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 μ M . 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 IC 50 values in the range of 269–363 mol ratio/32 pmol TPA, while these compounds exhibited no DPPH scavenging activities ( IC 50 >100 μ M ). On the other hand, the nine phenolic compounds, 1 – 9 , exhibited potent radical‐scavenging activities ( IC 50 1.4–10.9 μ M ) with weak inhibitory effects on EBV‐EA induction ( IC 50 460–518 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 ID 50 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 ( IC 50 13.9–73.2 μ M ).