Anti-Inflammatory Activities of Two Flavanones, Sigmoidin A and Sigmoidin B, from Erythrina sigmoidea

Abstract

Two prenylated flavanones isolated from Erythrina sigmoidea Hua (sigmoidin A and sigmoidin B) were studied for their ability to inhibit the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and arachidonic acid metabolism. In addition, the compounds were studied in two experimental models of inflammation induced in mouse ears by 12-O-tetradecanoylphorbol 13-acetate (TPA) and the phospholipase A₂-induced mouse paw oedema. Both sigmoidins A and B proved to be potent scavengers of the DPPH radical, while the study of the inhibition of arachidonic acid metabolism demonstrated that these same compounds were selective inhibitors of 5-lipoxygenase, with no effect on cyclooxygenase-1 activity. Dose-response inhibitor potency was established for sigmoidin A (IC₅₀ = 31 μM). In the assay of phospholipase A₂-induced mouse paw oedema, only the sigmoidin B derivative inhibited oedema formation at 60 min, showing a percentage of inhibition below that obtained with cyproheptadine (59 % vs. 74 %). In the TPA test, sigmoidins A and B decreased the induced oedema by 89 % and 83 %, respectively. This is the first time that the anti-inflammatory activity and antioxidant properties of these prenylflavanones have been reported. The results indicate that the compounds have different mechanisms of action depending on whether one or two prenyl groups are present in ring B.

Erythrina sigmoidea - Leguminosae - sigmoidin A - sigmoidin B - prenylflavanones - anti-inflammatory - antioxidant - 5-lipoxygenase inhibitors

References

• 1 Fomum Z T, Ayafor J F, Mbi C M. Erythrina studies: Part 2. Structures of the novel prenylated antibacterial flavanones sigmoidins A-C from Erythrina sigmoidea . J Chem Soc Perkin Trans 1 1986: 33-7
• 2 Ndom J C, Mbafor J T, Fomum Z T, Martin M T, Bodo M. ¹H and ¹³C NMR spectral assignment of the prenylflavanones sigmoidins A, B and C, by two-dimensional NMR techniques.  Magn Res Chem. 1993;  31 210-1
• 3 Fomum Z T, Nkenfack A E, Wandji J. Erythrina studies: Part 15. Pharmacological screening of three esters isolated from Erythrina plants.  Ann Fac Sci Chim. 1988;  2 79-104
• 4 Wandji J, Fomum Z T, Tillequin F, Seguin E, Koch M. Erythrina studies: Part 24. Two isoflavones from Erythrina senegalensis .  Phytochemistry. 1994;  35 245-8
• 5 Talla E, Njamen D, Mbafor J T, Fomum Z T, Kamanyi A, Mbanya J C, Giner R M, Recio M C, Máñez S, Ríos J L. Warangalone, the isoflavonoid anti-inflammatory principle of Erythrina addisoniae stem bark.  J Nat Prod. 2003;  66 891-3
• 6 Njamen D, Talla E, Mbafor J T, Fomum Z T, Kamanyi A, Mbanya J C, Cerdá-Nicolás M, Giner R M, Recio M C, Ríos J L. Anti-inflammatory activity of erycristagallin, a pterocarpane from Erythrina mildbraedii .  Eur J Pharmacol. 2003;  468 67-74
• 7 Cavin A, Hostettmann K, Dyatmyko W, Potterat O. Antioxidant and lipophilic constituents of Tinospora crispa .  Planta Med. 1998;  64 393-6
• 8 Cho E J, Yokozawa T, Rhyu D Y, Kim S C, Shibahara N, Park J C. Study on the inhibitory effects on Korean plants and their main compounds on the 1,1-diphenyl-2-picrylhydrazyl radical.  Phytomedicine. 2003;  10 544-51
• 9 Mosmann T. Rapid colorimetric assay for cellular growth and survival: applications to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 10 Sala A, Recio M C, Schinella G, Máñez S, Giner R M, Ríos J L. A new dual inhibitor of arachidonate metabolism isolated from Helichrysum italicum .  Eur J Pharmacol. 2003;  460 219-26
• 11 Safayhi H, Sailer S, Havens M. Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-β-boswellic acid.  Mol Pharmacol. 1995;  47 1212-6
• 12 Giner-Larza E M, Máñez S, Recio M C, Giner R M, Prieto J M, Cerdá-Nicolás M, Ríos J L. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.  Eur J Pharmacol. 2001;  428 137-43
• 13 Giner R M, Villalba M L, Recio M C, Máñez S, Cerdá-Nicolás M, Ríos J L. Anti-inflammatory glycoterpenoids from Scrophularia auriculata .  Eur J Pharmacol. 2000;  389 243-52
• 14 Chi Y S, Jong H G, Son K H, Chang H W, Kang S S, Kim H P. Effects of naturally occurring prenylated flavonoids on enzymes metabolizing arachidonic acid: cyclooxygenases and lipoxygenases.  Biochem Pharmacol. 2001;  62 1185-91
• 15 Ko F N, Cheng Z J, Lin C N, Teng C M. Scavenger and antioxidant properties of prenylflavones isolated from Artocarpus heterophyllus .  Free Radic Biol Med. 1998;  25 160-8
• 16 Cirino G, Peers S H, Wallace J L, Flowers R J. A study of phospholipase A₂-induced oedema in rat paw.  Eur J Pharmacol. 1989;  166 505-10
• 17 Middleton E J r, Drzewiecki G. Flavonoid inhibition of human basophil histamine release stimulated by various agents.  Biochem Pharmacol. 1984;  33 3333-8
• 18 Inoue T, Sugimoto Y, Masuda H, Kamei C. Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L.  Biol Pharm Bull. 2002;  25 256-9