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https://ptsldigital.ukm.my/jspui/handle/123456789/485638| Title: | Immunosuppressive effects of phyllanthus amarus and its bioactive compunds on signaling pathways U937 macrophages |
| Authors: | Hemavathy Harikrishnan (P80767) |
| Supervisor: | Ibrahim Jantan, Prof. Dato' Dr. |
| Keywords: | Swelling Sores Jaundice Inflammatory diseases Kidney disorders Diabetes Viral hepatitis Immunosuppressive Dissertations, Academic -- Malaysia Universiti Kebangsaan Malaysia -- Dissertations |
| Issue Date: | 13-Aug-2018 |
| Description: | Phyllanthus amarus Schum. & Thonn. (Family: Euphorbiaceae) has been used to treat swelling, sores, jaundice, inflammatory diseases, kidney disorders, diabetes and viral hepatitis, however the molecular and biochemical mechanisms underlying their immunosuppressive properties have not been well investigated. The present study was aimed to examine the effects of 80% ethanol extract of P. amarus (PA) and their bioactive metabolites on the MyD88-dependent NF-κB, MAPK and PI3K-Akt signaling pathways in LPS-activated U937 human macrophages. Qualitative and quantitative analyses were carried out by HPLC methods while LC-MS/MS was performed to profile the secondary metabolites of PA. The release of pro-inflammatory mediators, TNF-α, IL-1β and PGE2 were analysed by ELISA while Western blot technique was used to investigate the expression of mediators. qRT-PCR assay was carried out to quantify the relative gene expression of pro-inflammatory mediators (TNF-α, IL-1β and COX-2) at the transcriptional level. The LC-MS/MS analysis revealed the presence of various compounds in PA crude extract while the HPLC analysis showed the presence of phyllanthin (PHY), hypophyllanthin (HP) and niranthin (NIR). Further study on the inflammatory mediators showed that PA and its compounds significantly attenuated the expression of COX-2, TNF-α and IL-1β at protein and mRNA level in LPS induced U937 macrophage. Moreover, PA and its active compounds dose-dependently suppressed the phosphorylation of IKKα/β, IκBα, and NF-κBp65 and IκB degradation. Besides NF-κB pathway, PA, PHY and HP dose-dependently suppressed the MAPKs (JNK, ERK and p38) and Akt while NIR significantly suppressed the phosphorylation of JNK, ERK but not p38 and Akt in LPS induced U937 macrophages. PA, PHY, HP and NIR diminished the expression of upstream signaling molecules TLR4 and MyD88 which are important to initiate activation of NF-κB, MAPKs and PI3K-Akt signaling pathways. In conclusion, the suppressive effects of PA, PHY, HP and NIR on pro-inflammatory markers suggest that they have potential to be developed as therapeutic agents to treat various inflammatory disorders.,Ph.D. |
| Pages: | 212 |
| Call Number: | WH650.H487i 2018 9 tesis |
| Publisher: | UKM, Kuala Lumpur |
| Appears in Collections: | Faculty of Pharmacy / Fakulti Farmasi |
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| ukmvital_100749+Source01+Source010.PDF Restricted Access | 896.53 kB | Adobe PDF |  View/Open |
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