Phytochemical Studies Of Lippia Nodiflora (L.) Michx And Its Anti-Hyperuricemic Activity
| dc.contributor.author | Cheng, Lee Chuen | |
| dc.date.accessioned | 2017-02-01T01:09:56Z | |
| dc.date.available | 2017-02-01T01:09:56Z | |
| dc.date.issued | 2016-07 | |
| dc.description.abstract | Lippia nodiflora has been traditionally used in the Ayurvedic, Unani, Sindh, and Traditional Chinese Medicine for the treatment of knee joint pain, lithiasis, diuresis, urinary disorder and swelling. In the present study, methanol extract of L. nodiflora showed promising xanthine oxidase (XOD) inhibitory activity in vitro. Bioactivity-guided fractionation of methanol extract yielded four fractions (F1-F4) with F3 being identified as the most potent fraction. Further purification of F3 afforded five bioactive compounds, including two phenylethanoid glycosides arenarioside (1) and verbascoside (2), and three flavonoids 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5), of which 1 and 4 were first time isolated from L. nodiflora. The methanol extract, fractions, and chemical constituents were then tested for potential antihyperuricemic activity in vivo using potassium oxonate- and hypoxanthine-induced hyperuricemic rat model. Oral treatment with methanol extract effectively and dose-dependently reduced the serum uric acid level of hyperuricemic rats. F3 exhibited the highest rat serum uric acid lowering effect. Compound 3 was established as the most potent of the isolated chemical constituents whereby it significantly and dose-dependently reduced the serum uric acid level of hyperuricemic rats. Nonetheless, 3 did not lower the serum uric acid level of hyperuricemic rats below that of the normal control even at the highest dose given. Repeated administration of F3 or 3 to the hyperuricemic rats for 10 continuous days resulted in a significant and progressive serum uric acid lowering effect in hyperuricemic rats. In contrast to allopurinol, the methanol extract and F3 did not reduce serum uric acid level of normoruricemic rats. Furthermore, no toxic effect was observed in rats administered with 5000 mg/kg of methanol extract or F3, indicating their favorable safety profile. Subsequently, their mechanism(s) of antihyperuricemic activity were elucidated using in vivo rat liver XOD and xanthine dehydrogenase (XDH) inhibitory and uricosuric studies. Interestingly, 3 was able to inhibit both XOD and XDH activities in rat liver to an extent comparable to the allopurinol. Molecular docking of 3 revealed that 3 interacted with XOD in a manner similar to allopurinol but with a free energy of binding lower than allopurinol. On the other hand, F4 significantly increased the uric acid excretion of hyperuricemic rats. Meanwhile, a simple and reliable high performance liquid chromatography with ultraviolet detection method was developed and validated for the simultaneous determination of the five bioactive compounds. The method was then successfully applied for the phytochemical analysis and pharmacokinetic study of 1-5 in L. nodiflora plant samples and rat plasma samples, respectively, for the first time. Stems were found to contain the highest total content of phenylethanoid glycosides and flavonoids. The oral bioavailability of the compound 1, 2, 3, 4, and 5 was found to be low and incomplete with estimated absolute oral bioavailability values of 5.22, 2.10, 5.97, 3.13, and 0.93 %, respectively. Taken together, the potential application of L. nodiflora against hyperuricemia in rat in accordance with its traditional uses has been demonstrated in the present study for the first time. The antihyperuricemic effect possessed by L. nodiflora was contributed mainly by liver XOD and XDH inhibitory activities and partially by uricosuric effect. Flavonoids are mainly accountable for the uric acid lowering effect of L. nodiflora by acting as XOD inhibitor | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/3630 | |
| dc.subject | Phytochemical studies of lippia nodiflora (l.) Michx | en_US |
| dc.subject | and its anti-hyperuricemic activity. | en_US |
| dc.title | Phytochemical Studies Of Lippia Nodiflora (L.) Michx And Its Anti-Hyperuricemic Activity | en_US |
| dc.type | Thesis | en_US |
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