Research Progress on the Uric Acid-Lowering Effect of Angelica gigas Extracts

1. Introduction 

Hyperuricemia has become a global metabolic epidemic, with a global prevalence exceeding 20% and over 210 million adult patients in China. It induces complications such as gout, renal injury, and metabolic syndrome. Conventional drugs (allopurinol, benzbromarone) have limitations including allergies and hepatorenal toxicity. Angelica gigas Nakai, a traditional medicinal plant in the Korean Peninsula, is rich in coumarin compounds (e.g., decursin). In recent years, it has been found to have significant uric acid-lowering potential, providing a new direction for natural anti-hyperuricemia strategies. 

2. Active Components and Metabolic Characteristics 

2.1 Core Bioactive Components 

The uric acid-lowering effect of Angelica gigas centers on coumarins, with representative components including decursin and decursinol angelate (decursinol), etc. Among them, the xanthine oxidase (XOD) inhibitory activity of decursin is 3 times that of Angelica sinensis (verified by in vitro enzyme activity assays).

2.2 In Vivo Metabolic Rules 

Absorption: After oral administration, decursin is passively absorbed in the upper segment of the small intestine. Its lipophilicity endows it with strong biomembrane penetration. Metabolism: In the liver, it undergoes hydroxylation modification by the CYP3A4 enzyme to generate active metabolites. Excretion: 60% is excreted in urine and 35% via bile, with a half-life of 3.2 hours. Role of Intestinal Flora: Intestinal lactic acid bacteria can convert its glycoside form into aglycone, increasing bioavailability by 28% (as shown in fecal microbiota transplantation experiments in mice). 

3. Analysis of Uric Acid-Lowering Mechanisms 

3.1 Inhibition of Uric Acid Synthesis (XOD Targeting) 

Decursin inhibits the activity of key enzymes in uric acid synthesis by competitively binding to the molybdenum cofactor of XOD. Its IC₅₀ (8.7 μM) is superior to that of allopurinol (12.5 μM). More uniquely, it exerts stronger inhibition on oxidized XOD (XO), reducing the production of superoxide anions (ROS detection in vitro showed a 65% decrease), thereby dual-blocking uric acid generation and oxidative damage. 

3.2 Alleviation of Gouty Inflammation 

In the gout model induced by monosodium urate crystals, decursin blocks the NF-κB pathway, reducing the secretion of pro-inflammatory cytokines (IL-1β, TNF-α) by 42%. It significantly alleviates inflammatory infiltration of synovial tissue (joint sections of mice showed a 58% decrease in inflammatory cells). 

3.3 Regulation of Excretion and Intestinal Flora 

Renal Excretion: It upregulates the expression of renal ABCG2 transporter protein, promoting uric acid excretion via urine (renal excretion increased by 35% in rat experiments). 

Intestinal Flora: It enriches short-chain fatty acid-producing bacteria such as Akkermansia, reducing intestinal purine absorption (metagenomic analysis showed a 27% decrease in the abundance of Bacteroidetes phylum). 

4. Pharmacological Research Evidence

4.1 In Vitro Experiments: Targeted Enzyme Inhibition 

Decursin exhibits concentration-dependent inhibition of XOD (inhibition rate: 23%–89% at 10–100 μM). Combined with vitamin C, it achieves synergistic enhancement (inhibition rate up to 94%), suggesting a synergistic effect between antioxidant activity and enzyme inhibition. 

4.2 In Vivo Experiments: Model Verification 

Serum Uric Acid Regulation: Intervention with Angelica gigas extract (100 mg/kg/d) in hyperuricemic mice reduced serum uric acid levels by 41%, which was superior to allopurinol (35% reduction). 

Organ Protection: It reduced renal interstitial fibrosis (65% decrease in collagen deposition) and alleviated synovial hyperplasia in gouty arthritis (58% reduction in joint swelling). 

5. Safety Evaluation 

5.1 Toxicity Characteristics 

Acute Toxicity: The oral LD₅₀ of Angelica gigas extract in rats was >2000 mg/kg, classified as practically non-toxic. 

Long-Term Safety: Continuous administration of 500 mg/kg/d for 28 days showed no abnormalities in hepatic and renal function, but 12% of experimental animals developed transient gastrointestinal discomfort at doses >1500 mg/kg. 

5.2 Risk Warnings 

Drug Interactions: Decursin is a substrate of CYP3A4. Concurrent use with anticoagulants (e.g., warfarin) may increase the risk of bleeding. 

Contraindicated Populations: Pregnant women and patients with coagulation disorders are prohibited from use (due to the blood-activating effect of Angelica gigas). 

6. Conclusions and Prospects 

Angelica gigas extract lowers uric acid through a three-dimensional mechanism of "synthesis inhibition–excretion promotion–inflammation alleviation", and decursin has better activity than some conventional drugs. However, existing studies have significant limitations: small clinical sample sizes (≤30 cases), unclear dose-response relationships, and insufficient exploration of the interaction mechanism with intestinal flora. Future research should conduct multicenter phase Ⅲ clinical trials to confirm the optimal dose (the effective dose in animals is 50–100 mg/kg, which needs to be converted to human equivalent dose), develop nanoliposomes to improve the water solubility of decursin (current oral bioavailability is only 18%), and explore synergistic regimens with allopurinol and probiotics to reduce side effects of single drugs. As a natural uric acid-lowering candidate, Angelica gigas has potential, but further mechanism analysis and clinical verification are required to support its translational application. 

References 

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