Inhibitory Effects of the Standardized Extract of <i>Phyllanthus amarus</i> on Cellular and Humoral Immune Responses in Balb/C Mice

Ilangkovan, Menaga; Jantan, Ibrahim; Mesaik, M. Ahmed; Bukhari, Syed Nasir Abbas

doi:10.1002/ptr.5633

Cited by 23 publications

(12 citation statements)

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“…Moreover, the plant extracts have strong inhibitory effects on cellular and humoral immune responses (ceruloplasmin and lysozyme) suggesting the potential of the plant to be developed as an effective immunosuppressive agent which mainly acts through the inhibition of myeloperoxidase activity and nitric oxide release leading to the release of serum level immunoglobulins [ 104 ]. Phyllanthin, one of the main and active ingredient in many Phyllanthus species ( P. amarus ), has recently been reported to have hepatoprotective and immunosuppressive effects on various in Balb/C mice in a dose-dependent way through the inhibition of CD11b/CD18 adhesion, nitric oxide and myeloperoxidase activity release [ 105 ]. Based on the level of doses of phyllanthin, a significant inhibition in the proliferation of B and T lymphocytes and down-regulation of Th1 (IL-2 and IFN-γ) and Th2 (IL-4) cytokines, CD4+ and CD8+ was noted [ 105 ].…”

Section: Biological Activitiesmentioning

confidence: 99%

“…Phyllanthin, one of the main and active ingredient in many Phyllanthus species ( P. amarus ), has recently been reported to have hepatoprotective and immunosuppressive effects on various in Balb/C mice in a dose-dependent way through the inhibition of CD11b/CD18 adhesion, nitric oxide and myeloperoxidase activity release [ 105 ]. Based on the level of doses of phyllanthin, a significant inhibition in the proliferation of B and T lymphocytes and down-regulation of Th1 (IL-2 and IFN-γ) and Th2 (IL-4) cytokines, CD4+ and CD8+ was noted [ 105 ].…”

Section: Biological Activitiesmentioning

confidence: 99%

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Chemical Components and Biological Activities of the Genus Phyllanthus: A Review of the Recent Literature

Nisar

Ahmed

et al. 2018

Molecules

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Medicinal plants have served humans since prehistoric times to treat various ailments. Both developed and underdeveloped countries rely on traditional systems of medication using natural sources from plants. Phyllanthus is one of the largest genus in the family Phyllanthaceae, comprising over 700 well known species cosmopolitan in distribution mainly in the tropics and subtropics. Phyllanthus species are being in constant used in traditional medications to cure an array of human diseases (constipation, inhalation related, arthritis, loss of appetite, injuries, conjunctivitis, diarrhoea, running nose, common cold, malaria, blennorrhagia, colic, diabetes mellitus, dysentery, indigestion, fever, gout, gonorrheal diseases of males and females, skin itching, jaundice, hepatic disorders, leucorrhea, vaginitis, menstrual irregularities, obesity, stomach pains, and tumors), confectionaries, food industry, and in some pesticides. Phyllanthus species are rich in diversity of phytochemicals e.g., tannins, terpenes, alkaloids, glycosidic compounds, saponins, and flavones etc. More in depth studies are a direly needed to identify more compounds with specific cellular functions to treat various ailments.

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Section: Biological Activitiesmentioning

confidence: 99%

Section: Biological Activitiesmentioning

confidence: 99%

Chemical Components and Biological Activities of the Genus Phyllanthus: A Review of the Recent Literature

Nisar

Ahmed

et al. 2018

Molecules

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“…Previously we have reported the in vitro inhibitory effects of P. amarus and its isolates on phagocytic activity of human neutrophils and NO production, lymphocyte proliferation and cytokine release from phagocytes [ 26 , 27 ]. Immunosuppressive effects of the standardized extract of P. amarus on cellular and humoral immune responses in Balb/C mice and Wistar-Kyoto rats have also been investigated [ 28 , 29 ]. Despite its various pharmacological activities, there is no comprehensive investigation on molecular mechanisms underlying the anti-inflammatory effects of P. amarus extract in human macrophages.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. through inhibition of NF-κB, MAPK, and PI3K-Akt signaling pathways in LPS-induced human macrophages

Harikrishnan

Jantan

Haque

et al. 2018

BMC Complement Altern Med

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BackgroundPhyllanthus amarus has been used widely in various traditional medicines to treat swelling, sores, jaundice, inflammatory diseases, kidney disorders, diabetes and viral hepatitis, while its pharmacological and biochemical mechanisms underlying its anti-inflammatory properties have not been well investigated. The present study was carried out to investigate the effects of 80% ethanolic extract of P. amarus on pro-inflammatory mediators release in nuclear factor-kappa B (NF-кB), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Akt (PI3K-Akt) signaling activation in lipopolysaccharide (LPS)-induced U937 human macrophages.MethodsThe release of prostaglandin E2 (PGE2) and pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β in a culture supernatant was determined by ELISA. Determination of cyclooxygenase-2 (COX-2) protein and the activation of MAPKs molecules (JNK, ERK and p38 MAPK), NF-κB and Akt in LPS-induced U937 human macrophages were investigated by immunoblot technique. The relative gene expression levels of COX-2 and pro-inflammatory cytokines were measured by using qRT-PCR. The major metabolites of P. amarus were qualitatively and quantitatively analyzed in the extract by using validated reversed-phase high performance liquid chromatography (HPLC) methods.ResultsP. amarus extract significantly inhibited the production of pro-inflammatory mediators (TNF-α, IL-1β, PGE2) and COX-2 protein expression in LPS-induced U937 human macrophages. P. amarus-pretreatment also significantly downregulated the increased mRNA transcription of pro-inflammatory markers (TNF-α, IL-1β, and COX-2) in respective LPS-induced U937 macrophages. It downregulated the phosphorylation of NF-κB (p65), IκBα, and IKKα/β and restored the degradation of IκBα, and attenuated the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a dose-dependent manner. P. amarus extract also downregulated the expression of upstream signaling molecules, TLR4 and MyD88, which play major role in activation of NF-κB, MAPK and PI3K-Akt signaling pathways. The quantitative amounts of lignans, phyllanthin, hypophyllahtin and niranthin, and polyphenols, gallic acid, geraniin, corilagin, and ellagic acid in the extract were determined by HPLC analysis.ConclusionThe study revealed that P. amarus targeted the NF-κB, MAPK and PI3K-Akt signaling pathways to exert its anti- inflammatory effects by downregulating the prospective inflammatory signaling mediators.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2289-3) contains supplementary material, which is available to authorized users.

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“…The extracts were not chemically characterized, and the contributions of their chemical constituents to the bioactivities were not clearly correlated and identified. However, some of the extracts were analyzed qualitatively and quantitatively by using validated high performance liquid chromatography (HPLC) methods (Jantan et al, 2014; Ilangkovan et al, 2016b). Some of the compounds especially the lignans and flavonoids and some phenolic compounds have been isolated and identified based on their physicochemical properties and spectroscopy.…”

Section: Immunomodulatory Effects Of Phyllanthus Species and Their Bimentioning

confidence: 99%

“…Phyllanthin ( 4 ) isolated from P. amarus has been evaluated for its immunosuppressive effects on various humoral and cellular immune responses in Balb/C mice, following similar experimental design as above (Ilangkovan et al, 2016b). The compound suppressed cellular immunity via inhibition of T and B cell proliferation, differentiation of T-cells, and regulation of cytokines by Th1/Th2 cells and also by inhibition of DTH reaction in sRBC-immunized Balb/C mice.…”

Section: Immunomodulatory Effects Of Phyllanthus Species and Their Bimentioning

confidence: 99%

An Insight Into the Modulatory Effects and Mechanisms of Action of Phyllanthus Species and Their Bioactive Metabolites on the Immune System

et al. 2019

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Phyllanthus species (family; Euphorbiaceae ) have been intensively studied for their immunomodulating effects due to their wide-ranging uses to treat immune-related diseases in indigenous medicine, which are primarily lack of scientific basis. The focuses of this review are on the significance of Phyllanthus species and their bioactive metabolites particularly corilagin ( 1 ), geraniin ( 2 ), gallic acid ( 3 ), phyllanthin ( 4 ), hypophyllanthin ( 5 ), ellagic acid ( 6 ), phyltetralin ( 7 ), niranthin ( 8 ), catechin ( 9 ), quercetin ( 10 ), astragalin ( 11 ), and chebulagic acid ( 12 ) in the modulation of both innate and adaptive immune systems through various mechanisms and their possible therapeutic benefits for treatment of immune-related diseases. We have compiled all significant findings published in the literature, and the data were analyzed critically to provide perspectives and directions for future research for the plants as a prospective source of novel immunomodulating agents. Various Phyllanthus species particularly Phyllanthus amarus , Phyllanthus emblica , Phyllanthus niruri , and Phyllanthus urinaria have been documented to possess significant immunomodulatory effects. However, the possible challenges encountered by the application of extracts of various Phyllanthus species and their bioactive constituents as immunomodulators need to be addressed. Most reports on the biological and pharmacological studies of the plants were based on crude extracts. The extracts were not chemically characterized, and the contributions of their chemical constituents to the bioactivities were not identified. The underlying mechanisms involved in the immunomodulatory effects of the Phyllanthus species were not indepthly studied due to limitations in terms of design, conduct, and interpretation. Extensive experimental and preclinical studies on the immunomodulating potential of Phyllanthus species should be carried out to provide sufficient data to prove that their traditional uses are inherently effective and safe and will allow clinical trials to be pursued for their further development as therapeutic agents to treat immune-related disorders.

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Inhibitory Effects of the Standardized Extract of Phyllanthus amarus on Cellular and Humoral Immune Responses in Balb/C Mice

Cited by 23 publications

References 24 publications

Chemical Components and Biological Activities of the Genus Phyllanthus: A Review of the Recent Literature

Chemical Components and Biological Activities of the Genus Phyllanthus: A Review of the Recent Literature

Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. through inhibition of NF-κB, MAPK, and PI3K-Akt signaling pathways in LPS-induced human macrophages

An Insight Into the Modulatory Effects and Mechanisms of Action of Phyllanthus Species and Their Bioactive Metabolites on the Immune System

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