Biological activities of phenolic compounds isolated from galls of Terminalia chebula Retz. (Combretaceae)

The aqueous extract of galls from Terminalia chebula Retz. (Combretaceae) was fractionated on Diaion and refractionated on octadecyl silica column. Six phenolic compounds were isolated and identified as gallic acid (1), punicalagin (2), isoterchebulin (3), 1,3,6-tri-O-galloyl-β-D-glucopyranose (4), chebulagic acid (5) and chebulinic acid (6). All of the compounds showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and melanin inhibitory activities than ascorbic acid, butylated hydroxytoluene, α-tocopherol, arbutin and kojic acid, the reference compounds. Gallic acid (1) exhibited inhibitory activity against nitric oxide production in lipopolysaccharide-activated macrophages. However, all isolated compounds exhibited less activity than the reference compounds in mushroom tyrosinase inhibition and human tumour cytotoxicity assays. This study has demonstrated that the phenolic compounds isolated from galls of T. chebula might contribute significantly due to their antioxidant and whitening activities.     

3-O-(E)-p-coumaroyl tormentic acid from Eriobotrya japonica leaves induces caspase-dependent apoptotic cell death in human leukemia cell line

Eleven triterpene acids, 1-11, isolated from the leaves of Eriobotrya japonica, were evaluated for inhibition of DNA topoisomerase (Topo) I and cytotoxicity against human leukemia (HL60) and melanoma cell lines (CRL1579). Among the compounds tested, four compounds, δ-oleanolic acid (4), ursolic acid (5), 3-O-(E)-p-coumaroyl tormentic acid (8), and betulinic acid (10), exhibited potent Topo I inhibitory activity (IC(50) 20.3-36.5 μM) and cytotoxicity against HL60 (EC(50) 5.0-8.1 μM). Upon assessing the apoptosis-inducing activity in HL60 cells, compound 8 exhibited induction of apoptosis detected by the observation of DNA fragmentation and membrane phospholipid exposure in flow cytometry. Western blot analysis showed that compound 8 markedly reduced the levels of procaspases-3 and 9, while being increased the levels of cleaved caspases-3 and 9. On the other hand, compound 8 exerted almost no influence on the expression of caspase-8. In addition, compound 8 increased significantly Bax/Bcl-2 ratio and activated caspase-2. These results suggested that compound 8 induced apoptotic cell death in HL60 via mainly mitochondrial pathway by, at least in part, Topo I inhibition. Therefore, compound 8 may be promising lead compound for developing an effective drug for treatment of leukemia.     

Molecular interactions between phospholipids and mangostin in a lipid bilayer

Molecular interactions between phospholipids and mangostin in a lipid bilayer have been investigated in terms of the maximum additive concentration (MAC) of mangostin in liposomes, the surface potential, particle size, microscopic-viscosity and microscopic-polarity of liposomes, and the permeability of glucose. The mangostin used is a natural product extract: 1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9-xanthenenone.

The MAC of mangostin was fairly dependent upon the nature of the liposomes (uncharged, negatively charged or positively charged). Solubilization of mangostin in the liposomal bilayer resulted in both an increase in the negative charge on the liposomal surface, strenghthening the state of the bilayer membrane, and a depression in the release of the glucose involved. Mangostin was found to temporarily stabilize the liposomal bilayer, although the bilayer membrane is still unstable in the long run.