Cytotoxic Diterpenoids from the Roots of Aralia melanocarpa

Abstract

Five new diterpenoids (1–5) were isolated from the roots of Aralia melanocarpa, together with four known compounds, 7β-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (6), 18-norpimara-8(14),15-dien-4-ol (7), ent-16βH,17-isovalerate-kauran-19-oic acid (8), and ent-16α,17-dihydroxykauran-19-oic acid (9). Based on the MS, IR, and NMR spectral analysis, the structures of the five new diterpenoids (1–5) were elucidated. The cytotoxic activities of compounds 1–9 were assayed, and compounds 1 and 2 showed cytotoxicity in four cancer cell lines with IC₅₀s from 4.2 to 8.2 µM.

Key words

Aralia melanocarpa - Araliaceae - ent-pimarane - diterpenoid - cytotoxicity

• References

• 1 Flora of China Editorial Committee, Chinese Academy of Sciences. Flora of China, Vol. 54. Beijing: Science Press; 1978: 173-174
• 2 Collection of Chinese Herbal Medicines Compilation Group. Collection of Chinese Herbal Medicines, Vol. 2. Beijing: Peopleʼs Medical Publishing House; 1978: 197
• 3 Hanson JR, White AF. Diterpenes of spikenard root (Aralia racemosa). Phytochemistry 1970; 9: 1359-1361
• 4 Kang OH, Chae HS, Choi JG, Oh YC, Lee YS, Kim JH, Seung MJ, Jang HJ, Bae KH, Lee JH, Shin DW, Kwon DY. ent-Pimara-8(14), 15-dien-oic acid isolated from the roots of Aralia cordata inhibits induction of inflammatory mediators by blocking NF-κB activation and mitogen-activated protein kinase pathways. Eur J Pharmacol 2008; 601: 179-185
• 5 Choi RJ, Shin EM, Jung HA, Choi JS, Kim YS. Inhibitory effects of kaurenoic acid from Aralia continentalis on LPS-induced inflammatory response in RAW264.7 macrophages. Phytomedicine 2011; 18: 677-682
• 6 Cho JH, Lee JY, Sim SS, Whang WK, Kim CJ. Inhibitory effects of diterpene acids from root of Aralia cordata on IgE-mediated asthma in guinea pigs. Pulm Pharmacol Ther 2010; 23: 190-199
• 7 Lyu JH, Lee GS, Kim KH, Kim HW, Cho SI, Jeong SI, Kim HJ, Ju YS, Kim HK, Sadikot RT, Christman JW, Oh SR, Lee HK, Ahn KS, Joo M. ent-Kaur-16-en-19-oic acid, isolated from the roots of Aralia continentalis, induces activation of Nrf2. J Ethnopharmacol 2011; 137: 1442-1449
• 8 Wang QH, Zhang J, Ma X, Ye XY, Yang BY, Xia YG, Kuang HX. A new triterpenoid saponin from the leaves of Aralia elata . Chin J Nat Med 2011; 9: 17-21
• 9 Hsiao JJ, Chiang HC. Lignans from the wood of Aralia bipinnata . Phytochemistry 1995; 39: 899-902
• 10 Miyase T, Sutoh N, Zhang DM, Ueno A. Araliasaponins XII–XVIII, triterpene saponins from the roots of Aralia chinensis . Phytochemistry 1996; 42: 1123-1130
• 11 Nhiem NX, Lim HY, Kiem PV, Minh CV, Thu VK, Tai BH, Quang TH, Song SB, Kim YH. Oleanane-type triterpene saponins from the bark of Aralia elata and their NF-κB inhibition and PPAR activation signal pathway. Bioorg Med Chem Lett 2011; 21: 6143-6147
• 12 Satoh Y, Sakai S, Katsumata M, Nagasao M, Miyakoshi M, Ida Y, Shoji J. Oleanolic acid saponins from root-bark of Aralia elata . Phytochemistry 1994; 36: 147-152
• 13 Hu M, Ogawa K, Sashida Y, Xiao PG. Triterpenoid glucuronide saponins from root-bark of Aralia armata . Phytochemistry 1995; 39: 179-184
• 14 Lee MK, Hung TM, Min BS, Lee IS, Na MK, Woo MH, Son JK, Kim YH, Choi JS, Bae KH. Quantitative determination of diterpenoids from the roots of Aralia cordata . Nat Prod Sci 2009; 15: 50-54
• 15 Oh HL, Lim HY, Park Y, Lim Y, Koh HC, Cho YH, Lee CH. HY253, a novel compound isolated from Aralia continentalis, induces apoptosis via cytochrome c-mediated intrinsic pathway in HeLa cells. Bioorg Med Chem Lett 2009; 19: 797-799
• 16 Oh HL, Lee CH. HY251, a novel decahydrocyclopenta[a]indene analog, from Aralia continentalis induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells. Bioorg Med Chem Lett 2011; 21: 1347-1349
• 17 Lee JH, Jeong CS, Lee JH, Jeong C. Suppressive effects on the biosynthesis of inflammatory mediators by Aralia elata extract fractions in macrophage cells. Environ Toxicol Pharmacol 2009; 28: 333-341
• 18 Chung YS, Choi YH, Lee SJ, Choi S, Lee J, Kim H, Hong EK. Water extract of Aralia elata prevents cataractogenesis in vitro and in vivo . J Ethnopharmacol 2005; 101: 49-54
• 19 Jung HA, Lee EJ, Kim JS, Kang SS, Lee JH, Min BS, Choi JS. Cholinesterase and BACE1 inhibitory diterpenoids from Aralia cordata . Arch Pharm Res 2009; 32: 1399-1408
• 20 Lee CK, Fang JM, Cheng YS. Norditerpenes from Juniperus chinensis . Phytochemistry 1995; 39: 391-394
• 21 Kim YH, Kim HS, Lee SW, Uramoto M, Lee JJ. Kaurane derivatives from Acanthopanax koreanum . Phytochemistry 1995; 39: 449-451
• 22 Lin AS, Lin CR, Du YC, Lübken T, Chiang MY, Chen IH, Wu CC, Hwang TL, Chen SL, Yen MH, Chang FR, Wu YC. Acasiane A and B and farnesirane A and B, diterpene derivatives from the roots of Acacia farnesiana . Planta Med 2009; 75: 256-261
• 23 Rudi A, Kashman Y. Chelodane, barekoxide, and zaatirin- three new diterpenoids from the marine sponge Chelonaplysilla erecta . J Nat Prod 1992; 55: 1408-1414
• 24 Kuniyoshi M, Marma MS, Higa T, Bernardinelli G, Jefford CW. 3-Bromobarekoxide, an unusual diterpene from Laurencia luzonensis . Chem Commun 2000; 13: 1155-1156
• 25 Zinkel DF, Spalding BR. Structure of strobic acid. Tetrahedron 1973; 29: 1441-1444
• 26 Demaro PV, Farkas E, Doddrell D, Mylari BL, Wenkert E. Pyridine-induced solvent shifts in the nuclear magnetic resonance spectra of hydroxylic compounds. J Am Chem Soc 1968; 90: 5480-5486
• 27 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63