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.
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.
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