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An aqueous birch leaf extract of Betula pendula inhibits the growth and cell division of inflammatory lymphocytes.
J Ethnopharmacol 2011; 136(3):444-51JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Leaf extracts of Betula pendula have been traditionally used for the treatment of patients with rheumatoid arthritis (RA) or osteoarthritis.

AIM OF THE STUDY

We investigated the anti-proliferative capacity of an aqueous leaf extract of Betula pendula (BPE) on human primary lymphocytes in vitro, because activated lymphocytes play a major role in the initiation and maintenance of RA.

MATERIALS AND METHODS

Lymphocyte proliferation and cell division was measured by the activity of mitochondrial dehydrogenases and by using the membrane-permeable dye carboxyfluorescein diacetate succinimidyl ester (CFSE), respectively. Apoptosis was analyzed by surface staining of phosphatidylserine and intracellular activation of effector caspases 3 and 7 in comparison to the drug methotrexate using flow cytometric and photometrical analysis. In addition, the impact of the extract on cell cycle distribution was investigated by propidium iodide staining of DNA. For the bioassays BPE concentrations of 10-160 μg/mL were investigated. A phytochemical analysis, using LC-MS and HPLC, was conducted to identify the polyphenolic constituents of the birch leaf extract.

RESULTS

Leaf extracts of Betula pendula inhibited the growth and cell division (CD8(+): 40 μg/mL: 45%; 80 μg/mL: 60%; 160 μg/mL: 87%) (CD4(+): 40 μg/mL: 33%; 80 μg/mL: 54%; 160 μg/mL: 79%) of activated, but not of resting T lymphocytes in a significant dose-dependent manner. The inhibition of lymphocyte proliferation due to apoptosis induction (compared to untreated control: 40 μg/mL: 163%; 80 μg/mL: 240%; 160 μg/mL: 348%) and cell cycle arrest was comparable to that of methotrexate. LC-MS analyses showed that the extract contains different quercetin-glycosides.

CONCLUSION

Our results give a rational basis for the use of Betula pendula leaf extract for the treatment of immune disorders, like rheumatoid arthritis, by diminishing proliferating inflammatory lymphocytes.

Authors+Show Affiliations

Center for Complementary Medicine, Department of Environmental Health Sciences, University Medical Centre Freiburg, Breisacher Strasse 115B, Freiburg, Germany. carsten.gruendemann@uniklinik-freiburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21619918

Citation

Gründemann, Carsten, et al. "An Aqueous Birch Leaf Extract of Betula Pendula Inhibits the Growth and Cell Division of Inflammatory Lymphocytes." Journal of Ethnopharmacology, vol. 136, no. 3, 2011, pp. 444-51.
Gründemann C, Gruber CW, Hertrampf A, et al. An aqueous birch leaf extract of Betula pendula inhibits the growth and cell division of inflammatory lymphocytes. J Ethnopharmacol. 2011;136(3):444-51.
Gründemann, C., Gruber, C. W., Hertrampf, A., Zehl, M., Kopp, B., & Huber, R. (2011). An aqueous birch leaf extract of Betula pendula inhibits the growth and cell division of inflammatory lymphocytes. Journal of Ethnopharmacology, 136(3), pp. 444-51. doi:10.1016/j.jep.2011.05.018.
Gründemann C, et al. An Aqueous Birch Leaf Extract of Betula Pendula Inhibits the Growth and Cell Division of Inflammatory Lymphocytes. J Ethnopharmacol. 2011 Jul 14;136(3):444-51. PubMed PMID: 21619918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An aqueous birch leaf extract of Betula pendula inhibits the growth and cell division of inflammatory lymphocytes. AU - Gründemann,Carsten, AU - Gruber,Christian W, AU - Hertrampf,Anke, AU - Zehl,Martin, AU - Kopp,Brigitte, AU - Huber,Roman, Y1 - 2011/05/17/ PY - 2010/12/20/received PY - 2011/04/18/revised PY - 2011/05/11/accepted PY - 2011/5/31/entrez PY - 2011/5/31/pubmed PY - 2012/1/11/medline SP - 444 EP - 51 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 136 IS - 3 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Leaf extracts of Betula pendula have been traditionally used for the treatment of patients with rheumatoid arthritis (RA) or osteoarthritis. AIM OF THE STUDY: We investigated the anti-proliferative capacity of an aqueous leaf extract of Betula pendula (BPE) on human primary lymphocytes in vitro, because activated lymphocytes play a major role in the initiation and maintenance of RA. MATERIALS AND METHODS: Lymphocyte proliferation and cell division was measured by the activity of mitochondrial dehydrogenases and by using the membrane-permeable dye carboxyfluorescein diacetate succinimidyl ester (CFSE), respectively. Apoptosis was analyzed by surface staining of phosphatidylserine and intracellular activation of effector caspases 3 and 7 in comparison to the drug methotrexate using flow cytometric and photometrical analysis. In addition, the impact of the extract on cell cycle distribution was investigated by propidium iodide staining of DNA. For the bioassays BPE concentrations of 10-160 μg/mL were investigated. A phytochemical analysis, using LC-MS and HPLC, was conducted to identify the polyphenolic constituents of the birch leaf extract. RESULTS: Leaf extracts of Betula pendula inhibited the growth and cell division (CD8(+): 40 μg/mL: 45%; 80 μg/mL: 60%; 160 μg/mL: 87%) (CD4(+): 40 μg/mL: 33%; 80 μg/mL: 54%; 160 μg/mL: 79%) of activated, but not of resting T lymphocytes in a significant dose-dependent manner. The inhibition of lymphocyte proliferation due to apoptosis induction (compared to untreated control: 40 μg/mL: 163%; 80 μg/mL: 240%; 160 μg/mL: 348%) and cell cycle arrest was comparable to that of methotrexate. LC-MS analyses showed that the extract contains different quercetin-glycosides. CONCLUSION: Our results give a rational basis for the use of Betula pendula leaf extract for the treatment of immune disorders, like rheumatoid arthritis, by diminishing proliferating inflammatory lymphocytes. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/21619918/An_aqueous_birch_leaf_extract_of_Betula_pendula_inhibits_the_growth_and_cell_division_of_inflammatory_lymphocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(11)00354-0 DB - PRIME DP - Unbound Medicine ER -