A natural tetranortriterpenoid with immunomodulating properties as a potential anti-HSV agent

Abstract

Meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., prevents the development of herpetic stromal keratitis (HSK) in mice by diminishing the viral load in the eye and the severity of lesions caused by a virus-induced immunopathological reaction. The tetranortriterpenoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA purification, displays anti-herpetic activity and impedes nuclear factor kappaB (NF-kappaB) activation in HSV-1 infected conjunctival cells. To extend our understanding about CDM biological properties, we investigated its anti-HSV-1 activity as well as the effect on NF-kappaB activation and cytokine secretion induced by viral (HSV-1) and no-viral (LPS) stimuli, in corneal cells and macrophages. CDM exerted a potent anti-HSV-1 effect on corneal cells and inhibited NF-kappaB translocation to the nucleus, leading to a decrease in IL-6 production. Besides, CDM seemed to modulate IL-6 and TNF-alpha responses in macrophages, whether they were infected with HSV-1 or stimulated with LPS. However, CDM did not affect NF-kappaB activation in these cells, suggesting that an alternative NF-kappaB cell signaling pathway would be involved in the modulation of cytokine production. We conclude that, in addition to its antiviral effect, CDM would be acting as an immunomodulating compound which would be responsible for the improvement of murine HSK already reported.

A natural antiviral and immunomodulatory compound with antiangiogenic properties

“…We found that CDM delays the transport of viral glycoproteins that would account for the strong inhibition on viral multiplication (Barquero et al, 2004;Bueno et al, 2010). CDM also decreases IL-6 production in HSV-1-infected corneal cells, enhances TNF-α and reduces IL-6 secretion when macrophages are either infected with HSV-1 or stimulated with LPS (Bueno et al, 2009).…”

“…Considering that CDM suppressed IL-6 production in J774A.1 and HCLE cells infected with HSV-1 and stimulated with LPS (Bueno et al, 2009), and that IL-6 can stimulate corneal cells and macrophages to secrete VEGF (Biswas et al, 2006;M.E. Zheng et al, 2001), we decided to investigate the effect of CDM on VEGF transcription.…”

“…Bioassay guided purification of MA led to the isolation of the limonoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM) that hinders HSV-1 multiplication (Alché et al, 2003;Barquero et al, 2006;Bueno et al, 2009). We found that CDM delays the transport of viral glycoproteins that would account for the strong inhibition on viral multiplication (Barquero et al, 2004;Bueno et al, 2010).…”

Azadirachtolide: An anti-diabetic and hypolipidemic effects from Azadirachta indica leaves

“…[14] Alpha glucosidase (2U/ml) was premixed with 20 µl of azadirachtolide at various concentrations (10,20,40,60, 80 and 100 µg/ml) and incubated for 5 min at 37ºC. 1mM para-nitrophenyl glucopyanoside (20 µl) in 50mM of phosphate buffer (pH 6.8) was added to initiate the reaction.…”

“…[8] Tetranortriterpenoids has been reported for anticancer, antiviral, anti-allergic and anti-inflammatory activities. [9][10][11][12] There is no report on azadirachtolide (tetranortriterpenoid from Azadirachta indica leaves) for antidiabetic and hypolipidemic activities. Therefore, the effect of azadirachtolide (tetranortriterpenoid from Azadirachta indica leaves) on blood glucose and serum lipid profiles on streptozotocin-induced diabetic rats was investigated.…”