Bioassay-Guided Fractionation of Siparuna glycycarpa&nbsp;n-Butanol Extract with Inhibitory Activity against Influenza A(H1N1)pdm09 Virus by Centrifugal Partition Chromatography (CPC).

Carla Monteiro Leal,Amanda Resende Tucci,Isabel De Castro Rangel,Gilda Guimarães Leitão,Camilla Blanco De Assis,Milene Dias Miranda,Leonardo Luiz Oliveira De Mello,Hector Henrique Ferreira Koolen,Carolina De Queiroz Sacramento,Suzana Guimarães Leitão,Natalia Fintelman-Rodrigues,Rosineide Costa Simas,Boniek Gontijo Vaz,Carlos Vinicius Azevedo Da Silva

doi:10.3390/molecules27020399

Abstract

Siparuna glycycarpa occurs in the Amazon region, and some species of this genus are used in Brazilian folk medicine. A recent study showed the inhibitory effect of this species against influenza A(H1N1)pdm09 virus, and in order to acquire active fractions, a polar solvent system n-butanol-methanol-water (9:1:10, v/v) was selected and used for bioassay-guided fractionation of n-butanol extract by centrifugal partition chromatography (CPC). The upper phase was used as stationary phase and the lower phase as mobile (descending mode). Among the collected fractions, the ones coded SGA, SGC, SGD, and SGO showed the highest antiviral inhibition levels (above 74%) at 100 µg·mL−1 after 24 h of infection. The bioactive fractions chemical profiles were investigated by LC-HRMS/MS data in positive and negative ionization modes exploring the Global Natural Products Social Molecular Networking (GNPS) platform to build a molecular network. Benzylisoquinoline alkaloids were annotated in the fractions coded SGA, SGC, and SGD collected during elution step. Aporphine alkaloids, O-glycosylated flavonoids, and dihydrochalcones in SGO were acquired with the change of mobile phase from lower aqueous to upper organic. Benzylisoquinolinic and aporphine alkaloids as well as glycosylated flavonoids were annotated in the most bioactive fractions suggesting this group of compounds as responsible for antiviral activity.

Highlights

Influenza viruses are one of the most relevant etiological agents of acute respiratory infections
Some species of the genus Siparuna are used in Brazilian folk medicine [6,7], and recently, our group showed that the extracts from Amazonian Siparuna species presented inhibitory effect against influenza A(H1N1)pdm09 virus replication [8]
O- and C-flavonoid glycosides, dihydrochalcones, and a procyanidin dimer were annotated in these extracts, and according to the literature, they have been demonstrated as potential inhibitors of influenza virus [8,10,11]

Summary

Introduction

Influenza viruses are one of the most relevant etiological agents of acute respiratory infections. The search for anti-influenza compounds that may prevent and treat serious infections and reduce transmissibility is pivotal. Plants and their derived natural products could be a source for new antiviral drugs [4,5]. The n-butanol extracts from Siparuna glycycarpa (SG) and Siparuna sarmentosa (SS) demonstrated high antiviral activity, inhibiting, respectively, 96.0 ± 1.3% and 89.5 ± 0.8% of influenza virus replication 24 h post-infection. O- and C-flavonoid glycosides, dihydrochalcones, and a procyanidin dimer were annotated in these extracts, and according to the literature, they have been demonstrated as potential inhibitors of influenza virus [8,10,11]

Methods

Results

Conclusion