Murugaiyah Vikneswaran, Chan Kit-Lam
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
J Ethnopharmacol. 2009 Jul 15;124(2):233-9. doi: 10.1016/j.jep.2009.04.026. Epub 2009 May 3.
Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals.
The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents.
The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats.
Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone.
The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.
叶下珠（大戟科）在南美洲被用作民间药物治疗尿酸过多。我们的初步研究表明，叶下珠的甲醇提取物及其木脂素能够使高尿酸血症动物的血浆尿酸水平恢复正常。
本研究旨在探讨叶下珠及其木脂素成分抗高尿酸血症作用的机制。
通过黄嘌呤氧化酶测定以及在氧嗪酸钾和尿酸诱导的高尿酸血症大鼠中进行促尿酸排泄研究来探究作用机制。
叶下珠甲醇提取物在体外表现出对黄嘌呤氧化酶的抑制作用，IC50为39.39微克/毫升，在体内具有中等程度的黄嘌呤氧化酶抑制活性。然而，木脂素在体外对黄嘌呤氧化酶的抑制作用较弱，在10毫克/千克剂量时体内抑制活性相对较弱。另一方面，与高尿酸血症对照动物相比，腹腔注射叶下珠甲醇提取物可使尿尿酸排泄增加1.69倍。同样，木脂素、叶下珠素、次叶下珠素和叶下珠黄酮的尿尿酸排泄和清除率分别最高可提高2.51倍和11.0倍。叶下珠素与吡嗪酰胺联合给药显著抑制了叶下珠素的促尿酸排泄活性，类似于吡嗪酰胺与苯溴马隆联合给药的情况。
本研究表明，叶下珠甲醇提取物的抗高尿酸血症作用可能主要归因于其促尿酸排泄作用，部分通过抑制黄嘌呤氧化酶实现，而木脂素的抗高尿酸血症作用则归因于其促尿酸排泄作用。
