Further Phenols and Polyacetylenes from the Rhizomes of Atractylodes lancea and their Anti-Inflammatory Activity[1]

Abstract

From the rhizomes of Atractylodes lancea, 2-[(2′E)-3′,7′-dimethyl-2′,6′-octadienyl]-4-methoxy-6-methylphenol (1) was isolated as a new natural product. The compound showed strong inhibitory effects on 5-lipoxygenase (5-LOX) and cyclooxygenase-1 (COX-1), but exhibited only weak antioxidative activities [IC₅₀ =0.1 μM (5-LOX), 2 μM (COX-1), 9 μM (PMN/FMLP), 28 μM (PMN/OZ)]. Moreover, five new acetylenes were isolated and elucidated as (3Z,5E,11E)-tridecatriene-7,9-diynyl-1-O-(E)-ferulate (2), erythro-(1,3Z,11E)-tridecatriene-7,9-diyne-5,6-diyl diacetate (3), (1Z)-atractylodin (4), (1Z)-atractylodinol (5), (1Z)-acetylatractylodinol (6) plus the known (4E,6E,12E)-tetradecatriene-8,10-diyne-1,3-diyl diacetate (7). Among the acetylenes, only 2 showed strong inhibition of 5-LOX and COX-1 activity (IC₅₀ (5-LOX)=3 μM, IC₅₀ (COX-1)=1 μM). In addition, the fatty acids linoleic acid, oleic acid and palmitic acid with previously established 5-LOX-/COX-1 inhibitory actions were identified as major constituents of the n-hexane extract and thus seem to contribute to the plant’s in vitro activity.

Key words

Atractylodes lancea rhizomes - Asteraceae - polyacetylenes - hydroquinone - 5-lipoxygenase - cyclooxygenase-1 - anti-inflammatory activity - antioxidative activity - fatty acids

1 This work is part of the PhD thesis of M. Resch.

References

• 1 Tang W, Eisenbrand G. Chinese Drugs of Plant Origin. Springer Verlag Berlin Heidelberg New York; 1992: 199-201
• 2 Bruns K, Dolhaine H, Weber U. Atractylodes lancea DC. (Compositae). Contribution on the constituents of the essential oil. World Crops: Prod., Util., Descr 1982 7 (Aromatic Plants): 207-10
• 3 Yosioka I, Hikino H, Sasaki Y. Studies on the constituents of Atractylodes. VI - VIII. The structure of atractylodin. Chem. Pharm.  Bull.. 1960;  8 949-59
• 4 Nishikawa Y, Yasuda I, Watanabe Y, Seto T. Studies on the evaluation of crude drugs. II. Identification of the ingredients of Atractylodes by thin-layer chromatography, gas chromatography and gas chromatography-mass spectrometry, and the physical and chemical evaluation.  Shoyakugaku Zasshi. 1976;  30 132-7
• 5 Resch M. Zur Inhaltsstofführung und antiphlogistischen Wirkung der Rhizome von Atractylodes lancea und verwandter Arten. PhD Thesis, University of Düsseldorf, Aachen, Germany; Verlag Mainz 1999
• 6 Lehner M S, Steigel A, Bauer R. Diacetoxy-substituted polacetylenes from Atractylodes lancea .  Phytochemistry. 1997;  46 1023-8
• 7 Resch M, Steigel A, Chen Z L, Bauer R. 5-Lipoxygenase and cyclooxygenase-1 inhibitory active compounds from Atractylodes lancea. J. Nat.  Prod.. 1998;  61 347-50
• 8 Heilmann J, Resch M, Bauer R. Antioxidant activity of constituents from Atractylodes lancea. Pharm. Pharmacol.  Lett.. 1998;  8 69-71
• 9 Fales H M, Jaouni T M, Babashak J F. Simple device for preparing ethereal diazomethane without resorting to codestillation. Anal.  Chem.. 1973;  45 2302-3
• 10 Bohlmann F, Köhn S, Arndt C. Die Polyine der Gattung Carthamus L. Chem.  Ber.. 1966;  99 3433-6
• 11 Kano Y, Komatsu K I, Saito K I, Bando H, Sakurai T. A new polyacetylene compound from Atractylodes rhizome. Chem. Pharm.  Bull.. 1989;  37 193-4
• 12 Zschocke S, Lehner M, Bauer R. 5-Lipoxygenase and cyclooxygenase inhibitory active constituents from Qianghuo (Notopterygium incisum).  Planta Med.. 1997;  63 203-6
• 13 Redl K, Breu W, Davis B, Bauer R. Anti-inflammatory active polyacetylenes from Bidens campylotheca .  Planta Med.. 1994;  60 58-62
• 14 Weiss M, Mirow N, Birkhahn A, Schneider M, Wernet P. Benzodiazepines and their solvents influence neutrophil granulocyte function. Br. J.  Anaesth.. 1993;  70 317-21
• 15 Merfort I, Heilmann J, Weiss M, Pietta P, Gardana C. Radical scavenger activity of three flavonoid metabolites studied by inhibition of chemiluminescence in human PMNs.  Planta Med.. 1996;  62 289-92
• 16 Pelter A, Drake R. Hindered organoboron groups in organic chemistry. 28. The solvolyses of bis(2,6-dimethyl-4-methoxyphenyl)organylboranes.  Tetrahedron. 1994;  50 13 801-28
• 17 Capon R J, Ghisalberti E L, Jefferies P R. Isoprenoid dihydroquinones from a brown alga, Cystophora sp.  Phytochemistry. 1981;  20 2598-600
• 18 Zschocke S. Phytochemische und pharmakologische Untersuchungen von Notopterygium incisum Ting ex H.T. Chang und Angelica sinensis (Oliv.) Diels sowie verwandter antiinflammatorischer Arzneidrogen aus der Familie der Umbelliferae. PhD Thesis University of Düsseldorf, Germany; 1998
• 19 Otsuka H, Sasaki Y, Yamasaki K, Takeda Y, Seki T. 6-O-α-L-(2′′-O- and 3′′-O-Isoferuloyl) rhamnopyranosylcatalpols from Premna japonica .  Phytochemistry. 1989;  28 3069-71
• 20 Nkengfack A E, Vouffo T W, Vardamides J C, Kouam J, Fomum Z T, Meyer M, Sterner O. Phenolic metabolites from Erythrina species.  Phytochemistry. 1997;  46 573-8
• 21 Nishikawa Y, Yasuda I, Watanabe Y, Seto T. Studies on the components of Atractylodes. II. New polyacetylenic compounds in the rhizome of Atractylodes lancea De Candolle var. chinensis Kitamura.  Yakugaku Zasshi. 1976;  96 1322-6

1 This work is part of the PhD thesis of M. Resch.