Research Progress of Dihydromyricetin in Uric Acid-Lowering

Hyperuricemia caused by abnormal uric acid metabolism has become a common metabolic disease worldwide. It not only easily induces gout but is also closely associated with complications such as kidney damage and cardiovascular diseases, posing a serious threat to human health. As a key active flavonoid component in plants like Ampelopsis grossedentata (vine tea), dihydromyricetin (DMY) has attracted increasing attention in uric acid-lowering research in recent years due to its natural origin, good safety, and diverse biological activities. This article reviews the source and physicochemical properties of DMY, systematically summarizes its research progress in uric acid-lowering, including the inhibition of uric acid production-related enzyme activity, promotion of uric acid excretion, and intervention in urate crystal formation. Meanwhile, it analyzes the existing problems in current research and prospects its future application, aiming to provide theoretical support and practical guidance for the in-depth exploration and practical application of DMY in uric acid-lowering related fields.

Keywords: Dihydromyricetin; Hyperuricemia; Uric Acid-Lowering; Uric Acid Metabolism; Gout

1. Introduction

Hyperuricemia is a metabolic disease characterized by disorders of purine metabolism or uric acid excretion in the body, resulting in blood uric acid levels exceeding 420 μmol/L. With the increase in the intake of high-purine foods in people's diet and changes in lifestyle, the global incidence of hyperuricemia has been rising year by year, showing a younger trend. Under the condition of long-term hyperuricemia, uric acid tends to deposit in tissues such as joints, cartilage, and kidneys in the form of urate crystals, triggering diseases like gouty arthritis, uric acid kidney stones, and chronic kidney damage. At the same time, it also increases the risk of hypertension, diabetes, and cardiovascular diseases, causing multi-system harm to the body's health. Therefore, searching for safe and effective natural uric acid-lowering components has become a research hotspot. Dihydromyricetin is the main active component of vine tea and also exists in small amounts in other plants such as grapes and waxberries. As a natural flavonoid compound, DMY has been proven to possess various biological activities including antioxidant, anti-inflammatory, hepatoprotective, and hypoglycemic effects. In recent years, a growing number of in vitro experiments, animal experiments, and preliminary clinical studies have shown that DMY has significant potential in regulating uric acid metabolism and lowering serum uric acid levels, providing a new direction for the prevention and treatment of hyperuricemia.

2. Plant Source of Dihydromyricetin

The main natural source of DMY is vine tea (Ampelopsis grossedentata), a plant of the Ampelopsis genus in the Vitaceae family. It is widely distributed in the southwest and south China regions and has a long history of medicinal use in folk medicine, often used to relieve sore throat, clear heat, and promote diuresis. The content of DMY in the tender stems and leaves of vine tea can reach 20%-30% of the dry weight, making it the most important plant raw material for extracting DMY currently. In addition, small amounts of DMY have also been detected in other Vitaceae plants (e.g., grape leaves) and Myricaceae plants (e.g., waxberry bark), but their contents are much lower than that in vine tea, so they do not have economic value for large-scale extraction.

3. Uric Acid-Lowering Effects of Dihydromyricetin and Related Research

3.1 Inhibition of Uric Acid Production-Related Enzyme Activity

Uric acid is the end product of purine metabolism in the body, and its production process mainly relies on the catalysis of xanthine oxidase (XOD) and xanthine dehydrogenase (XDH): XDH first converts hypoxanthine to xanthine, and then XOD further oxidizes xanthine to uric acid. Among them, XOD is the key rate-limiting enzyme in the uric acid production pathway, and inhibiting XOD activity is the core target for reducing uric acid production. In the in vitro XOD activity detection system, after adding different concentrations of DMY, the rate of XOD-catalyzed xanthine conversion to uric acid decreased significantly, and the inhibitory effect showed a dose-dependent manner. When the concentration reached 80 μmol/L, the inhibition rate of XOD activity could reach more than 60%, and its inhibitory effect was close to that of allopurinol, a commonly used clinical uric acid-lowering drug (the inhibition rate was about 65% at the same concentration). Further studies found that DMY may bind to the molybdenum cofactor in the active center of XOD, changing the spatial conformation of the enzyme, thereby reducing the enzyme's affinity for substrates and achieving the inhibition of uric acid production. In addition, DMY can inhibit the activity of upstream enzymes in purine synthesis, reducing the production of uric acid precursor substances from the source and further lowering serum uric acid levels.

3.2 Promotion of Uric Acid Excretion

Uric acid excretion mainly depends on the kidneys, with approximately 70% of uric acid excreted from the body through glomerular filtration, renal tubular reabsorption, and secretion processes. Among them, urate transporters in renal tubular epithelial cells play a key role in uric acid excretion. Animal experiments have confirmed that DMY can improve the renal uric acid excretion capacity by inhibiting uric acid reabsorption transporters and enhancing the function of uric acid secretion transporters. In addition, DMY can further improve the filtration and excretion efficiency of uric acid by increasing renal blood flow and promoting glomerular filtration rate. In a study on healthy mice, after intravenous injection of DMY, the glomerular filtration rate of mice increased by 15% within 30 minutes, the urinary uric acid excretion rate accelerated significantly, and this effect could last for more than 2 hours.

3.3 Intervention in Urate Crystal Formation and Deposition

Under the condition of long-term hyperuricemia, when serum uric acid exceeds its solubility, it will precipitate in the form of monosodium urate crystals and deposit in joint cavities, and cartilage, triggering inflammatory reactions and tissue damage. This is the core pathological mechanism of gout attacks and uric acid nephropathy. DMY can reduce the tissue damage caused by hyperuricemia by interfering with the formation and deposition of urate crystals. Further studies have confirmed that DMY molecules can bind to uric acid molecules through hydrogen bonds, changing the aggregation mode of uric acid molecules and preventing the formation of ordered crystal structures. At the same time, it can also adsorb on the surface of formed crystals, inhibiting further growth and agglomeration of the crystals. In addition, in a rat model of gouty arthritis, inflammation was induced by intra-articular injection of urate crystals, and at the same time, DMY was administered by gavage. After one week, the deposition of urate crystals in the joint cavity of rats decreased by 45% compared with the model group, the degree of joint swelling was reduced by 30%, and the content of inflammatory factors in joint tissue decreased significantly. This suggests that DMY can not only reduce the deposition of urate crystals but also alleviate the tissue inflammation caused by crystals through anti-inflammatory effects, exerting a dual protective effect on gouty arthritis.

4. Application Status of Dihydromyricetin in Uric Acid-Lowering

4.1 Food and Health Product Field

Due to its natural plant origin, high safety, and clear uric acid-lowering potential, DMY has been applied in the food and health product field. Currently, there are products such as tea bags and solid beverages made from vine tea on the market. These products retain DMY in vine tea and provide daily health care options for people with high uric acid levels. Consumer feedback shows that serum uric acid levels decrease to a certain extent after long-term consumption, with no obvious adverse reactions. In addition, health products with purified DMY as the core component are also being developed gradually, with common dosage forms including capsules and tablets. The added dose is usually 100-200 mg per capsule/tablet, and the recommended daily intake is 1-2 capsules/tablets, mainly used for auxiliary regulation of serum uric acid levels. Some products also compound other natural ingredients with uric acid-lowering or anti-inflammatory effects (such as geniposide and apigenin) to enhance the uric acid-lowering effect through synergistic action.

4.2 Pharmaceutical Field

Research on DMY in the pharmaceutical field of uric acid-lowering is still in the preclinical stage, but it has shown good potential for drug development. In animal experiments, DMY has a stable effect on lowering serum uric acid in hyperuricemia model animals and can improve kidney damage and joint inflammation caused by urate crystals. Its clear mechanism of action lays a foundation for subsequent clinical research. In addition, research on the combined application of DMY and clinical uric acid-lowering drugs is also underway. Preliminary results show that when DMY (50 mg/kg/d) is used in combination with low-dose allopurinol (20 mg/kg/d), the serum uric acid reduction rate of hyperuricemia mice can reach 55%, which is significantly higher than that of using allopurinol alone (40%) or DMY alone (30%), and no increased risk of liver and kidney function damage is observed. This suggests that DMY may reduce the dosage of clinical drugs through synergistic effects and decrease adverse reactions.

5. Safety and Side Effects of Dihydromyricetin

Multiple preclinical studies and some small-scale human trials have shown that DMY generally has good tolerance when used within the recommended dosage range, and no serious adverse reactions have been reported. Common adverse reactions are mostly mild and temporary, mainly including mild gastrointestinal discomfort such as nausea, abdominal distension, or loose stools. These symptoms usually resolve spontaneously after drug withdrawal or dosage reduction. Long-term toxicity studies have also not found obvious liver and kidney function damage or hematopoietic system toxicity. In addition, DMY is derived from natural plants with a clear structure and good bioavailability. Compared with other uric acid-lowering drugs, it has certain advantages in terms of safety. Overall, the existing evidence supports DMY as a uric acid-lowering active component with high safety, but larger-scale and long-term clinical trials are still needed to further comprehensively evaluate its human safety and potential side effects.

6. Conclusion

Dihydromyricetin has significant advantages in the field of uric acid-lowering and is a highly valuable natural candidate molecule. It can regulate uric acid metabolism through multiple targets: it not only inhibits xanthine oxidase to reduce uric acid synthesis but also regulates renal urate transporters to enhance excretion, resulting in a comprehensive and stable uric acid-lowering effect. In addition, as a natural flavonoid compound, DMY has good safety and tolerance. It causes no obvious damage to the liver and kidneys at effective concentrations, and its adverse reactions are much lower than those of used chemical uric acid-lowering drugs, making it suitable for long-term use in the management of hyperuricemia. At the same time, DMY has multiple effects such as anti-inflammatory and antioxidant activities, which can reduce tissue damage caused by uric acid crystals and lower the risk of complications. Moreover, the plants from which it is derived are widely distributed, and the extraction process is mature, indicating good prospects for industrial development. All these factors provide an important direction for the prevention and treatment of hyperuricemia and gout.

References

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[3] Sun ZR, Peng HZ, Fan MS, et al. Dihydromyricetin ameliorates hyperuricemia through inhibiting uric acid reabsorption. J Sci Food Agric, 2025, 105(8): 4178-4190.