Immunomodulatory effect of Phyllanthus niruri

Introduction

The human immune system is well organized comprising of many different immune cells like macrophages, neutrophils, T-lymphocytes, natural killer cells and various other specialized immune molecules like cytokines, antibodies and complement proteins that have evolved to mediate resistance against infections which is due to presence of active ingredients like bioactive phytochemicals which include lignans, flavonoids, terpenoids, alkaloids, polyphenols, coumarins, saponins, tannins and broad pharmacological actions.^[1] The methanol extract of P. niruri was reported to modulate both innate and adaptive immune responses. Among the compounds abundantly identified in the plant, catechin, quercetin, and astragalin have been reported for their ability to regulate the immune system.^[2], ^[3]

Human studies

Repandusinic acid inhibited human immune deficiency virus by type-1 reverse transcriptase (HIV-1-RT) with an ID50 value of 0.05mM. It showed 10-fold more sensitivity towards HIV-1-RT compared with human DNA polymerase-a, which is an indication of good selectivity in inhibiting HIV replication without harming normal cells of the body when they were exposed to extract. In addition, 4.5 mM of this compound inhibited 50% of HIV-1 induced giant cell formation. Also, at 2.5 mM it inhibited HIV-1 specific p24 antigen production in Clone H9 cell system. The compound showed strong inhibitory activity against HIV-1 protease, with an IC50 value of 12.5 mM.^[4], ^[5]

Model	Extract	Dose	Parameter	Result
Female C57BL/6 Mice	Aqueous extracts	0, 12.5, 25, 50, 100 & 200 μg/ml	FACS analysis	Production of surface activation maker B and T lymphocyte proliferation Stimulation of naive splenocytes	[6]
Transgenic OT-1 mice	Aqueous extracts	25, 50, and 100 microg/mL for 48 h	BM/DCs	Expression of MHC complex-ii and markers for dendritic cell maturation, activation & stimulation	[7]
TB patients	Aqueous extract	Dose dependent	Peripheral blood mononuclear cells (PBMCs) and macrophages were collected from active pulmonary TB patients	Boosting the immune system Elevates the phagocytic activity of macrophages	[8]
Swiss albino Mice	Methanol extract	200,400 mg/kg	Total leucocytes count	Inhibiting sRBC-induced DTH	[9]
Swiss albino Mice	Methanol extract	200,400 mg/kg	Total leucocytes count	Regulated serum levels	[10]
Musculous swiss male mice	Spray-dried standardized extracts	100, 200, 800, 1600 mg/kg	Analytical balance	Inhibition of carrageen induced edema & thioglycolate induced neutrophil migration	[11]
Fishes	Aqueous extracts	0.002 to 20 mg/kg body weight	Blood samples	Enhance the efficacy of vaccines	[12]

Table 1 Immunomodulatory effects of P. niruri

Invitro studies

Nworu and others found the effect of Aqueous extracts of P. niruri on spleen cells of female C57BL/6 mice (at a dose of 12.5-200 μg/ml for 18 h), there was increase in the expression of induced surface activation marker (CD69), B and T lymphocyte proliferation. The extract stimulated naive splenocyte by increasing the release of interferon gamma (IFN- γ) and interleukin-4 (IL-4) in a concentration dependent manner. Then various indices of activation and functions of murine bone marrow derived macrophages, such as phagocytosis, lysosomal enzyme activity and TNF-alpha release were significantly enhanced by pretreatment with P. niruri extract, which also modulated macrophage nitric oxide by release.^[6] They also studied the effect of Aqueous extracts of P. niruri on female C57BL/6 mice and transgenic OT-1 mice (at a dose of 25-100 μg/ml for 48 h), there was an increase in the expression of major histocompatibility complex-II and markers for dendritic cell maturation (CD40), activation (CD83) and co-stimulation (CD86).^[7] Putrid and coworkers found that the effect of Aqueous extracts of P. niruri on tuberculosis, patient there was an increase in nitric oxide, phagocytic activity and boosts the immune system in a dose dependent fashion, ultimately modulating the immune responses.^[8]

Animal studies

Bonilla and oettgen found the effect of methanol extract of P. niruri on Swiss albino mice (at a dose of 200, 400 mg/kg) which helps in regulation of cellular immune responses by inhibiting sRBC induced DTH (Delayed-Type-Hypersensitivity) reaction. DTH is an important cell-mediated immune response and occupies the central role to protect the body against intracellular pathogens. This cellular response is primarily mediated by T helper type-1 cells which releases the cytokine IFN-γ. This cytokine causes the activation of macrophages and accounts for the symptoms of inflammation. Also, cytotoxic T cells and memory T cells are considered to be involved in DTH reaction^[9], ^[13] Animal studies by Muthulakshmi and others found the effect of Aqueous extracts of P. niruri on Oreochromis mossambicus (at a dose of 0.02 to 20 mg/kg body weight) stimulating effects on neutrophil activation and the antibody response and later it can be used either as a routine feed supplement to activate the immune system of farmed fishes or as an adjuvant to enhance the efficacy of vaccines.^[12] Eze and co-workers found the effect of methanol extract of P. niruri on Swiss albino mice (at a dose of 200, 400mg/kg) and found to regulate the serum levels of primary and secondary antibodies.^[10] Porto and others worked on spray-dried standardized extracts with varied concentrations of 100, 200, 800, 1600 mg/kg have found to inhibit carrageen induced edema and thioglycolate induced neutrophil migration in musculus Swiss male mice.^[11]

References

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