title: Pedilanthus tithymaloides Inhibits HSV Infection by Modulating NF-κB 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 μg/ml, respectively), with nearly complete inhibition at 86.5-101.8 and 40.2-49.6 μg/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-κB activation, we examined whether the observed extract-induced inhibition of HSV-2 was related to NF-κB inhibition. Interestingly, we observed that treatment of HSV-2-infected cells with extract or luteolin suppressed NF-κB activation. Although NF-κB, 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)-α, Interleukin (IL)-1β, IL-6, NO and iNOS and the production of gamma interferon (IFN-γ), which are directly involved in controlling the NF-κB signaling pathway. Thus, our results indicate that both PT leaf extract and luteolin modulate the NF-κB signaling pathway, resulting in the inhibition of HSV-2 replication.
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Durbadal
authors.initials: D
authors.lastname: Ojha
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Das
authors.affiliation: Department of Microbiology, College of Cell Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Parveen
authors.initials: P
authors.lastname: Sobia
authors.affiliation: Department of Microbiology, College of Cell Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Vedprakash
authors.initials: V
authors.lastname: Dwivedi
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India; Department of Pharmaceutical Technology, Jadavpur University, Raja SC Mallick Road, Kolkata 700032, India.
authors.forename: Soma
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Raja SC Mallick Road, Kolkata 700032, India.
authors.forename: Amalesh
authors.initials: A
authors.lastname: Samanta
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Debprasad
authors.initials: D
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D005260:Female; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D007378:Interleukins / Q000378:metabolism; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000821:virology; D019684:Magnoliopsida / Q000737:chemistry; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D047311:Luteolin