Immunomodulatory effects of betulinic acid from the bark of white birch on mice

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-α 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.

[1]  Yong Li,et al.  Immunomodulatory effects of marine oligopeptide preparation from Chum Salmon (Oncorhynchus keta) in mice , 2009 .

[2]  A. Kijjoa,et al.  Immunomodulatory effects of Abnormal Savda Munsiq, a traditional Uighur medicine, on the combined stress mice. , 2009, Journal of ethnopharmacology.

[3]  K. Suresh,et al.  Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: implications for immunoadjuvant potential. , 2009, Journal of ethnopharmacology.

[4]  H. Meisel Editorial [Hot Topic:Food-Derived Bioactive Proteins and Peptides as Potential Components of Nutraceuticals (Executive Editor: H. Meisel)] , 2007 .

[5]  S. Alakurtti,et al.  Pharmacological properties of the ubiquitous natural product betulin. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[6]  J. Scheller,et al.  Interleukin‐6 Trans‐Signalling in Chronic Inflammation and Cancer , 2006, Scandinavian journal of immunology.

[7]  I. Bae,et al.  Purification and identification of angiotensin I-converting enzyme inhibitory peptide from buckwheat (Fagopyrum esculentum Moench) , 2006 .

[8]  G. Tolstikov,et al.  Activation of apoptosis by derivatives of betulinic acid in human tumor cells in vitro , 2006, Doklady Biochemistry and Biophysics.

[9]  Dominique Charron,et al.  MHC class II signaling in antigen-presenting cells. , 2004, Current opinion in immunology.

[10]  E. Park,et al.  Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages , 2003, Archives of pharmacal research.

[11]  W. Rzeski,et al.  Differential effect of betulin and betulinic acid on cytokine production in human whole blood cell cultures. , 2003, Polish journal of pharmacology.

[12]  G. Tolstikov,et al.  Synthesis of Betulinic Acid from Betulin Extract and Study of the Antiviral and Antiulcer Activity of Some Related Terpenoids , 2002, Pharmaceutical Chemistry Journal.

[13]  K. Ogihara,et al.  Three new naphthoquinone derivatives from Diospyros maritima Blume. , 2002, Chemical & pharmaceutical bulletin.

[14]  T. Scior,et al.  Ethnopharmacology and bioinformatic combination for leads discovery: application to phospholipase A(2) inhibitors. , 2001, Phytochemistry.

[15]  Simon A. Jones,et al.  The soluble interleukin 6 receptor: mechanisms of production and implications in disease , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  J. Heilmann,et al.  New triterpenoids with antibacterial activity from Zizyphus joazeiro. , 1999, Planta medica.

[17]  S. Kuo,et al.  Terpenoids of Syzygium formosanum. , 1999, Journal of natural products.

[18]  G. Bringmann,et al.  Betulinic acid: isolation from Triphyophyllum peltatum and Ancistrocladus heyneanus, antimalarial activity, and crystal structure of the benzyl ester. , 1997, Planta medica.

[19]  Geoffrey A. Cordell,et al.  Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis , 1995, Nature Medicine.

[20]  M. Recio,et al.  Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas. , 1995, Planta medica.

[21]  R. Sasaki,et al.  Isolation and characterization of oryzatensin: a novel bioactive peptide with ileum-contracting and immunomodulating activities derived from rice albumin. , 1994, Biochemistry and molecular biology international.

[22]  K. Murphy,et al.  Role of cytokines in determining T-lymphocyte function. , 1994, Current opinion in immunology.

[23]  W. Janzen,et al.  Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids. , 1994, Journal of natural products.

[24]  F. Yamauchi,et al.  Immunological effects of dietary peptide derived from soybean protein , 1993 .

[25]  P. Galan,et al.  Lymphocyte subpopulations in the thymus, lymph nodes and spleen of iron-deficient and rehabilitated mice. , 1991, The Journal of nutrition.

[26]  F. L. Adler STUDIES ON MOUSE ANTIBODIES. II. MERCAPTOETHANOL-SENSITIVE 7 S ANTIBODIES IN MOUSE ANTISERA TO PROTEIN ANTIGENS. , 1965, Journal of immunology.

[27]  A. Durnev,et al.  Immunotoxicity and allergenic properties of betulin-containing birch bark dry extract , 2007, Pharmaceutical Chemistry Journal.

[28]  T. Hirano,et al.  IL-6 signal transduction and its physiological roles: the signal orchestration model. , 2003, Reviews of physiology, biochemistry and pharmacology.

[29]  N. Enwerem,et al.  Anthelmintic activity of the stem bark extracts of Berlina grandiflora and one of its active principles, Betulinic acid. , 2001, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[30]  S. Constant,et al.  Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. , 1997, Annual review of immunology.