Antiviral Action of Synthetic Stigmasterol Derivatives on Herpes Simplex Virus Replication in Nervous CellsIn Vitro

Abstract

Polyfunctionalized stigmasterol derivatives, (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2), inhibit herpes simplex virus type 1 (HSV-1) replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds 1 and 2 have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied.

Elucidation of the Anti-Inflammatory Mechanisms of Bupleuri and Scutellariae Radix Using System Pharmacological Analyses

“…In a previous study, Saikogenin G was demonstrated to exhibit an anti-inflammatory activity against carrageenan produced plantar edema in rats [ 16 ]. Stigmasterol has exhibited anti-inflammatory and immunomodulatory effects through the downregulation of proinflammatory cytokines; moreover, it has been shown to inhibit herpes simplex virus replication in nervous cells in vitro [ 17 , 18 ]. Devi and Periyanayagam found that Salvigenin derived from Plectranthus amboinicus exerted anti-inflammatory effects through human red blood cell (HRBC) membrane stabilization [ 19 ].…”

Enzymatic synthesis of novel purine nucleosides bearing a chiral benzoxazine fragment

“…Investigation of anti‐herpes activity of the compounds in vitro was carried out in accordance with the internationally accepted cytopathic effect (CPE) inhibition assay (De Clercq et al., ; Fedorov et al., ; Petrera, Níttolo, & Alché, ) . In 96‐well plastic plates (Linbro, Flow Laboratories, UK) with the generated cell monolayers, the twofold serial dilutions of the compounds were prepared in the support medium (Eagle medium and medium 199, 1: 1).…”

Therapeutic Potential of Brassinosteroids in Biomedical and Clinical Research

“…Presently, eight different human herpes viruses have been recognized out of which herpes simplex (HSV) is omnipresent. Herpes infection is characterized by their aptitude to cause lifelong infections [84].…”

“…It was suggested that these two compounds suppressed the replication of HSV-1 in nervous cells and its proliferation in human epithelial cells. Cytokine levels were determined after treatment with these compounds which reflected decreased levels of IL-6 and IFN-α in HSV-1 infected-Neuro-2a cells that demonstrated anti-inflammatory activities within them [84]. Reports by Michelini et al [54] suggested that this compound reduced cytokine production in LPS activated macrophages and enhanced pro-inflammatory cytokine production in HSV-1 infected epithelial cells of mice cells.…”