Polyacetylenes from Radix et Rhizoma Notopterygii Incisi with an Inhibitory Effect on Nitric Oxide Production In Vitro

Abstract

Notopterygium roots (Qiang Huo) have been used in traditional Chinese medicine for treating colds, inflammatory diseases like rheumatoid arthritis, and as an analgesic. The anti-inflammatory activity of the roots of Notopterygium incisum has been evaluated by testing the inhibitory activity on nitric oxide production by inducible nitric oxide synthase. The apparent authenticity of the sample was checked by DNA sequence comparison. Using activity-guided isolation, different compounds were isolated and structurally characterized by means of NMR and mass spectroscopy. Eight polyacetylenes could be identified and were tested on their inhibitory activity on nitric oxide production in RAW 264.7 mouse macrophages using the Griess assay. Different 3-hydroxy allyl polyacetylenes exhibited significant activity (IC₅₀: 8-acetoxyfalcarinol, 20.1 µM; falcarindiol, 9.2 µM; 9-epoxyfalcarindiol, 8.8 µM; and crithmumdiol, 23.6 µM).

Key words

Notopterygium incisum - Apiaceae - polyacetylenes - nitric oxide - iNOS - Griess assay - DNA sequencing

• References

• 1 Pharmacopoeia Commission of Peopleʼs Republic of China. Pharmacopoeia of the Peopleʼs Republic of China, 2010 edition. Beijing: China Medical Science Press; 2010: 299-300
• 2 Yan YQ, Yu CL, Huang TK, Ding ZZ, Gao XL, Zhang ZD. Dictionary of Chinese Medicine. Beijing: China Medico-Pharmaceutical Science and Technology Publishing House; 1996: 372-376
• 3 Sun Y, Xu Q. Aqueous extract from Rhizoma Notopterygii reduces contact sensitivity by inhibiting lymphocyte migration via down-regulating mettalloproteinase activity. Pharmacol Res 2002; 46: 333-337
• 4 Okuyama E, Nishimura S, Ohmori S, Ozaki Y, Satake M, Yamazaki M. Analgesic component of Notopterygium incisum TING. Chem Pharm Bull 1993; 41: 926-929
• 5 Zschocke S, Lehner M, Bauer R. 5-Lipoxygenase and cyclooxygenase inhibitory active constituents from Qianghuo (Notopterygium incisum). Planta Med 1997; 63: 203-206
• 6 Mitsui S, Torii K, Fukui H, Tsujimura K, Maeda A, Nose M, Nagatsu A, Mizukami H, Morita A. The herbal medicine compound falcarindiol from Notopterygii Rhizoma suppresses dendritic cell maturation. J Pharmacol Exp Ther 2010; 333: 954-960
• 7 Tang SY, Cheah IK, Wang H, Halliwell B. Notopterygium forbesii Boiss extract and its active constituent phenethyl ferulate attenuate pro-inflammatory responses to lipopolysaccharide in RAW 264.7 macrophages. A “protective” role for oxidative stress?. Chem Res Toxicol 2009; 22: 1473-1482
• 8 Clancy RM, Amin AR, Abramson SB. The role of nitric oxide in inflammation and immunity. Arthritis Rheum 1998; 41: 1141-1151
• 9 Kleinert H, Pautz A, Linker K, Schwarz PM. Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 2004; 500: 255-266
• 10 Heubl G. New aspects of DNA-based authentication of Chinese medicinal plants by molecular biological techniques. Planta Med 2010; 76: 1963-1974
• 11 Sucher NJ, Carles MC. Genome-based approaches to the authentication of medicinal plants. Planta Med 2008; 74: 603-623
• 12 Doyle J. DNA protocols for plants. In: Hewitt GM, Johnston AWB, Young JPW, editors Molecular techniques in taxonomy.1st edition. Berlin: Springer; 1991: 283-285
• 13 Tamura K, Dudley J, Nei M, Kumar S. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 2007; 24: 1596-1599
• 14 Dang NH, Zhang XF, Zheng MS, Son KH, Chang HW, Kim HP, Bae K, Kang SS. Inhibitory constituents against cyclooxygenases from Aralia cordata Thunb. Arch Pharm Res 2005; 28: 28-33
• 15 Eckenbach U, Lampman RL, Seigler DS, Ebinger J, Novak RJ. Mosquitocidal activity of acetylenic compounds from Cryptotaenia canadensis . J Chem Ecol 1999; 25: 1885-1893
• 16 Schmiech L, Alayrac C, Witulski B, Hofmann T. Structure determination of bisacetylenic oxylipins in carrots (Daucus carota L.) and enantioselective synthesis of falcarindiol. J Agric Food Chem 2009; 57: 11030-11040
• 17 Appendino G, Pollastro F, Verotta L, Ballero M, Romano A, Wyrembek P, Szczuraszek K, Mozrzymas J, Taglialatela-Scafati O. Polyacetylenes from Sardinian Oenanthe fistulosa: a molecular clue to risus sardonicus . J Nat Prod 2009; 72: 962-965
• 18 Deng S, Chen SN, Yao P, Nikolic D, van Breemen RB, Bolton JL, Fong HHS, Farnsworth NR, Pauli GF. Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis . J Nat Prod 2006; 69: 536-541
• 19 Deng S, Wang Y, Inui T, Chen SN, Farnsworth NR, Cho S, Franzblau SG, Pauli GF. Anti-TB polyynes from the roots of Angelica sinensis . Phytother Res 2008; 22: 878-882
• 20 Ruberto G, Vincenzo A. Crithmumdiol: a new C17-acetylene derivative from Crithmum maritimum . Planta Med 1999; 65: 681-682
• 21 Yamazoe S, Hasegawa K, Shigemori H. Growth inhibitory indole acetic acid polyacetylenic ester from Japanese ivy (Hedera rhombea Bean). Phytochemistry 2007; 68: 1706-1711
• 22 Huang HQ, Zhang X, Shen YH, Su J, Liu XH, Tian JM, Lin S, Shan L, Zhang WD. Polyacetylenes from Bupleurum longiradiatum . J Nat Prod 2009; 72: 2153-2157
• 23 Bohlmann F, Miethe R. Polyacetylenverbindungen, 196. Synthesen von Acetylenverbindungen aus Oenanthe crocata L. und Pittosporum buchanani Hook. Chem Ber 1971; 104: 1362-1374
• 24 Hirakura K, Takagi H, Morita M, Nakajima K, Niitsu K, Sasaki H, Maruno M, Okada M. Cytotoxic activity of acetylenic compounds from Panax ginseng . Nat Med 2000; 54: 342-345
• 25 Kobayashi M, Mahmud T, Umezome T, Wang W, Murakami N, Kitagawa I. The absolute stereostructures of the polyacetylenic constituents of Ginseng Radix Rubra. Tetrahedron 1997; 53: 15691-15700
• 26 Mayer SF, Steinreiber A, Orru RVA, Faber K. Chemoenzymatic asymmetric total syntheses of antitumor agents (3R,9R,10R)- and (3S,9R,10R)-panaxytriol and (R)- and (S)-falcarinol from Panax ginseng using an enantioconvergent enzyme-triggered cascade reaction. J Org Chem 2002; 67: 9115-9121
• 27 Hirakura K, Morita M, Nakajima K, Ikeya Y, Mitsuhashi H. Three acetylenic compounds from roots of Panax ginseng . Phytochemistry 1992; 31: 899-903
• 28 Schinkovitz A, Stavri M, Gibbons S, Bucar F. Antimycobacterial polyacetylenes from Levisticum officinale . Phytother Res 2008; 22: 681-684
• 29 Bernart MW, Cardellina JH, Balaschak MS, Alexander MR, Shoemaker RH, Boyd MR. Cytotoxic falcarinol oxylipins from Dendropanax arboreus . J Nat Prod 1996; 59: 748-753
• 30 Ohtani I, Kusumi T, Kashman Y, Kakisawa H. High-field FT NMR application of Mosherʼs method. The absolute configurations of marine terpenoids. J Am Chem Soc 1991; 113: 4092-4096
• 31 Shiao Y, Lin Y, Sun Y, Chi C, Chen C, Wang C. Falcarindiol impairs the expression of inducible nitric-oxide synthase by abrogating the activation of IKK and JAK in rat primary astrocytes. Br J Pharmacol 2005; 144: 42-51
• 32 Baer HP, Schmidt K, Mayer B, Kukovetz WR. Pentamidine does not interfere with nitrite formation in activated RAW 264.7 macrophages but inhibits constitutive brain nitric oxide synthase. Life Sci 1995; 57: 1973-1980
• 33 Konkimalla VB, Blunder M, Bauer R, Efferth T. Inhibition of inducible nitric oxide synthase by bis(helenalinyl)glutarate in RAW264.7 macrophages. Biochem Pharmacol 2010; 79: 1573-1580