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Title: | Antihyperuricemic and anti-inflammatory effects of marantodes pumilum var. alata, var. pumila and var. lanceolata on gouty condition in vitro and in vivo |
Authors: | Eldiza Puji Rahmi (P67970) |
Supervisor: | Jamia Azdina Jamal, Associate Professor Dr. |
Keywords: | Gout Arthritis Hyperuricemic Dissertations, Academic -- Malaysia |
Issue Date: | 9-Dec-2016 |
Description: | Gout is the most common inflammatory arthritis that is related to hyperuricemic condition. In Malaysia, Marantodes pumilum has been traditionally used for the treatment of “sickness in the bones” and it was previously revealed that its extracts inhibited xanthine oxidase (XO) activity in vitro. In this study, sixextracts of ethanol 80% (EtOH80) and 18 sequential fractionated extracts of dichloromethane (DCM), methanol (MeOH) and water (H2O) of leaves and roots of M. pumilum var. alata, var. pumila, and var. lanceolata were investigated on antihyperuricemic and anti-inflammatory activities in vitro and in vivo. The antihyperuricemic activity was assessed using spectrophotometric XO inhibitory in vitro assay using xanthin as a substrate. The XO inhibitory activity was determined by measuring the increase in absorbance at 295 nm which is associated with uric acid formation as a final product of the reaction. The most active EtOH80 extract was further investigated on hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels and liver XO activity. The in vitro anti-inflammatory activity was carried out on monosodium urate crystals (MSU)-induced or lipopolysaccharide (LPS)-induced pro-inflammatory cytokines (i.e. interleukins (IL)-1?, IL-1?, IL-6, IL-8, and tumor necrosis factor (TNF)-?) secretion using ELISA, and prostaglandin E2 (PGE2) secretion using radioimmunoassay. The most active EtOH80 extract was then investigated on MSU-induced inflammationto determine pro-inflammatory cytokines and PGE2 secretion levels in the synovial fluid of rat knee joint. Quantitative analysis using validated high performance liquid chromatography was performed on the most active extracts to determine presence of bioactive flavonoids. The findings revealed that among all samples tested, EtOH80 extract of M. pumilum var. pumila leaves gave the highest inhibitory activity on XO (IC50 130.5 ?g/mL) compared to allopurinol (IC50 0.13 ?g/mL, p?0.001). Oral administration of EtOH80 extract of M. pumilum var. pumila leaves at a dose of 200 mg/kg (p.o)significantly (p≤0.05) reduced serum uric acid levels in hyperuricemic rats to baseline levels and it was as effective as allopurinol (5 mg/kg, p.o) (p>0.05). However, the extract weakly inhibited liver XO activity (25.34%) and was not comparable to allopurinol (44.85%, p?0.05). In vitro anti-inflammatory assay revealed that EtOH80 extract of M. pumilum var. pumila roots inhibited MSU-induced secretion of IL-1?, IL-1?, IL-8, TNF-? and PGE2 with IC50 values of 35.71, 25.06, 38.4, 17.68 and 45.52 ?g/mL respectively. Out of 18 sequentialextracts,DCM extract of M. pumilumvar. lanceolata roots possessed the highest inhibitory activities of IL-1?, IL-1?, IL-6, IL-8, TNF-? and PGE2 secretion with the IC50 values of 11.2, 8.92, 12.29, 49.51, 9.60 and 31.58 ?g/mL respectively. Oral administration of EtOH80 extract of M. pumilum var. pumila roots (200 mg/kg, p.o) significantly (p?0.05) decreased IL-1?, IL-1?, IL-6, TNF-? and PGE2 levels in rat's synovial fluid as effective as indomethacin (3 mg/kg, p.o) (p>0.05). Additionally, EtOH80 extracts of M. pumilum var. pumila roots and DCM extract of M. pumilumvar. lanceolata roots were also found to inhibit pro-inflammatory cytokines and PGE2 secretion induced by LPS in vitro.M. pumilum var. pumila extracts showed presence of bioactive myricetin, quercetin and kaempferol as antihyperuricemic and anti-inflammatory agents. These results indicated that M. pumilum var. pumila exhibited antihyperuricemic and strong anti-inflammatory activities that may be promising for complementary therapy of gout.,Ijazah Sarjana Sains |
Pages: | 125 |
Call Number: | QV20.5.R147a 2017 9 |
Publisher: | UKM, Kuala Lumpur |
Appears in Collections: | Faculty of Pharmacy / Fakulti Farmasi |
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