Study on the Hepatoprotective Effects of Angelica gigas Nakai

 1. Introduction 

The liver is susceptible to damage from alcohol, drugs, high-fat diets, and toxins, leading to diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and drug-induced liver injury (DILI). Angelica gigas Nakai (Korean angelica), a plant of the Apiaceae family, has been used in traditional Chinese and Korean medicine to regulate qi and blood. Modern studies have revealed that it contains active components such as decursin, decursinol angelate, and decursinol, which exhibit definite hepatoprotective effects, capable of alleviating liver damage and improving liver function. This article reviews these core components, as well as the mechanisms, research progress, and safety of the hepatoprotective effects of Angelica gigas Nakai, providing references for subsequent research and clinical applications. 

2. Core Hepatoprotective Components of Angelica gigas Nakai 

The hepatoprotective activity of Angelica gigas Nakai relies on three categories of core components, with coumarins—primarily the key monomers decursin, decursinol angelate, and decursinol—playing a central role: 

Coumarins (accounting for 30%-40% of active components): Decursin is the most abundant core monomer (50%-60% of total coumarins), followed by decursinol angelate (approximately 15%-20%) and decursinol (approximately 10%-15%). All three are mainly enriched in the phloem of the roots and rhizomes. After oral administration, decursin is absorbed in the intestine via passive diffusion and enters the liver, where it is catalyzed by the CYP3A4 enzyme to form decursinol (with 2-3 times stronger antioxidant and anti-inflammatory activities than the parent compound); decursinol angelate is decomposed into decursinol by intestinal esterases before entering the liver via the portal vein; decursinol in its original form can be directly absorbed by the liver. Over 80% of the metabolites of these three components are excreted via bile within 24 hours of a single administration, with no significant in vivo accumulation. 

Polysaccharides (AGP): Composed of monosaccharides such as glucose and galactose, AGP is decomposed into oligosaccharides by intestinal flora (e.g., Bifidobacterium and Lactobacillus) after oral administration. It then enters the liver via the portal vein, directly participates in the regulation of hepatocyte metabolism, and exerts synergistic protective effects with coumarins. 

Volatile oils (e.g., butylidenephthalide): After absorption via the respiratory or digestive tract, volatile oils are rapidly distributed to the liver, where they enhance the anti-inflammatory effects of coumarins such as decursin. They have a short metabolic half-life (approximately 2-3 hours) and are mainly excreted via the kidneys. 

3. Hepatoprotective Mechanisms of Angelica gigas Nakai 

Centered on core components including decursin, decursinol angelate, and decursinol, and combined with polysaccharides (AGP) and volatile oils (e.g., butylidenephthalide), Angelica gigas Nakai forms a multi-pathway hepatoprotective network: 

3.1 Antioxidative Stress 

Decursin activates the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in hepatocytes. Its metabolite, decursinol, exhibits stronger ability to scavenge superoxide anions and hydroxyl radicals. Decursinol angelate inhibits the production of malondialdehyde (MDA), a product of lipid peroxidation. Together, these three components synergistically alleviate alcohol- or toxin-induced oxidative damage to hepatocytes. In terms of inhibiting hepatocyte apoptosis: Decursinol downregulates the expression of the pro-apoptotic protein Bax and upregulates the level of the anti-apoptotic protein Bcl-2, blocking the caspase-3/9 activation pathway. Polysaccharides can enhance this anti-apoptotic effect and improve hepatocyte survival rate. 

3.2 Regulation of Lipid Metabolism 

Decursin inhibits the activity of key enzymes involved in hepatic triglyceride synthesis (e.g., fatty acid synthase). Decursinol activates peroxisome proliferator-activated receptor α (PPARα) and promotes the expression of genes related to fatty acid β-oxidation (e.g., CPT1A). Together, they reduce hepatic lipid accumulation and improve steatosis. 

3.3 Anti-Inflammatory Effect 

Decursinol angelate inhibits the phosphorylation and nuclear translocation of the NF-κB p65 subunit, reducing the release of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Volatile oils can enhance this anti-inflammatory effect and reduce the infiltration of inflammatory cells (e.g., neutrophils and macrophages) in liver tissue. 

4. Summary of Research Progress on the Hepatoprotective Effects of Angelica gigas Nakai 

Current research on the hepatoprotective effects of Angelica gigas Nakai mainly focuses on animal experiments and in vitro studies, with an emphasis on the roles of decursin, decursinol angelate, and decursinol:  

4.1 Animal Experiments 

In a rat model of alcohol-induced ALD, intragastric administration of Angelica gigas Nakai extract containing decursin alleviated hepatic steatosis and inflammation. 

In a mouse model of acetaminophen-induced DILI, intervention with decursinol increased the content of GSH in liver tissue and decreased the levels of oxidative damage markers. 

In a mouse model of high-fat diet-induced NAFLD, decursinol angelate reduced hepatic triglyceride levels and downregulated the expression of the inflammatory factor IL-1β. 

4.2 In Vitro Studies 

In a model of HepG2 hepatocyte injury induced by hypoxia/reoxygenation, decursinol increased cell survival rate and decreased apoptosis rate. 

Decursin inhibited free fatty acid-induced lipid accumulation in HepG2 cells and upregulated the expression of the lipid metabolism-related protein PPARγ. 

Decursinol angelate inhibited the release of inflammatory factors from hepatocytes induced by lipopolysaccharide (LPS). 

5. Safety of Angelica gigas Nakai in Hepatoprotective Applications 

Based on the properties of decursin, decursinol angelate, and decursinol, four safety aspects should be noted when using Angelica gigas Nakai for hepatoprotection: 

Dose safety: Animal experiments show that decursin (10-50 mg/kg/day), decursinol (5-20 mg/kg/day), and decursinol angelate (8-30 mg/kg/day) cause no hepatotoxicity. However, excessive total coumarins (>800 mg/kg of crude drug extract, corresponding to >40 mg/kg of decursin) may lead to a slight increase in liver enzymes. Clinically, it is recommended that adults take no more than 3 g of extract (crude drug weight, containing 15-30 mg of decursin) per day. 

Allergic reactions: Approximately 2%-3% of individuals allergic to Apiaceae plants may be sensitive to coumarins such as decursin, experiencing symptoms like rash and pruritus. A skin patch test (using a 0.5% decursin normal saline solution) is required before first use. 

Drug interactions: Decursin may inhibit the activity of the CYP3A4 enzyme. When used in combination with statin lipid-lowering drugs (e.g., atorvastatin) or immunosuppressants (e.g., cyclosporine), blood drug concentrations should be monitored to avoid drug accumulation. 

Contraindicated populations: Individuals with yin deficiency and fire excess (symptoms such as dry mouth and tidal fever) or coagulation disorders should use it with caution, as components like decursin may slightly enhance anticoagulant effects. Pregnant women must use it under medical advice to avoid the impact of blood-activating effects on the fetus. 

6. Conclusions and Prospects 

Angelica gigas Nakai exerts hepatoprotective effects through multiple mechanisms—including antioxidation, anti-apoptosis, lipid regulation, and anti-inflammation—via core components such as decursin, decursinol angelate, and decursinol, combined with polysaccharides and volatile oils. Evidence from animal and in vitro studies is sufficient, but clinical research is insufficient, and the specific targets of these components remain unclear. Future research should conduct multi-center clinical trials to verify the efficacy of components such as decursin and decursinol, and use molecular docking technology to clarify their binding mechanisms with targets such as SOD, PPARα, and NF-κB. Meanwhile, nanocarrier technology (e.g., liposomes) can be used to improve the bioavailability of these components and develop liver-targeted preparations. With a basis in traditional application and support from modern pharmacology, monomer components such as decursin hold promise as potential candidates for adjuvant treatment of liver injury. 

References 

[1] Kim S Y, Oh K J, Seo Y R, et al. Comparative Study on Hepatoprotective Effects of Traditional Herbs, Roots of Angelica gigas Nakai, Glycyrrhiza uralensis Fischer, Zizyphus jujuba Mill., and Fruits of Paeonia lactiflora Pall., on Ethanol-Induced Liver Injury in Mice[J]. Antioxidants, 2024, 13(9): 1137. 

[2] Kim W T, Kim K M, Kang J S. Effect of Angelica gigas Nakai extract on hepatic damage in rats[J]. Tropical Journal of Pharmaceutical Research, 2020, 19(5): 1059-1064. 

[3] Noh H M, Ahn E M, Yun J M, et al. Angelica keiskei Koidzumi extracts improve some markers of liver function in habitual alcohol drinkers: a randomized double-blind clinical trial[J]. Journal of Medicinal Food, 2015, 18(2): 166-172. 

[4] Jung H K, Park P S, Huh N C, et al. Inhibitory effect of Angelica keiskei Koidz green juice on the liver damage in CCl₄-treated rats[J]. 1998.