In vivo Anti-Inflammatory and Antinociceptive Effects of Liriodendrin Isolated from the Stem Bark of Acanthopanax senticosus

Abstract

In the present study, liriodendrin isolated by activity-guided fractionation from the ethyl acetate (EtOAc) extracts of the stem bark of Acanthopanax senticosus, was evaluated for anti-inflammatory and antinociceptive activities. Liriodendrin (5, 10 mg/kg/day, p. o.) significantly inhibited the increase of vascular permeability induced by acetic acid in mice and reduced an acute paw edema induced by carrageenan in rats. When the analgesic activity was measured by the acetic acid-induced writhing test and hot plate test, liriodendrin showed a dose-dependent inhibition in animal models. In addition, syringaresinol, the hydrolysate of liriodendrin, more potently inhibited the LPS-induced production of NO, PGE₂ and TNF-α production of macrophages than liriodendrin. Consistent with these observations, the expression level of iNOS and COX-2 enzyme was decreased by syringaresinol in a concentration-dependent manner. These results suggest that the anti-inflammatory and antinociceptive effects of liriodendrin after oral administration were attributable to the in vivo transformation to syringaresinol, which may function as the active constituent.

Key words

Acanthopanax senticosus - Araliaceae - liriodendrin - syringaresinol - anti-inflammation - antinociceptive

References

• 1 Shao C J, Kasai R, Xu J , Tanaka O. Saponins from leaves of Acanthopanax senticosus Harms., Ciwujia: Structures of ciwujianosides B, C1, C2, C3, C4, D1, D2 and E.  Chem Pharm Bull. 1988;  36 601-8
• 2 Shao C J, Kasai R, Xu J D, Tanaka O. Saponins from leaves of Acanthopanax senticosus Harms., Ciwujia: II. Structures of ciwujianosides A1, A2, A3, A4 and D3.  Chem Pharm Bull. 1989;  37 42-5
• 3 Nishibe S, Kinoshita H, Takeda H, Okano G. Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmaceutical effect in chronic swimming stressed rats.  Chem Pharm Bull. 1990;  38 1763-5
• 4 Fujikawa T, Yamaguchi A, Morita I, Takeda H, Nishibe S. Protective effects of Acanthopanax senticosus Harms from Hokkaido and its components on gastric ulcer in restrained cold water stressed rats.  Biol Pharm Bull. 1996;  19 1227-30
• 5 Fang J N, Proksch A, Wagner H. Immunologically active polysaccharides of Acanthopanax senticosus .  Phytochemistry. 1985;  24 2619-22
• 6 Hibasami H, Fujikawa T, Takeda H, Nishibe S, Satoh T, Fujisawa T, Nakashima K. Induction of apoptosis by Acanthopanax senticosus Harms and its component, sesamin in human stomach cancer KATO III cells.  Oncol Rep. 2000;  7 1213-6
• 7 Tsukamoto H, Hisada S, Nishibe S. Coumarins from Fraxunus japonicus and F. mandshurica var.  japonica, Chem Pharm Bull. 1985;  33 4069-73
• 8 Deyama T, Ikawa T, Nishibe S. The constituents of Eucommia ulmoides Oliv. II. Isolation and structures of three new lignan glycosides.  Chem Pharm Bull. 1985;  33 3651-7
• 9 Park H J, Kwon S H, Lee J H, Lee K H, Miyamoto K, Lee K T. Kalopanaxsaponin A is a basic saponin structure for the anti-tumor activity of hederagenin monodesmosides.  Planta Medica. 2001;  67 118-21
• 10 Higuchi R, Miyahara K, Kawasaki T. Seed saponins of Akebia quinata Decne I. Hederagenin 3-O-glycosides.  Chem Pharm Bull. 1972;  20 1935-9
• 11 Whittle B A. The use of change in capillary permeability to distinguish between narcotic and anagesic.  Br J Pharmacol. 1949;  22 246-460
• 12 Matsuda H, Samukawa K, Kubo M. Anti-inflammatory activity of ginsenoside Ro.  Planta Medica. 1990;  56 19-23
• 13 Bieth J, Metais P, Warter J. Activation, inhibition and protection of tryptic and α-chymotryptic activity by normal human serum.  Clin Chimica Acta. 1969;  20 69-80
• 14 Fritz H, Trautschold I, Werle E. Determination of the molecular weight of new trypsin inhibitors with the aid of sephadex gel filtration.  Hoppe Seyler Z Physiol Chem. 1965;  342 253-63
• 15 Eddy N B, Leimback D. Synthetic analgesics. II. Dithienbutenyl- and dithienbutenylamines.  J Pharmacol Exp Ther. 1953;  107 385-93
• 16 Carvalho J C, Silva M F, Maciel M A, Pinto A C, Nunes D S, Lima R M, Bastos J K, Sarti S J. Investigation of anti-inflammatory and antinociceptive activities of trans-dehydrocrotonin, a 19-nor-clerodane diterpene from Croton cajucara. Part 1.  Planta Medica. 1996;  62 402-4
• 17 Green L C, Wagner D A, Glogowsky J, Skipper P L, Wishnok J S, Tannenbaum S R. Analysis of nitrate, nitrite, and (¹⁵N)nitrate in biological fluids.  Anal Biochem. 1982;  126 131-8
• 18 Choi J W, Huh K, Kim S H, Lee K T, Park H J, Han Y N. Antinociceptive and anti-rheumatoidal effects of Kalopanax pictus extract and its saponin components in experimental animals.  J Ethnopharmacol. 2002;  79 199-204
• 19 Kim D H, Lee K T, Bae E A, Han M J, Park H J. Metabolism of liriodendrin and syringin by human intestinal bacteria and their relation to in vitro cytotoxicity.  Arch Pharm Res. 1999;  22 30-4
• 20 Watkins L R, Maier S F, Goehler L E. Immune activation: the role of proinflammatory cytokines in inflammation, illness response and pathological pain states.  Pain. 1995;  63 289-302