Betulinic acids are lupine-type pentacyclic triterpenoid saponins commonly found in some plants of Betulaceae family, especially in the bark of betula alba (birch). The potent anti-HIV and anti-tumor activities of betulinic acids have been greatly concerned. The natural betulinic acids include betulinic acid, 23-hydroxy betulinic acid, betulin and so on. Some investigations on the structural modifications of betulinic acids were carried out, and many derivatives with excellent biological activity have been obtained nowadays. In this paper, the research advances of the structural modification of betulinic acids, as well as their anti-HIV and anti-tumor activities are reviewed.
Anti-HIV Agents ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Betula ; chemistry ; Cell Line, Tumor ; HIV ; drug effects ; Humans ; Plant Bark ; chemistry ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Triterpenes ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; therapeutic use

The objective of this study was to explore the immunomodulatory effects of betulinic acid (BA) extracted from the bark of white birch on mice. Female mice were orally administered BA for 14 days in doses of 0, 0.25, 0.5, and 1 mg/kg body weight. We found that BA significantly enhanced the thymus and spleen indices, and stimulated lymphocyte proliferation induced by Concanavalin A and lipopolysaccharide as shown by MTT assay. Flow cytometry revealed that BA increased the percentage of CD4+ cells in thymus as well as the percentage of CD19+ and the ratios of CD4+/CD8+ in spleen. BA increased the number of plaque-forming cell and macrophage phagocytic activity as indicated by a neutral red dye uptake assay, and the peritoneal macrophages levels of TNF-alpha were also increased. In contrast, serum levels of IgG and IgM and serum concentrations of IL-2 and IL-6 were significantly decreased in BA-treated mice compared to the control as assayed by haemagglutination tests and ELISA, respectively. Taken together, these results suggest that BA enhances mouse cellular immunity, humoral immunity, and activity of macrophages. Thus, BA is a potential immune stimulator and may strengthen the immune response of its host.
Adaptive Immunity/*drug effects ; Animals ; Betula/*chemistry ; Cell Proliferation/drug effects ; Cytokines/blood ; Female ; Immunity, Innate/*drug effects ; Immunologic Factors/*pharmacology ; Macrophages/drug effects ; Mice ; Phagocytosis/drug effects ; Random Allocation ; Spleen/cytology ; Thymus Gland/cytology ; Triterpenes/*pharmacology

OBJECTIVETo investigate the anticancer effects of betulinic acid (BA) on Jurkat cells in vitro and its molecular mechanism.

METHODSThe effects of betulinic acid on the growth of Jurkat cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was assessed by Hoechst33258 staining and annexin-V/PI double-labeled cytometry. The effect of betulinic acid on the cell cycle of Jurkat cells was studied by propidium iodide staining. RT-PCR and Western blot were used to analyze the changes of cyclin D3, bcl-xl mRNA and protein levels in Jurkat cells after treatment with betulinic acid.

RESULTSThe proliferation of Jurkat cells was decreased in betulinic acid-treated group at a 24 h IC50 value of 70.0 micromol/L. The effect of betulinic acid to induce apoptosis in Jurkat cells was in a time- and dose-dependent manner. Jurkat cells treated with betulinic acid showed an increase of G0/G1 phase and decrease of S phase. The Jurkat cells treated with 0, 20, 60, 100 micromol/L betulinic acid for 24 h, showed an increased G0/G1 phase from 31.0% to 58.8%, whereas decreased S phase from 61.5% to 35.8%, respectively. PBMC was less sensitive to the cytotoxic effect of betulinic acid than Jurkat cells. The expression of cyclin D3, bcl-xl mRNA and protein were decreased sharply in Jurkat cells treated with betulinic acid.

CONCLUSIONBetulinic acid can inhibit the proliferation of Jurkat cells by regulating the cell cycle that arrests cells at G0/G1 phase and induces apoptosis in Jurkat cells. The antitumor effects of betulinic acid may be related to down-regulation of the expression of cyclin D3 and bcl-xl.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Betula ; chemistry ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cyclin D3 ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Jurkat Cells ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Triterpenes ; pharmacology ; bcl-X Protein ; genetics ; metabolism

OBJECTIVETo study the betulonic acid on the cell cycle and related protein expressions on mice of bearing H22 tumor cells.

METHODFlow cytometray was used to observe the changes of betulonic acid on the cell cycle and P53 of H22 tumor cells. Immunohistochemistry was determined the espressions of PI3K and AKT.

RESULTIncreasing the doses of betulonic acid, the number of H22 cells in S phase and G2 phase was increasing gradually, it can speculate that when the betulonic acid act on cells, the cells were blocked in S and G2 phase and inhibited the protein expressions of PI3K and AKT.

CONCLUSIONBetulonic acid may be up-regulate the activity of P53 and inhibite the expressions of PI3K and AKT, so that it inhibited the survival pathway of tumor cells.

Animals ; Betula ; chemistry ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Female ; Flow Cytometry ; G2 Phase ; drug effects ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Male ; Mice ; Neoplasm Transplantation ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Tumor Suppressor Protein p53 ; metabolism