Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan.
OBJECTIVES; To evaluate therapeutic efficacy of arctigenin in an experimental model of Japanese encephalitis (JE).


METHODS
Four- to 5-week-old BALB/c mice of either sex were infected intravenously with lethal dose of 3 x 10(5) pfu of Japanese encephalitis virus (JEV). By the 9th day post-infection, all untreated animals succumbed to the infection. Arctigenin was dissolved in DMSO at a concentration of 0.5 mg/mL and stored at 4 degrees C. After one day following virus inoculation, animals were given arctigenin intraperitoneally, twice daily (10 mg/kg of body weight) for next 7 days.


RESULTS
Treatment with arctigenin provided complete protection against experimental JE. Arctigenin's neuroprotective effect was associated with marked decreases in: (i) viral load; (ii) active caspase-3 activity; (iii) reactive oxygen species and reactive nitrogen species; (iv) microgliosis and proinflammatory cytokines; (v) levels of stress-associated signalling molecules; and (vi) neuronal death. Furthermore, treatment with arctigenin also improves the behavioural outcome following JE.


CONCLUSIONS
In conclusion, our findings provide a novel mechanistic insight into the actions of arctigenin in JE. Results from our in vivo and in vitro experiments clearly indicate that arctigenin reduced (i) viral load and viral replication within the brain, (ii) neuronal death and (iii) secondary inflammation and oxidative stress resulting from microglial activation, thereby suggesting its potential for treating JE. The antiviral, neuroprotective, anti-inflammatory and antioxidative effects of arctigenin successfully reduced the severity of disease induced by JEV.
Swarup
Vivek
V
National Brain Research Centre, Manesar, Gurgaon, Haryana 122050, India.
Ghosh
Joydeep
J
Mishra
Manoj Kumar
MK
Basu
Anirban
A
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004672:Encephalitis, Japanese / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D005260:Female; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use*; D022321:Japanese Encephalitis Vaccines / Q000494:pharmacology / Q000627:therapeutic use; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy
D005663:Furans; D022321:Japanese Encephalitis Vaccines; D017705:Lignans; C071942:arctigenin