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Ethnopharmacological Relevance: Herbaceous peony (Paeonia lactiflora Pall.) flower has been used widely in dietotherapy in China and other countries. It has good ethnopharmacological value in the treatment of various metabolic diseases. However, the molecular mechanisms by which it lowers serum uric acid are unknown. The development of pharmaceutical resources is very important. Here, we sought to elucidate the mode of action of herbaceous peony in terms of reducing uric acid levels., Aim of the Study: In the present research, the effects of the total glucosides of herbaceous peony flower were investigated in a rat hyperuricaemia model. Another aim of the study was to clarify the mechanism by which herbaceous peony flower (TGPF) lowers serum uric acid levels., Materials and Methods: A hyperuricaemic rat model was induced via intragastric administration of 100 mg/kg adenine and 250 mg/kg ethambutol hydrochloride (EH) for 23 d. Then TongFengShu 600 mg/kg, allopurinol 42 mg/kg, or TGPF (50 mg/kg, 100 mg/kg, or 200 mg/kg) was administered 1 h after the adenine and EH treatments., Results: TGPF improved weight loss and decreased serum UA, XOD, MCP-1, TNF-α, Cr, and BUN in the rats with hyperuricaemic nephropathy. TGPF downregulated renal URAT1 and GLUT9, upregulated renal OAT1, and ameliorated histopathological changes in the thymus, spleen, and kidney., Conclusion: TGPF is promising as a therapeutic agent against hyperuricaemia. It regulates the uric acid transporters and diminished serum uric acid levels, and alleviates renal pathology associated with hyperuricaemia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Cordyceps militaris was recorded in the classic traditional Chinese medicine book with the main functions of "protecting liver and enhancing kidney functions", influencing serum uric acid levels., Aim of Study: The aim is to investigate the hypouricemic effects and possible mechanism of C. militaris in hyperuricemic mice., Materials and Methods: A water extract (WECM) was prepared by decocting C. militaris directly at 80 °C in water bath, followed by lyophilization. WECM at 50, 100 and 200mg/kg was orally administered to hyperuricemic mice induced by potassium oxonate and hypoxanthine combinedly and allopurinol (5mg/kg) was served as a positive control., Results: WECM exhibited excellent hypouricemic activity, which could decrease the serum uric acid levels of the hyperuricemic mice (306μmol/L) to 189, 184 and 162μmol/L at different doses respectively (P<0.01), approaching the levels of normal mice (184μmol/L). The urate transporter 1 (URAT1) protein levels of kidney at different doses of WECM were 28.15, 17.43, 9.03pg/mL respectively, much lower than that in the hyperuricemia group (93.45pg/mL, P<0.01); and suggested WECM may interact with URAT1. Docking simulations using modeled structure of URAT1 suggested that LYS145, ARG325, ARG477 and ASP168 of URAT1 are key functional residues of URAT1. Four active compounds in C. militaris were identified and their interaction energies with target were estimated between -200 and -400kcal/mol., Conclusions: These findings suggested that C. militaris produced significant hypouricemic actions and the hypouricemic effects of WECM may be attributed to the inhibitive effect of WECM on URAT1 protein levels. The results of blood urine nitrogen and serum creatinine levels and liver, kidney and spleen coefficients showed that WECM have no negative impacts on liver, renal and spleen functions. The screened four active compounds using molecular docking method deserve further investigation in other work., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ermiao wan, which is composed of phellodendri cortex and atractylodis rhizome, is described as eliminating heat, excreting dampness and anti-edema prescription in traditional Chinese medical literatures including Danxi's Experiences in Medicine and State Pharmacopoeia of People's Republic of China. So it is being used clinically in the treatment of gout and hyperuricemia in China. In the present study, the water extracts of Ermiao wan and phellodendri cortex at 840 and 480 mg/kg/day orally for 7 days were demonstrated to possess in vivo potent hypouricemic effects both in hyperuricemic mice pretreated with oxonate and in normal mice, respectively. In the hyperuricemic animals, the effect of Ermiao wan was equal to that of the reference drug allopurinol (at 10 mg/kg/day orally for 7 days), but in the normal mice, the former was weaker than latter. In addition, both Ermiao wan and phellodendri cortex were found to have in vivo relatively inhibitory effects on mouse liver xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities at the same dose described above. These inhibitory effects were weaker than that observed for allopurinol. Atractylodis rhizome at 340 mg/kg/day orally for 7 days did not show any effects on the above experiments. These results suggested that atractylodis rhizomes assisted and enhanced the effect of phellodendri cortex on reduction of serum uric acid level in hyperuricemic mice, and hypouricemic effects of Ermiao wan and phellodendri cortex may be achieved by other mechanism partly instead of the XDH and XO inhibition.

Xanthine oxidase (XOD) is a key enzyme playing a role in hyperuricemia, catalyzing the oxidation of hypoxanthine to xanthine and then to uric acid. This study aimed to identify the XOD inhibitors from the leaves of Lagerstroemia speciosa (L.) Pers. (Lythraceae), which was traditionally used as a folk medicine in the Philippines. Using a bioassay-guided fractionation technique, two active compounds were isolated from the aqueous extracts of the Lagerstroemia speciosa leaves, namely valoneic acid dilactone (VAD) and ellagic acid (EA). The result demonstrated that the XOD-inhibitory effect of VAD was a stronger than that of allopurinol, a clinical drug used for XOD inhibitor, with a non-competitive mode for the enzyme with respect to xanthine as the substrate. These results may explain and support the dietary use of the aqueous extracts from Lagerstroemia speciosa leaves for the prevention and treatment of hyperuricemia.