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

Abstract

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 ( ) 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.

Betulinic acid‑induced expression of nicotinamide adenine dinucleotide phosphate‑diaphorase in the immune organs of mice: A possible role of nitric oxide in immunomodulation

“…Although the function of NO in the thymus and spleen has not been demonstrated, the findings of the current study indicate that there is an association between the immunological effects induced by BetA. The major effect of BetA-induced NO appears to be involved in maintenance of the immune system ( 38 – 40 ) and the current results support other reports in which the presence of NO was demonstrated in the immune system ( 33 , 41 ).…”

Acute Thymic Involution and Mechanisms for Recovery

“…Several therapeutic agents such as betulinic acid have also been implicated in immune reconstitution and the reversal of ATI. These agents possess pharmacological properties that improve the cellular as well as humoral immunity (Choi et al 2016;Jine et al 2012;Mullauer et al 2010). Treatment with these agents enhances the total number of thymocytes, thus causing an increase in the thymus weight index (Yi et al 2010), and has a protective effect against DM-induced thymocyte apoptosis in mice (Yi et al 2016).…”

Phytochemical analyses of Ziziphus jujuba Mill. var. spinosa seed by ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry

“…25 It is also a potential biological response modier capable of strengthening the immune system of the host. 14 Both share similar structural characteristics as pentacyclic triterpene acid, which implies similar bioactivities.…”