Three New Triterpenes from Nerium oleander and Biological Activity of the Isolated Compounds

Abstract

New ursane-type triterpene 1, oleanane-type triterpene 2, and dammarane-type triterpene 15 were isolated from the leaves of Nerium oleander together with 12 known triterpenes, 3beta-hydroxy-12-ursen-28-oic acid (ursolic acid, 3), 3beta,27-dihydroxy-12-ursen-28-oic acid (4), 3beta,13beta-dihydroxyurs-11-en-28-oic acid (5), 3beta-hydroxyurs-12-en-28-aldehyde (6), 28-norurs-12-en-3beta-ol (7), urs-12-en-3beta-ol (8), urs-12-ene-3beta,28-diol (9), 3beta-hydroxy-12-oleanen-28-oic acid (oleanolic acid, 10), 3beta,27-dihydroxy-12-oleanen-28-oic acid (11), 3beta-hydroxy-20(29)-lupen-28-oic acid (betulinic acid, 12), 20(29)-lupene-3beta,28-diol (betulin, 13), and (20S,24R)-epoxydammarane-3beta,25-diol (14). On the basis of their spectroscopic data, the structures of the new compounds 1, 2, and 15 were established as 3beta,20alpha-dihydroxyurs-21-en-28-oic acid, 3beta,12alpha-dihydroxyoleanan-28,13beta-olide, and (20S,24S)-epoxydammarane-3beta,25-diol, respectively. The anti-inflammatory activity of the seven isolated compounds and methyl esters of ursolic acid and oleanoic acid in vitro was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). The anticancer activity of the 14 isolated compounds, including 1, 2, 15, and methyl esters of ursolic acid and oleanolic acid in vitro was examined on the basis of the cell growth inhibitory activities toward three kinds of human cell lines.

Apoptosis-Induced Cell Death due to Oleanolic Acid in HaCaT Keratinocyte Cells -a Proof-of-Principle Approach for Chemopreventive Drug Development

“…XTT result (Figure 4) showed only a moderate cytotoxicity on HaCaT cells after 24, 48 and 72 hrs of incubation. However, OA was found to be very cytotoxic in the studies conducted previously (Ko et al, 1999;Jie et al, 2002;Fu et al, 2005) in various cancer cell lines.…”

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

“…Although its activity was relatively weak in several studies (Njoku et al, 1997;Kim et al, 2000;Chiang et al, 2003b;Fu et al, 2005), it did show some selectivity (Taniguchi et al, 2002). In vitro studies into 83's effects indicated that it acted by inducing apoptosis (Fernandes et al, 2003;Huang et al, 2003b;Urech et al, 2005), but it also had other effects: it inhibited the invasive, adhesive, and migration abilities of lung cancer cells (Huang et al, 2003b); showed antiangiogenic activity, possibly by inhibiting proliferation of vascular endothelial cells (Sohn et al, 1995); and induced differentiation, which does not proceed normally in some cancer types (Umehara et al, 1992).…”

“…5.3.5.2. Cancer: Several ursanes were active against cancer cell lines in vitro, including regelin (96), regelinol (97) (Hori et al, 1987), 3β-acetoxy-ursolic acid (103) Chiang et al, 2005), and α-amyrin (99) (weakly) (Fu et al, 2005). 3β-Acetoxy-ursolic acid (103) was also antimutagenic in the umu test (Miyazawa et al, 2005) and had antitumor activity in vivo (Dominic and Subbaiyan, 1993) and some aromatase-inhibiting activity in vitro (Jeong et al, 2000).…”

Beneficial actions of oleanolic acid in an experimental model of multiple sclerosis: A potential therapeutic role

“…It remains to be further investigated whether OA actions in neurovascular functions during EAE are exclusively related to its antiimmune/inflammatory properties or represent pleiotropic effects. Although some natural triterpenes have shown neuroprotective effects [36], inhibitory properties in arachidonic-acidmetabolizing enzymes [37], anti-oxidative properties and membrane-stabilizing actions [20], and inhibitory activity in the induction of ICAM-1 [38], no study to our knowledge had in fact been performed linking these actions to BBB integrity.…”