Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596830
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Antiviral and anti-proliferative in vitro activities of piperamides from black pepper

CE Mair
1  Department of Pharmacognosy, University of Vienna, Althanstraße 14, AT-1009 Vienna, Austria
,
R Liu
1  Department of Pharmacognosy, University of Vienna, Althanstraße 14, AT-1009 Vienna, Austria
,
AG Atanasov
1  Department of Pharmacognosy, University of Vienna, Althanstraße 14, AT-1009 Vienna, Austria
,
M Schmidtke
2  Department of Virology and Antiviral Therapy, Jena University Hospital, Hans-Knoell-Straße 2, DE-07745 Jena, Germany
,
VM Dirsch
1  Department of Pharmacognosy, University of Vienna, Althanstraße 14, AT-1009 Vienna, Austria
,
JM Rollinger
1  Department of Pharmacognosy, University of Vienna, Althanstraße 14, AT-1009 Vienna, Austria
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

 

The dried unripe fruits of Piper nigrum L. (black pepper) are known in almost every cuisine worldwide and are often referred to as “king of spices”. Moreover, P. nigrum is described to be endowed with health beneficial and disease preventing properties, like e.g. anti-inflammatory, antiviral, antipyretic, immune and bioavailability enhancing qualities [1]. Its main alkaloid piperine (1) has been confirmed to be mainly responsible for the medicinal value and pungency [2]. In this work, ten piperamides (Fig. 1) were isolated from a combined methanol/dichloromethane extract (PNE) of black pepper fruits, and investigated for (i) their antiviral properties against three viruses related to upper respiratory tract infections, and (ii) their anti-proliferative activity in vascular smooth muscle cells (VSMCs), which is a key element in the prevention of restenosis. Concerning the antiviral effect, the extract of P. nigrum was found to inhibit coxsackie virus type B3 (CVB3) with an IC50 of 10.6 µg/mL in a cytopathic effect inhibition assay [3]. It showed no activity against further two investigated viruses, i.e. human rhinovirus type 2 (HRV2), and influenza virus type A (HK68). Out of the ten isolates, 6, 7, and 9 showed moderate activity against CVB3 with IC50s between 10.0 – 28.7µM, but also distinct cytotoxicity in HeLa cells. Interestingly, although PNE was not tested positive against HRV2, 1 inhibited this virus with moderate activity (IC50 of 29.9µM) without noteworthy cytotoxicity. Besides the detected antiviral effects, we found 1 to inhibit the proliferation of VSMCs with an IC50 of 21.6µM in a resazurin conversion assay. Investigation of the other isolated constituents revealed pipertipine (10) to be even more potent with an IC50 of 3.4µM [4]. This could be confirmed with a second assay, the 5-bromo-2'-deoxyuridine (BrdU) incorporation immunoassay. With these findings we add some insight into the pharmacological potential behind the famous reputation of black pepper.

Zoom Image
Fig. 1: Chemical structures of piperamides (1-10) isolated from P. nigrum fruits.

Acknowledgements: CEM is grateful for her position funded by the Austrian Science Fund (FWF): P24587.

Keywords: Piper nigrum, piperine, anti-viral, inhibition of vascular smooth muscle cell proliferation.

References:

[1] Meghwal M, Goshwami T. Chemical composition, nutritional, medicinal and functional properties of black pepper: A review. Open Access Sci Rep. 2012; 1:1 – 5.

[2] Vasavirama K, Upender M. Piperine: a valuable alkaloid from piper species. Int J Pharm Pharm Sci. 2014: 6:34 – 38

[3] Mair, CE, Grienke U, Draschl, C, Kramer, C, Richter, M, von Grafenstein S, Kirchmair J, Liedl KR, Schmidtke M, Rollinger JM. Linking ethnopharmacology with phenotypic and virtual screening for the identification of antiviral agents from natural sources. Planta Med 2014: 80: WS17.

[4] Mair CE, Liu R, Atanasov AG, Wimmer L, Nemetz-Fiedler D, Sider N, Heiss EH, Mihovilovic MD, Dirsch VM, Rollinger JM. Piperine congeners as inhibitors of vascular smooth muscle cell proliferation. Planta Med 2015; 81: 1065 – 1074