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Antiviral activity and possible mechanism of action of constituents identified in Paeonia lactiflora root toward human rhinoviruses.

ABSTRACT: Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-?-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 ?M) and HRV-4 (17.33 ?M) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3->8.5). The 100 ?g/mL PA and 20 ?g/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1?), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV.

SUBMITTER: Ngan LT

PROVIDER: S-EPMC4393083 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Antiviral activity and possible mechanism of action of constituents identified in Paeonia lactiflora root toward human rhinoviruses.

Ngan Luong Thi My LT Jang Myeong Jin MJ Kwon Min Jung MJ Ahn Young Joon YJ

PloS one 20150410 4

Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-li ...[more]

PMID: 25860871

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Project description:BACKGROUND:Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4. METHODS:The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin. RESULTS:As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 ?g/mL), HRV-3 (31 ?g/mL), and HRV-4 (29 ?g/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 ?g/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 ?g/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 ?g/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules. CONCLUSIONS:Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the prevention or treatment of HRV infection.

Dataset Information

Antiviral activity and possible mechanism of action of constituents identified in Paeonia lactiflora root toward human rhinoviruses.

Publications

Antiviral activity and possible mechanism of action of constituents identified in Paeonia lactiflora root toward human rhinoviruses.

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