New Sesquiterpenoids from Ainsliaea macrocephala and Their Nitric Oxide Inhibitory Activity

Abstract

Investigation of the ethanol extract of the whole plant of Ainsliaea macrocephala led to the isolation of five new sesquiterpenoids, namely ainsliadimer C (1), ainsliadimer D (2), ainsliaolide B (3), ainsliatone B (4), and ainsliaolide C (5), together with seventeen known sesquiterpenes and sesquiterpene glycosides (6–22). Their structures were elucidated by spectroscopic methods. The relative stereochemistry of ainsliadimers C (1) and D (2) were further confirmed by single crystal X-ray diffraction analysis. Total extract of A. macrocephala and compounds 1–22 were tested for inhibitory activity against the production of nitric oxide in RAW 264.7 cells stimulated by LPS, as well as for cytotoxicity against RAW 264.7 macrophages. Of all samples tested, purified compounds 4, 7, and 12 strongly inhibited the production of nitric oxide with IC₅₀ values of 8.78, 2.50, and 7.11 µM, and simultaneously showed low cytotoxicity against RAW 264.7 macrophages.

Ainsliaea macrocephala - Asteraceae - sesquiterpenoid - nitric oxide production

References

• 1 Wu Q X, Shi Y P, Jia Z J. Eudesmane sesquiterpenoids from the Asteraceae family.  Nat Prod Rep. 2006;  23 699-734
• 2 Macias F A, Varela R M, Torres A, Molinillo J G. Heliespirone A, the first member of a novel family of bioactive sesquiterpenes.  Tetrahedron Lett. 1998;  39 427-430
• 3 Kim J H, Kim H K, Jeon S B, Son K H, Kim E H, Kang S K, Sung N D, Kwon B M. New sesquiterpene-monoterpene lactone, artemisolide, isolated from Artemisia argyi.  Tetrahedron Lett. 2002;  43 6205-6208
• 4 Editorial committee .Flora of China, Vol. 79. Beijing; Science Press 1996: 23
• 5 Bohlmann F, Chen Z L. Guaianolides from Ainsliaea fragrans.  Phytochemistry. 1982;  21 2120-2122
• 6 Jin H. Studies on the constituents of Ainsliaea acerifolia SCH.-BIP. var. subapoda NAKAI.  Yakugaku Zasshi. 1982;  102 911-922
• 7 Miyase T, Fukushima S. Sesquiterpene lactones from Ainsliaea acerifolia SCH. BIP. and A. dissecta FRANCH. et SAV.  Chem Pharm Bull. 1984;  32 3043-3046
• 8 Pu J X, Zhao J F, Yang X D, Mei S X, Zhang H B, Li L. A new sesquiterpene lactone from Ainsliaea bonatii.  Chin Chem Lett. 2004;  15 1454-1456
• 9 Wu Z J, Xu X K, Shen Y H, Tian J M, Liang S, Li H L, Liu R H, Zhang W D. A new sesquiterpene lactone dimer with an unusual carbon skeleton from Ainsliaea macrocephala.  Org Lett. 2008;  10 2397-2400
• 10 Adegawa S, Miyase T, Ueno A. Sesquiterpene lactones from Diaspananthus uniflorus (SCH. BIP.) KITAM.  Chem Pharm Bull. 1987;  35 1479-1485
• 11 Agumo S, Izawa K, Higashiyama K, Nagai M. A bitter principle of Pertya robusta (MAXIM.) BEAUV.  Yakugaku Zasshi. 1980;  100 27-30
• 12 Rustaian A, Niknejad A, Zdero C, Bohlmann F. A guaianolide from Centaurea behen.  Phytochemistry. 1981;  20 2427-2429
• 13 Ashok K S, Pritish K C, Ram P S, Jogendra N B, Werner H. Guaianolides from Tricholepis glaberrima.  Phytochemistry. 1982;  21 462-463
• 14 Krishna K, Mashilamani S, Ganesh M R, Aravind S. Microbial transformation of zaluzanin D.  Phytochemistry. 2003;  62 1101-1104
• 15 Alain F, Victoria M, Francois R, Reynald H, Andre C, Charles G J. Antiprotozoal activity of dehydrozaluzanin C, a sesquiterpene lactone isolated from Munnozia maronii (asteraceae).  Phytother Res. 1993;  7 111-115
• 16 Tsichritzis F, Jakupovic J, Bohlmann F. Sesquiterpene lactones and farnesol derivatives from Arctotis and Arctotheca species.  Phytochemistry. 1990;  29 195-203
• 17 Miyase T, Ueno A, Noro T. Studies on sesquiterpenes glycosides from Crepis japonica BENTH.  Chem Pharm Bull. 1985;  33 4451-4456
• 18 Miyasw T, Yamada M, Fukushima S. Studies on sesquiterpene glycosides from Prenanthes acerifolia BENTH.  Chem Pharm Bull. 1987;  35 1969-1974
• 19 Seto M, Miyase T, Seigo F. Sesquiterpene lactones from Ixeris dentate NAKAI.  Chem Pharm Bull. 1986;  34 4170-4176
• 20 Miyase T, Yamaki K, Fukushima S. Studies on sesquiterpenes from Macroclinidium trilobum MAKINO.I.  Chem Pharm Bull. 1984;  32 3912-3917
• 21 Miyase T, Kuroyanagi M, Noro T, Ueno A, Fukushima S. Studies on sesquiterpenes from Macroclinidium trilobum MAKINO. II.  Chem Pharm Bull. 1985;  33 4445-4450
• 22 Bohlmann F, Ahmed M, Jakupovic J, King R M, Robinson H. Dimeric sesquiterpene lactones and kolavane derivatives from Gochnatia paniculata.  Phytochemistry. 1983;  22 191-195
• 23 Fortuna A M, de Riscala E C, Catalan C A N, Gedris T E, Herz W. Sesquiterpene lactones from Centaurea tweediei.  Biochem Syst Ecol. 2001;  29 967-971
• 24 Helal A M, Nakamura N, Meselhy M R, El-Fishawy A M, Hattori M, Mahran G H. Guaianolides from Centaurea scoparia.  Phytochemistry. 1997;  45 551-554
• 25 Mericli A H, Tuzlaci E. Constituents of Turkish Onopordum species–a new endesmane from O. anatolicum.  Pharmazie. 1989;  44 303
• 26 Calixto J B, Otuki M F, Santos A R. Anti-inflammatory compounds of plant origin. Part I. Action on arachidonic acid pathway, nitric oxide and nuclear factor κ B.  Planta Med. 2003;  69 973-983

Reference (Erratum)

• 1 Wang Y, Shen Y H, Jin H Z, Fu J J, Hu X J, Qin J J, Liu J H, Chen M, Yan S K, Zhang W D. Ainsliatrimers A and B, the first two guaianolide trimers from Ainsliaea fulvioides.  Org Lett. 2008;  10 5517-5520