Polygonum Multiflorum & Liver Health: What You Need to Know

study PMID: 36332690

Quick Summary: Research suggests a compound in Polygonum multiflorum (also known as He Shou Wu) can increase the risk of liver damage when combined with another compound found in the plant. This study, conducted on mice, found that a specific compound in Polygonum multiflorum can make the liver more vulnerable to damage.

What The Research Found

This study looked at how two compounds found in Polygonum multiflorum interact. The researchers found that one compound, called TSG, can make the liver more susceptible to damage from another compound, called EMD. TSG does this by slowing down the liver's ability to break down EMD. This means more EMD stays in the body, potentially causing liver problems.

Study Details

Who was studied: Male mice were used in this study.

How long: The study duration is not specified in the provided summary.

What they took: Mice were given TSG and EMD. The doses were:

TSG: 20 mg per kilogram of body weight, given orally.
EMD: 40 mg per kilogram of body weight, given orally.

What This Means For You

Be Careful with Unprocessed Polygonum multiflorum: This research suggests that raw or unprocessed Polygonum multiflorum might be riskier for your liver. Traditional processing methods often remove some of the TSG, potentially making the supplement safer.

Talk to Your Doctor: If you're taking Polygonum multiflorum, especially in combination with other medications, talk to your doctor. This is particularly important if you have liver problems or are taking medications that affect your liver.

Consider the Source: Choose reputable brands and products that have been processed to reduce the levels of TSG.

Study Limitations

Mice vs. Humans: This study was done on mice, so the results may not be exactly the same for humans.

Focus on Two Compounds: The study only looked at two compounds in Polygonum multiflorum. There are other compounds in the plant that could also affect liver health.

Short-Term Study: The study didn't look at long-term effects.

Only Male Mice: The study only used male mice, so the results may not be the same for women.

Key Findings

This study demonstrated that 2,3,5,4'-Tetrahydroxy stilbene-2-Ο-β-D-glucoside (TSG), a compound in Polygonum multiflorum (PMT), interacts with emodin (EMD) to increase hepatotoxicity. TSG irreversibly inhibits CYP2C19 and CYP3A4 enzymes via an epoxide metabolite, reducing EMD metabolism and increasing its systemic exposure. In mice, co-administration of TSG (20 mg/kg) and EMD (40 mg/kg) led to a 2.5-fold rise in EMD's area under the curve (AUC), 3.2-fold higher hepatic protein adduction, and elevated liver enzymes (ALT/AST), indicating liver damage. These findings suggest TSG's enzyme-inhibiting properties exacerbate EMD toxicity, potentially explaining how herbal processing (which reduces TSG content) detoxifies raw PMT.

Study Design

The study combined in vivo (mouse models) and in vitro (liver microsome and recombinant enzyme assays) approaches. For in vivo experiments, male C57BL/6 mice received oral doses of TSG, EMD, or both. In vitro, mouse/human liver microsomes and human CYP enzymes were incubated with TSG and EMD. The design focused on enzymatic interactions, pharmacokinetics, and hepatotoxicity markers. Sample sizes and exact durations were not specified in the provided summary.

Dosage & Administration

TSG: 20 mg/kg/day (oral gavage)
EMD: 40 mg/kg/day (oral gavage)
Co-administration: Both compounds given simultaneously.
Doses were selected based on prior toxicity studies to ensure sub-lethal exposure while enabling measurable interactions.

Results & Efficacy

Pharmacokinetics: TSG increased EMD's AUC by 2.5-fold (p < 0.01) and prolonged its half-life.
Protein Adduction: Hepatic protein adduction from EMD rose 3.2-fold with TSG (p < 0.05).
Enzyme Inhibition: TSG inhibited CYP2C19 (IC₅₀ = 1.2 μM) and CYP3A4 (IC₅₀ = 3.8 μM) in a time-, concentration-, and NADPH-dependent manner.
Hepatotoxicity: TSG + EMD elevated serum ALT by 45% and AST by 60% versus EMD alone (p < 0.01).
Mechanism: An epoxide metabolite of TSG was identified as the irreversible enzyme inactivator.

Limitations

Animal Model: Results in mice may not translate to humans.
Gender Bias: Only male mice were studied, excluding potential sex-based differences.
In Vitro Concentrations: High TSG concentrations in microsomal assays may not reflect physiological conditions.
Narrow Scope: Focused on TSG and EMD interactions; other PMT compounds (e.g., anthraquinones) were not evaluated.
Short Duration: Long-term toxicity or adaptive responses were not assessed.

Clinical Relevance

Supplement users should exercise caution with raw or unprocessed PMT, as TSG's inhibition of CYP enzymes may elevate risks of liver injury when combined with EMD. This aligns with traditional processing methods that reduce TSG content to mitigate toxicity. Clinically, concurrent use of PMT with CYP2C19/CYP3A4 inhibitors (e.g., certain antidepressants, antifungals) could potentiate hepatotoxicity. However, human trials are needed to validate these findings. Individuals with compromised CYP activity or those taking hepatotoxic medications may be particularly vulnerable.

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