Pedilanthus tithymaloides Inhibits HSV Infection by Modulating NF-?B Signaling.

ABSTRACT: Pedilanthus tithymaloides (PT), a widely used ethnomedicinal plant, has been employed to treat a number of skin conditions. To extend its utility and to fully exploit its medicinal potential, we have evaluated the in vitro antiviral activity of a methanolic extract of PT leaves and its isolated compounds against Herpes Simplex Virus type 2 (HSV-2). Bioactivity-guided studies revealed that the extract and one of its constituents, luteolin, had potent antiviral activity against wild-type and clinical isolates of HSV-2 (EC50 48.5-52.6 and 22.4-27.5 ?g/ml, respectively), with nearly complete inhibition at 86.5-101.8 and 40.2-49.6 ?g/ml, respectively. The inhibitory effect was significant (p<0.001) when the drug was added 2 h prior to infection, and was effective up to 4 h post-infection. As viral replication requires NF-?B activation, we examined whether the observed extract-induced inhibition of HSV-2 was related to NF-?B inhibition. Interestingly, we observed that treatment of HSV-2-infected cells with extract or luteolin suppressed NF-?B activation. Although NF-?B, JNK and MAPK activation was compromised during HSV replication, neither the extract nor luteolin affected HSV-2-induced JNK1/2 and MAPK activation. Moreover, the PT leaf extract and luteolin potently down-regulated the expression of tumor necrosis factor (TNF)-?, Interleukin (IL)-1?, IL-6, NO and iNOS and the production of gamma interferon (IFN-?), which are directly involved in controlling the NF-?B signaling pathway. Thus, our results indicate that both PT leaf extract and luteolin modulate the NF-?B signaling pathway, resulting in the inhibition of HSV-2 replication.

SUBMITTER: Ojha D 

PROVIDER: S-EPMC4583282 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature