Biological activities of phenolic compounds and triterpenoids from the galls of Terminalia chebula.
Nine phenolic compounds, including two phenolic carboxylic acids, 1 and 2, seven hydrolyzable tannins, 3-9, eight triterpenoids, including four oleanane-type triterpene acids, 10-13, and four of their glucosides, 14-17, isolated from a MeOH extract of the gall of Terminalia chebula Retz. (myrobalan tree; Combretaceae), were evaluated for their inhibitory activities against melanogenesis in B16 melanoma cells induced by α-melanocyte-stimulating hormone (α-MSH), against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, and against TPA-induced inflammation in mice. Their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and cytotoxic activities against four human cancer cell lines were also evaluated. Compounds 6-9 and 12 exhibited potent inhibitory activities against melanogenesis (39.3-66.3% melanin content) with low toxicity to the cells (74.5-105.9% cell viability) at a concentration of 10 μM. Western-blot analysis revealed that isoterchebulin (8) reduced the protein levels of MITF (=microphtalmia-associated transcription factor), tyrosinase, and TRP-1 (=tyrosine-related protein 1), mostly in a concentration-dependent manner. Eight triterpenoids, 10-17, showed potent inhibitory effects on EBV-EA induction with the IC50 values in the range of 269-363 mol ratio/32 pmol TPA, while these compounds exhibited no DPPH scavenging activities (IC50 >100 μM). On the other hand, the nine phenolic compounds, 1-9, exhibited potent radical-scavenging activities (IC50 1.4-10.9 μM) with weak inhibitory effects on EBV-EA induction (IC50 460-518 mol ratio/32 pmol TPA). The tannin 6 and seven triterpenoids, 10-16, have been shown to inhibit TPA-induced inflammation (1 μg/ear) in mice with the ID50 values in the range of 0.06-0.33 μmol/ear. Arjungenin (10) exhibited inhibitory effect on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and with TPA as promoter. Compounds 1, 2, 4, 5, 7-9, 12, and 13, against HL60 cell line, compounds 1 and 4, against AZ521 cell line, and compounds 1, 11, and 12, against SK-BR-3 cell line, showed moderate cytotoxic activities (IC50 13.9-73.2 μM).
Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand. pmpti005@chiangmai.ac.th
Aranya
A
Manosroi
Pensak
P
Jantrawut
Eri
E
Ogihara
Ayako
A
Yamamoto
Makoto
M
Fukatsu
Ken
K
Yasukawa
Harukuni
H
Tokuda
Nobutaka
N
Suzuki
Jiradej
J
Manosroi
Toshihiro
T
Akihisa
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D017495:Hyperpigmentation / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D008543:Melanins / Q000037:antagonists & inhibitors; D000432:Methanol / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D029766:Terminalia / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
D016166:Free Radical Scavengers; D008543:Melanins; D010636:Phenols; D014315:Triterpenes; D000432:Methanol
Anti-inflammatory activity; Anti-tumor-promoting activity; Antioxidant activity; Cytotoxic activity; Melanogenesis inhibition; Tannins; Terminalia chebula; Triterpenoids