Immunosuppressive effects of the standardized extract of Phyllanthus amarus on cellular immune responses in Wistar-Kyoto rats

Drug Des Devel Ther. 2015 Aug 26:9:4917-30. doi: 10.2147/DDDT.S88189. eCollection 2015.

Abstract

Phyllanthus amarus (family: Euphorbiaceae) is of immense interest due to its wide spectrum of biological activities. In the present study, the standardized 80% ethanol extract of P. amarus was investigated for its modulatory activity on various cellular immune parameters, including chemotaxis of neutrophils, engulfment of Escherichia coli by neutrophils, and Mac-1 expression, in leukocytes isolated from treated/nontreated Wistar-Kyoto rats. The detailed cell-mediated activity of P. amarus was also investigated, including analysis of the effects on T- and B-cell proliferation and CD4(+) and CD8(+) T-cell subsets in splenic mononuclear cells, and estimation of serum cytokine production by activated T-cells. The main components of the extract, phyllanthin, hypophyllanthin, corilagin, geraniin, ellagic acid, and gallic acid were identified and quantitatively analyzed in the extracts, using validated reversed-phase high-performance liquid chromatography (HPLC) methods. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophils isolated from rats administered with the extract of P. amarus, at doses ranging from 100 to 400 mg/kg for 14 days, revealed a significant dose-dependent reduction in neutrophil migration (P<0.05). Similar patterns of inhibition were also observed in phagocytic activity and in fMLP-induced changes in expression of β2 integrin polymorphonuclear neutrophils. The results in P. amarus-treated rats also demonstrated a dose-dependent inhibition of both lipopolysaccharide-stimulated B-cell proliferation and concanavalin A-stimulated T-cell proliferation as compared with sensitized control. At a dose of 400 mg/kg (P<0.01), there was a significant decrease in the (%) expression of CD4(+) and CD8(+) in splenocytes and in serum cytokines of T helper (Th1) (IL-2 and IFN-γ) and Th2 (IL-4). In conclusion, P. amarus showed effective immunosuppressive activities in cellular immune response, by various immune regulatory mechanisms, and may be useful for improvement of immune-related disorders.

Keywords: T- and B-cell proliferation; immunosuppression; leukocytes migration; phagocytic activity; splenic mononuclear cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemotaxis, Leukocyte / drug effects
  • Cytokines / blood
  • Dose-Response Relationship, Drug
  • Immunity, Cellular / drug effects*
  • Immunosuppressive Agents / isolation & purification
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / toxicity
  • Leukocytes / drug effects*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Leukocytes / microbiology
  • Lymphocyte Activation / drug effects
  • Macrophage-1 Antigen / metabolism
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / microbiology
  • Phagocytosis / drug effects
  • Phyllanthus* / chemistry
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / toxicity
  • Plants, Medicinal
  • Rats, Inbred WKY
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Macrophage-1 Antigen
  • Plant Extracts