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Flavonoids and phenylethanoid glycosides from Lippia nodiflora as promising antihyperuricemic agents and elucidation of their mechanism of action.
J Ethnopharmacol. 2015 Dec 24; 176:485-93.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Lippia nodiflora has been traditionally used in the Ayurvedic, Unani, and Sidha systems, as well as Traditional Chinese Medicine (TCM) for the treatment of knee joint pain, lithiasis, diuresis, urinary disorder and swelling.

AIM OF THE STUDY

The present study aims to investigate the antihyperuricemic effect of the L. nodiflora methanol extract, fractions, and chemical constituents and their mechanism of action in the rat model.

MATERIALS AND METHODS

The mechanisms were investigated by performing xanthine oxidase inhibitory, uricosuric, and liver xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitory studies in potassium oxonate- and hypoxanthine-induced hyperuricemic rats. The plant safety profile was determined using acute toxicity study. The molecular docking of the active compound to the xanthine oxidase was simulated using computer aided molecular modeling analysis.

RESULTS

Oral administration of methanol extract showed a dose-dependent reduction effect on the serum uric acid level of hyperuricemic rats. F3 was the most potent fraction in lowering the serum uric acid level of hyperuricemic rats. Bioactivity-guided purification of F3 afforded two phenylethanoid glycosides, arenarioside (1) and verbascoside (2) and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). The highest serum uric acid reduction effect was exhibited by 3 (66.94%) in hyperuricemic rats, followed by 5 (55.97%), 4 (49.16%), 2 (29.03%), and 1 (22.08%) at 0.2 mmol/kg. Dose-response investigation on 3 at doses of 0.05, 0.1, and 0.3 mmol/kg produced a significant dose-dependent reduction on the serum uric acid level of hyperuricemic rats. 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, methanol extract and F3 did not reduce serum uric acid level of normoruricemic rats. In addition, F4 significantly increased the uric acid excretion of hyperuricemic rats at 200mg/kg. No toxic effect was observed in rats administered with 5000 mg/kg of methanol extract or F3.

CONCLUSION

The potential application of L. nodiflora against hyperuricemia in the animal 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/XDH inhibitory activities and partially by uricosuric effect. Flavonoids mainly accountable for the uric acid lowering effect of L. nodiflora through the inhibition of XOD/XDH activities.

Authors+Show Affiliations

Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, University of Science Malaysia (Universiti Sains Malaysia), 11800 Minden, Penang, Malaysia.Discipline of Pharmacology, School of Pharmaceutical Sciences, University of Science Malaysia (Universiti Sains Malaysia), 11800 Minden, Penang, Malaysia.Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, University of Science Malaysia (Universiti Sains Malaysia), 11800 Minden, Penang, Malaysia. Electronic address: kitlamc@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26593216

Citation

Cheng, Lee-Chuen, et al. "Flavonoids and Phenylethanoid Glycosides From Lippia Nodiflora as Promising Antihyperuricemic Agents and Elucidation of Their Mechanism of Action." Journal of Ethnopharmacology, vol. 176, 2015, pp. 485-93.
Cheng LC, Murugaiyah V, Chan KL. Flavonoids and phenylethanoid glycosides from Lippia nodiflora as promising antihyperuricemic agents and elucidation of their mechanism of action. J Ethnopharmacol. 2015;176:485-93.
Cheng, L. C., Murugaiyah, V., & Chan, K. L. (2015). Flavonoids and phenylethanoid glycosides from Lippia nodiflora as promising antihyperuricemic agents and elucidation of their mechanism of action. Journal of Ethnopharmacology, 176, 485-93. https://doi.org/10.1016/j.jep.2015.11.025
Cheng LC, Murugaiyah V, Chan KL. Flavonoids and Phenylethanoid Glycosides From Lippia Nodiflora as Promising Antihyperuricemic Agents and Elucidation of Their Mechanism of Action. J Ethnopharmacol. 2015 Dec 24;176:485-93. PubMed PMID: 26593216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flavonoids and phenylethanoid glycosides from Lippia nodiflora as promising antihyperuricemic agents and elucidation of their mechanism of action. AU - Cheng,Lee-Chuen, AU - Murugaiyah,Vikneswaran, AU - Chan,Kit-Lam, Y1 - 2015/11/28/ PY - 2015/09/02/received PY - 2015/10/19/revised PY - 2015/11/12/accepted PY - 2015/11/24/entrez PY - 2015/11/26/pubmed PY - 2016/10/7/medline KW - Antihyperuricemic KW - Hypoxanthine-induced hyperuricemic rat KW - Lippia nodiflora KW - Liver xanthine oxidase and xanthine dehydrogenase KW - Serum uric acid KW - Uric acid excretion SP - 485 EP - 93 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 176 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Lippia nodiflora has been traditionally used in the Ayurvedic, Unani, and Sidha systems, as well as Traditional Chinese Medicine (TCM) for the treatment of knee joint pain, lithiasis, diuresis, urinary disorder and swelling. AIM OF THE STUDY: The present study aims to investigate the antihyperuricemic effect of the L. nodiflora methanol extract, fractions, and chemical constituents and their mechanism of action in the rat model. MATERIALS AND METHODS: The mechanisms were investigated by performing xanthine oxidase inhibitory, uricosuric, and liver xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitory studies in potassium oxonate- and hypoxanthine-induced hyperuricemic rats. The plant safety profile was determined using acute toxicity study. The molecular docking of the active compound to the xanthine oxidase was simulated using computer aided molecular modeling analysis. RESULTS: Oral administration of methanol extract showed a dose-dependent reduction effect on the serum uric acid level of hyperuricemic rats. F3 was the most potent fraction in lowering the serum uric acid level of hyperuricemic rats. Bioactivity-guided purification of F3 afforded two phenylethanoid glycosides, arenarioside (1) and verbascoside (2) and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). The highest serum uric acid reduction effect was exhibited by 3 (66.94%) in hyperuricemic rats, followed by 5 (55.97%), 4 (49.16%), 2 (29.03%), and 1 (22.08%) at 0.2 mmol/kg. Dose-response investigation on 3 at doses of 0.05, 0.1, and 0.3 mmol/kg produced a significant dose-dependent reduction on the serum uric acid level of hyperuricemic rats. 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, methanol extract and F3 did not reduce serum uric acid level of normoruricemic rats. In addition, F4 significantly increased the uric acid excretion of hyperuricemic rats at 200mg/kg. No toxic effect was observed in rats administered with 5000 mg/kg of methanol extract or F3. CONCLUSION: The potential application of L. nodiflora against hyperuricemia in the animal 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/XDH inhibitory activities and partially by uricosuric effect. Flavonoids mainly accountable for the uric acid lowering effect of L. nodiflora through the inhibition of XOD/XDH activities. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/26593216/Flavonoids_and_phenylethanoid_glycosides_from_Lippia_nodiflora_as_promising_antihyperuricemic_agents_and_elucidation_of_their_mechanism_of_action_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(15)30226-9 DB - PRIME DP - Unbound Medicine ER -