Abstract
Simultaneous oral intake of herbal medicine with chemical drugs may result in beneficial pharmacodynamic efficacy, including additive and synergistic effects with reduced toxicity. Gnaphalium affine D. Don (GAD) is a traditional Chinese Medicine that has been used for the management of hyperuricemia and gout. Benzbromarone (BBR) is one of the first-line drugs used for urate-lowering therapy in China but is toxic to the liver. The present study aimed to determine the effects of GAD and BBR, both alone and in co-treatment (with dosing interval of 1 hour), on chronic hyperuricemic nephropathy (HN) and hepatotoxicity in rats. Our data indicated that GAD significantly inhibited the elevation of serum uric acid, blood urea nitrogen, and creatinine levels in chronic HN rats at doses of 450 and 900 mg/kg/day. The rise in serum alanine aminotransferase and aspartate aminotransferase in BBR (or vehicle)-treated HN rats was significantly reduced by pre- (or post)-administration of GAD (450 mg/kg/day). The q-value >1.15 (by Jin method) indicated synergistic effects of co-treatments of BBR (50 mg/kg) with GAD (450 mg/kg). The synergistic beneficial effects were validated by comparison of BBR alone at a dose of clinical usage (4.5 mg/kg/day, in two divided doses) and BBR + GAD at half dose plus half dose (2.25 + 225 mg/kg/day) or half dose plus full dose (2.25 + 450 mg/kg/day). In conclusion, co-treatment with GAD and BBR holds promise for the management of hyperuricemia and gout.
Highlights
In China, due to the therapeutic benefits for enhancing efficacy and reducing side effects, the concomitant use of herbal medicine with conventional drug treatment plays a crucial role in the clinical therapies of major difficult and complicated diseases as well as major infectious diseases, such as cancers,[1] rheumatoid arthritis,[2] coronavirus diseases,[3] etc.Gnaphalium affine D
Effects of Gnaphalium affine D. Don (GAD) on Hyperuricemia and Renal Function in hyperuricemic nephropathy (HN) rats (Results from Experiment 1) Over 21 days, a significant decrease in body weight (BW) gain was observed in HN-group rats versus normal control (NC)-group rats (p < 0.01) (►Table 2)
HN rats showed a remarkable increase in serum UA (p < 0.001), CRE (p < 0.01), and blood urea nitrogen (BUN) (p < 0.01) when compared with the NC rats from day 7 and the hyperuricemia and the renal damage progressively aggravated over time (►Fig. 1)
Summary
In China, due to the therapeutic benefits for enhancing efficacy and reducing side effects, the concomitant use of herbal medicine with conventional drug treatment plays a crucial role in the clinical therapies of major difficult and complicated diseases as well as major infectious diseases, such as cancers,[1] rheumatoid arthritis,[2] coronavirus diseases,[3] etc.Gnaphalium affine D. The ethanolic crude extract of the aerial parts of G. affine revealed promising hypouricemic effects.[4,5] An activity-guided separation procedure was conducted to find the active fractions, which led to the findings of two fractions with different urate-lowering mechanisms (production inhibition and excretion promotion of urate) and the identification of active compounds (caffeoylquinic acids, flavonoids, and chalcone). A fraction exhibited a nephroprotective effect against urate-induced renal dysfunction in mice. Don extract named “GAD.” Other groups reported that G. affine showed significant urate lowering effect on potassium oxonate (PO)-induced acute hyperuricemia and antigouty arthritis activity on monosodium urate (MSU) crystal-induced paw edema in mice.[6] there are no reports about the hypouricemic and nephroprotective effects of G. affine in chronic hyperuricemic conditions. G. affine (or G. tranzschelii) extract exhibited antioxidant activity against oxidative liver damage[7] and a hepatoprotective effect on CCl4-induced liver jury in mice.[8]
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