In Vitro Evaluation of Secoiridoid Glucosides from the Fruits of Ligustrum lucidum as Antiviral Agents.

Abstract

Oleuropein is a phenolic secoiridoid glucoside widespread in members of the family Oleaceae. It has been shown to possess a wide range of biological activities. It increased coronary blood flow and showed antiarrhythmic and spasmolytic effects.1,2) Oleuropein exhibited hypoglycemic effect and increased tolerance of orally administered glucose. It also showed anti-oxidative and anti-inflammatory properties. [3][4][5][6][7] Other reported effects of oleuropein included the potentiation of cellular and organismal protection through the macrophage-mediated response, 4) the inhibition of platelet aggregation and eicosanoid production, 8) reduction of the low density lipoproteins (LDL) level, 9) the potent and protective antioxidant action on LDL, 10) the inhibitory effects on cytochrome P450 and 17b-hydroxysteroid dehydrogenase activity, 11) potent cytotoxic effects on tumor cell lines including P-388, L-1210. 12) inhibitory effects on of lipoxygenase activity, 13) and antibacterial functions. 14-18) Recently, oleuropein was also claimed in a U.S. patent to have potent antiviral activities against herpes mononucleosis, hepatitis virus, rotovirus, bovine rhinovirus, canine parvovirus and feline leukaemia virus. 19) On the other hand, But and his research team recently reported the isolation of oleuropein (4), lucidumoside C (1) and other secoiridoid glucosides from the fruits of Ligustrum lucidum, another member of Oleaceae.3) They demonstrated strong anti-oxidative effects in these secoiridoid glucosides (Table 1). Oleuropein and lucidumoside C were found to have stronger anti-oxidative potency than trolox, their IC 50 being 25.0, 9.3, and 55.0 mM, respectively. Based on such anti-oxidative capabilities and also the antiviral effects claimed in the U.S. patent, the authors suggested that "it would be interesting to check if oleuropein's antiviral effect is related to its anti-oxidant property and also if lucidumoside C has stronger antiviral function". 3)This suggestion actually posed two important questions: 1) is anti-oxidative potency of a compound correlated with its antiviral potency? and 2) is anti-oxidation a mechanism against viruses?In the present paper, we present the in vitro evaluation of six secoiridoid glucosides from the fruits of Ligustrum lucidum against herpes simplex type 1 virus (HSV-1), influenza type A virus (Flu A), respiratory syncytial virus (RSV) and parainfluenza type 3 virus (Para 3). The relationship of antiviral activities of secoiridoid glucosides with their anti-oxidative effects were analysed. Results and DiscussionThe six secoiridoid glucosides isolated from L. lucidum did not show any antiviral activities against Flu A and HSV-1, except oleoside dimethylester (2) which showed a little antiviral activity against HSV-1 (Tables 2, 3).The in vitro antiviral activities of the six isolated compounds against RSV are summarized in Table 4. Oleuropein showed potent anti-RSV activity with an IC 50 value of 23.4 mg/ml and a large therapeutic index comparable to that of ribavirin, an approved d...

Antioxidant capacity of the extracts from pulp of Osmanthus fragrans and its components

“…1. Antiviral activity of oleoside dimethyl ester was reported by Ma et al (2001). It is reported that oleoside dimethyl ester showed potent or moderate antiviral activities against Para 3 (parainfluenza type 3 virus) with IC 50 values of 15.6-20.8 mg/ml.…”

Protective effects of Ligustrum lucidum fruit extract on acute butylated hydroxytoluene-induced oxidative stress in rats

“…Ethanol extract of Ligustrum lucidum fruits and its secoiridoid glucosides, namely oleoside dimethylester, oleuropein, neonuezhenide, lucidumoside B and lucidumoside C, were shown to inhibit the free radical induced hemolysis in red blood cells (He et al, 2001b). Oleuropein also exhibited antiviral activities against respiratory syncytial virus (RSV) and parainfluenza type 3 virus (Para 3), whereas oleoside dimethylester, lucidumoside C and ligustroside were active against Para 3 virus (Ma et al, 2001). ELL contains a large amount of oleanolic acid and ursolic acid, which have been demonstrated to be effective in treating inflammation, hepatotoxicity, pain and hyperlipidermic (Yim et al, 2001;Liu et al, 2003).…”

Antiviral efficacy against hepatitis B virus replication of oleuropein isolated from Jasminum officinale L. var. grandiflorum

“…Studies have shown that Ole possesses a wide range of pharmacologic and health promoting properties including anti-inflammatory (Diaz et al, 2000), anti-rheumatic (Visioli et al, 1998), diuretic (Ribeiro Rde et al, 1986, anti-atherogenic (Visioli and Galli, 2001), antipyretic (Visioli et al, 1995) and antiviral (Ma et al, 2001;Micol et al, 2005) effects. The results reported in this paper provide the first experimental evidence of notable anti-HBV activity of Ole both in vitro and in vivo.…”