Synergistic Uric Acid-Lowering Effects of the Combination of Chrysanthemum indicum Linne Flower and Cinnamomum cassia (L.) J. Persl Bark Extracts

Abstract

Chrysanthemum indicum Linne flower (CF) and Cinnamomum cassia (L.) J. Persl bark (CB) extracts have served as the main ingredients in several prescriptions designed to treat hyperuricemia and gout in traditional Chinese and Korean medicine. However, little is known about the combination effects of a CF and CB (CC) mixture on hyperuricemia. In our study, we investigated the antihyperuricemic effects of CC mixture and the mechanisms underlying these effects in normal and potassium oxonate- (PO-) induced hyperuricemic rats. The CC mixture significantly decreased uric acid levels in normal and PO-induced hyperuricemic rats and showed the enhanced hypouricemic effect compared to CF or CB alone. Furthermore, the CC mixture increased renal uric acid excretion in PO-induced hyperuricemic rat. We found that CC mixture and its major components, chlorogenic acid, 3,4-dicaffeoylquinic acid (isochlorogenic acid), coumarin, cinnamaldehyde, trans-cinnamic acid, and o-methoxycinnamaldehyde, inhibit the activity of xanthine oxidase (XOD) in vitro. The CC mixture exerts antihyperuricemic effects accompanied partially by XOD activity inhibition. Therefore, the CC mixture may have potential as a treatment for hyperuricemia and gout.

Figure 1

Effects of CB and CF and their combination on serum uric acid levels in PO-induced hyperuricemic rats (a) and normal rats (b). NC, normal control group; PO, potassium oxonate-induced hyperuricemia group; CF, 200 mg/kg Chrysanthemum indicum Linne flower ethanol extract; CB, 200 mg/kg Cinnamomum cassia (L.) J. Persl bark ethanol extract; CC, mixture of CF and CB; AP 10, 10 mg/kg allopurinol. Data are expressed as the mean ± SEM (n = 8). ^###p < 0.001 versus the NC group; ^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.001 versus the PO group; ^ap < 0.05 versus the CF group; ^bp < 0.05 versus the CF group.

Figure 2

Dose-dependent effects of the CC12 mixture on serum (a), urine (b), uric acid levels, and fractional excretion of uric acid (FEUA) (c) in PO-induced hyperuricemic rat. NC, normal control group; PO, potassium oxonate-induced hyperuricemia group; CC12, mixture of CF and CB at a ratio of 1 : 2; AP 10, 10 mg/kg allopurinol. Data are expressed as the mean ± SEM (n = 8). ^##p < 0.01 and ^###p < 0.01 versus the NC group; ^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.01 versus the PO group.

Figure 3

Representative HPLC chromatograms of a standard solution (a), CF (b), CB (c), and the CC12 mixture (d): (1) chlorogenic acid, (2) coumarin, (3) 3,4-dicaffeoylquinic acid, (4) cinnamaldehyde, (5) trans-cinnamic acid, and (6) o-methoxycinnamaldehyde.