Celery Powder's Hepatoprotective Effects and Mechanisms of Action in Liver-Related Diseases

1. Introduction

Liver diseases represent a global health challenge, with incidence and mortality rates rising annually. Conditions such as fatty liver, alcoholic liver disease, viral hepatitis, and liver fibrosis not only severely reduce patients' quality of life but may also progress to end-stage liver diseases like cirrhosis and liver cancer, imposing a heavy burden on society and families. In recent years, with increased health awareness, the hepatoprotective effects of natural products have gained significant attention. Celery powder (derived from the stems and seeds of Apium graveolens L.), rich in bioactive compounds, has become a research hotspot due to its potential.

2. Active Components and Their Metabolism

2.1 Main Active Components

Celery powder contains multiple classes of active components: Flavonoids, with apigenin as the core component, possess strong antioxidant and anti-inflammatory properties, assisted by luteolin and kaempferol for synergistic liver protection; Coumarins promote liver detoxification and enhance metabolic function; Vitamins (A, C, E) and Minerals (calcium, iron, zinc) support liver function and participate in the antioxidant defense system to reduce hepatic oxidative damage; Dietary fiber promotes intestinal motility, shortens toxin residence time, and indirectly alleviates the liver's detoxification burden.

2.2 Metabolic Process

The core active component, apigenin, is primarily metabolized by the liver, undergoing transformations such as glucuronidation, sulfation, and methylation. Its oral bioavailability is low due to poor solubility (both water and lipid), necessitating absorption in the intestines. Research focuses on preparing sulfonated derivatives and 8-dimethylaminomethyl-substituted derivatives to improve solubility and bioavailability. Metabolites concentrate relatively highly in the liver, providing a basis for its protective effects, and are ultimately excreted mainly by the kidneys. Understanding the metabolic process is crucial for optimizing dosage regimens and enhancing hepatoprotective efficacy.

3. Hepatoprotective Mechanisms of Celery Powder

3.1 Antioxidant Effects

Liver metabolism generates free radicals like superoxide anions and hydroxyl radicals, which can induce oxidative stress and damage hepatocytes. The phenolic hydroxyl groups in apigenin can provide hydrogen atoms to stabilize free radicals; in vitro experiments show apigenin significantly reduces reactive oxygen species (ROS) levels in hepatocytes. Simultaneously, it enhances the activity of endogenous antioxidant enzymes in the liver, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GR), strengthening the liver's antioxidant defense system.

3.2 Anti-inflammatory Effects

Chronic inflammation is key to the progression of liver disease. Apigenin can inhibit the activation and migration of inflammatory cells like macrophages and neutrophils, reducing the release of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6. It also inhibits IκBα degradation, preventing nuclear translocation of nuclear factor kappa-B (NF-κB) and blocking its mediated inflammatory signaling pathways. In animal models, it alleviates the degree of liver inflammation.

3.3 Regulation of Liver Enzyme Activity

The liver’s cytochrome P450 enzyme system (CYP) is responsible for drug metabolism and detoxification. Apigenin specifically regulates CYP enzyme activity, with a strong inhibitory effect on CYP2E1—a key mediator of alcoholic liver injury, as it generates large amounts of free radicals during alcohol metabolism—thus reducing oxidative damage. It also modulates enzymes such as CYP3A4 to avoid abnormal drug metabolism and protect against drug-induced liver injury.

3.4 Anti-fibrotic Effects

The activation of hepatic stellate cells (HSCs) and their production of excessive extracellular matrix (ECM) is central to liver fibrosis. Apigenin can inhibit the TGF-β/Smad signaling pathway, reducing ECM production. It also dose-dependently reverses fibrosis-related molecular changes; multi-omics analysis shows it can reversely regulate 82 biological processes/molecular functions at the mRNA and protein levels, delaying or even reversing the progression of liver fibrosis.

4. Pharmacological Research

4.1 Alcoholic Liver Injury

Animal experiment results show that apigenin groups had significantly reduced serum ALT and AST levels, increased antioxidant enzyme activities (GSH, GR) in liver tissue, and decreased MDA. Western Blot confirmed it upregulates PPARα/γ and CPT-1, and downregulates SREBP-1c, FAS, CYP2E1, etc. It promotes the degradation of acetaldehyde (an alcohol metabolite) and inhibits ROS-mediated liver injury.

4.2 Non-Alcoholic Fatty Liver Disease (NAFLD)

In a rat NAFLD model induced by a high-sugar, high-fat diet, apigenin and its derivatives improved serum INS, FFA, MDA, and TNF-α levels, increased liver SOD activity, and reduced fat deposition. Structurally modified Derivative A, with superior solubility and bioavailability, performed better than natural apigenin. In vitro, in an FFA-induced L02 cell model, Derivative D reduced TNF-α and IL-8, increased Glut-4 and IR, improved inflammation and insulin resistance, and reduced lipid deposition.

4.3 Liver Fibrosis

In a mouse liver fibrosis model induced by carbon tetrachloride (CCl₄), transcriptomic and proteomic analyses revealed that apigenin reverses fibrosis-related molecular changes in a dose-dependent manner. Forty-eight key proteins were identified, among which 6 core "hub molecules" (including extracellular matrix remodeling proteins and metabolic regulators) have translational medical value. Apigenin also reduced ALT and AST levels (by 30%-50% compared with the control group) and decreased collagen deposition in liver tissue, alleviating the degree of fibrosis.

5. Safety Verification

Celery powder is not suitable for everyone: Individuals allergic to celery should avoid it to prevent reactions like rash and itching; patients with gastric ulcers, chronic gastritis, or other stomach conditions are not advised to consume it to avoid aggravating their illness; prolonged use may cause dizziness or nausea in individuals with low blood pressure; pregnant and breastfeeding women should consult a professional before deciding whether to use it.

6. Summary and Outlook

6.1 Summary

Celery powder (core active component: apigenin) protects the liver through mechanisms including antioxidant, anti-inflammatory, regulation of liver enzymes, and anti-fibrotic effects. Pharmacological studies confirm its efficacy in models of alcoholic liver injury, NAFLD, and liver fibrosis. However, clinical application faces challenges: low apigenin content, poor bioavailability, lack of large-scale human trials, and pending evaluation of long-term, high-dose safety.

6.2 Outlook

Future work needs to focus on developing apigenin derivatives/novel drug delivery systems, conducting human trials, and exploring combination therapies with agents like milk thistle extract. As a natural dietary supplement, celery powder holds broad prospects for liver protection. Combined with a healthy lifestyle, it could aid liver function and potentially become an auxiliary tool for the prevention and treatment of liver diseases.

References

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