Evaluationof Cytotoxicity and Anti-herpes simplex Virus Effect of Triptolide and (S)-10 Hydroxycamptothecinon Normal Primary Rabbit Kidney Cells and A549 Human Contentious Cell line

Background and Objectives: Herpes simplex virus (HSVs) infections are considered a significant worldwide health concern. The infections appeared with different clinical manifestations, ranging from mild to severe or even life-threatening conditions. HSV can involve oral cavity, skin, mucosal tissue, CNS, and eyes. The virus can led to serious infections in immunocompromised patients. It is estimated that approximately 50- 90% of the world population are seropositive for HSV-1.Natural product components have been a valuable source of medical therapeutic agents, we compared cell toxicity and anti-HSV effectiveness of two NPs: Triptolide and 1-Hydroxycamptothecin in different cell culture systems. Materials and Methods: Two types of cells were used in this study; A549, a human continuous cell tine and primary rabbit kidney (PRK) cells. The cells were used to determineCC50% (50% cytotoxic concentration) and EC50% values (effective concentration that inhibitedof 50%viral plaques).PRK and A549 cells were treated with Triptolide (at concentrations of 0.5, 1.0, 1.5, 2.0, 4.0 and 8.0 μg/mL), 10-Hydroxycamptothecin (at concentrations of 0.05, 0.1, 1.5, 2, 2.5 and 5 μg/mL) to investigate the cytotoxicity of them. Following incubation for 48 h, cell viability was measured using a WST-1 assay. The in vitro cytotoxicity of Triptolide and (S)-10-Hydroxycamptothecin on A549 and primary cells was determined by WST-1(Roche Applied Science, Canada) assay. ECD50% were determined by standard plaque assay. Results: The CC50% of Triptolide and 10-Hydroxycamptothecin on A549 cells were calculated as: 4.454 and 3.596 μM/mL, and CC50% of these compound on PRK cells were also 21.46 and 6.111μM/mL, respectively. Also, the results revealed that Triptolide and 10-Hydroxycamptothecin were capable of reducing HSV-1 plaques with an EC50% value at 0.05, 0.07 μM/mL, respectively. Hence, the selective indexes (SI) for Triptolide and 10-Hydroxycamptothecin were 89.08 and 51.37 μM/mL on A549, and 61.11 and 330.15 μM/mL on PRK cells, respectively. SIs were calculated by regression analysis of the dose–viability curve. Conclusion: In this research, we assessed EC50% and CC50%of Triptolide and (S)-10-Hydroxycamptothecin on primary rabbit kidney cell culture as a normal cell type andon A549 cell line as a tumoralcontentious cell linetodiscriminate between anti-tumoral and antiviral activity of the compounds. As SIshave shown, Triptolide and10-Hydroxycamptothecin were highly effective on reducing HSV-1 titration on PRK cells as well as A549 with much lower cell toxicity or anti cell proliferation action.Finally, it seems these two NPs have potency to conduct more detailed study on them as anti-HSV.