In Vitro Anti-HSV-1 Activity of Polyphenol-Rich Extracts and Pure Polyphenol Compounds Derived from Pistachios Kernels (Pistacia vera L.) - PubMed (original) (raw)
In Vitro Anti-HSV-1 Activity of Polyphenol-Rich Extracts and Pure Polyphenol Compounds Derived from Pistachios Kernels (Pistacia vera L.)
Maria Musarra-Pizzo et al. Plants (Basel). 2020.
Abstract
Natural compounds are a prominent source of novel antiviral drugs. Several reports have previously shown the antimicrobial activity of pistachio polyphenol extracts. Therefore, the aim of our research was to investigate the activity of polyphenol-rich extracts of natural shelled (NPRE) pistachios kernels (Pistacia vera L.) on herpes simplex virus type 1 (HSV-1) replication. The Vero cell line was used to assess the cytotoxicity and antiviral activity. The cell viability was calculated by detection of cellular ATP after treatment with various concentrations of NPRE. For antiviral studies, five nontoxic-concentrations (0.1, 0.2, 0.4, 0.6, 0.8 mg/mL) were tested. Our study demonstrated that treatment with NPRE (0.4, 0.6, 0.8 mg/mL) reduced the expression of the viral proteins ICP8 (infected cell polypeptide 8), UL42 (unique long UL42 DNA polymerase processivity factor) , and US11 (unique short US11 protein), and resulted in a decrease of viral DNA synthesis. The 50% cytotoxic concentration (CC50), 50% inhibitory concentration (EC50), and the selectivity index (SI) values for NPRE were 1.2 mg/mL, 0.4mg/mL, and 3, respectively. Furthermore, we assessed the anti-herpetic effect of a mix of pure polyphenol compounds (NS MIX) present in NPRE. In conclusion, our findings indicate that natural shelled pistachio kernels have remarkable inhibitory activity against HSV-1.
Keywords: antiviral; herpes simplex virus; pistachios; polyphenols.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Figure 1
Cell viability of Vero cells treated with increasing concentration of polyphenol-rich extracts from natural shelled pistachios kernels (NPRE). The cell proliferation index (%) was calculated by means of cellular ATP level measured after 72 h treatment. The values were expressed as percentages of treated vs. control cells (DMSO). Each value is the mean ± standard deviation (SD) of three experiments.
Figure 2
Effects of NPRE on herpes simplex 1 (HSV-1) replication by plaque reduction assay. Vero cells were infected with HSV-1 (50 plaque forming units (PFU)/100 µL) for 1 h and then treated with NPRE (0.1, 0.2, 0.4, 0.6, 0.8 mg/mL). The DMSO was used in the control samples and acyclovir (20 µM) was used as positive control. Data are expressed as a mean (± SD) of at least three experiments, and asterisks (**, and ***) indicate the significance of _p_-values less than 0.01 and 0.001, respectively.
Figure 3
Analysis of viral protein expression by Western blot analysis.
Figure 4
Relative quantization of viral DNA with specific HSV-1 TaqMan probe in real-time PCR. DMSO was used in the infected control samples. Data are expressed as a mean (± SD) of at least three experiments and asterisks (* and **) indicate the significance of _p_-values less than 0.05 and 0.01, respectively.
Figure 5
Effect of the NP MIX treatment on HSV-1 replication. Vero cells were either infected or mock-infected with HSV-1-VP26 GFP (green fluorescent protein-tagged capsid protein VP26) at multiplicity of infection (MOI) 1, as described in the Materials and Methods section. Then, the cells were analysed at 24 h post infection (p.i.): (a) fluorescent images showed the green dots representing the VP26 GFP viral antigen localization (I)—Hoechst (blue) was used to stain the nuclei (II) and the merged images are shown in column III; (b) the graph is indicative of the percentage of VP26 GFP-positive cells; (c) Western blot analysis of VP26 GFP-tagged protein. Data are expressed as a mean (± SD) of at least three experiments, and asterisks (***) indicate the significance of _p_-values less than 0.001.
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