# Therapeutic Impact of Caffeic Acid Phenethyl Ester and Acyclovir Combination on Human Gingival Fibroblasts (HGF‐1) Infected With Herpes Simplex Type 1 ICP0

## TL;DR

This study investigates how combining CAPE and acyclovir affects human gingival cells infected with HSV-1 ICP0 protein, suggesting a potential new treatment.

## Contribution

The novel contribution is the evaluation of CAPE and acyclovir combination effects on HSV-1 ICP0-induced immune responses in gingival cells.

## Key findings

- CAPE and acyclovir combination significantly increased IFN-β, IFN-γ, IRF3, β-catenin, and WNT-1 protein levels.
- Groups treated with ICP0 + acyclovir showed higher increases than those with ICP0 + CAPE.
- The combination may reduce adverse effects of ICP0 and acyclovir.

## Abstract

Herpes simplex virus Type 1 (HSV‐1) is a prevalent infectious agent globally, often causing oral infections like gingivostomatitis. The ICP0 protein of HSV‐1 exacerbates infection severity by inhibiting antiviral responses. Our study explored how combinations of CAPE (caffeic acid phenethyl ester) and acyclovir influenced immune responses in gingival cells treated with ICP0 We applied ICP0 protein, CAPE, acyclovir, and their combinations to HGF‐1 cells for 24 h. IC50 dose amounts were determined using the MTT cell viability test, gene expressions were assessed by RT‐PCR, and protein levels were gauged by the ELISA method. No statistically significant changes were noted between the ICP0 applied groups and the control groups (p > 0.05). However, significant increases were observed in the IFN‐β (p < 0.0001), IFN‐γ (p < 0.0001), IRF3 (p < 0.0001), β‐catenin (p < 0.0001), WNT‐1 (p < 0.0001). protein levels of the ICP0 + CAPE applied groups. The increases in all groups administered ICP0 + acyclovir surpassed those administered ICP0 + CAPE (p < 0.0001). The combination of CAPE and acyclovir could potentially reduce both the adverse effects caused by the ICP0 protein and the undesirable side effects that may be caused by the acyclovir used in the treatment. This combination could serve as a potential therapy in the treatment of HSV‐1.