Boswellia serrata oleo-gum-resin and beta-boswellic acid inhibits HSV-1 infection in vitro through modulation of NF-kappa B and p38 MAP kinase signaling

Background: Herpes Simplex Virus (HSV), a highly contagious pathogen, is responsible for causing lifelong oral to genital infection in human. Boswellia serrata oleo-gum-resin possesses a strong traditional background of treating diverse skin ailments including infection but its effect on HSV-1 has not been examined yet. Purpose: To exploit its potential, we aimed to explore the antiviral activity of methanol extract of B. serrata oleo-gum-resin (BSE) and one of its major constituent beta-boswellic acid (BA) against HSV-1 along with the underlying mechanism of action involved. Methods: BSE was subjected to RP-HPLC analysis to quantify the active constituent. Cytotoxicity (CC50) and antiviral activity were evaluated by MTT and plaque reduction assay, followed by the determination of median effective concentration (EC50). The mode of antiviral activity was assessed by time-of-addition assay and confirmed by reverse transcriptase-PCR (RT-PCR). Further, the expressions of various cytokines were measured by RT-PCR, while the proteins by Western blot. Results: BSE and BA potently inhibited wild-type and a clinical isolate of HSV-1 (EC50 5.2-6.2 and 12.1-14.63 mu g/ml), with nearly-complete inhibition (EC99) at 10 and 30 mu g/ml, respectively. The inhibitory effect was significant at 1 h post-infection and effective up to 4 h. Based on target analysis we examined the inhibition of NF-kappa B, essential for virus replication, and observed significant down-regulation of NF-kappa B, and p38 MAP-kinase activation, with reduced expression of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1 beta and IL-6, involved in scheming NF-kappa B signaling. Conclusion: Thus, our results support the ethnomedicinal use of BSE in skin infection by inhibiting HSV-1 through the modulation of NF-kappa B and p38 MAPK pathway.