title: Anti-herpes virus activities of bioactive fraction and isolated pure constituent of Mallotus peltatus: an ethnomedicine from Andaman Islands.
abstract: BACKGROUND
  Viral infections, particularly the infections caused by herpes simplex virus (HSV), represent one of the most serious public health concerns globally because of their devastating impact. The aim of this study was to evaluate the antiviral potential of methanolic crude extract of an ethnomedicine Mallotus peltatus, its active fraction and pure compound, against HSV-1 F and HSV-2 G.
  
  
  RESULTS
  The cytotoxicity (CC(50), the concentration of 50% cellular toxicity), antiviral effective concentration (EC(50), the concentration required to achieve 50% protection against virus-induced cytopathic effect), plaque reduction and the selectivity index (SI, the ratio of CC(50) and EC(50)) was determined. Results showed that the crude methanolic extract of M. peltatus possessed weak anti-HSV activity. In contrast, the active fraction A and isolated ursolic acid from fraction A exhibited potent antiherpesvirus activity against both HSV-1 (EC(50)= 7.8 and 5.5 μg/ml; SI = 22.3 and 20) and HSV-2 (EC(50)= 8.2 and 5.8 μg/ml, and SI = 21.2 and 18.97). The fraction A and isolated ursolic acid (10 μg/ml) inhibited plaque formation of HSV-1 and HSV-2 at more than 80% levels, with a dose dependent antiviral activity, compared to acyclovir. The time response study revealed that the anti-HSV activity of fraction A and isolated ursolic acid is highest at 2-5 h post-infection. Moreover, the time kinetics study by indirect immunofluorescence assay showed a characteristic pattern of small foci of single fluorescent cells in fraction A- treated virus infected cells at 2 h and 4 h post-infection, suggesting drug inhibited viral dissemination. Further, the PCR study with infected cell cultures treated with fraction A and isolated ursolic acid at various time intervals, failed to show amplification at 48-72 h, like acyclovir treated HSV-infected cells. Moreover, fraction A or isolated ursolic acid showed no interaction in combination with acyclovir.
  
  
  CONCLUSIONS
  This study revealed that bioactive fraction A and isolated ursolic acid of M. peltatus has good anti-HSV activity, probably by inhibiting the early stage of multiplication (post-infection of 0-5 h), with SI value of 20, suggesting its potential use as anti-HSV agents.
authors.affiliation: ICMR Virus Unit, ID & BG Hospital, General Block 4, First floor, 57 Dr Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Paromita
authors.initials: P
authors.lastname: Bag
authors.forename: Debprasad
authors.initials: D
authors.lastname: Chattopadhyay
authors.forename: Hemanta
authors.initials: H
authors.lastname: Mukherjee
authors.forename: Durbadal
authors.initials: D
authors.lastname: Ojha
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Mandal
authors.forename: Mamta Chawla
authors.initials: MC
authors.lastname: Sarkar
authors.forename: Tapan
authors.initials: T
authors.lastname: Chatterjee
authors.forename: Gobardhan
authors.initials: G
authors.lastname: Das
authors.forename: Sekhar
authors.initials: S
authors.lastname: Chakraborti
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D019665:Euphorbiaceae / Q000737:chemistry*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D008519:Medicine, Traditional; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D014709:Vero Cells; D010948:Viral Plaque Assay; D000097245:Ursolic Acid
chemical_list: D000998:Antiviral Agents; D010936:Plant Extracts; D014315:Triterpenes; D000097245:Ursolic Acid