Anti-hyperuricemic and Anti-inflammatory Effects of Marantodes pumilum as Potential Treatment for Gout

Abstract

Marantodes pumilum (Primulaceae) has been used in Malaysian folk medicine to help women regain strength after delivery and for "sickness in the bones." It was previously revealed that its extracts inhibited xanthine oxidase (XO) activity in vitro. The leaves and roots of M. pumilum var. alata (MPA), var. pumila (MPP), and var. lanceolata (MPL) were individually extracted in ethanol (80%). The anti-hyperuricemic activity was initially assessed by XO inhibition with a spectrophotometric in vitro assay. The most active extract was further investigated on hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels and liver XO effect. The in vitro anti-inflammatory activity was carried out on monosodium urate (MSU) crystal-induced pro-inflammatory cytokines (i.e., interleukin (IL)1α, IL-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α) secretion using human peripheral blood mononuclear cells and ELISA technique, and prostaglandin E₂ (PGE₂)secretion using radioimmunoassay. The active extract was then investigated on gout-induced inflammation with MSU crystals to determine pro-inflammatory cytokines and PGE₂ secretion levels in the synovial fluid of rat knee joint. Quantitative analysis using validated HPLC was performed on the extracts to determine presence of bioactive flavonoids. The findings revealed that extract of MPP leaves gave the highest inhibitory activity on XO (IC₅₀ 130.5 μg/mL) compared to other extracts tested. However, all extracts possessed significantly lower activity compared to allopurinol (IC₅₀ 0.13 μg/mL). Oral administration of MPP leaf extract (200 mg/kg) significantly reduced serum uric acid level in hyperuricemic rats in time-dependent manner to the baseline level and it was as effective as allopurinol (5 mg/kg). The extract also inhibited liver XO activity (25%) compared to allopurinol (45%). In vitro anti-inflammatory assay showed that extract of MPP roots inhibited MSU crystals-induced secretion of IL-1α, IL-1β, IL-8, TNF-α, and PGE₂ with IC₅₀ values of 36, 25, 38, 18, and 46 μg/mL, respectively. Oral administration of the MPP root extract (200 mg/kg) significantly decreased IL-1α, IL-1β, IL-6, TNF-α, and PGE₂ levels in rat's synovial fluid as effective as indomethacin. There were no significant body weight changes of all experimental animals. MPP extracts showed presence of myricetin, quercetin and kaempferol. Myricetin was detected with values of 0.2 and 0.6 mg/g for root and leaf extracts, respectively. The anti-hyperuricemic of MPP leaf and anti-inflammatory of MPP root indicated that MPP may be promising for complementary therapy of gout.

Keywords: Labisia pumila; Marantodes pumilum; hyperuricemia; monosodium urate crystals; pro-inflammatory cytokines; prostaglandin E2; xanthine oxidase inhibitor.