The Boswellia species (Burseraceae), which are trees native to Ethiopia, Somalia, India, and the Arabic peninsula, produce a gum resin that is known as olibanum (frankincense). The resin of B. carteri and B. serrata has been used for the treatment of rheumatoid arthritis and other inflammatory diseases in the traditional medicine in many countries.
1)The search for the active principles of the resin resulted in the isolation of boswellic acids that belong to ursane-and oleanane-type pentacyclic triterpenes.1-6) These acids have also been shown to possess potential chemopreventive effects, e.g., these inhibited growth of brain tumor 7) and meningioma cells, 8) and induced apoptosis in human leukemia 9) and hepatoma cells. 10) In view of the pharmacological importance of the natural compounds derived from Boswellia resin, 1,6) we were especially interested to undertake investigation on the constituents of Boswellia resin in order to evaluate their further pharmacological potentials. In our recent paper, 11) we have reported the isolation and identification of fifteen triterpene acids (1-14, 16) and two diterpenes (17, 18) from the MeOH extract of the resin of B. carteri along with the evaluation of the inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice of compounds 1-14, 16-18, and 15 (the acetyl derivative of 14). This paper describes the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA in Raji cells and on activation of (Ϯ)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, and cytotoxic activities against three human neuroblastoma cell lines, IMR-32, NB-39, and SK-N-SH in vitro for compounds 1-18.
MATERIALS AND METHODS
Materials and ChemicalsThe olibanum resin with certified botanical origin, Boswellia carteri Birdwood (Somalia), was purchased from Scents of Earth (Sun City, CA, U.S.A.; http://www.scents-of-earth.com).11) Chemicals were purchased as follows: TPA from ChemSyn Laboratories (Lenexa, KS, U.S.A.), b-carotene, glyzyrrhizin, and cisplatin (CDDP) from Sigma Chemical Co. (St. Louis, MO, U.S.A.), the EBV cell culture reagents and n-butanoic acid from Nacalai Tesque, Inc. (Kyoto, Japan), and NOR 1 and carboxy-PTIO from Dojindo Laboratories (Kumamoto, Japan). Three human neuroblastoma cell lines, IMR-32, NB-39, and SK-N-SH, were maintained in RPMI-1640 medium (Invitrogen) supplemented with 100 U/ml penicillin, 100 mg/ml streptomycin, and 10% fetal bovine serum (FBS) (Invitrogen). All of them were maintained at 37°C/5% CO 2 in a humid environment.Extraction and Isolation Extraction of the resin of B. carteri and isolation of compounds 1-18 from the extract was described in our recent paper.11) In brief, the pulverized resin of B. carteri (10 g) was extracted with MeOH to yield extract (8.95 g). The extract was suspended in n-hexaneMeOH-H 2 O (19 : 19 : 2), giving n-hexane (5.05 g) and MeOH-H 2 O fractions. The latter fraction was partitioned in EtOAc-H 2 O (1 : 1, v/v), yielding E...