Corilagin

• Antioxidant Protection
• Anti-inflammatory Effects
• Hepatoprotective Activity

• Anticancer Potential
• Antiviral Properties
• Antidiabetic Properties
• Cardiovascular Support
• Antimicrobial Activity

Corilagin’s bioavailability, distribution, metabolism, and elimination characteristics significantly influence its biological effects and practical applications. As a polyphenolic ellagitannin found in various medicinal plants, corilagin’s pharmacokinetic properties present both challenges and opportunities for its therapeutic use. Absorption of corilagin following oral administration is limited in mammals, representing one of the significant barriers to its clinical application. Gastrointestinal absorption of intact corilagin is typically less than 10% of the administered dose, with most studies showing plasma concentrations in the low nanomolar to low micromolar range even after relatively high oral doses.

This poor absorption results from several factors including limited aqueous solubility at gastric pH, molecular size (molecular weight of 634.45 Da), extensive first-pass metabolism, and potential efflux by intestinal transporters. The primary site of corilagin absorption appears to be the small intestine, where it can be taken up by enterocytes through both passive diffusion and potentially active transport mechanisms, though the specific transporters involved remain incompletely characterized. However, once inside enterocytes, corilagin undergoes extensive phase II metabolism (primarily glucuronidation and sulfation), with the resulting conjugates being either transported back into the intestinal lumen or passed into the portal circulation. Several factors influence corilagin’s limited absorption.

Solubility in gastrointestinal fluids significantly affects the amount of corilagin available for absorption. As a polyphenolic compound with multiple hydroxyl groups, corilagin demonstrates pH-dependent solubility, with better dissolution in the slightly alkaline environment of the small intestine compared to the acidic stomach. However, its overall aqueous solubility remains limited, restricting the concentration gradient driving passive diffusion across the intestinal membrane. Food effects on corilagin absorption appear complex, with some evidence suggesting that consumption with dietary fats may enhance solubilization and absorption through incorporation into mixed micelles.

However, other food components, particularly proteins, may bind corilagin and reduce its availability for absorption. The net effect of food on corilagin bioavailability remains incompletely characterized but appears modest given the overall poor absorption regardless of administration conditions. Intestinal metabolism represents a major barrier to corilagin absorption, with UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) in enterocytes rapidly conjugating corilagin to form glucuronide and sulfate metabolites. These conjugation reactions significantly reduce the amount of free corilagin that can reach the systemic circulation, with studies suggesting that over 80% of absorbed corilagin undergoes conjugation before reaching the portal blood.

Efflux transport by P-glycoprotein (P-gp) and potentially other transporters further limits corilagin absorption, as these transporters actively pump both parent corilagin and its conjugates back into the intestinal lumen. Studies using transporter inhibitors suggest that these efflux mechanisms may reduce corilagin absorption by 20-50% compared to conditions where the transporters are inhibited. Absorption mechanisms for corilagin primarily involve passive diffusion across intestinal membranes due to its moderate lipophilicity, though some evidence suggests potential involvement of active transport systems. Unlike some nutrients, no specific transporters for corilagin uptake have been definitively identified, limiting its ability to overcome the various barriers to absorption.

Some evidence suggests potential involvement of organic anion transporting polypeptides (OATPs) in the uptake of certain polyphenolic compounds, though their specific contribution to corilagin absorption remains unclear. Microbial metabolism in the colon represents another important aspect of corilagin’s fate after oral administration. Corilagin that is not absorbed in the small intestine reaches the colon where it can be extensively metabolized by gut microbiota. These microbial transformations typically involve hydrolysis of the ellagitannin structure to release ellagic acid, which can be further metabolized to various urolithins (particularly urolithin A, B, and C).

These microbial metabolites may have different biological activities than parent corilagin and could potentially contribute to systemic effects, though their specific contributions remain incompletely characterized. Distribution of absorbed corilagin and its metabolites follows patterns typical of polyphenolic compounds, though the extremely low bioavailability limits the physiological relevance of distribution for many potential applications. After reaching the systemic circulation, corilagin and its metabolites demonstrate high plasma protein binding, primarily to albumin, with bound fractions typically 90-98% for parent corilagin and somewhat lower for conjugated metabolites. This high protein binding limits the free concentration available for tissue distribution and target engagement.

Tissue distribution studies in animals suggest some accumulation in the liver, kidneys, and intestinal tissues, with limited penetration into the brain and other tissues protected by tight barriers. However, the overall tissue concentrations remain very low due to the poor oral bioavailability, with most tissues showing concentrations in the low nanomolar to low micromolar range even after high oral doses. The apparent volume of distribution for corilagin is moderate (approximately 0.5-2.0 L/kg based on animal data), reflecting its limited distribution beyond the vascular and highly perfused tissues. Metabolism of corilagin is extensive and occurs in multiple sites, significantly limiting the systemic exposure to free, unconjugated corilagin.

Intestinal metabolism, as mentioned earlier, represents the first major site of corilagin biotransformation, with UGT and SULT enzymes in enterocytes rapidly forming glucuronide and sulfate conjugates. These conjugation reactions occur primarily at the hydroxyl groups, with multiple potential conjugation sites leading to various mono- and di-conjugated metabolites. The resulting conjugates have substantially different physicochemical properties and potentially different biological activities compared to parent corilagin. Hepatic metabolism further contributes to corilagin biotransformation, with additional glucuronidation and sulfation of any free corilagin reaching the liver through the portal circulation.

The liver may also convert some corilagin to methylated metabolites through catechol-O-methyltransferase (COMT), though these oxidative pathways appear minor compared to conjugation reactions. Hydrolysis of the ellagitannin structure can also occur, leading to the formation of ellagic acid and subsequently various smaller phenolic compounds. Microbial metabolism in the colon, as mentioned earlier, represents another important route of corilagin transformation. The urolithins produced through microbial metabolism can be absorbed from the colon and further metabolized in the liver, primarily through conjugation reactions.

These microbial metabolites may circulate at higher concentrations and for longer periods than parent corilagin, potentially contributing significantly to the biological effects observed after oral corilagin administration. Elimination of corilagin and its metabolites occurs through multiple routes, with fecal elimination representing the predominant pathway. Fecal elimination accounts for approximately 60-90% of an oral corilagin dose, primarily as unabsorbed parent compound, bacterial metabolites, and conjugates excreted in bile. This high fecal elimination reflects corilagin’s poor oral absorption and extensive enterohepatic circulation of conjugated metabolites.

Urinary elimination accounts for approximately 5-30% of an oral corilagin dose, primarily as glucuronide and sulfate conjugates of both parent corilagin and its metabolites, including urolithins. These conjugates are efficiently excreted by the kidneys due to their increased water solubility compared to parent corilagin. The elimination half-life for corilagin and its primary metabolites appears relatively short (approximately 2-6 hours) based on limited pharmacokinetic data, reflecting efficient metabolism and excretion processes. However, certain microbial metabolites, particularly urolithins, may demonstrate longer half-lives (12-48 hours), potentially allowing for more sustained biological effects despite the rapid elimination of parent corilagin.

This short half-life for parent corilagin suggests that multiple daily dosing would be necessary to maintain potentially therapeutic concentrations, though the poor bioavailability raises questions about whether effective systemic levels can be achieved through oral administration regardless of dosing frequency. Pharmacokinetic interactions with corilagin have been observed with various compounds, though their clinical significance remains uncertain given corilagin’s limited bioavailability. Enzyme inhibition by corilagin has been demonstrated in vitro for several drug-metabolizing enzymes, including certain cytochrome P450 isoforms (particularly CYP3A4) and UGT enzymes. These inhibitory effects could theoretically increase the exposure to drugs metabolized by these pathways when co-administered with corilagin.

However, the low systemic concentrations achieved with oral corilagin supplementation suggest that significant clinical interactions through systemic enzyme inhibition are unlikely except possibly with drugs having very narrow therapeutic indices. Transporter inhibition represents another potential interaction mechanism, as corilagin has demonstrated inhibitory effects on P-glycoprotein and certain other transporters in vitro. These effects could theoretically increase the absorption or reduce the elimination of drugs that are substrates for these transporters. However, as with enzyme interactions, the low systemic concentrations of corilagin following oral administration limit the likelihood of clinically significant effects except possibly within the intestinal lumen where local corilagin concentrations may be higher.

Absorption competition may occur between corilagin and other polyphenolic compounds or drugs utilizing similar absorption pathways or subject to the same metabolizing enzymes. Co-administration of multiple polyphenols could potentially result in either increased absorption through competitive inhibition of efflux transporters or decreased absorption through competition for metabolizing enzymes, though the net effect appears highly dependent on the specific compounds and their relative concentrations. Bioavailability enhancement strategies for corilagin have been explored through various approaches to overcome its poor oral absorption. Pharmaceutical formulation modifications represent one approach to enhancing corilagin bioavailability.

Nanoparticle formulations, including solid lipid nanoparticles, polymeric nanoparticles, and nanoemulsions, have shown promise in preclinical studies, with some demonstrating 2-5 fold increases in corilagin bioavailability compared to unformulated corilagin. These delivery systems may enhance absorption by increasing solubility, protecting from intestinal metabolism, and potentially bypassing efflux transporters. Phospholipid complexes (phytosomes) have shown potential for enhancing corilagin absorption by increasing its lipophilicity and membrane permeability. Some preclinical studies suggest 2-4 fold increases in bioavailability with these formulations, though human data remains limited.

Inclusion complexes with cyclodextrins have been investigated to enhance corilagin’s aqueous solubility, with some promising results in preclinical models showing 2-3 fold increases in absorption compared to free corilagin. Co-administration with absorption enhancers represents another strategy for improving corilagin bioavailability. Piperine, an alkaloid from black pepper, has shown potential to increase polyphenol absorption by inhibiting both intestinal metabolism (UGT and SULT enzymes) and efflux transporters (P-gp). Studies with similar polyphenolic compounds suggest that co-administration with 5-20 mg of piperine may increase bioavailability by 30-200% depending on specific conditions, though specific data for corilagin-piperine combinations remains limited.

Quercetin and certain other flavonoids may enhance corilagin absorption through competitive inhibition of metabolizing enzymes and efflux transporters, though the magnitude and consistency of these effects require further investigation. Surfactants and emulsifiers, including various natural and synthetic compounds, may enhance corilagin solubility and absorption by improving its dispersion in gastrointestinal fluids and potentially forming mixed micelles that facilitate uptake. Prodrug approaches for corilagin have been explored in research settings, with various ester derivatives showing potential for enhanced absorption and subsequent hydrolysis to release free corilagin. However, these modified compounds represent new chemical entities rather than natural corilagin and would require extensive safety and efficacy evaluation before clinical application.

Alternative administration routes have been investigated to bypass the limitations of oral absorption. Topical application allows for direct delivery to skin and superficial tissues, bypassing gastrointestinal absorption barriers. This approach has shown promise for dermatological applications, though penetration through the skin barrier remains a challenge for achieving effects in deeper tissues. Sublingual or buccal administration theoretically could bypass first-pass metabolism, though the poor aqueous solubility of corilagin limits its dissolution in the small fluid volume available at these sites, and significant absorption enhancement compared to oral administration remains unproven.

Formulation considerations for corilagin supplements include several approaches to optimize its limited bioavailability. Particle size reduction through micronization or nanonization can significantly increase the surface area available for dissolution, potentially enhancing the rate (though not necessarily the extent) of corilagin absorption. Commercial products utilizing these approaches often claim improved bioavailability, though the magnitude of enhancement varies considerably between specific formulations. Solubilizing excipients including various surfactants, co-solvents, and natural solubilizers may improve corilagin dissolution in gastrointestinal fluids, potentially enhancing its absorption.

Products containing these excipients may show improved bioavailability compared to simple powder formulations, though again the magnitude of enhancement varies with specific formulation details. Enteric coating or delayed-release formulations have been suggested to potentially reduce presystemic metabolism by releasing corilagin further down the gastrointestinal tract, though the overall impact on bioavailability remains uncertain given the presence of metabolizing enzymes throughout the intestine. Combination products containing corilagin alongside bioavailability enhancers like piperine, quercetin, or phospholipids may offer practical approaches to improving absorption without requiring specialized pharmaceutical technologies. These combinations potentially address multiple barriers to corilagin absorption simultaneously, though the optimal ratios and specific combinations remain incompletely defined.

Monitoring considerations for corilagin are complicated by its poor bioavailability and rapid metabolism. Plasma or serum corilagin measurement is technically challenging due to the very low concentrations typically achieved (low nanomolar to low micromolar range) and requires sensitive analytical methods such as liquid chromatography-tandem mass spectrometry (LC-MS/MS). Even with such methods, free corilagin is often below detection limits, with primarily conjugated metabolites being measurable. Urinary metabolite assessment may provide a more practical approach to confirming corilagin consumption and absorption, as the conjugated metabolites reach higher concentrations in urine than in plasma.

However, standardized methods and reference ranges for these measurements are not widely established. Biological effect monitoring, such as measuring changes in inflammatory markers or antioxidant capacity for anti-inflammatory and antioxidant applications, may provide indirect evidence of corilagin activity despite its poor bioavailability. However, the relationship between such markers and corilagin exposure remains incompletely characterized. Special population considerations for corilagin bioavailability include several important groups.

Elderly individuals may experience altered drug metabolism and transporter function, potentially affecting corilagin absorption and disposition. Age-related changes in gastrointestinal function, including reduced intestinal blood flow and altered pH, could theoretically influence corilagin absorption, though specific data in this population is limited. Children and adolescents have not been specifically studied regarding corilagin pharmacokinetics, and routine supplementation is generally not recommended in these populations due to limited safety data. Individuals with liver impairment might theoretically experience increased exposure to corilagin due to reduced metabolic clearance, though the clinical significance of this effect is uncertain given corilagin’s already limited bioavailability in healthy individuals.

Those with gastrointestinal disorders affecting absorption function might experience further reduced corilagin bioavailability, though again the clinical significance is questionable given its already poor absorption under normal conditions. In summary, corilagin demonstrates limited oral bioavailability (<10%) due to poor aqueous solubility, extensive presystemic metabolism, and potential efflux by intestinal transporters. These pharmacokinetic limitations significantly constrain its potential therapeutic applications, as the low systemic concentrations achieved with conventional oral supplementation may be insufficient for many of its proposed effects, particularly those requiring high tissue concentrations. Various bioavailability enhancement strategies including nanoformulations, phospholipid complexes, and co-administration with absorption enhancers have shown promise in preclinical studies, with potential for 2-5 fold increases in absorption depending on the specific approach.

However, even with such enhancements, absolute bioavailability likely remains relatively low, highlighting the challenges of achieving therapeutically relevant systemic concentrations through oral administration. Microbial metabolism to urolithins and other compounds may represent an important aspect of corilagin’s effects after oral administration, as these metabolites may achieve higher concentrations and longer circulation times than parent corilagin. These bioavailability considerations suggest that either local applications (such as topical use for skin conditions) or effects mediated through gut-based mechanisms (including interactions with intestinal microbiota) may represent more promising applications for corilagin than those requiring significant systemic exposure to the parent compound.

Corilagin demonstrates a generally favorable safety profile based on available research, though certain considerations warrant attention when evaluating its use as a supplement. As a naturally occurring polyphenolic ellagitannin found in various medicinal plants including Phyllanthus species, Geranium species, and Terminalia chebula, corilagin’s safety characteristics reflect both its limited bioavailability and its specific biological activities. Adverse effects associated with corilagin supplementation are generally mild and infrequent when used at typical doses based on limited available data. Gastrointestinal effects represent the most commonly reported adverse reactions, including mild stomach discomfort (affecting approximately 3-8% of users), occasional nausea (2-5%), and infrequent changes in bowel habits (1-3%).

These effects appear dose-dependent, with higher doses (>600 mg daily) more likely to cause discomfort than lower doses. The astringent properties of corilagin, common to many tannins, may contribute to these gastrointestinal effects, particularly when taken on an empty stomach. Headache has been reported by some users (approximately 1-3%), though it remains unclear whether this represents a direct effect of corilagin or an indirect consequence of other factors. The incidence appears higher with larger doses and typically resolves with continued use or dose reduction.

Allergic reactions to corilagin appear rare in the general population but may occur in individuals with existing allergies to plants containing high levels of tannins. Symptoms may include skin rash, itching, or in rare cases, more severe manifestations. The estimated incidence is less than 1% based on limited available data. Potential anti-nutrient effects represent a theoretical concern given corilagin’s tannin structure and potential to bind to proteins and certain minerals, potentially reducing their absorption.

However, at typical supplemental doses and when taken separately from meals, this effect is likely minimal for most individuals. The severity and frequency of adverse effects are influenced by several factors. Dosage significantly affects the likelihood of adverse effects, with higher doses (typically >600 mg daily) associated with increased frequency and severity of gastrointestinal symptoms and other potential effects. At lower doses (100-300 mg daily), adverse effects are typically minimal and affect a smaller percentage of users.

At moderate doses (300-600 mg daily), mild adverse effects may occur in approximately 3-10% of users but rarely necessitate discontinuation. Duration of use appears to influence tolerance, with some initial effects diminishing over time as the body adapts. Initial use often produces more pronounced effects that moderate with continued supplementation over 1-2 weeks. Individual factors significantly influence susceptibility to adverse effects.

Those with sensitive digestive systems may experience more pronounced gastrointestinal symptoms and might benefit from taking corilagin with meals rather than on an empty stomach. Individuals with existing inflammatory conditions or immune dysregulation may potentially experience more noticeable effects related to corilagin’s immunomodulatory properties, though clinical evidence for such effects remains limited. Formulation characteristics affect the likelihood and nature of adverse effects, with different delivery systems potentially influencing both effectiveness and side effect profiles. Enhanced bioavailability formulations might theoretically increase both beneficial effects and potential adverse effects by increasing systemic exposure, though specific comparative safety data for different formulations remains limited.

Contraindications for corilagin supplementation include several considerations, though absolute contraindications are limited based on current evidence. Known allergy to corilagin or plants containing high levels of ellagitannins represents a clear contraindication due to the risk of allergic reactions. Individuals with a history of adverse reactions to tannin-rich foods or supplements should approach corilagin supplementation with caution due to potential cross-reactivity. Pregnancy and breastfeeding warrant caution due to limited safety data in these populations.

While no specific adverse effects have been documented, the conservative approach is to avoid corilagin supplementation during these periods until more safety data becomes available. Bleeding disorders or use of anticoagulant/antiplatelet medications represent theoretical concerns due to corilagin’s potential mild anticoagulant effects observed in some preclinical studies. While clinical evidence for significant effects on coagulation is lacking, prudent caution is advisable in these populations, particularly at higher doses. Medication interactions with corilagin warrant consideration in several categories, though the limited bioavailability of standard corilagin formulations may reduce the clinical significance of many potential interactions.

Iron and mineral-containing medications or supplements may theoretically experience reduced absorption if taken simultaneously with corilagin due to its tannin structure and potential binding properties. Separating administration by at least 2 hours may minimize potential interactions. Medications metabolized by certain cytochrome P450 enzymes, particularly CYP3A4, may potentially be affected by corilagin, which has demonstrated inhibitory effects on these enzymes in vitro. However, the limited systemic bioavailability of corilagin likely minimizes the clinical significance of these potential interactions except possibly with drugs having very narrow therapeutic indices.

Medications affected by P-glycoprotein or other transporters might theoretically experience altered absorption or elimination when co-administered with corilagin, which has shown effects on these transport systems in some experimental models. Again, the clinical significance of these potential interactions is likely limited by corilagin’s poor bioavailability. Anticoagulant and antiplatelet medications warrant theoretical caution, as some preclinical studies suggest mild anticoagulant effects of corilagin. While specific evidence for clinically significant interactions between corilagin and these medications is lacking, prudent monitoring may be advisable, particularly when initiating or discontinuing corilagin supplementation in individuals taking these medications.

Immunomodulatory medications, including both immunosuppressants and immunostimulants, warrant theoretical consideration due to corilagin’s potential effects on various immune parameters observed in preclinical studies. The clinical significance of these potential interactions remains uncertain given the limited human data on corilagin’s immune effects. Toxicity profile of corilagin appears favorable based on available research, though long-term human studies remain limited. Acute toxicity studies in animals have shown low toxicity, with LD50 values (median lethal dose) typically exceeding 2000 mg/kg body weight, suggesting a wide margin of safety relative to typical supplemental doses.

Subchronic toxicity studies (28-90 days) have generally failed to demonstrate significant adverse effects on major organ systems, blood parameters, or biochemical markers at doses equivalent to 3-5 times typical human supplemental doses when adjusted for body weight and surface area. Genotoxicity and mutagenicity studies have generally shown negative results, with most in vitro and in vivo tests suggesting no significant genotoxic concerns at relevant doses. Some studies have actually demonstrated anti-mutagenic and DNA-protective effects of corilagin at physiologically relevant concentrations. Reproductive toxicity has not been extensively studied for corilagin specifically, though some research on plant extracts containing corilagin suggests no significant adverse effects on reproductive parameters at typical doses.

Nevertheless, due to limited specific data, caution is advised regarding use during pregnancy and breastfeeding. Special population considerations for corilagin safety include several important groups. Elderly individuals may experience altered drug metabolism and potentially different responses to corilagin’s effects on various enzyme systems and inflammatory pathways. While specific safety concerns have not been identified, starting at the lower end of dosage ranges may be prudent for elderly individuals.

Children and adolescents have not been studied regarding corilagin supplementation, and routine use in these populations is generally not recommended due to limited safety data. Individuals with liver conditions should approach corilagin supplementation with caution, as the liver represents the primary site of polyphenol metabolism. While specific hepatotoxicity concerns have not been identified for corilagin, and some preclinical research actually suggests hepatoprotective effects, those with existing liver disease may process corilagin differently and potentially experience altered effects or tolerability. Those with kidney disease may theoretically experience altered elimination of corilagin metabolites, though the clinical significance of this effect is uncertain given corilagin’s already limited bioavailability in healthy individuals.

Individuals with autoimmune conditions should consider potential immunomodulatory effects of corilagin observed in preclinical studies. While these effects might theoretically be beneficial in some contexts, they could potentially influence disease activity or medication effectiveness in unpredictable ways, suggesting a need for careful monitoring if corilagin is used in these populations. Individuals taking multiple medications should consider potential interaction effects as described earlier and may benefit from discussing corilagin supplementation with healthcare providers, particularly for medications with narrow therapeutic indices. Regulatory status of corilagin varies by jurisdiction and specific formulation.

In the United States, corilagin may be present in dietary supplements, provided no specific disease claims are made. It has not been approved as a drug for any specific indication. In the European Union, corilagin is not specifically approved as a novel food ingredient, though it may be present in traditional botanical preparations depending on specific national regulations. In Japan and some Asian countries, corilagin-containing plants have a longer history of traditional use in various herbal formulations, though specific regulations regarding isolated corilagin vary.

These regulatory positions reflect the limited clinical research on corilagin as a standalone supplement rather than specific safety concerns. Quality control considerations for corilagin safety include several important factors. Purity specifications should address potential contaminants including heavy metals, pesticide residues, and microbial contamination, with limits typically aligned with general dietary supplement standards. Higher-quality products often specify limits below regulatory requirements as an additional safety margin.

Source identification is important, as corilagin can be derived from various plant sources which may contain different co-occurring compounds that could influence both effects and safety profile. Products should specify the plant source and extraction method used to obtain corilagin. Standardization approaches should specify corilagin content, typically expressed as a percentage of the total product or as absolute content per serving. Higher-quality products typically provide third-party verification of content claims to ensure accurate dosing.

Risk mitigation strategies for corilagin supplementation include several practical approaches. Starting with lower doses (100-200 mg daily) and gradually increasing as tolerated can help identify individual sensitivity and minimize adverse effects. Taking corilagin with meals rather than on an empty stomach may reduce the likelihood of gastrointestinal discomfort in sensitive individuals. Separating corilagin supplementation from mineral-containing supplements or medications by at least 2 hours may minimize potential binding interactions that could reduce absorption of these nutrients or drugs.

Separating corilagin supplementation from medications with narrow therapeutic indices by at least 2-3 hours may minimize potential interactions, particularly for medications where consistent absorption is critical. Monitoring for any unusual symptoms or changes in health status when initiating corilagin supplementation allows for early identification of potential adverse effects and appropriate dose adjustment or discontinuation if necessary. In summary, corilagin demonstrates a generally favorable safety profile based on available research, with adverse effects typically mild and primarily affecting the gastrointestinal system. The most common adverse effects include mild stomach discomfort, occasional nausea, and infrequent headache, particularly at higher doses or during initial use.

Contraindications are limited but include known allergy to corilagin or related compounds, pregnancy and breastfeeding (due to limited safety data), and potentially bleeding disorders or use of anticoagulant medications (as a precautionary measure). Medication interactions require consideration, particularly regarding mineral-containing supplements, drugs with narrow therapeutic indices, and medications affecting coagulation, though the clinical significance of many potential interactions may be limited by corilagin’s poor bioavailability. Toxicity studies consistently demonstrate a wide margin of safety with no evidence of significant acute or subchronic toxicity at relevant doses. Regulatory status across multiple jurisdictions reflects corilagin’s position as a component of various botanical supplements rather than an approved therapeutic agent.

Quality control considerations including purity, source identification, and standardization are important for ensuring consistent safety profiles. Appropriate risk mitigation strategies including gradual dose titration, taking with meals, and attention to timing relative to medications can further enhance the safety profile of corilagin supplementation.