## 4 Discussion
### Anti-Hyperuricemic Effects of C. morifolium in Potassium Oxonate-Induced Rats  
Potassium oxonate serves as a uricase inhibitor, causes hyperuricemia by inhibiting uric acid decomposition [1], and thereby increases the uric acid level in the negative control. Our results showed that the oral administration of F10 significantly reduced the SUA level at both doses. However, the SUA levels of rats treated with 25 mg/kg of the F10 were significantly higher than the normal and positive control. In contrast, the SUA levels in the 50 mg/kg treatment and positive control were similar to that of the normal control (not induced to be hyperuricemic). This revealed the effectiveness of the 50 mg/kg treatment (55.58 \(\pm\) 4.81% reduction relative to the negative control) in lowering SUA levels, comparable to the positive control, allopurinol (50.27 \(\pm\) 5.05% reduction relative to the negative control). This agrees with a previous report which demonstrates the effectiveness of _Chrysanthemum_ flower oil in reducing SUA levels [1]. Thus, it is noteworthy that F10 at 50 mg/kg exhibited excellent anti-hyperuricemic effects, comparable to that of allopurinol. Oral administration of F10 lowered the rats' UUA levels at both doses, but the level was higher than that of the positive control. The reduced, but higher than normal UUA level in the F10 treated rats might be due to the enhanced excretion of uric acid. The uric acid-lowering effect of _C. morifolium_ is a consequence of both enhanced excretion and suppressed production of uric acid, in which the uric acid transporter genes in the kidney is upregulated in rats treated with _Chrysanthemum_ flower oil [1]. The goal of gout therapy is long-term management of hyperuricemia, which can be achieved by SUA suppression as well as uric acid excretion enhancement. Therefore, this study suggested that the oral consumption of 50 mg/kg of F10 may be suitable to be used as a long-term serum-uric acid lowering therapy for the management of hyperuricemia, and as a preventive measure for gout. It could be explored further as a potential source of natural anti-hyperuricemic and uricosuric agent. XO is an enzyme that catalyses the oxidation of hypoxanthine and xanthine to uric acid in purine catabolism [1]. Since hyperuricemia results from uric acid overproduction, XO inhibitors that can inhibit the production of uric acid have been considered for hyperuricemia treatment. In this study, the administration of F10 extract significantly reduced the XO levels in rats. This result suggested that one of the uric acid-lowering mechanisms associated with F10 administration involved the suppression of uric acid production via XO enzyme inhibition. This corroborates the findings of [PERSON] et al. (2014), which demonstrate that the administration of _Chrysanthemum_ flower oil suppresses uric acid production by inhibiting the XO enzyme in the liver [1]. Our finding also agrees with a previous report which depicted that _C. morifolium_ possesses significant XO inhibitory activity in a concentration-dependent manner [7]. According to [PERSON] and [PERSON] (2020), xanthine accumulates when XO enzyme is inhibited [26]. In the present study, the xanthine and hypoxanthine levels increased relative to the normal control after the administration of F10. Therefore, it was suggested that the suppression of uric acid production in rats was achieved by XO enzymes inhibition. However, both hypoxanthine and xanthine showed only slight increases compared to the negative control. This might be explained by the re-utilization or enhanced excretion of xanthine and hypoxanthine when XO action is inhibited. [PERSON] et al. (1988) reported a direct relationship between the excretion of uric acid, xanthine, and hypoxanthine [27]. In addition, our results also suggested that the lower XO activity may be attributed to the downregulation of XO gene expression. However, to date, there is no report about the regulation of XO gene expression by semi-purified plant sub-fraction.