Corilagin

Pharmacology & Research

Corilagin is a hydrolyzable tannin (ellagitannin) — closely related to ellagic acid and to geraniin (which hydrolyses to corilagin) — found in Phyllanthus, Terminalia, Geranium and many plants. Its best-characterised, most-replicated action is anti-inflammatory, centred on the NLRP3 inflammasome and NF-κB ^{4Reference 4Luo J et al. · 2022Corilagin restrains NLRP3 inflammasome activation and pyroptosis through the ROS/TXNIP axisView study →}. Two honesty points frame the page. First, the famous Phyllanthus “anti-hepatitis-B” reputation is not supported by isolated-corilagin data — the real isolate antiviral signal is against herpesviruses ^{8Reference 8Guo YJ et al. · 2015Corilagin protects against HSV-1 encephalitis via inhibiting the TLR2 signalling pathwaysView study →}. Second, as a large water-soluble tannin, corilagin has poor oral bioavailability ^{16Reference 162025ReviewTherapeutic potential of ellagitannins: a comprehensive review of key representativesView study →}, and its entire evidence base is preclinical (in vitro and rodent).

1. Anti-inflammatory

The best-characterised action. Corilagin restrains the NLRP3 inflammasome via ROS/TXNIP and blocks pyroptosis ^{4Reference 4Luo J et al. · 2022Corilagin restrains NLRP3 inflammasome activation and pyroptosis through the ROS/TXNIP axisView study →}, inhibits NLRP3 through Olfr2 signalling to alleviate atherosclerosis ^{11Reference 112024Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 pathwayView study →}, and reduces acute lung injury by inhibiting RIP1-driven necroptosis (with SPR-confirmed target binding) ^{12Reference 122025Corilagin alleviates acute lung injury by inhibiting RIP1-driven necroptosisView study →} — with genus-level NF-κB/MAPK support from Terminalia tannin fractions ^{15Reference 152022The hydrolysable-tannin fraction of Terminalia chebula modulates NF-κB and MAPK signallingView study →}.

Gap: each study uses a different disease model and a different upstream node, with no single dose/target replicated head-to-head, and the TNF-α/NF-κB effects are downstream readouts rather than proven primary targets ^{4,12Reference 4Luo J et al. · 2022Corilagin restrains NLRP3 inflammasome activation and pyroptosis through the ROS/TXNIP axisView study →Reference 122025Corilagin alleviates acute lung injury by inhibiting RIP1-driven necroptosisView study →}.

2. Antiviral (herpes)

The real isolate antiviral story is herpesvirus. Corilagin protected against HSV-1 encephalitis via TLR2 inhibition ^{8Reference 8Guo YJ et al. · 2015Corilagin protects against HSV-1 encephalitis via inhibiting the TLR2 signalling pathwaysView study →}, interfered with TLR3-mediated responses in herpes-simplex encephalitis ^{9Reference 92019Corilagin interferes with the TLR3-mediated immune response in herpes-simplex encephalitisView study →}, and blocked HSV-2 replication via the cGAS–STING axis ^{10Reference 102026Corilagin interferes with HSV-2 replication via the cGAS–STING axisView study →}.

Gap: the “anti-HBV / Phyllanthus” reputation is not supported by isolated-corilagin data — that traces to whole-decoction work — so the isolate signal is herpesvirus, not hepatitis B ^{8Reference 8Guo YJ et al. · 2015Corilagin protects against HSV-1 encephalitis via inhibiting the TLR2 signalling pathwaysView study →}.

3. Anticancer

Corilagin inhibited ovarian cancer growth by blocking TGF-β/Smad/ERK/AKT ^{5Reference 5Jia L et al. · 2013Corilagin inhibits ovarian cancer growth by blocking the TGF-β signalling pathwayView study →} and suppressed esophageal squamous-cell carcinoma via DNA damage and RNF8 downregulation with cisplatin sensitisation ^{6Reference 6Qiu F et al. · 2019Corilagin in esophageal squamous-cell carcinoma: DNA damage and RNF8 downregulationView study →}, as synthesised in a dedicated review ^{13Reference 13Gupta A et al. · 2019Corilagin in cancer: a critical evaluation of anticancer activities and molecular mechanismsView study →}.

Gap: cell-line and xenograft only, at high in-vitro concentrations, with no pharmacokinetic bridge to achievable human exposure — nowhere near clinical ^{5,6Reference 5Jia L et al. · 2013Corilagin inhibits ovarian cancer growth by blocking the TGF-β signalling pathwayView study →Reference 6Qiu F et al. · 2019Corilagin in esophageal squamous-cell carcinoma: DNA damage and RNF8 downregulationView study →}.

4. Hepatoprotective

Corilagin restored glutathione and SOD, lowered ALT/AST, and suppressed TNF-α/NF-κB/COX-2 in a bioassay-guided Phyllanthus niruri study ^{1Reference 1Ezzat SM et al. · 2020In-depth hepatoprotective mechanistic study of Phyllanthus niruri: in-vitro and in-vivo studies and its chemical characterizationView study →} — where it also contributes α-glucosidase inhibition in the extract assays ^{2Reference 2Najari Beidokhti M et al. · 2017Investigation of antidiabetic potential of Phyllanthus niruri (α-glucosidase)View study →}.

Gap: corilagin is one of several actives in the fraction, so the effect is co-attributed, not cleanly isolate-only ^{1Reference 1Ezzat SM et al. · 2020In-depth hepatoprotective mechanistic study of Phyllanthus niruri: in-vitro and in-vivo studies and its chemical characterizationView study →}.

5. Antimicrobial (MRSA)

Corilagin potentiates β-lactams against MRSA by inactivating the resistance protein PBP2a ^{3Reference 3Shiota S et al. · 2004Restoration of effectiveness of β-lactams against MRSA by corilaginView study →}.

Gap: in-vitro only, and narrow — an adjuvant effect rather than a standalone antibiotic, with no in-vivo confirmation ^{3Reference 3Shiota S et al. · 2004Restoration of effectiveness of β-lactams against MRSA by corilaginView study →}.

Mechanisms

Target / pathway	Effect	Relevant to
NLRP3 inflammasome (ROS/TXNIP; Olfr2)	↓ activation, blocks pyroptosis	anti-inflammatory
RIP1 / necroptosis	direct binding → inhibits necroptosis	anti-inflammatory (lung injury)
NF-κB / MAPK; TNF-α, COX-2	suppression	anti-inflammatory, hepatoprotective
TLR2 / TLR3; cGAS–STING	↓ signalling / ↓ viral replication	antiviral (herpes)
TGF-β/Smad, ERK/AKT; DNA damage / RNF8	blockade; pro-apoptotic	anticancer
PBP2a	inactivation → restores β-lactam efficacy	antimicrobial (MRSA)

Pharmacokinetics

Poor oral bioavailability is expected and load-bearing. Corilagin is a large (~634 Da), highly hydroxylated, water-soluble hydrolyzable tannin, subject to the class-level absorption barrier of ellagitannins — gastrointestinal hydrolysis (to gallic acid and ellagic-acid/HHDP fragments) and extensive gut-microbial metabolism, so intact-corilagin plasma exposure is low ^{16Reference 162025ReviewTherapeutic potential of ellagitannins: a comprehensive review of key representativesView study →}. No clean isolated-corilagin human ADME study exists, so this is an inference from ellagitannin class behaviour. One concrete interaction datapoint has emerged: corilagin influenced the pharmacokinetics of sitagliptin via CYP450 in a 2025 study ^{14Reference 142025CYP450/network-pharmacology study of corilagin’s influence on sitagliptin pharmacokineticsView study →}.

Clinical trials

There are no human trials of isolated corilagin. All efficacy evidence is in-vitro or rodent, and human exposure to date is only incidental — via Phyllanthus and other tannin-containing herbal teas and extracts, where corilagin is a minor fraction, not a characterised isolate dose ^{7Reference 7Colombo R et al. · 2009Validated HPLC method for the standardisation of Phyllanthus niruri using corilaginView study →}.

Last checked: July 2026.

Toxicity & Safety

No specific isolated-corilagin toxicity signal surfaced across the reviewed pharmacology, and effective doses in rodent inflammation and cancer models were tolerated — but there is no formal toxicology study, so the honest statement is “not formally characterised in humans,” not “safe.” As a hydrolyzable tannin, high oral intakes can be astringent and gastrointestinally irritating, and the interaction profile is real for the class: tannins bind non-heme iron and can reduce its absorption (relevant with iron supplements or deficiency) and complex with proteins and some co-administered drugs, and corilagin specifically altered sitagliptin pharmacokinetics via CYP450 ^{14Reference 142025CYP450/network-pharmacology study of corilagin’s influence on sitagliptin pharmacokineticsView study →} — so caution is warranted with narrow-therapeutic-index or CYP-substrate co-medication.

Pregnancy & lactation

Avoid. There is no reproductive or developmental safety data for isolated corilagin, its anticancer mechanisms include DNA damage and TGF-β/cell-cycle interference ^{5,6Reference 5Jia L et al. · 2013Corilagin inhibits ovarian cancer growth by blocking the TGF-β signalling pathwayView study →Reference 6Qiu F et al. · 2019Corilagin in esophageal squamous-cell carcinoma: DNA damage and RNF8 downregulationView study →}, and tannins impair iron absorption — an unfavourable combination in pregnancy, so it should not be used in pregnancy or lactation.

Dosage

There is no established human dose, and nothing here is a recommendation. Rodent studies use mg/kg intraperitoneal or oral doses that do not translate to a human recommendation, especially given poor oral bioavailability, and real-world exposure is only as a minor fraction (~2.4–6.7%) of Phyllanthus/chanca-piedra aqueous extracts ^{7Reference 7Colombo R et al. · 2009Validated HPLC method for the standardisation of Phyllanthus niruri using corilaginView study →}.

References