Bergenin (C-Glucoside of 4-O-methylgallic acid)

Bergenin is a C-glucoside of 4-O-methylgallic acid, a phenolic compound found in plants like Bergenia species. It modulates TRPA1/TRPV1 channels and NR2B receptors, showing promise for neuropathic pain relief and cognitive protection in animal studies.

Origin & History

Bergenin is a C-glucoside of 4-O-methylgallic acid, a bioactive polyphenolic compound naturally sourced from plants including Mallotus japonicus, Bergenia ligulata, and Bergenia purpurascens. This compound can be obtained through both natural extraction from plant cortex and laboratory synthesis.

Historical & Cultural Context

Bergenin-containing plants have been used in Eastern traditional medicine for centuries, including applications in traditional cancer treatments. Specific traditional medicine systems and historical indications are not detailed in available research.

Health Benefits

• Neuropathic pain relief: Preclinical evidence shows dose-dependent reduction in chemotherapy-induced pain through TRPA1/TRPV1/NR2B modulation (animal studies only)
• Cognitive protection: Animal studies demonstrate recovery from dementia-like symptoms and reduced amyloid-β accumulation (preliminary evidence)
• Anti-inflammatory effects: Suppresses Th17 cell differentiation and NF-κB pathway signaling (in vitro evidence)
• Kidney protection: Restores mitochondrial function and reduces injury markers in hyperoxaluria models (animal studies only)
• Tuberculosis adjunct therapy: Shows additive effects with isoniazid against drug-resistant strains (preclinical evidence only)

How It Works

Bergenin reduces neuropathic pain through dose-dependent modulation of TRPA1 and TRPV1 ion channels along with NR2B receptor inhibition. For cognitive protection, it appears to reduce amyloid-β accumulation, though the specific molecular pathways remain under investigation. The C-glucoside structure of 4-O-methylgallic acid contributes to its bioactivity and stability.

Scientific Research

Current research consists entirely of preclinical studies in animal models and cell cultures, with no human clinical trials identified. Key studies include rat models of chemotherapy-induced neuropathic pain (PMID: 38149571), sodium azide-induced dementia (PMID: 36249784), and tuberculosis co-treatment (PMID: 30975902).

Clinical Summary

Current evidence for bergenin comes exclusively from preclinical animal studies with no human clinical trials available. Animal research demonstrates dose-dependent reduction in chemotherapy-induced neuropathic pain and recovery from dementia-like symptoms. Studies show measurable decreases in amyloid-β accumulation in rodent models of cognitive decline. The lack of human data significantly limits the applicability of these findings to therapeutic use.

Nutritional Profile

Bergenin is a pure isolated bioactive compound (C-glucoside of 4-O-methylgallic acid), not a whole food ingredient, and therefore has no conventional macronutrient or micronutrient profile. Molecular formula: C14H16O9; molecular weight: 328.26 g/mol. It is classified as an isocoumarin-related polyphenolic glycoside. As a compound, it contains no protein, fat, dietary fiber, or caloric value in pharmacological dosing contexts. Bioactive composition is 100% bergenin when in purified form. Natural source concentrations vary: found at approximately 0.5–2% dry weight in Bergenia crassifolia rhizomes, ~1–3% in Ardisia japonica aerial parts, and trace amounts (0.1–0.5%) in Saccharum officinarum (sugarcane) bark and Flueggea microcarpa. Solubility: moderately water-soluble (~1.8 mg/mL in water at 25°C), with improved solubility in polar organic solvents (DMSO, methanol). Bioavailability: oral bioavailability is limited due to poor gastrointestinal absorption and rapid hepatic metabolism; preclinical studies suggest peak plasma concentrations reached at 1–2 hours post-oral administration in rodent models, with a half-life of approximately 3–5 hours. Gut microbiota-mediated hydrolysis may partially convert bergenin to norbergenin (demethylated metabolite), which retains partial bioactivity. No clinically established human pharmacokinetic data is currently available. Relevant co-occurring phytochemicals in plant sources include gallic acid, catechins, and flavonoids, which may exhibit synergistic bioavailability enhancement.

Preparation & Dosage

Animal studies have used 10 mg/kg body weight intraperitoneally for renal protection. No human dosage recommendations or standardized extracts have been established. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

PPAR-γ agonists, antioxidants, anti-inflammatory compounds, mitochondrial support nutrients, neuroprotective agents

Safety & Interactions

Safety data for bergenin in humans is extremely limited due to the absence of clinical trials. No established side effect profile, drug interactions, or contraindications have been documented. Pregnant and breastfeeding women should avoid bergenin supplements due to insufficient safety data. Individuals taking medications for neurological conditions should consult healthcare providers before use given its effects on ion channels and neurotransmitter receptors.