Lignan and Phenylpropanoid Glycosides from Phillyrea latifolia and their In Vitro Anti-Inflammatory Activity

Abstract

Three phenylpropanoid glycosides (salidroside, syringin and coniferin) and one lignan (phillyrin) isolated from the leaves of Phillyrea latifolia L. (Oleaceae) were tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in calcium-stimulated mouse peritoneal macrophages and human platelets, and for their effects on cell viability. These compounds are capable of exerting inhibitory actions on enzymes of the arachidonate cascade. Phillyrin, salidroside and syringin exert a preferential effect on the cyclo-oxygenase pathway, inhibiting release of the cyclo-oxygenase metabolites prostaglandin E₂ (IC₅₀ values 45.6 μM, 72.1 μM and 35.5 μM, respectively) and to a lesser extent reducing thromboxane B₂ levels (IC₅₀ values 168 μM, 154 μM and 29.3 μM, respectively). In contrast, coniferin can be classified as a ”dual inhibitor”, since it produces reduction in generation of both cyclo-oxygenase (IC₅₀ values 75.2 μM for prostaglandin E₂ and 619 μM for thromboxane B₂) and 5-lipoxygenase metabolites, but the effects are greater against leukotriene C₄ (IC₅₀ value 63.6 μM). Structure-activity relationships of the three phenylpropanoid glycosides are discussed. Thus, like some other compounds found in medicinal herbs, our molecules possess an array of potentially beneficial anti-eicosanoid properties which may, alongside other constituents, contribute to the claimed therapeutic properties of the plant from which they are derived.

Key words

Phillyrea latifolia - Oleaceae - anti-inflammatory drugs - cyclo-oxygenase - 5-lipoxygenase

References

• 1 Cometa F, Tomassini L, Nicoletti M, Pieretti S. Phenylpropanoid glycosides. Distribution and pharmacological activity.  Fitoterapia. 1993;  3 195-217
• 2 Garnier G. Ressources médicinales de la flore francaise . Vol. 2 1961: 991-2
• 3 Lopez Gonzáles G. Guía de Incafo de los árboles y arbustos de la Peninsula Ibérica. 1982: 753
• 4 Pieroni A, Huang Y, Vlietinck A J, Heimler D. Anticomplementary activity of extractives of Phillyrea latifolia leaf.  Fitoterapia. 1998;  5 469-70
• 5 Chiba M, Hishada S, Nishibe S, Thieme H. ¹³C NMR Analysis of symplocosin and (+)-epipinoresinol glucoside.  Phytochemistry. 1980;  19 335-6
• 6 Inouye H, Nishioka T. Monoterpene glucosides and related natural products. XIX. Structure of nuezhenide, a bitter tasting D-glucoside from Ligustrum lucidum and Ligustrum japonicum .  Tetrahedron. 1972;  28 4231-7
• 7 Mizutani K, Yuda M, Tanaka O, Saruwatari Y, Jia M R, Ling Y K, Py X F. Tangshenosides I and II from Chuan-Dangshen, the root of Conodopsis tangshen Oliv.  Chemical and Pharmaceutical Bulletin. 1988;  36 2726-9
• 8 Woerdenbag H J, Merfort I, Pabreiter C M, Schmidt T J, Willuhn G, Van Uden W, Pras N, Kampinga H H, Konings A W. Cytotoxicity of flavonoids and sesquiterpene lactones from Arnica species against the GLC₄ and the COLO 320 cell lines.  Planta Medica. 1994;  60 434-7
• 9 Pradelles P, Antoine C, Lellouche J P, Maclouf J. Enzyme immunoassays for leukotriene C₄ and E₄ using acetylcholinesterase.  Methods of Enzymology.. 1990;  187 82-9
• 10 Williams J D, Czop J K, Austen K F. Release of leukotriene by human monocytes on stimulation of their phagocytic receptor for particulate activators.  Journal of Immunology. 1984;  132 3034-40
• 11 Funk C D, Funk L B, Kennedy M E, Pong A S, Fitzgerald G A. Human platelet-erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression and gene chromosomal assignement.  FASEB Journal. 1991;  5 2304-12
• 12 Klimek B, Tokar M. Biologically active compounds from the flowers of Forsythia suspensa Vahl.  Acta Polonian Pharmaceutical Drug Research. 1998;  55 499-504
• 13 Shi L, Ma Y, Cai Z. Quantitative determination of salidroside and specunezhenide in the fruits of Ligustrum lucidum Ait by high performance liquid chromatography.  Biomedical Chromatograghy. 1998;  12 27-30
• 14 Park H J, Lee M S, Lee K T, Sohn I C, Han Y N, Miyamoto K I. Studies on constituents with cytotoxic activity from the stem bark of Syringa velutina .  Chemical and Pharmaceutical Bulletin. 1999;  47 1029-31
• 15 Ye Y C, Chen Q M, Jin K P, Zhou S X, Chai F L, Hai P. Effect of salidroside on cultured myocardial cells anoxia/reoxygenation injuries.  Chung Kuo Yao Li Hsueh Pao. 1993;  14 424-6
• 16 Li H, Miyahara T, Tezuka Y, Namba T, Nemoto N, Tonami S, Seto H, Tada T, Kadota S. The effect of Kampo formulae on bone resorption in vitro and in vivo. I. Active constituents of Tsu-kan-gan.  Biological and Pharmaceutical Bulletin. 1998;  21 1322-6
• 17 Kapil A, Sharma S. Immunopotentiating compounds from Tinospora cordifolia .  Journal of Ethnopharmacology. 1997;  58 89-95
• 18 Park H J, Jung W T, Basnet P, Kadota S, Namba T. Syringin 4-O-β-glucoside, a new phenylpropanoid glycoside, and costunolide, a nitric oxide synthase inhibitor, from the stem bark of Magnolia sieboldii .  Journal of Natural Products. 1996;  59 1128-30
• 19 Kim D H, Lee K T, Bae E A, Han M J, Park H J. Metabolism of liriodendroin and syringin by human intestinal bacteria and their relation to in vitro cytotoxicity.  Archives of Pharmaceutical Research. 1999;  22 30-4
• 20 Ahmad M, Aftab K. Hypotensive action of syringin from Syringa vulgaris .  Phytotherapy Research. 1995;  9 452-4