acetone and thiolysis assays (Grabber et al, 2013;Krueger et al, 2013;Engström et al, 2014;Hixson et al, 2015;Ropiak et al, 2016b;Wang et al, 2016). We emphasize the unsuitability of commercially available CTs from quebracho [Schinopsis quebracho-colorado (Schltdl.)…”

Identification and characterization of two novel C‐type lectins from the larvae of housefly, Musca domestica L.

“…The antiviral activities of MdCTL1-2 against influenza virus H 1 N 1 were measured using the MTT assay according to the method reported by Song et al (2010) and Andrea et al (2014). This experiment was divided into three groups: neg- The cell control group was incubated in DMEM medium containing 2% FBS.…”

Hydroalkoholischer Extrakt aus Sauerampferkraut (Rumex acetosa L.) zur Prophylaxe von Mundschleimhauterkrankungen und Periodontitis: Hemmung der bakteriellen Adhäsion und zentraler Virulenzfaktoren von Porphyromonas gingivalis

“…Im Rahmen eines breiten Screenings erwies sich ein Proanthocanydin-angereicherter Extrakt aus Sauerampfer (Rumex acetosa L., Polygonaceae) als wirksam gegenüber P. gingivalis. Traditionell und auch in der neueren Literatur ist die Verwendung der oberirdischen Teile der Droge bei Hautreizungen, Durchfällen, aber auch bei viralen Erkrankungen wie Herpes und Influenza dokumentiert [30,31]. Extrakte aus Sauer ampferkraut finden sich allerdings auch in modernen, zugelassenen Arzneimitteln in Europa zur Behandlung akuter und chronischer Infektionen der Atemwege.…”