Corilagin

Other Names

1,3,6-Trigalloyl glucose1-O-galloyl-3,6-hexahydroxydiphenic acid-β-D-glucopyranose1-O-Galloyl-3,6-hexahydroxydiphenol-b-D-GlucopyranoseBenzoic acid, 3,4,5-trihydroxy-, (8R,10S,11R,12S,19R)-5,7,8,11,12,14-hexahydro-1,2,3,11,16,17,18,19-octahydroxy-5,14-dioxo-8,12-methano-10H-dibenzo[j,l][1,4,8]trioxacyclotetradecin-10-yl esterbeta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose[(1S,19R,21S,22R,23R)-6,7,8,11,12,13,22,23-octahydroxy-3,16-dioxo-2,17,20-trioxatetracyclo[17.3.1.04,9.010,15]tricosa-4,6,8,10,12,14-hexaen-21-yl] 3,4,5-trihydroxybenzoateβ-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose

Synopsis

Corilagin: A Comprehensive Reference

1. Identity and Chemical Characterization

Nomenclature and Classification

Corilagin is a naturally occurring polyphenolic compound belonging to the class of hydrolyzable tannins. More specifically, it is classified as an ellagitannin — and, because of its structural hybrid character, it is sometimes described simultaneously as a gallotannin. Corilagin, widely distributed in Phyllanthus and Terminalia species, is recognized for its hybrid structure exhibiting features of both gallotannins and ellagitannins: a gallic acid ester at one glucose hydroxyl, and a single HHDP at two others.

Its systematic chemical name is β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose. Its formal name is cyclic 3,6-[(1R)-4,4′,5,5′,6,6′-hexahydroxy[1,1′-biphenyl]-2,2′-dicarboxylate] 1-(3,4,5-trihydroxybenzoate)-beta-D-glucopyranose, with CAS number 23094-69-1 and molecular formula C₂₇H₂₂O₁₈, with a formula weight of 634.5. Corilagin is an off-white acicular crystalline powder that easily dissolves in MeOH, EtOH, acetone, and DMSO.

Structural Features

Its core structure consists of a β-D-glucopyranose unit esterified at the anomeric position (C-1) with a galloyl group (3,4,5-trihydroxybenzoyl) and bridged at the C-3 and C-6 positions by a hexahydroxydiphenoyl (HHDP) moiety, specifically (R)-hexahydroxybiphenyl-2,2′-dicarboxylate. This macrocyclic HHDP linkage is the defining structural feature that distinguishes ellagitannins from simple gallotannins. One of the primary challenges in synthesizing corilagin lies in controlling the axial orientation of substituents on the glucose core in its rare ¹C₄ chair conformation. This ring-flipped form, essential for the natural product's biaryl axial chirality and macrocyclic structure, is prone to epimerization or reversion to the more stable ⁴C₁ conformation under acidic or basic conditions.

Discovery

Corilagin was first isolated in 1951 by Schmidt et al. from divi-divi (Caesalpinia coriaria (Jacq.) Willd.). However, in the next 34 years, people were largely unaware of its bioactivity. The compound derives its name from Caesalpinia coriaria, the plant from which it was first described. This discovery occurred through a multi-step extraction process involving aqueous and organic solvent partitioning of the plant material, followed by fractional precipitation to yield crystalline corilagin as a tannin component. The isolation employed early chromatographic techniques, including paper chromatography for preliminary separation of tannin fractions.

2. Natural Sources and Distribution

After the discovery of corilagin in 1951, corilagin has been identified in as many as 53 plants throughout the world. Corilagin is found mainly in the families Euphorbiaceae (20 species), Geraniaceae (10 species), and Combretaceae (7 species), and in species such as P. niruri L., P. emblica L., P. urinaria L., Geranium sibiricum L., and Terminalia catappa L.

The most intensively studied sources include the following:

Phyllanthus urinaria L. and Phyllanthus niruri L. (family Euphorbiaceae) — among the richest known herbal sources of corilagin and the most widely used in pharmacological research.
Phyllanthus emblica L. (amla, Indian gooseberry) — the fruit of amla contains several bioactive phytochemicals, the majority of which are polyphenols, including corilagin among others.
Geranium wilfordii Maxim. — the dried aboveground part of Geranium wilfordii Maxim. is a traditional Chinese herbal medicine named lao-guan-cao. It has long been used for dispelling wind-dampness, unblocking meridians, and stopping diarrhea and dysentery. Previous investigations have revealed that 50% ethanolic extract of G. wilfordii has anti-inflammatory and anti-proliferation activities. Corilagin is a main compound in G. wilfordii with content up to 1.69 mg/g.
Terminalia chebula Retz. (haritaki) — a component of the Ayurvedic polyherbal formulation Triphala; corilagin also exists in Dimocarpus longan Lour., Canarium album (Lour.) Raeusch., and Terminalia chebula Retz.
Punica granatum (pomegranate) — corilagin can also be found in Alchornea glandulosa and in the leaves of Punica granatum (pomegranate).
Dimocarpus longan (longan) — corilagin is also present in longan (Dimocarpus longan), known as lumyai in Thailand, a subtropical fruit extensively cultivated across China and Southeast Asia.

Despite its smaller molecular size, absorption studies show that corilagin itself is poorly transported across intestinal epithelia and displays enhanced hydrolytic breakdown compared to larger macrocyclic and polymeric ellagitannins. Importantly, corilagin is also a typical hydrolysis product of larger ellagitannins (notably geraniin), which justifies its occurrence in decoctions and processed plant extracts.

3. Traditional and Historical Use

Ayurvedic Medicine (India)

Corilagin is not historically used as an isolated compound; rather, it is encountered as a key constituent of plants and polyherbal formulas long employed in traditional medicine systems across Asia. In Indian Ayurveda, Phyllanthus emblica (amla) has been revered for centuries. This dietary globular fruit is of immense use in various folk and Indian traditional medicinal systems. P. emblica (known in India as "Amla") is used to treat diarrhoea, jaundice, and inflammation. Corilagin is one of the polyphenolic constituents responsible for many of these traditionally attributed effects.

P. emblica is commonly used together with Terminalia chebula and T. belerica and called "Triphala." "Triphala" is used as a clinical treatment protocol for gastropathy in India and as a remedy for pestilence and fatigue in China. Triphala has a long history in Indian and Chinese traditional medicine as a complementary and alternative therapy for chronic diseases. It is considered a multipurpose therapeutic drug with anti-inflammatory, analgesic, hypoglycemic, antibacterial, and antioxidant properties. In traditional usage, Triphala is applied in the treatment of gastritis, hepatitis, colitis, and other digestive diseases.

Traditional Chinese Medicine (TCM)

Phyllanthus urinaria and Phyllanthus niruri have been employed in Traditional Chinese Medicine (TCM) for their hepatoprotective, antiviral, and anti-inflammatory properties. Phyllanthus urinaria is a popular herb belonging to the Phyllanthaceae family and has been used in traditional antidiabetic, antiviral, and gastrointestinal treatments. P. niruri L. is a popular folk medicine for treating nephritic, urocystic, gastrointestinal, and hepatic infections.

Geranium wilfordii (lao-guan-cao) represents another important TCM source. The dried aboveground part of Geranium wilfordii Maxim. is a traditional Chinese herbal medicine named lao-guan-cao. It has long been used for dispelling wind-dampness, unblocking meridians, and stopping diarrhea and dysentery. G. wilfordii is used in traditional Chinese medicine for the treatment of rheumatism, osteoporosis, and as an antidiarrhetic agent.

In Tibetan medicine, plants containing corilagin as an active component have also been employed for blood and bile disorders. Preparations are clinically applicable to hypertension and anuria. In Thailand, it is named "makham pom" and is employed to treat gastrointestinal chronic diseases.

P. niruri is probably the most widespread herb of Phyllanthus, named "chanka piedra," "bhuiamlki," "zhuzicao," "dukung anak," "quebra-pedra," and "chanca piedra." Its whole plant can treat inflammation, lithiasis, fever, malaria, hepatitis, and gonorrhea.

Traditional Use Context and Preparations

In all these traditions, corilagin-containing plants were typically prepared as aqueous decoctions (water-boiled extracts) or ethanol/hydroethanolic extracts. The generation of corilagin in decoctions is facilitated by the hydrolysis of larger ellagitannins under heating, making aqueous preparations a meaningful delivery route for the compound. Some proprietary Chinese medicines containing corilagin have been used in clinical applications, being clinically applied to treat chronic liver disease, viral hepatitis B, rheumatoid arthritis, and other diseases.

4. Key Constituents, Co-Occurring Phytochemicals, and Active Metabolites

As an isolated compound, corilagin is the primary subject of pharmacological study. However, in its plant matrices, it co-occurs with a range of other bioactive polyphenols. In Phyllanthus species, co-occurring compounds include geraniin (itself a source of corilagin upon hydrolysis), ellagic acid, gallic acid, brevifolin carboxylate, flavonoids, and lignans. More than 510 compounds have been isolated from Phyllanthus, the majority of which are lignins, triterpenoids, flavonoids, and tannins.

Upon ingestion, corilagin undergoes hydrolysis. Previous studies have shown that corilagin is hydrolyzed to ellagic acid and gallic acid under physiological conditions in the intestine, which are moderately absorbed and metabolized by gut microbiota. So far, biological activity of only two metabolites — ellagic acid and gallic acid — has been studied properly. Therefore, it is important to investigate the pharmacological activities and the mechanism of action of metabolites for better understanding of corilagin as an anticancer agent. The gut microbiota further converts ellagic acid into urolithins, a class of bioactive metabolites increasingly recognized as mediators of ellagitannin health effects.

5. Mechanisms of Action

Corilagin exerts its biological activities through modulation of multiple molecular signaling pathways. The following are the best-characterized mechanisms supported by published experimental research:

Anti-inflammatory Mechanisms

Corilagin treatment effectively protects against APAP-induced liver injury in mice through anti-inflammatory and anti-oxidation mechanisms, and by inhibition of ERK/JNK MAPK and NF-κB pathways. Studies demonstrated an anti-inflammatory effect, as indicated by the reduction in the level of NO, TNF-α, IL-6, IL-1β, IL-10, and ROS in RAW264.7 cells induced by LPS. Results suggest that corilagin reduced the expression of TNF-α, IL-6, COX-2, and iNOS genes. The downregulation of the phosphorylation of IκB-α protein related to the toll-like receptor signaling pathway and upregulation of the phosphorylation of key proteins in the MAPK signaling pathway, P65 and JNK, resulted in reduced tolerance toward lipopolysaccharide.

Corilagin, a polyphenolic monomer, exhibits diverse pharmacological properties including antitumor, antioxidant, and anti-inflammatory effects. It can ameliorate inflammatory lesions in macrophages by inhibiting NLRP3 inflammasome activation and pyroptosis.

Antioxidant Mechanisms

Corilagin post-treatment significantly attenuated APAP-induced liver injury, inflammatory cell infiltration, hepatic proinflammatory cytokine levels, and hepatic oxidative stress. Furthermore, corilagin attenuated the protein levels of NOX1, NOX2, STAT3, and NF-κB in APAP-induced liver injury. These results indicated that the antioxidant, anti-inflammatory, and protective effects of corilagin in APAP-induced liver injury might involve the regulation of IL-6/STAT3 and MAPK/NF-κB signaling pathways through NOX-derived ROS. Increasing evidence reveals that natural products counteract oxidative stress by upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways, which are essential for the prevention and treatment of many diseases, including acute liver failure.

Apoptosis and Anticancer Pathways

Corilagin has shown inhibitory activity against the growth of numerous cancer cells by prompting cell cycle arrest at the G2/M phase and augmented apoptosis. Corilagin-induced apoptosis and autophagic cell death depends on production of intracellular reactive oxygen species in breast cancer cell lines. It blocks the activation of both the canonical Smad and non-canonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways. The potential apoptotic action of corilagin is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, and Bcl-2/Bax.

In cholangiocarcinoma (CCA), in vitro, corilagin inhibited CCA cell proliferation, migration and invasion, and induced apoptosis of CCA cells by inhibiting the Notch signaling pathway. Moreover, corilagin has shown potential to promote the antitumor activity of cisplatin and doxorubicin in HCC cells.

Cardiovascular Mechanisms

Results indicate that corilagin significantly reduced the serum levels of TC, TG, and LDL-C, increased the HDL-C levels, decreased intimal thickening in the thoracic aorta, and reduced the formation of foam cells in an HFD-induced rabbit atherosclerosis model. Moreover, corilagin suppressed the proliferation and migration of ox-LDL-induced VSMCs and reduced LOX-1, MyD88, NF-κB, MCP-1, and TNF-α mRNA and protein expression in vivo and in vitro.

Squalene Epoxidase Inhibition

Corilagin is a polyphenol and hydrolyzable tannin that can be isolated from a variety of plants. It inhibits squalene epoxidase (IC₅₀ = 4.0 µM), a key enzyme in cholesterol synthesis. This activity may contribute to its antiatherogenic properties.

Antidiabetic Mechanisms

In animal studies, corilagin has been shown to improve insulin sensitivity by activating the PPARγ pathway, mirroring the mechanism of established antidiabetic medications such as rosiglitazone.

Antiviral Mechanisms

Corilagin exhibited antiviral effect on human immunodeficiency virus (HIV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV). Reports found that corilagin derived from Excoecaria agallocha L. showed potential inhibition of hepatitis C virus (HCV) NS3-4A protease. Against herpes simplex virus type 2, in vitro assays confirmed that corilagin effectively mitigated the overactivation of the cGAS-STING pathway, alleviated inflammation and inhibited apoptosis in HaCaT cells, thereby demonstrating a therapeutic potential against HSV-2 infection.

Antimicrobial Mechanisms

While its activity against many pathogens such as Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus subtilis is generally weaker, corilagin exhibits potent antibacterial effects against Staphylococcus aureus, with reported minimum inhibitory concentrations (MICs) ranging from 25 to 256 μg/mL. Importantly, corilagin has shown the ability to significantly reduce the MICs of β-lactam antibiotics against both β-lactamase-positive and -negative methicillin-resistant Staphylococcus aureus (MRSA) strains by inhibiting penicillin-binding protein 2′ (PBP2a), a key factor in MRSA antibiotic resistance.

6. Scientific Evidence by Area of Use

Important caveat: The overwhelming majority of published evidence on corilagin derives from in vitro (cell culture) and in vivo (animal model) studies. It prevents the growth of various types of cancer cells in vitro and CCA cells in vivo. Most of the studies have been performed in vitro with only few in vivo results and possibly no clinical study has been reported. All sections below reflect this limitation explicitly.

6.1 Hepatoprotection

Hepatoprotective activity is among the most robustly demonstrated effects of corilagin across multiple experimental models. The hepatoprotective effects of corilagin have been reported in some liver-related diseases, such as liver fibrosis, drug-induced liver damage, and hepatic carcinoma.

Drug-induced hepatotoxicity (animal models): In mice intraperitoneally injected with a hepatotoxic APAP dose (300 mg/kg), corilagin was injected intraperitoneally at concentrations of 0, 1, 5, 10, and 20 mg/kg after 30 minutes of APAP administration; mice were then sacrificed after 16 hours for further analysis. The study demonstrated that corilagin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity by down-regulating the inflammatory response and by inhibiting ERK/JNK MAPK and NF-κB signaling pathways.

Hemorrhagic shock liver injury (rodent model): Hemorrhagic shock was induced in male Sprague-Dawley rats; mean blood pressure was maintained at 35–40 mm Hg for 90 minutes, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. A single dose of corilagin (5 mg/kg) with and without Wortmannin (a PI3K inhibitor) was also tested. Results suggested an Akt-dependent hepatoprotective mechanism. Another study demonstrated that corilagin has protective effects on hemorrhagic shock-induced liver injury through the regulation of the Akt-dependent pathway.

Immune-mediated hepatitis (murine model): The present study aimed to investigate the effects of corilagin on immune-mediated hepatic injury using a murine model of concanavalin A (Con A)-induced hepatitis, which is well-characterized to study acute immune-mediated hepatitis. Mice were administered corilagin (25 mg/kg) intraperitoneally twice at 12-hour intervals, and 1 hour later, the mice were challenged with Con A (20 mg/kg body weight).

Schistosomiasis-associated liver fibrosis (animal models): Studies demonstrated that corilagin can ameliorate schistosomiasis hepatic fibrosis by regulating the IL-13, GATA3, and miR21/smad7/ERK signaling pathways. Results revealed that corilagin significantly reduced the expression of PPARγ, KLF4, SOCS1, p-STAT6, and TGF-β compared with model group. The inhibitory effect of corilagin showed significant dose-dependence. The area of fibrosis and distribution of M2 macrophages in mouse liver tissue were reduced significantly and dose-dependently with corilagin treatment.

Hepatitis C virus (preclinical): Corilagin blocks hepatitis C virus (HCV) replication and modulates oxidative stress, thereby reducing liver damage. Corilagin is defined as an ellagitannin known for its significant inhibition of NS3 protease and NS5B RNA-dependent RNA polymerase, along with notable antiviral and antioxidant properties. It also demonstrates improved oral bioavailability and reduces collagen deposition and HCV RNA levels in mouse models.

Evidence strength: Preclinical (animal and cell culture) only. No published randomized clinical trials in humans on corilagin alone for any liver disease indication. Some proprietary Chinese medicines containing corilagin have been used in clinical applications, being clinically applied to treat chronic liver disease and viral hepatitis B, but isolated compound human trial data are absent from the published literature.

6.2 Anticancer Activity

Anticancer activity has attracted the greatest research attention. Cancer types studied in vitro or in animal models include ovarian cancer, hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), gastric cancer, breast cancer, glioblastoma, colorectal cancer, and esophageal cancer.

Ovarian cancer (cell lines and mouse models): Research provides evidence that TGF-β/Smad/AKT/ERK signaling is the target of corilagin and that this herbal medicine could be an effective ovarian cancer therapeutic agent. Research demonstrated that corilagin enhanced the sensitivity of ovarian cancer cells to chemotherapy. Ovarian cancer cell lines (SKOv3ip, Hey, and HO-8910PM-Snail) were treated with different concentrations of corilagin in combination with paclitaxel and carboplatin. Corilagin distinctly enhanced the inhibitory effects of paclitaxel and carboplatin.

Hepatocellular carcinoma (cell lines): In previous research, the group reported that corilagin could inhibit the proliferation of hepatocellular carcinoma (HCC) cells by inducing G2/M phase arrest. Observation of morphological changes showed that corilagin induced apoptosis of HCC cells as determined by AO/EB and Hoechst 33258 staining assays. Following treatment with corilagin, upregulation of Fas and FasL and activation of caspase-8 represented activation of the death receptor pathway, and downregulation of Bcl-2 and survivin was also attributed to the antitumor effect of corilagin. These results suggest that corilagin significantly induced the apoptosis of HCC cells through both the mitochondrial apoptotic pathway and the death receptor pathway.

Cholangiocarcinoma (CCA) (cell lines and xenograft): Gu and coworkers studied the anticancer potential of corilagin against CCA cell lines and reported that it inhibited proliferation and cell cycle progression, suppressed invasion and migration, and promoted CCA cell apoptosis. In nude mice, corilagin suppressed cholangiocarcinoma growth and downregulated the expression of Notch1 and mammalian target of rapamycin.

Gastric cancer (cell lines): It was first exhibited that corilagin markedly inhibited cell proliferation in a concentration-dependent manner in SGC7901 and BGC823 cells. Furthermore, it was demonstrated that corilagin showed less toxicity towards normal cells, for example, GES-1 human gastric mucosal epithelial cells.

Colorectal cancer (cell lines, combination study): It was shown that corilagin significantly inhibited cell proliferation in CRC cell lines (HCT-8 and SW480) in a concentration-dependent manner. Furthermore, CRC cell lines exhibited higher sensitivity to corilagin treatment compared to 5-FU treatment.

Evidence strength: Entirely preclinical. It prevents the growth of various types of cancer cells in vitro and CCA cells in vivo. Most of the studies have been performed in vitro with only few in vivo results and possibly no clinical study has been reported. The mechanisms underlying the anti-tumor activity of corilagin are not fully understood. Therefore, more investigations of the mechanisms driving the pharmacological effects of corilagin must be conducted before it can be a licensed drug.

6.3 Anti-inflammatory Activity

The antinociceptive and anti-inflammatory effects of corilagin, which is isolated from Geranium bellum, make this compound a candidate for the treatment of mild pain. Multiple cell-based studies have confirmed suppression of key pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), COX-2, and iNOS expression. Pathways confirmed include NF-κB, MAPK (ERK, JNK, p38), TLR4, and NLRP3 inflammasome signaling.

Rheumatoid arthritis (preclinical): Pharmacology studies showed that corilagin (as a main compound of G. wilfordii) has anti-inflammatory, anti-tumor, anti-microorganism, anti-oxidant, and hepatoprotective effects. However, there was no prior investigation on its anti-proliferation and anti-inflammation effects in rheumatoid arthritis (RA). A study aimed to evaluate the potential pharmacological mechanisms of anti-proliferation and anti-inflammation effects of corilagin in RA.

Evidence strength: In vitro and animal model data only. No human clinical trials of corilagin specifically for inflammatory conditions are available in the published literature.

6.4 Cardiovascular and Atherosclerosis

Several studies have indicated corilagin's potential in preventing and treating atherosclerosis, finding that corilagin probably mitigates atherosclerosis by inhibiting the TLR4 signaling pathway. Modern pharmacological research showed that corilagin could inhibit the development of atherosclerosis in piglets or rabbits. In the present study, ApoE−/− mice fed with a high-fat diet, RAW264.7 cells induced with lipopolysaccharide (LPS), and molecular docking strategies analysis were applied to evaluate the effects and mechanisms of corilagin anti-inflammatory action on atherosclerosis.

Evidence strength: Preclinical (animal and cell culture). No published human studies.

6.5 Antimicrobial Activity

Corilagin exhibits potent antibacterial effects against Staphylococcus aureus, with reported minimum inhibitory concentrations (MICs) ranging from 25 to 256 μg/mL. Corilagin has shown the ability to significantly reduce the MICs of β-lactam antibiotics against both β-lactamase-positive and -negative MRSA strains by inhibiting penicillin-binding protein 2′ (PBP2a), a key factor in MRSA antibiotic resistance. The effect of corilagin and oxacillin was synergistic. Corilagin showed a bactericidal action when added to the growth medium in combination with oxacillin.

Evidence strength: In vitro microbiological data. No human clinical studies on corilagin as an antimicrobial agent.

6.6 Antiviral Activity

Corilagin has exhibited antiviral effects against human immunodeficiency virus (HIV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV). Research into SARS-CoV-2 has also been conducted at the molecular docking and in vitro level. Some studies have confirmed corilagin's effects on ameliorating sepsis as well as its anti-oxidative and anti-inflammatory effects, and suppressive effects on HSV-1 encephalitis.

Evidence strength: Predominantly in vitro or in silico (molecular docking). No published human trials on corilagin for any viral infection.

6.7 Antidiabetic Activity

Corilagin was found to exert beneficial effects in managing type II diabetes. In animal studies, corilagin has been shown to improve insulin sensitivity by activating the PPARγ pathway, mirroring the mechanism of established antidiabetic medications such as rosiglitazone.

Evidence strength: Animal model studies only. No human clinical trial data.

6.8 Neuroprotective Activity

Corilagin has been found to exert neuroprotective activities. Research has indicated protective effects against radiation-induced brain injury. Previous research has indicated that corilagin provides protection against LPS-induced liver injury, radiation-induced brain injury, and bleomycin-induced lung injury by mitigating oxidative stress and apoptosis pathways.

Evidence strength: Animal models only. No human data.

6.9 Pulmonary Protection

Corilagin, a major polyphenolic constituent of Phyllanthus urinaria, exhibits various pharmacological activities, including antioxidative, anti-inflammatory, and antiapoptotic effects. Previous research has indicated that corilagin provides protection against LPS-induced liver injury, radiation-induced brain injury, and bleomycin-induced lung injury by mitigating oxidative stress and apoptosis pathways. Its protective role in LPS-induced acute lung injury (ALI) has been attributed to the attenuation of the NADPH oxidase 2 (NOX2) and ERK/NF-κB signaling pathways.

Evidence strength: Animal studies only.

7. Body Systems and Health Areas Associated with Corilagin

Hepatic system: Protection against drug-induced, immune-mediated, and infectious (viral) liver damage; anti-fibrotic effects in schistosomiasis-associated hepatic fibrosis.
Oncology (preclinical): Ovarian, hepatocellular, cholangiocarcinoma, gastric, breast, colorectal, esophageal, and glioblastoma cell types.
Cardiovascular system: Anti-atherosclerotic, antihypertensive, antiatherogenic activity; lipid regulation in animal models.
Immune/inflammatory system: Macrophage modulation, NLRP3 inflammasome suppression, suppression of pro-inflammatory cytokine production.
Infectious disease (preclinical): Activity against MRSA, HIV, HCV, EBV, HSV-1, HSV-2, and SARS-CoV-2 (in vitro/in silico only).
Metabolic/endocrine: PPARγ activation, insulin sensitization, antihyperglycemic effects in rodent models.
Nervous system: Attenuation of radiation-induced brain injury; anti-neuroinflammatory effects in animal models.
Respiratory system: Protection against acute lung injury in murine models.
Musculoskeletal system (preclinical): Anti-inflammatory effects relevant to rheumatoid arthritis models; corilagin is a main compound in G. wilfordii (lao-guan-cao), used traditionally for rheumatic conditions.

8. Pharmacokinetics and Bioavailability

Bioavailability of ellagitannins is low in human and animal models due to their hydrophobic nature. Despite its smaller molecular size, absorption studies show that corilagin itself is poorly transported across intestinal epithelia and displays enhanced hydrolytic breakdown compared to larger macrocyclic and polymeric ellagitannins.

Previous studies have shown that corilagin is hydrolyzed to ellagic acid and gallic acid under physiological conditions in the intestine, which are moderately absorbed and metabolized by gut microbiota. Recently, HPLC-Q-TOFMS/MS has been used to characterize corilagin and its metabolites in various biological samples. The study reported the presence of corilagin and their metabolites in plasma and liver tissue.

In vivo studies in rat and mice after oral administration of corilagin (1500 mg/kg) were conducted. They analyzed plasma samples at different time intervals using HPLC-ESI-MS, which showed peak bioavailability of corilagin at 2 hours with maximum concentration of about 55 µg/mL in blood, and half-life was found to be about 6 hours.

Despite their broad therapeutic spectrum, clinical translation is limited by challenges such as poor bioavailability, host-gut microbiota variability, and a lack of robust in vivo evidence. The low bioavailability of corilagin and its metabolites is a major concern. To overcome this issue, there is a need to explore existing and newer drug delivery systems as viable options for delivering remedial concentrations of corilagin into the systemic circulation.

9. Dosage Forms and Dosages Reported in Studies

No standardized therapeutic dose of corilagin has been established for humans. The following doses have appeared specifically in published preclinical studies:

Intraperitoneal (mouse, APAP hepatotoxicity model): Mice were intraperitoneally injected with a hepatotoxic APAP dose (300 mg/kg). After 30 minutes of APAP administration, corilagin was injected intraperitoneally at concentrations of 0, 1, 5, 10, and 20 mg/kg.
Intraperitoneal (mouse, APAP, second study): Mice were intraperitoneally administered 300 mg/kg APAP or equal volume of saline, with or without various concentrations of corilagin (0, 1, 5, or 10 mg/kg) administered after 30 minutes.
Intravenous (rat, hemorrhagic shock): During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered.
Intraperitoneal (mouse, Con A-induced hepatitis): Mice were administered corilagin (25 mg/kg) intraperitoneally twice at 12-hour intervals.
Oral (rat, acute toxicity): In vivo studies in rat and mice after oral administration of corilagin (1500 mg/kg) were conducted as part of pharmacokinetic profiling.

In terms of dosage forms, corilagin has been studied as a pure isolated compound (typically obtained by column chromatography or semi-synthesis), administered as a solution dissolved in DMSO, saline, or similar vehicles in preclinical models. Corilagin is a naturally occurring water-soluble retrogallic acid tannin, which can be extracted from many kinds of plants. Its water solubility facilitates preparation of aqueous solutions for injection but presents challenges for stable oral formulations due to rapid hydrolysis.

As a commercial reference standard, corilagin with purity ≥98% is available from multiple chemical suppliers (e.g., Cayman Chemical) for research purposes. No licensed pharmaceutical product containing isolated corilagin has been approved by regulatory agencies such as the FDA or EMA as of the date of this writing.

10. Safety Considerations

Preclinical Toxicology

An in vivo acute toxicity study in BALB/c mice revealed that corilagin exhibited maximum tolerance level up to 3500 mg/kg (LD50 3500–5000 mg/kg). The findings suggested that it can be safe and non-toxic even at higher dosages. Acute toxicity data indicate an oral LD50 of 1.78 g/kg in mouse, with intraperitoneal TDLO of 1 mg/kg in mouse. No irritant effect on skin or eye, and no sensitizing effects known.

Corilagin showed a low level of toxicity toward normal cells and tissues. Because of its low cytotoxicity in normal tissues and cells, it is regarded as a candidate molecule for the treatment of cancer.

Lack of Carcinogenic Classification

Corilagin is not listed by the International Agency for Research on Cancer (IARC), and is not listed by the National Toxicology Program (NTP).

Bioavailability and Hydrolysis Limitations

A key pharmacological consideration is that corilagin undergoes significant hydrolysis in the intestinal environment, breaking down to ellagic acid and gallic acid. Previous studies have shown that corilagin is hydrolyzed to ellagic acid and gallic acid under physiological conditions in the intestine, which are moderately absorbed and metabolized by gut microbiota. This limits the systemic concentrations achievable after oral dosing.

Knowledge Gaps: Drug Interactions and Long-Term Safety

More investigations of the mechanisms driving the pharmacological effects of corilagin must be conducted before it can be a licensed drug. In addition, in future research, toxicology and pharmacokinetic studies of corilagin, as well as identification of its molecular targets, are necessary areas of investigation. No peer-reviewed studies examining formal drug–drug interactions of isolated corilagin in humans were identified in the published literature. As a hydrolyzable tannin, corilagin has the theoretical potential — shared by tannins as a class — to bind to certain dietary minerals and proteins; however, specific interaction data for corilagin in humans have not been published.

Clinical Application Context

Given the limited efficacy of first-line treatments for many diseases such as oncology, chronic liver disease, and rheumatic immune system diseases, and the potential for adverse effects to outweigh the therapeutic effects, attention is being focused on alternative treatments. Some proprietary Chinese medicines containing corilagin have been used in clinical applications, being clinically applied to treat chronic liver disease, viral hepatitis B, rheumatoid arthritis, and other diseases. These clinical uses, however, involve complex multi-ingredient preparations rather than isolated corilagin and have not been evaluated in rigorous controlled trials.

11. Research Status and Future Directions

Corilagin was found to exert a variety of pharmacological effects, including anti-tumor, anti-microorganism, antioxidant, hepatoprotective, anti-inflammatory, neuroprotective, and cardiovascular protective activities and has been found to be beneficial in managing type II diabetes. Despite this broad preclinical profile, the compound remains at an early stage of translational research.

The 2023 review titled Agent in Urgent Need of Clinical Practice: Corilagin underscores the translational gap. Corilagin can participate in a variety of signaling pathways in vivo and has multiple biological activities, including antitumor, anti-microbial, anti-oxidation, anti-inflammation, hepatoprotective, anti-allergy, and anti-proliferation activities. Given the limited efficacy of first-line treatments for many diseases such as oncology, chronic liver disease, and rheumatic immune system diseases, and the potential for adverse effects to outweigh the therapeutic effects, attention is being focused on alternative treatments.

Despite their broad therapeutic spectrum, clinical translation is limited by challenges such as poor bioavailability, host-gut microbiota variability, and a lack of robust in vivo evidence. Ongoing research directions include novel nanoparticle-based or liposomal delivery systems to improve oral bioavailability, combination strategies with established chemotherapeutic agents, and elucidation of metabolite pharmacology.

References

Health Conditions

Health conditions that Corilagin may help support.

No conditions available.

Body Systems

Body systems that Corilagin may help support.

No body systems available.