lupeol and betulin

Impaired wound healing is one of the main risk factors associated with diabetes mellitus. Few options are available to treat diabetic wounds, and therefore efficient remedies are urgently needed. An interesting option might be an extract of birch bark (TE) that has been clinically proven to accelerate acute wound healing. We investigated the effects of TE and its main components betulin and lupeol in cultured normal keratinocytes and dermal fibroblasts from diabetic and nondiabetic donors. These in vitro models can provide insights into possible beneficial effects in wound healing. TE and betulin treatment led to increased mRNA levels of chemokines, pro-inflammatory cytokines, and mediators important in wound healing, e.g., IL-6, TNFα, IL-8, and RANTES. We observed a pronounced upregulation of MIF, IL-8, and RANTES on the protein level. Furthermore, a shape change of the actin cytoskeleton was seen in keratinocytes and fibroblasts, and the Rho-GTPases and p38-MAPK were found to be activated in keratinocytes. On the basis of our results, TE is worthy of further study as a potential option to influence wound-healing processes under diabetic conditions. These first insights need to be confirmed by clinical studies with diabetic patients.

Topics: Betula; Cytokines; Diabetes Mellitus; Female; Fibroblasts; Humans; Interleukin-6; Interleukin-8; Keratinocytes; p38 Mitogen-Activated Protein Kinases; Pentacyclic Triterpenes; Plant Bark; rho GTP-Binding Proteins; Triterpenes; Wound Healing

The concise synthesis, via a stepwise glycosylation approach, of lupeol, betulin and betulinic acid O-glycosides bearing a chacotriosyl moiety at the C-3 position is described. All neosaponins as well as their rearrangement products of the germanicane-type were evaluated in vitro for their anticancer and haemolytic activities. Although betulinic acid and betulin 3beta-O-chacotriosides were neither cytotoxic nor haemolytic, their rearrangement products allobetulin and 28-oxoallobetulin 3beta-O-chacotriosides (9 and 10) exhibited a cytotoxicity profile up to fourfold superior to betulinic acid against human breast (MCF7) and prostate (PC-3) adenocarcinomas cell lines (IC(50)=10-18 microM). One important result was that only chacotriosides featuring non-polar functions at the C-28 position (6, 9 and 10) exerted a haemolytic activity against red blood cells.

Topics: Animals; Cell Line, Tumor; Cytotoxins; Erythrocytes; Hemolytic Agents; Humans; Saponins; Sheep; Triterpenes; Tropanes

Two new triterpenoids, 18alpha,19beta-20(30)-taraxasten-3beta,21alpha-diol (cichoridiol) (1) and 17-epi-methyl-6-hydroxyangolensate (intybusoloid) (2), were obtained from the methanolic extract of seeds of Cichorium intybus along with 11 known compounds, lupeol (3), friedelin (4), beta-sitosterol (5), stigmasterol (6), betulinic acid (7), betulin (8), betulinaldehyde (9), syringic acid (10), vanillic acid (11) 6,7-dihydroxycoumarin (12), and methyl-alpha-D-galactopyranoside (13). Compounds 1, 1a, and 11 showed a good alpha-glucosidase inhibitory activity.

Topics: alpha-Glucosidases; Cichorium intybus; Glycoside Hydrolase Inhibitors; Molecular Structure; Pentacyclic Triterpenes; Plants, Medicinal; Saccharomyces; Seeds; Triterpenes

In a study to investigate the relationship between the chemical structure and the differentiation-inducing activity of pentacyclic triterpenes, several lupane, oleanane, and ursane triterpenes were prepared and their effects on B16 2F2 melanoma cell differentiation and growth were examined. Eleven lupane triterpenes used in this study acted on the melanoma cells as a melanogen, but no induction of melanogenesis of B16 2F2 cells by oleanane and ursane was detected. The differences at C-17 of the lupane series and acetylation of the OH group at C-3 did not markedly influence their activities. However, the ED(50) value for up-regulation of melanin biosynthesis was markedly decreased by the oxidation of the OH group at C-3 of lupeol (1). Betulinic acid (11), its methyl ester (12), lup-28-al-20(29)-ene-3beta-ol (9), and lup-28-al-20(29)-en-3-one (10) inhibited B16 2F2 cell proliferation by induction of apoptosis. These findings suggested that the carbonyl group at C-17 might be essential for the apoptotic effects of these compounds on B16 2F2 cells.

Topics: Animals; Apoptosis; Betulinic Acid; Cell Differentiation; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Melanoma, Experimental; Mice; Molecular Structure; Oxidation-Reduction; Pentacyclic Triterpenes; Pyridinium Compounds; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Triterpenes; Tumor Cells, Cultured

DNA topoisomerases (Topos) are enzymes that play a crucial role in DNA metabolism events such as replication, transcription, recombination, and chromosome segregation at mitosis. Thus, Topo inhibitors could be expected to have antitumor effects. Naturally occurring lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus were screened for human Topos I and II inhibitory activities. Olean-12-en-3 beta,15 alpha-diol (1), olean-12-en-3 beta,15 alpha,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo II activity with IC(50) values in the range of 10-39 microM.

Topics: Antineoplastic Agents, Phytogenic; DNA; Dose-Response Relationship, Drug; Electrophoresis, Agar Gel; Enzyme Inhibitors; Etoposide; Humans; Inhibitory Concentration 50; Molecular Structure; Oleanolic Acid; Pentacyclic Triterpenes; Phyllanthus; Plant Bark; Plants, Medicinal; Plasmids; Stereoisomerism; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Triterpenes