DKB114, A Mixture of Chrysanthemum Indicum Linne Flower and Cinnamomum Cassia (L.) J. Presl Bark Extracts, Improves Hyperuricemia through Inhibition of Xanthine Oxidase Activity and Increasing Urine Excretion

Lee, Young-Sil; Kim, Seung-Hyung; Yuk, Heung Joo; Kim, Dong-Seon

doi:10.3390/nu10101381

Cited by 18 publications

(16 citation statements)

References 34 publications

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“…In another study, Chen, Li, Wu, Li, and Ma (2019) and Chen et al (2013) reported that lemon water and rutin exhibited urate lowering potential in a similar fashion. Previously, many natural products as well as their bioactive compounds are reported to inhibit XOD enzyme potently (Hongyan et al, 2016; Jhang et al, 2016; Kumar et al, 2018; Lee, Kim, Yuk, & Kim, 2018; Lee, Kim, Yuk, Lee, & Kim, 2018; Li et al, 2017; Liu et al, 2019; Mehmood, Zhao, Wang, Nadeem, et al, 2019; Peng, Lin, Zhao, & Sun, 2019; Wan et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Genome‐wide association studies reported that around 90% hyperuricemia patients exhibit under‐excretion of uric acid. The reabsorption and excretion of uric acid handle by multiple transporters in the intestine and renal tissues such as; URAT1, GLUT9, and breast cancer resistance protein or ATP‐binding cassette, subfamily G, 2 (BCRP, ABCG2) (Ichida et al, 2012; Lee, Kim, Yuk & Kim, 2018; Lee, Kim, Yuk, Lee, et al, 2018, 2019).…”

Section: Discussionmentioning

confidence: 99%

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Uricostatic and uricosuric effect of grapefruit juice in potassium oxonate‐induced hyperuricemic mice

et al. 2020

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The aim of this study was to examine the preventive action of grapefruit juice (GFJ) against potassium oxonate‐induced hyperuricemic mice. The results showed that GFJ significantly (p < .05) inhibit the serum and hepatic xanthine oxidase enzyme, lower uric acid level, serum creatinine, uromodulin, and blood urea nitrogen levels to normal and lower inflammation related genes IL‐1β, caspase‐1, NLRP3, and ASC. Furthermore, histopathology analysis revealed that GFJ markedly improve the renal and intestinal morphology. The mRNA expression of urate transporter 1, glucose transporter 9 were downregulated, whereas ATP‐binding cassette transporter (ABCG2) was upregulated in the GFJ‐treated group. The results of immunohistochemistry revealed that the ABCG2 protein expression in the small and large intestine was significantly upregulated after the GFJ administration. These results suggested that GFJ can be used as a urate lowering agent and future mechanistic studies should be conducted. Practical applications The results of current study indicated that utilization of GFJ as an anti‐hyperuricemic agent for the treatment of hyperuricemia. This article will be very valuable for all those peoples which are directly or indirectly linked with this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Uricostatic and uricosuric effect of grapefruit juice in potassium oxonate‐induced hyperuricemic mice

et al. 2020

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“…DKB114 decreased cellular uric acid uptake in oocytes, and HEK293 cells expressing human urate transporter (hURAT)1 and decreased the protein expression levels of urate transporters, URAT1, and glucose transporter, GLUT9, associated with reabsorption of uric acid in the kidney. DKB114 exerts antihyperuricemic effects and uricosuric effects, which are accompanied by a reduction in the production of uric acid and promotion of uric acid excretion via inhibition of xanthine oxidase activity and reabsorption of uric acid (22).…”

Section: Discussionmentioning

confidence: 99%

“…Co. Ltd, Suwon, Korea, Lot number is BPD170926-1) was prepared as described previously. Briefly, DKB114 was selected and prepared by mixing previously prepared C. indicum flower and C. cassia bark extracts at a weight ratio of 1:2 based on our previous report [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study demonstrated that DKB114 (a mixture of Chrysanthemum indicum Linn flower extract and Cinnamomum cassia extract) reduced serum uric acid level in normal rats and rats with PO-induced hyperuricemia and promoted excretion of uric acid in the urine, indicating that DKB114 has an anti hyperuricemic effect and may be a potent uricosuric agent. In addition, DKB114 inhibited xanthine oxidase activity and hepatic uric acid production in vitro and in vivo, as well as cellular uptake of uric acid in vitro [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial for Evaluation of the Efficacy and Safety of DKB114 on Reduction of Uric Acid in Serum

et al. 2020

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This study sought to investigate the antihyperuricemia efficacy and safety of DKB114 (a mixture of Chrysanthemum indicum Linn flower extract and Cinnamomum cassia extract) to evaluate its potential as a dietary supplement ingredient. This clinical trial was a randomized, 12-week, double-blind, placebo-controlled study. A total of 80 subjects (40 subjects with an intake of DKB114 and 40 subjects with that of placebo) who had asymptomatic hyperuricemia (7.0–9.0 mg/dL with serum uric acid) was randomly assigned. No significant difference between the DKB114 and placebo groups was observed in the amount of uric acid in serum after six weeks of intake. However, after 12 weeks of intake, the uric acid level in serum of subjects in the DKB114 group decreased by 0.58 ± 0.86 mg/dL and was 7.37 ± 0.92 mg/dL, whereas that in the placebo group decreased by 0.02 ± 0.93 mg/dL and was 7.67 ± 0.89 mg/dL, a significant difference (p = 0.0229). In the analysis of C-reactive protein (CRP) change, after 12 weeks of administration, the DKB114 group showed an increase of 0.05 ± 0.27 mg/dL (p = 0.3187), while the placebo group showed an increase of 0.10 ± 0.21 mg/dL (p = 0.0324), a statistically significant difference (p = 0.0443). In the analysis of amount of change in apoprotein B, after 12 weeks of administration, the DKB114 group decreased by 4.75 ± 16.69 mg/dL (p = 0.1175), and the placebo group increased by 3.13 ± 12.64 mg/dL (p = 0.2187), a statistically significant difference between the administration groups (p = 0.0189). In the clinical pathology test, vital signs and weight measurement, and electrocardiogram test conducted for safety evaluation, no clinically significant difference was found between the ingestion groups, confirming the safety of DKB114. Therefore, it may have potential as a treatment for hyperuricemia and gout. We suggest that DKB114 as a beneficial and safe food ingredient for individuals with high serum uric acid. Trial registration (CRIS.NIH. go. Kr): KCT0002840.

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Inhibitory interaction of flavonoids with organic cation transporter 2 and their structure–activity relationships for predicting nephroprotective effects

Tan

Wang

et al. 2023

J of Applied Toxicology

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Organic cation transporter 2 (OCT2) is mainly responsible for the renal secretion of various cationic drugs, closely associated with drug‐induced acute kidney injury (AKI). Screening and identifying potent OCT2 inhibitors with little toxicity in natural products in reducing OCT2‐mediated AKI is of great value. Flavonoids are enriched in various vegetables, fruits, and herbal products, and some were reported to produce transporter‐mediated drug–drug interactions. This study aimed to screen potential inhibitors of OCT2 from 96 flavonoids, assess the nephroprotective effects on cisplatin‐induced kidney injury, and clarify the structure–activity relationships of flavonoids with OCT2. Ten flavonoids exhibited significant inhibition (>50%) on OCT2 in OCT2‐HEK293 cells. Among them, the six most potent flavonoid inhibitors, including pectolinarigenin, biochanin A, luteolin, chrysin, 6‐hydroxyflavone, and 6‐methylflavone markedly decreased cisplatin‐induced cytotoxicity. Moreover, in cisplatin‐induced renal injury models, they also reduced serum blood urea nitrogen (BUN) and creatinine levels to different degrees, the best of which was 6‐methylflavone. The pharmacophore model clarified that the aromatic ring, hydrogen bond acceptors, and hydrogen bond donors might play a vital role in the inhibitory effect of flavonoids on OCT2. Thus, our findings would pave the way to predicting the potential risks of flavonoid‐containing food/herb–drug interactions in humans and optimizing flavonoid structure to alleviate OCT2‐related AKI.

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DKB114, A Mixture of Chrysanthemum Indicum Linne Flower and Cinnamomum Cassia (L.) J. Presl Bark Extracts, Improves Hyperuricemia through Inhibition of Xanthine Oxidase Activity and Increasing Urine Excretion

Cited by 18 publications

References 34 publications

Uricostatic and uricosuric effect of grapefruit juice in potassium oxonate‐induced hyperuricemic mice

Uricostatic and uricosuric effect of grapefruit juice in potassium oxonate‐induced hyperuricemic mice

A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial for Evaluation of the Efficacy and Safety of DKB114 on Reduction of Uric Acid in Serum

Inhibitory interaction of flavonoids with organic cation transporter 2 and their structure–activity relationships for predicting nephroprotective effects

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