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https://ptsldigital.ukm.my/jspui/handle/123456789/485637| Title: | Immunomodulating effects of zingiber zerumbet (L.) roscoe ex sm. and tinospora crispa (L.) hook. F. & thomson on the signaling pathways in human macrophages |
| Authors: | Md. Areeful Haque (P80281) |
| Supervisor: | Ibrahim Jantan, Professor Dato' Dr. |
| Keywords: | Immunity Macrophages Dissertations, Academic -- Malaysia |
| Issue Date: | 20-Jun-2018 |
| Description: | Zingiber zerumbet (L.) Roscoe ex Sm. and Tinospora crispa (L.) Hook. f. & Thomson were found to be effective against numerous immune disorders, however, the molecular and biochemical mechanisms underlying their immunomodulatory properties have not been well justified. The present study was aimed to examine the effects of 80% ethanol extracts of Z. zerumbet (ZZE) and T. crispa (TCE) 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 ZZE and TCE. The release of pro-inflammatory mediators, TNF-α, IL-1β and PGE2 were analysed by ELISA while Western blot technique was employed to elucidate the expression of mediators associated to MyD88-dependent NF-κB/MAPK/PI3K-Akt pathways. qRT-PCR assay was employed to quantify the relative gene expression of respective pro-inflammatory mediators at the transcriptional level. The HPLC and LC-MS/MS analysis of ZZE and TCE revealed the presence of several metabolites including zerumbone (ZER) in ZZE, and magnoflorine (MAG) and syringin (SYR) in TCE. ZZE, ZER and SYR significantly suppressed the release and mRNA expression of the pro-inflammatory mediators, while TCE and MAG enhanced the upregulation of these respective markers. Moreover, ZZE, ZER and SYR downregulated the phosphorylation of IKKα/β, IκBα and NF-κB (p65) as well as restored the degradation of IκBα. Correspondingly, ZZE, ZER and SYR showed remarkable attenuation of the phosphorylation of Akt, JNK, ERK and p38 MAPKs in a concentration-dependent manner. In contrast, TCE and MAG enhanced the NF-κB activation by prompting the IKKα/β, IκBα and NF-κB (p65) phosphorylation and IκBα degradation, and concentration-dependently augmented the phosphorylation of respective MAPKs as well as Akt. ZZE, ZER and SYR diminished the expression of upstream signaling molecules TLR4 and MyD88, while TCE and MAG upregulated these adaptor molecules prerequisite for the NF-κB, MAPKs and PI3K-Akt activation. In conclusion, the suppressive effects of ZZE, ZER and SYR, and the stimulant effects of TCE and MAG on the activation of pro-inflammatory markers suggest that they have potential to be developed as immunomodulators for the management of various immune disorders.,Doktor Falsafah |
| Pages: | 316 |
| Call Number: | QV20.5.M478i 2018 9 |
| Publisher: | UKM, Kuala Lumpur |
| Appears in Collections: | Faculty of Pharmacy / Fakulti Farmasi |
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|---|---|---|---|---|
| ukmvital_99861+Source01+Source010.PDF Restricted Access | 3.46 MB | Adobe PDF |  View/Open |
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