Corilagin (Ellagitannin)

Corilagin is a bioactive ellagitannin polyphenol found in plants such as Phyllanthus urinaria and Terminalia species that exerts hepatoprotective, anticancer, and anti-inflammatory effects. It primarily acts by modulating oxidative stress pathways, downregulating GRP78 endoplasmic reticulum stress proteins, and inhibiting NF-κB signaling to produce its therapeutic actions.

Origin & History

Corilagin is an ellagitannin, a subclass of hydrolyzable tannins, primarily sourced from plants such as Phyllanthus urinaria and other polyphenol-rich species. It is typically extracted and purified from plant materials using methods like solvent extraction or chromatography, though specific extraction protocols are not detailed in available research.

Historical & Cultural Context

While corilagin is noted as an anti-tumor natural product from plants like Phyllanthus urinaria, which has traditional medicinal uses, no specific historical or traditional medicine contexts for corilagin itself are documented in available research. The compound appears to be primarily studied as an isolated bioactive rather than a traditional remedy.

Health Benefits

• Liver protection: Reduced liver enzymes (ALT, AST, ALP, GGT) by up to comparable levels to UDCA in rat cholestasis models (n=5 per group, preclinical evidence)
• Cancer cell synergy: Enhanced 5-fluorouracil effectiveness against colorectal cancer cells through GRP78 downregulation and ROS production (in vitro evidence only)
• Anti-inflammatory effects: Inhibited NF-κB signaling and reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in mouse hepatotoxicity models (preclinical evidence)
• Bile acid regulation: Upregulated FXR and bile transporters while downregulating bile synthesis enzymes in cholestasis models (animal studies only)
• Antioxidant activity: Induced protective responses against acetaminophen-induced oxidative stress at doses of 1-20 mg/kg in mice (preclinical evidence)

How It Works

Corilagin reduces hepatic injury by suppressing oxidative stress markers and lowering liver enzymes ALT, AST, ALP, and GGT through antioxidant pathway activation, including Nrf2 upregulation. In cancer cells, it downregulates GRP78, a key endoplasmic reticulum chaperone protein, triggering unfolded protein response-mediated apoptosis and increasing intracellular reactive oxygen species (ROS) production. It also inhibits the NF-κB inflammatory signaling cascade and modulates TGF-β/Smad pathways, contributing to its anti-fibrotic and immunomodulatory effects.

Scientific Research

No human clinical trials, RCTs, or meta-analyses on corilagin have been conducted; all evidence is limited to preclinical studies using in vitro cell lines and animal models. Key studies include colorectal cancer cell research (PMID: 38114593) and rat cholestasis models (PMC5811621), with dosages ranging from 1-40 mg/kg in animals.

Clinical Summary

The majority of corilagin research is preclinical, conducted in cell lines and rat models, with no large-scale human clinical trials published to date. In rat cholestasis models (n=5 per group), corilagin reduced liver enzymes ALT, AST, ALP, and GGT to levels comparable to the bile acid drug ursodeoxycholic acid (UDCA), suggesting meaningful hepatoprotective potency. In vitro colorectal cancer studies demonstrate that corilagin enhances 5-fluorouracil cytotoxicity through GRP78 downregulation and ROS amplification, though these findings have not been validated in human trials. Overall, the evidence base is promising but remains limited to animal and cell-culture models, and translation to human clinical outcomes requires further investigation.

Nutritional Profile

Corilagin (C₂₇H₂₂O₁₈, MW 634.45) is a hydrolyzable ellagitannin, not a nutritional macronutrient source. It is a polyphenolic bioactive compound composed of one galloyl group, one HHDP (hexahydroxydiphenoyl) group, and a glucose core. Key profile: • Classification: Ellagitannin (subclass of hydrolyzable tannins); • Natural concentrations in plant sources: Found at approximately 0.5–5% (w/w dry weight) in Phyllanthus species (e.g., P. niruri, P. amarus, P. urinaria), Terminalia catappa leaves (~1–3% dry weight), Caesalpinia coriaria pods (historically named source), and Dimocarpus longan (longan) fruit pericarps; also detected in pomegranate husk, Geranium species, and various Euphorbiaceae; • No appreciable protein, fat, carbohydrate, vitamin, or mineral contribution as an isolated compound; • Bioactive metabolites: Undergoes hydrolysis in the gut to release ellagic acid and gallic acid, which are further metabolized by gut microbiota into urolithins (urolithin A, B, C, D) — the primary systemically bioavailable metabolites; • Bioavailability: Parent corilagin has low oral bioavailability (~1–5% estimated) due to high molecular weight, extensive hydrogen bonding, poor membrane permeability, and rapid hydrolysis in alkaline intestinal pH; plasma Cmax in rodent models typically reaches 0.2–2 µg/mL after oral doses of 50–100 mg/kg; urolithin metabolites show significantly higher systemic bioavailability and longer half-lives (8–24 hours); • Protein binding: High affinity for proline-rich proteins (characteristic of tannins), which can reduce bioavailability when co-consumed with protein-rich foods; • Solubility: Water-soluble (moderately, ~10–50 mg/mL depending on pH and temperature); soluble in methanol, ethanol, DMSO; • Antioxidant capacity: ORAC value estimated at >10,000 µmol TE/g (among the highest for individual polyphenols), with strong DPPH radical scavenging (IC₅₀ ~2–8 µM in vitro); • Key functional groups responsible for bioactivity: Multiple phenolic hydroxyl groups (11 OH groups) enabling metal chelation (Fe²⁺, Cu²⁺), ROS scavenging, and protein interaction; • Stability notes: Sensitive to alkaline pH (hydrolysis accelerates above pH 7.5), heat (partial degradation above 80°C), and prolonged light exposure; relatively stable at acidic pH (2–5); • No known essential nutrient contributions — value is entirely as a bioactive/pharmacological polyphenol.

Preparation & Dosage

No clinically studied human dosages exist. Animal studies used: 1-20 mg/kg (oral/intraperitoneal) for hepatotoxicity in mice, 10-40 mg/kg (oral) for cholestasis in rats. Preparations included 0.4% suspensions in sodium carboxymethylcellulose. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

5-fluorouracil (studied), milk thistle, turmeric, green tea polyphenols, quercetin

Safety & Interactions

Corilagin has not been formally evaluated for safety in human clinical trials, so its side effect profile, tolerable upper limits, and long-term safety in humans are not established. Given its potent inhibition of oxidative stress pathways and potential interaction with cytochrome P450 enzymes, it may theoretically alter metabolism of drugs such as warfarin or chemotherapeutic agents including 5-fluorouracil, requiring caution with co-administration. Pregnant and breastfeeding women should avoid corilagin supplements due to complete absence of safety data in these populations. Individuals with pre-existing liver conditions or those on immunosuppressive therapy should consult a healthcare provider before use, as its immunomodulatory effects via NF-κB and TGF-β pathways could produce unpredictable interactions.