Bryophyllum pinnatum leaves ethanol extract inhibit maturation and promote apoptosis of systemic lupus erythematosus BALB/c mice B cells
Background: B cells play a key role in systemic lupus erythematosus (SLE). Targeting B cells as SLE therapy is a plausible approach. This study investigated the potential effects of Bryophyllum pinnatum leaves with ethanol extract in decreasing percentages of maturation, increasing percentages of apoptosis, and decreasing NF-κB p65 expressions of SLE BALB/c mice B cells.
Methods: Culturing B cells from pristane induced SLE BALB/c mice's spleen will resulted in this in vitro study. B cells were activated by BAFF, LPS, IL-4, and anti-CD40 yielding CD19+ >80%. B cells were cultured by adding those stimulants with and without B. pinnatum leaves (0, 0.02, 0.1, or 0.5 µg/ml) for 72 hours at 37°C. Flow cytometry was performed to determine The Percentages of maturation (CD19+CD38+) and apoptosis (Annexin V+PI+) of B cells. Further analysis to determine the expressions of transcription factor of maturation and apoptosis of B cells, NF-κB p65, were performed using immunocytochemistry. Data were analyzed using SPSS version 22.
Results: Flow cytometry assay showed significant decrease in percentages of maturation of B cells in all doses and significant increase in percentage of apoptosis of B cells in dose 0.5 µg/ml. Immunocytochemistry results showed significant decrease expressions of NF-κB p65 in all doses. Percentages of maturation, apoptosis, and expressions of NF-κB p65 of B cells were significantly correlated.
Conclusion: This in vitro study revealed that B. pinnatum leaves with ethanol extract decreased the percentages of maturation, increased the percentage of apoptosis, and decreased NF-κB p65 expressions of SLE BALB/c mice B cells significantly.
Jacob N, Stohl W. Autoantibody-dependent and autoantibody-independent roles for B cells in systemic lupus erythematosus: past, present, and future. Autoimmunity. 2010; 43(1): 84–97. https://doi.org/10.3109/08916930903374600
Pateinakis P, Pyrpasopoulou A. Targeting the B-cell pathway in lupus nephritis: current evidence and future perspectives. Sci World J. 2013;2013:745239. https://doi.org/10.1155/2013/745239
Leiss H, Niederreiter B, Bandur T, Schwarzecker B, Blüml S, Steiner G, et al. Pristane-induced lupus as a model of human lupus arthritis: evolvement of autoantibodies, internal organ and joint inflammation. Lupus. 2013;22(8):778–92. https://doi.org/10.1177/0961203313492869
Reeves WH, Lee PY, Weinstein JS, Satoh M, Lu L. Induction of autoimmunity by pristane and other naturally occurring hydrocarbons. Trends Immunol. 2009;30(9):455–64. https://doi.org/10.1016/j.it.2009.06.003
Zhuang H, Szeto C, Han S, Yang L, Reeves WH. Animal models of interferon signature positive lupus. Front Immunol. 2015;6(291):1–6. https://doi.org/10.3389/fimmu.2015.00291
Postal M, Costallat LT, Appenzeller S. Biological therapy in systemic lupus erythematosus. Int J Rheumatol. 2012;2012:578641. https://doi.org/10.1155/2012/578641
Anolik JH. B cell biology: implications for treatment of systemic lupus erythematosus. Lupus. 2013;22(4):342–9. https://doi.org/10.1177/0961203312471576
Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, TegzovÃ¡ D, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30. https://doi.org/10.1002/art.30613
Hahn BH. Belimumab for systemic lupus erythematosus. N Engl J Med. 2013;368(16):1528–35. https://doi.org/10.1056/NEJMct1207259
Vincent FB, Morand EF, Schneider P, Mackay F. The BAFF/APRIL system in SLE pathogenesis. Nat Rev Rheumatol. 2014;10(6):365–73. https://doi.org/10.1038/nrrheum.2014.33
Fürer K, Simões-Wüst AP, Von Mandach U, Hamburger M, Potterat O. Bryophyllum pinnatum and related species used in anthroposophic medicine: constituents, pharmacological activities, and clinical efficacy. Planta Med. 2016;82(11–12):930–41. https://doi.org/10.1055/s-0042-106727
Oufir M, Seiler C, Gerodetti M, Gerber J, Fürer K, Mennet-von EM, et al. Quantification of bufadienolides in Bryophyllum pinnatum leaves and manufactured products by UHPLC-ESIMS/MS. Planta Med. 2015;81(12–13):1190–7. https://doi.org/10.1055/s-0035-1546126
Anjoo K, Kumar SA. Microscopical and preliminary phytochemical studies on aerial part (leaves and stem) of Bryophyllum Pinnotum Kurz. Phcog J. 2010;2(9):254–9. https://doi.org/10.1016/S0975-3575(10)80113-0
Nwali BU, Okaka ANC, Ibiam UA, Aja PM. Phytochemical composition of Bryophyllum pinnatum leaves. Int J Adv Biol Res. 2012;2(4):614–6.
Zhang X-A, Zhang S, Yin Q, Zhang J. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B pathway. Pharmacogn Mag. 2015;11(42):404–9. https://doi.org/10.4103/0973-1296.153096
Simões-Wüst AP, Jeschke E, Mennet M, Schnelle M, Matthes H, von Mandach U. Prescribing pattern of Bryophyllum preparations among a network of anthroposophic physicians. Forsch Komplementmed. 2012;19(6):293–301. https://doi.org/10.1159/000345841
Gründemann C, Diegel C, Sauer B, Garcia-Käufer M, Huber R. Immunomodulatory effects of preparations from Anthroposophical Medicine parenteral use. BMC Complement Altern Med. 2015;15:219. https://doi.org/10.1186/s12906-015-0757-6
Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49–63. https://doi.org/10.1038/nrm3722
Kalim H, Handono K, Khalasa T, Pratama MZ, Dantara TWI, Wulandari AP, et al. Immune modulation effects of curcumin in pristane induced lupus mice. Indian J Rheumatol. 2017;12(2):86–93. https://doi.org/10.4103/injr.injr_95_16
Pawar RD, Goilav B, Xia Y, Zhuang H, Herlitz L, Reeves WH. Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin. Clin Immunol. 2014;154(1):49–65. https://doi.org/10.1016/j.clim.2014.06.007
Yaniv G, Twig G, Shor DBA, Furer A, Sherer Y, Mozes O, et al. A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients. Autoimmun Rev. 2015;14(1):75–9. https://doi.org/10.1016/j.autrev.2014.10.003
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