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

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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<sup>+</sup> and CD8<sup>+</sup> 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 β<inf>2</inf> 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<sup>+</sup> and CD8<sup>+</sup> 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.

Original languageEnglish
Pages (from-to)4917-4930
Number of pages14
JournalDrug Design, Development and Therapy
Volume9
DOIs
Publication statusPublished - 26 Aug 2015

Fingerprint

Phyllanthus
Inbred WKY Rats
Immunosuppressive Agents
Cellular Immunity
Neutrophils
Cell Proliferation
B-Lymphocytes
methionyl-leucyl-phenylalanine
Ellagic Acid
Euphorbiaceae
Cytokines
T-Lymphocytes
N-Formylmethionine Leucyl-Phenylalanine
Gallic Acid
Immune System Diseases
T-Lymphocyte Subsets
Chemotaxis
Reverse-Phase Chromatography
Serum
Integrins

Keywords

  • Immunosuppression
  • Leukocytes migration
  • Phagocytic activity
  • Splenic mononuclear cells
  • T- and B-cell proliferation

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

@article{20adad3cf75e40139d684eb5bb7accf0,
title = "Immunosuppressive effects of the standardized extract of Phyllanthus amarus on cellular immune responses in Wistar-Kyoto rats",
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 = "Immunosuppression, Leukocytes migration, Phagocytic activity, Splenic mononuclear cells, T- and B-cell proliferation",
author = "Menaga Ilangkovan and Ibrahim Jantan and {Mohammed Ahmed Hassan}, {Osman Mesaik} and {Syed Nasir Abbas}, Bukhari",
year = "2015",
month = "8",
day = "26",
doi = "10.2147/DDDT.S88189",
language = "English",
volume = "9",
pages = "4917--4930",
journal = "Drug Design, Development and Therapy",
issn = "1177-8881",
publisher = "Dove Medical Press Ltd.",

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TY - JOUR

T1 - Immunosuppressive effects of the standardized extract of Phyllanthus amarus on cellular immune responses in Wistar-Kyoto rats

AU - Ilangkovan, Menaga

AU - Jantan, Ibrahim

AU - Mohammed Ahmed Hassan, Osman Mesaik

AU - Syed Nasir Abbas, Bukhari

PY - 2015/8/26

Y1 - 2015/8/26

N2 - 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.

AB - 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.

KW - Immunosuppression

KW - Leukocytes migration

KW - Phagocytic activity

KW - Splenic mononuclear cells

KW - T- and B-cell proliferation

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U2 - 10.2147/DDDT.S88189

DO - 10.2147/DDDT.S88189

M3 - Article

VL - 9

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EP - 4930

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SN - 1177-8881

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