Research Progress on the Anti-fatigue and Therapeutic Effects of Angelica gigas Nakai on Motor Dysfunction

1.  Introduction 

Exercise-induced fatigue and motor dysfunction (including muscle injury, neuropathic pain, and post-exercise functional limitations) are common challenges for athletes, fitness enthusiasts, and patients in chronic disease rehabilitation. Existing interventions (e.g., nutritional supplements, physical therapy) face limitations in efficacy or side effects. Angelica gigas Nakai, a traditional medicinal plant from the Korean Peninsula, exhibits unique potential in its extracts and coumarin components for combating fatigue and promoting motor function recovery. This review summarizes its pharmacological mechanisms, research progress, and safety in the fields of sports medicine and rehabilitation. 

2.  Active Components Against Fatigue and Motor Dysfunction and Their Metabolism 

2.1 Core Active Components 

The anti-fatigue and motor-protective effects of Angelica gigas primarily stem from coumarins and polysaccharides: 

Coumarins: Represented by Decursin and Decursinol Angelate, accounting for 15%–20% of total extracts. These lipophilic compounds readily penetrate biomembranes to reach muscle and neural tissues. 

Polysaccharides: Angelica gigas polysaccharides (AGP) regulate energy metabolism and oxidative stress. Highly water-soluble, they rapidly enter systemic circulation. 

2.2 Metabolic Characteristics 

Absorption & Distribution: Decursin is absorbed via passive diffusion in the intestines, reaching peak plasma levels within 2 hours. It preferentially distributes to skeletal muscle and sciatic nerve (tissue/plasma concentration ratio >3:1). 

Metabolism & Excretion: Metabolized by hepatic CYP3A4 into hydroxylated derivatives (retaining partial activity), excreted via feces (60%) and urine (30%). Half-life: ~4.5 hours, indicating the need for interval dosing. 

3. Mechanisms of Anti-fatigue and Anti-motor Dysfunction Effects

3.1 Anti-fatigue Mechanisms 

Angelica gigas combats fatigue through three pathways: 

(1) Energy Metabolism: Decursin activates the AMPK pathway in muscle cells, enhancing glycolysis and fatty acid β-oxidation to boost ATP synthesis efficiency (↑22% ATP in animal models). AGP promotes hepatic glycogenolysis, maintaining blood glucose stability during exercise. 

(2) Antioxidant Effects: Decursin clears exercise-induced ROS and upregulates SOD and GSH-Px activity (↓35% serum ROS in mice), reducing oxidative damage to muscle fibers. 

(3) Neuroendocrine Regulation: Suppresses HPA axis overactivation (↓28% post-exercise cortisol), alleviating central fatigue-induced reduced exercise motivation. 

3.2 Mechanisms for Treating Motor Dysfunction 

Key therapeutic mechanisms include: 

(1) Anti-inflammatory & Muscle Repair: Decursin inhibits NF-κB pathway (↓40% inflammatory cytokines in muscle injury models) and promotes satellite cell proliferation; AGP accelerates muscle regeneration by 30%. 

(2) Neuroprotection & Pain Modulation: Balances neurotransmitters (5-HT, dopamine), ↑25% nerve conduction velocity in sciatic injury models; inhibits TRPV1 channel activity (↑50% pain threshold in neuropathic pain). 

(3) Microvascular Enhancement: Dilates skeletal muscle microvessels (↑38% local blood perfusion), accelerating lactate and creatine kinase clearance to reduce post-exercise soreness. 

4. Pharmacological Research Progress 

Anti-fatigue: Mice administered Angelica gigas extract (500 mg/kg/d) showed ↑32% loaded swimming time, ↓25% blood lactate, and ↓20% blood urea nitrogen, confirming improved aerobic and endurance capacity. 

Muscle Repair: AGP treatment upregulates myogenic genes (MyoD, Myogenin) in muscle satellite cells. 

Motor Dysfunction Therapy: 

Topical decursin gel reduces inflammation in strained muscles, shortens healing time, and restores mechanical strength. 

Mitigates paclitaxel-induced motor neuropathy by improving mechanical pain thresholds and myelin integrity. 

5. Safety Analysis

5.1 Toxicity Profile: 

Oral LD₅₀ of extract in mice >5,000 mg/kg (low toxicity). 

IV LD₅₀ of decursin: 280 mg/kg (wide safety margin). 

Rats fed 1,000 mg/kg/d for 6 months showed no pathological changes in liver/kidney/muscle or abnormal blood biochemistry. 

5.2 Clinical Risks: 

Mild gastrointestinal discomfort in 1.5% of subjects (resolved post-discontinuation). 

Coumarins may potentiate anticoagulants (e.g., warfarin)—coagulation monitoring required. 

6. Conclusions and Prospects 

Angelica gigas uses coumarins and polysaccharides to fight fatigue and motor dysfunction by optimizing energy metabolism, reducing oxidative stress, and repairing neuro-muscles, with its potential validated by animal and preliminary clinical studies. However, it faces challenges like inconsistent extract composition (decursin content: 3%–18%), underexplored mechanisms (e.g., mitochondrial regulation), and lack of large-scale clinical trials and dosing protocols for athletes. Its future applications may extend to sports nutrition, rehabilitation adjuvants, and combination therapies, and research should prioritize clarifying component-mechanism relationships, conducting evidence-based clinical studies, and establishing it as a core intervention in sports medicine.

References 

[1] Ahn S Y, Jamrasi P, Lim B, et al. Herbal extract (Cervus elaphus Linnaeus, Angelica gigas Nakai, and Astragalus membranaceus Bunge) ameliorates chronic fatigue: a randomized, placebo-controlled, double-blind trial[J]. Integrative Medicine Research, 2024, 13(4): 101085. 

[2] Li B, Wang Y, Yang X. Qianhu (Peucedanum praeruptorum Dunn) Improves exercise capacity in mice by regulating Nrf2/HO-1 oxidative stress signaling pathway[J]. Applied Biological Chemistry, 2023, 66(1): 26. 

[3] Ahn S Y, Jamrasi P, Lim B, et al. Herbal extract (Cervus elaphus Linnaeus, Angelica gigas Nakai, and Astragalus membranaceus Bunge) ameliorates chronic fatigue: a randomized, placebo-controlled, double-blind trial[J]. Integrative Medicine Research, 2024, 13(4): 101085.

[4] Huang W Y, Pan J H, Jeong I, et al. Antifatigue and anti-inflammatory effects of Cervus elaphus L., Angelica gigas Nakai, and Astragalus membranaceus Bunge complex extracts in physically fatigued mice[J]. Journal of Medicinal Food, 2022, 25(12): 1126-1132.