Influence of betulinic acid on lymphocyte subsets and humoral immune response in mice

• Autorzy: Jine Y. , Lis M. , Szczypka M. , Obminska-Mrukowicz B.
• Języki publikacji: EN

Abstrakty

EN

Betulinic acid is a pentacyclic triterpene found in many plant species, among others, in the bark of white birch Betula alba. Betulinic acid was reported to display a wide range of biological effects, including antiviral, antiparasitic, antibacterial, anticancer and anti-inflammatory activities. The effects of betulinic acid (50, 5, 0.5 mg/kg) administered orally five times at 24 hours intervals to non-immunized and red blood cells (SRBC)-immunized mice were determined. The present study examined the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes, and the percentage of subsets of T cells (CD4+CD8+, CD4-CD8-, CD4+, CD8+) in thymus, T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the spleen and mesenteric lymph nodes, as well as white blood cell (WBC) and differential leukocyte counts in non-immunized mice, and humoral immune response in SRBC-immunized mice. SRBC was injected 24 hours after administration of the last dose of betulinic acid. It was found that betulinic acid administered orally five times at the dose of 0.5 mg/kg increased the total number of thymocytes, splenocytes, lymphocytes of mesenteric lymph node cells, and the weight ratio of the spleen and mesenteric lymph nodes in non-immunized mice. Betulinic acid also changed the percentage of T cell subsets in the thymus and T and B lymphocytes in peripheral lymphatic organs. The effects of betulinic acid on T and B cell subpopulations depended on the dose applied. The strongest stimulating effect of betulinic acid was observed when the drug was administered at the dose of 0.5 mg/kg. Five exposures to betulinic acid (0.5 mg/kg) decreased the percentage of immature CD4+CD8+ thymic cells with corresponding increases in the percentage and absolute count of mature, single-positive CD4+ thymocytes and decreased the percentage and total count of CD3+ splenocytes and mesenteric lymph node cells with corresponding decreases in the percentage and absolute count of CD4+ and CD8+ cells. Multiple administration of betulinic acid at the investigated doses augmented the percentage and absolute count of CD19+ cells in the peripheral lymphatic organs. Moreover, betulinic acid at the dose of 5 mg/kg administered prior to SRBC immunization increased the number of plaque forming cells (PFC) but decreased the production of anti-SRBC antibodies on day 4 after priming. Thus, betulinic acid is a potential biological response modifier and may strengthen the immune response of its host.

• Wydawca: -
• Czasopismo: Polish Journal of Veterinary Sciences
• Rocznik: 2012
• Tom: 15
• Numer: 2
• Opis fizyczny: p.305-313,fig.,ref.

Twórcy

autor

Jine Y.

• College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China

autor

Lis M.

autor

Szczypka M.

autor

Obminska-Mrukowicz B.

Bibliografia

• Bauvois B, Dauzonne D (2006) Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations and therapeutic prospects. Med Res Rev 26: 88-130.
• Chandramu C, Manohar RD, Krupadanam DG, Dashavantha RV (2003) Isolation, characterization and biological activity of betulinic acid and ursolic acid from Vitex negundo L. Phytother Res 17: 129-134.
• Cichewicz RH, Kouzi SA (2004) Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med Res Rev 24: 90-114.
• Dang Z, Lai W, Qian K, Ho P, Lee KH, Chen CH, Huang L (2009) Betulinic acid derivatives as human immunodeficiency virus type 2 (HIV-2) inhibitors. J Med Chem 52: 7887-7891.
• Eichenmuller M, Hemmerlein B, von Schweinitz D, Kappler R (2010) Betulinic acid induces apoptosis and inhibits hedgehog signaling in rhabdomyosarcoma. Br J Cancer 103: 43-51.
• Kindt TJ, Osborne BA, Goldsby RA (2007) Kuby Immunology. 6th ed., WH Freeman and Company, New York, USA, pp. 37-44
• Kommera H, Kaluderovic GN, Kalbitz J, Paschke R (2011) Lupane triterpenoids- betulin and betulinic acid derivatives induce apoptosis in tumor cells. Invest New Drugs 29: 266-272.
• Look AT, Ashmun RA, Shapiro LH, Peiper SC (1989) Human myeloid plasma membrane glycoprotein CD 13 (gp150) is identical to aminopeptidase N. J Clin Invest 83: 1299-1307.
• Luan Y, Xu W (2007) The structure and main functions of aminopeptidase N. Curr Med Chem 14: 639-647.
• Melzig MF, Bormann H (1998) Betulinic acid inhibits aminopeptidase N activity. Planta Med 64: 655-657.
• Mishell RI, Dutton RW (1967) Immunization of dissociated spleen cell cultures from normal mice. J Exp Med 126: 423-442.
• Mullauer FB, Kessler JH, Medema JP (2010) Betulinic acid, a natural compound with potent anticancer effects. Anticancer Drugs 21: 215-227.
• Nakagawa-Goto K, Yamada K, Taniguchi M, Tokuda H, Lee KH (2009) Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents. Bioorg Med Chem Lett 19: 3378-3381.
• Recio MC, Giner RM, Manez S, Gueho J, Julien HR, Hostettmann K, Rios JL (1995) Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas. Planta Med 61: 9-12.
• Schuhly W, Heilmann J, Calis I, Sticher O (1999) New triterpenoids with antibacterial activity from Zizyphus joazeiro. Planta Med 65: 740-743.
• Viji V, Helen A, Luxmi VR (2011) Betulinic acid inhibits endotoxin-stimulated phosphorylation cascade and pro-inflammatory prostaglandin E(2) production in human peripheral blood mononuclear cells. Br J Pharmacol 162: 1291-1303.
• Xu W, Li Q (2005) Progress in the development of aminopeptidase N (APN/CD13) inhibitors. Curr Med Chem Anticancer Agents 5: 281-301.
• Yamashita K, Lu H, Lu J, Chen G, Yokoyama T, Sagara Y, Manabe M, Kodama H (2002) Effect of three triterpenoids, lupeol, betulin, and betulin acid on the stimu-lus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Clin ChimActa 325: 91-96.
• Yi JE, Obmińska-Mrukowicz B, Yuan LY, Yuan H (2010) Immunomodulatory effects of betulinic acid from thebark of white birch on mice. J Vet Sci 11: 305-313.
• Yogeeswari P, Sriram D (2005) Betulinic acid and its derivatives: a review on their biological properties. Curr Med Chem 12: 657-666.
• Yun Y, Han S, Park E, Yim D, Lee S, Lee CK, Cho K, Kim K (2003) Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages. Arch Pharm Res 26: 1087-1095.
• Zdzisińska B, Rzeski W, Paduch R, Szuster-Ciesielska A, Kaczor J, Wejksza K, Kandefer-Szerszeń M (2003) Differential effect of betulin and betulinic acid on cytokine production in human whole blood cell cultures. Pol J Pharmacol 55: 235-238.

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