Research Progress on the Uric Acid-Lowering Effects of Polygonum cuspidatum

1. Introduction

Polygonum cuspidatum Sieb. et Zucc. is a medicinal and edible plant used in Traditional Chinese Medicine (TCM) for "clearing dampness and relieving jaundice," treating damp-heat jaundice, and joint pain. Modern research indicates that components in its extract, such as emodin and polydatin, possess uric acid-lowering, anti-inflammatory, and antioxidant effects. Hyperuricemia (HUA), a metabolic disorder caused by purine metabolism dysfunction or impaired uric acid excretion, has an adult prevalence rate of 13.3% in China and is often accompanied by gout and renal damage. While existing drugs like allopurinol and febuxostat can rapidly control uric acid levels, they carry risks of adverse effects such as liver injury and cardiovascular events. Polygonum cuspidatum extract can ameliorate HUA through dual pathways of "lowering uric acid + controlling inflammation," showing significant potential for clinical application.

2. Active Components and Their Metabolism

2.1 Core Uric Acid-Lowering Components

The uric acid-lowering activity of Polygonum cuspidatum extract primarily relies on three types of components: Anthraquinones (e.g., emodin and rhein) synergistically reduce uric acid by inhibiting key enzymes in uric acid production and promoting renal excretion; Stilbenes (e.g., polydatin and resveratrol), besides regulating uric acid transporter expression to promote excretion, also have anti-inflammatory and antioxidant effects, alleviating inflammation caused by urate crystals; Flavonoids (e.g., quercetin and rutin) protect renal excretion function by scavenging free radicals and reducing oxidative stress. These three classes of components work synergistically through multiple pathways.

2.2 In Vivo Metabolic Characteristics

After oral administration, Polygonum cuspidatum extract exhibits characteristics of "intestinal targeting" and "renal enrichment." Emodin and polydatin are absorbed through the intestines with bioavailabilityes of 18% and 32% respectively, which can be increased when taken with food. The effective components reach concentrations in the kidney up to 3.8 times that in plasma, facilitating uric acid excretion. Metabolized primarily by liver CYP3A4, they are excreted mainly through urine and feces, with a half-life of about 8.2 hours, supporting once or twice daily dosing.

3. Uric Acid-Lowering Mechanisms

3.1 Inhibiting Uric Acid Production

Polygonum cuspidatum exerts its uric acid-lowering effects through a triple pathway of "inhibiting production - promoting excretion - anti-inflammatory and kidney protection." Regarding inhibition of uric acid production, emodin competitively binds to the active center of xanthine oxidase (XOD), blocking the conversion of xanthine to uric acid; Rhein downregulates the mRNA expression of xanthine dehydrogenase (XDH) in the liver, reducing the conversion of XDH to XOD, thereby decreasing uric acid synthesis at the source.

3.2 Promoting Uric Acid Excretion

Emodin downregulates the expression of URAT1 (a key protein for uric acid reabsorption) in renal tubular epithelial cells, reducing uric acid reabsorption; Polydatin activates ABCG2 (a uric acid secretion protein) and OAT1 (organic anion transporter), promoting uric acid secretion into the renal tubule lumen.

3.3 Anti-inflammatory and Kidney Protection

Emodin and polydatin inhibit the NF-κB signaling pathway, reducing the release of inflammatory factors to alleviate joint inflammation; Resveratrol scavenges reactive oxygen species, mitigating renal oxidative stress damage and maintaining renal tubular excretory function.

4. Pharmacological Research

4.1 Animal Study Evidence

Multiple animal studies have confirmed the uric acid-lowering effects of Polygonum cuspidatum extract: In hyperuricemic mouse models, gavage administration of the extract led to decreased serum uric acid levels, inhibited xanthine oxidase activity, and regulated the expression of renal uric acid transporters; In gout rat models, the extract reduced inflammatory cell infiltration in joint cavities, lowered inflammatory cytokine concentrations, and also decreased serum uric acid.

4.2 Clinical Research Progress

Clinical studies are primarily small-scale interventions, preliminarily showing auxiliary uric acid-lowering effects: Patients with simple hyperuricemia taking Polygonum cuspidatum extract orally experienced decreased serum uric acid levels without significant adverse reactions; Gout patients in the remission phase using the extract combined with low-dose allopurinol had higher rates of achieving target serum uric acid levels and lower joint pain recurrence rates compared to allopurinol alone.

5. Safety Assessment

5.1 Toxicity Studies

Acute toxicity: For mice receiving intragastric administration of Polygonum cuspidatum extract, there are clear median lethal dose (LD50) and safe dose range. The recommended daily dose for adults is much lower than the upper limit of the safe dose. Exceeding the safe dose may cause gastrointestinal irritation symptoms such as diarrhea and abdominal pain.

Chronic toxicity: No abnormal liver and kidney function was observed in rats after continuous intragastric administration of the extract. Only a few rats showed mild intestinal mucosal edema, which recovered after 1 week of drug withdrawal, indicating high safety for long-term use.

5.2 Adverse Reactions

Among adverse reactions, mild gastrointestinal discomfort is common, mostly caused by excessive dose or fasting administration, which can be alleviated after dose adjustment. Allergic reactions are rare and subside after drug withdrawal. In terms of drug interactions, components of Polygonum cuspidatum may affect the activity of specific enzymes. When used in combination with relevant drugs, the blood drug concentration should be monitored; when used in combination with anticoagulants, attention should be paid to the risk of bleeding.

6. Conclusion and Prospects

6.1 Research Conclusion

Leveraging its "multi-component, multi-target" advantage, Polygonum cuspidatum and its extracts demonstrate clear potential in the field of uric acid reduction: Its core components, emodin and polydatin, achieve "uric acid lowering" by inhibiting XOD and regulating renal uric acid transporters, while also possessing anti-inflammatory and kidney-protective effects, making them suitable as adjunctive therapy for hyperuricemia and gout; Furthermore, they exhibit high safety, with adverse reactions primarily being mild gastrointestinal irritation, and good tolerance for long-term use.

6.2 Future Research Directions

Current research on the uric acid-lowering effects of Polygonum cuspidatum still has shortcomings. Future efforts need breakthroughs in three areas: deepening the understanding of intestinal uric acid excretion regulation and the "gut-kidney axis" mechanism, optimizing targeted sustained-release formulations, and conducting multi-center, large-sample clinical studies. It provides new ideas for the natural auxiliary treatment of hyperuricemia and is expected to become an important candidate drug for integrated traditional Chinese and Western medicine in treating metabolic diseases.

References

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