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      Inhibitory effects of compounds from Phyllanthus amarus on nitric oxide production, lymphocyte proliferation, and cytokine release from phagocytes

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          Abstract

          Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC 50) values of 1.07 μM and 1.82 μM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC 50 values of 0.91 μM and 1.07 μM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC 50 value of 7.39 μM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1β release with an IC 50 value of 16.41 μM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps.

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          Most cited references 40

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          Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.

          A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+, Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and KLH. The relationship between these two types of T cells and previously described subsets of T helper cells is discussed.
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            A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential.

            The plants of the genus Phyllanthus (Euphorbiaceae) are widely distributed in most tropical and subtropical countries, and have long been used in folk medicine to treat kidney and urinary bladder disturbances, intestinal infections, diabetes, and hepatitis B. In recent years, the interest in the plants has increased considerably. Substantial progress on their chemistal and pharmacological properties, as well as a few clinical studies of some Phyllanthus species have been made. This review discusses the current knowledge of their chemistry, the in vitro and in vivo pharmacological, biochemical, and clinical studies carried out on the extracts, and the main active constituents isolated from different species of plants of the genus Phyllanthus. These studies carried out with the extracts and purified compounds from these plants support most of their reported uses in folk medicine as an antiviral, in the treatment of genitourinary disorders, and as antinociceptive agents. However, well-controlled, double-binding clinical trials are lacking. Several compounds including alkaloids, flavonoids, lignans, phenols, and terpenes were isolated from these plants and some of them interact with most key enzymes. Together this data strongly supports the view that the plants belonging to the genus Phyllanthus have potential beneficial therapeutic actions in the management of hepatitis B, nefrolitiase, and in painful disorders.
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              Phyllanthus amarus: ethnomedicinal uses, phytochemistry and pharmacology: a review.

              Phyllanthus amarus Schum. & Thonn. belongs to the family Euphorbiaceae is a small herb well known for its medicinal properties and widely used worldwide. P. amarus is an important plant of Indian Ayurvedic system of medicine which is used in the problems of stomach, genitourinary system, liver, kidney and spleen. It is bitter, astringent, stomachic, diuretic, febrifuge and antiseptic. The whole plant is used in gonorrhea, menorrhagia and other genital affections. It is useful in gastropathy, diarrhoea, dysentery, intermittent fevers, ophthalmopathy, scabies, ulcers and wounds. The present review covers a literature across from 1980 to 2011. Some information collected from traditional Ayurvedic texts and published literature on ethanomedicinal uses of Phyllanthus amarus in different countries worldwide. Phytochemical studies have shown the presence of many valuable compounds such as lignans, flavonoids, hydrolysable tannins (ellagitannins), polyphenols, triterpenes, sterols and alkaloids. The extracts and the compounds isolated from P. amarus show a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, anti-inflammatory, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective nephroprotective and diurectic properties. The present review summarizes information concerning the morphology, ecology, ethnopharmacology, phytochemistry, biological activities, clinical applications and toxicological reports of P. amarus. This review aims at gathering the research work undertaken till date on this plant in order to provide sufficient baseline information for future works and commercial exploitation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                09 June 2016
                : 10
                : 1935-1945
                Affiliations
                [1 ]Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
                [2 ]Falkultas Farmasi, Universitas Sumatera Utara, USU-Kampus, Medan, Indonesia
                [3 ]Biomedical Science Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia
                Author notes
                Correspondence: Ibrahim Jantan, Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia, Tel +60 1 6288 6445, Fax +60 3 2698 3271, Email profibj@ 123456gmail.com
                Article
                dddt-10-1935
                10.2147/DDDT.S105651
                4907639
                27354767
                © 2016 Yuandani et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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