Liverwort

Other Names

American liver leafAmerican liverleafAmerican liverwortAnémone à Lobes AigusAnemone acutilobaAnemone americanaAnémone d'AmériqueAnemone hepaticaAnemone hepatica var. acutaAnemone hepatica var. japonicaAnemone hepatica var. obtusaAnémone HépatiqueAnemone praecoxAnemone trilobaBlå AnemoneblåsippablåveisBryopsidéeChrystalwortcommon hepaticacommon liverwortcrystalwortgolden trefoilHaplomitriopsidahepatichepáticahepaticaHepatica acutilobaHepatica americanaHepatica hepaticaHepatica nobilisHepatica nobilis var. acutaHepatica nobilis var. japonicaHepatica nobilis var. obtusaHepatica trilobaHepaticaeHepatici Noblis HerbahepaticsHépatique à Lobes Aigushépatique à trois lobesHépatique d'AmériqueHepatophytaherb trinityJungermanniopsidakidney liver leafkidney wortkidneywortLeberbluemchenkrautLeberblümchenLeberblümchenkrautliferwyrtliver leafliver plantliver wortliverflowerliverleafliverweedliverwort-leafliverwyrtMarchantia polymorphaMarchantiophytaMarchantiophytinaMarchantiopsidamayflowernoble liverwortpennywortround-lobe hepaticaround-lobed hepaticaroundlobe hepaticasharp-lobe hepaticaskógarblámitrefoilumbrella liverwort

Synopsis

Liverwort: A Comprehensive Reference

1. Identity and Botanical Classification

1.1 Taxonomic Position and Phylum

Liverworts (Marchantiophyta) are among the earliest diverging lineages of extant land plants. They constitute one of the three major groups of non-vascular terrestrial plants, alongside mosses (Bryophyta) and hornworts (Anthocerotophyta). Liverworts are a group of non-vascular plants that possess unique metabolism not found in other plants.

Marchantia polymorpha L., also known as common liverwort or umbrella liverwort, is a spore-forming plant belonging to the Marchantiaceae family. This thallose liverwort has gained importance as a model plant, mainly because of its global distribution and easy and rapid in vitro culturing.

The term "liverwort" as used in the context of dietary supplements and traditional medicine encompasses several distinct genera and species. The most pharmacologically studied include:

Marchantia polymorpha L. — the common or umbrella liverwort, the species most documented in both historical European ethnopharmacy and modern pharmacological research.
Marchantia paleacea Bertol. — used in ethnomedicine across parts of Asia, with documented investigation for hepatoprotective properties.
Radula marginata Taylor ex Gottsch. — a subtropical liverwort endemic to New Zealand and Tasmania, notable for containing perrottetinene, a cannabinoid-type compound. Radula marginata Taylor is a subtropical liverwort, endemic to the Northern island of New Zealand in the Pacific region.
Radula perrottetii Gottsche ex Steph. and Radula laxiramea Steph. — other members of the genus Radula from which cannabinoid-type bibenzyls have been isolated.
Conocephalum conicum (L.) Underw. — documented in Italian pharmacy and European ethnomedicine.

1.2 Morphology and Habitat

All species are terrestrial and cosmopolitan in distribution. The habitat of the species is moist and shady places like wet open woodlands, banks of streams, wood rocks or on shaded rocks; it is often seen that the plant grows best after forest fire on burnt soil.

Among their unique features, most liverworts contain membrane-bound oil bodies, organelles that accumulate diverse secondary metabolites, especially terpenoids. Liverworts belonging to orders Marchantiales and Jungermanniales possess oil bodies. In Marchantia polymorpha L., oil bodies are confined to scattered idioblastic oil body cells.

1.3 Common Forms and Preparations

Liverwort is encountered in several commercial and traditional forms:

Crude dried herb: The whole thallus (vegetative body) dried and powdered, used in traditional preparations.
Aqueous extracts / infusions / decoctions: Prepared by boiling or steeping the fresh or dried plant material in water.
Ethanolic (methanolic) extracts: The most commonly used preparation in laboratory pharmacological research. LC-MS and GC-MS analysis of methanolic extract revealed the presence of numerous phytochemicals responsible for its antibacterial and anti-inflammatory potential.
Ethyl acetate and hexane extracts: Used in isolation studies to obtain specific classes of secondary metabolites.
Dried wild-harvested plant material: In the case of Radula marginata, dried R. marginata collected in the wild is currently sold on the internet as a legal high, making reference to cis-PET being structurally similar to THC.
Supplement capsules and tinctures: Commercially available standardized extracts, though no regulatory pharmacopeial monograph (EP, USP, WHO) currently governs standardized liverwort supplement products.

2. Traditional and Historical Use

2.1 European Ethnopharmacy

Medicinal use of bryophytes dates to ancient times, but it has always been marginal due to their small size, difficult identification, lack of conspicuous organs which would attract attention (flowers, fruits) and insipid taste of the herb. The earliest testimonies of their medical use come from the 1500s.

A 2021 review in the journal Plants (Drobnik & Stebel) systematically examined European historical sources. Historical printed sources from 1616 to 1889 were queried. Bryophyte species found were taxonomically identified and presented against the background of their confirmed properties and ecology. The study was supplemented with historical vs. modern ethnomedicinal data. In 26 publications, 28 species were identified. Modern usage was known for 10 of them. Medicinal properties of 16 species were confirmed.

The greatest number of biochemical and pharmacological reports on European bryophytes concern Marchantia polymorpha. The first pharmaceutical reference comes from Tournefort's 1708 Materia Medica. References to liverwort can be found in the pages of Maude Grieve's 1931 Modern Herbal and in the Physician's Desk Reference for Herbal Medicine.

A central driver of historical European use was the Doctrine of Signatures: Historically, due to the "Doctrine of Signatures," it was assumed the liver-like shape of certain thalloid liverworts implied a beneficial effect on liver health. Thus, "liverwort" was occasionally integrated into older European herbal lore for hepatic or gallbladder concerns.

Liverwort has been classified as an astringent, gentle herb suitable for topical applications in healing wounds and biliary complaints, from gallstones to jaundice. Grieve considered liverwort as an expectorant useful in bronchial conditions. Liverwort has also been used as a diuretic agent in European countries.

Species of wide geographical distribution range were (or are still being) used in local folk medicines. Historical ethnobiological and ethnopharmaceutical uses of them are sometimes convergent with their confirmed properties, mostly external (as antimicrobial or cytotoxic remedies).

The interest in medicinal bryophytes diminished considerably in the 1880s, except for Sphagnum spp., which became a source of dressing material. The second half of the 20th century saw the revival of the study of bryophyte chemistry.

2.2 Chinese and East Asian Traditional Medicine

Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. Marchantia polymorpha, known as a traditional Chinese herbal medicine, was used in the treatment of cuts, fractures, snake bites, burns, scalds, and open wounds. Chinese people used it to treat jaundice and inflammation also.

In China, liverworts have been used for a variety of ailments including cuts, burns and bruises, pulmonary tuberculosis, convulsions and neurasthenia.

2.3 Global Indigenous and Ethnobotanical Uses

This plant has been traditionally used to treat boils, fractures, poisonous snakebites, abscesses, wounds, and hepatic disorders.

Ethnobotanical surveys indicate widespread use across cultures. Liverwort has been used as a healing substance by tribal cultures for centuries to treat liver disorders, skin diseases, fight fevers, support heart health, and to heal wounds. Its long history as an ethnomedicine used uniquely by differing tribal peoples from all around the world from Africa, to South America, to Australia, to China, to Nepal and India indicates the plant's powerful physical and spiritual healing attributes.

Marchantia polymorpha and Conocephalum conicum, for example, are used to cure hepatic disorders as their structures resemble the lobes of livers. Marchantia palmata and M. polymorpha are used to treat boils and abscesses as the developing archegonium of these liverworts emerges as a protuberance that resembles a tiny boil.

Pellia neesiana has been used in traditional medicine by Hesquiat people for children's sore mouths, and Conocephalum salebrosum has been used as an eye medicine by the Ditidaht.

Regarding Radula marginata and Māori use: Radula marginata may have been used in rongoā (Māori herbal medicine), but there is no firm evidence of this.

2.4 Use in Ethnobotany for Skin and Wound Care

Herbal remedies for skin and hair care are by far the most commonly reported (25.0%); antipyretic uses of bryophytes account for 12.2%, while taxa used as medicinal treatments for respiratory and gastro-intestinal systems amount to 12.1% and 9.9%. Indigenous cultures worldwide have also recognized some species for minor uses, from wound coverings to mild analgesic or antiseptic applications.

3. Key Constituents and Active Compounds

3.1 Overview of Phytochemical Classes

A review of the literature on the chemical composition of the umbrella liverwort shows that it is characterized by great diversity. The following groups of chemical compounds have been identified so far in Marchantia: mono-, sesqui- and diterpenoids, sterols and triterpenoids, bibenzyls, bisbibenzyls, phenanthrene derivatives, flavonoids, lipids and other compounds.

The major metabolites in M. polymorpha are polyphenols (bis-bibenzyls and flavonoids), long-chain polyunsaturated fatty acids (AA, EPA), and terpenoids.

Most of the liverworts studied elaborate characteristic odiferous, pungent, and bitter-tasting compounds, of which many show antimicrobial, antifungal, antiviral, allergic contact dermatitis, cytotoxic, insecticidal, anti-HIV, plant growth regulatory, neurotrophic, NO production and superoxide anion radical release inhibitory, muscle relaxing, antiobesity, piscicidal, and nematocidal activities.

The biological effects ascribed to liverworts are mainly due to lipophilic sesqui- and diterpenoids, phenolic compounds, and polyketides, which are the principal constituents of their oil bodies.

3.2 Bisbibenzyls — The Signature Compounds

The most characteristic compound occurring in M. polymorpha is a macrocyclic bisbibenzyl, marchantin A. Marchantin-type aromatic compounds together with other bisbibenzyls, such as riccardin D, isoriccardin C or perrottetin E, were proven to withhold antifungal and antibacterial properties in various studies.

Key bisbibenzyls documented across the Marchantia genus include:

Marchantin A — the most characteristic macrocyclic bisbibenzyl of M. polymorpha; demonstrated antibacterial, antifungal, cytotoxic, and muscle-relaxant properties.
Marchantin B, C, H, M — further macrocyclic bisbibenzyls with documented cytotoxic, pro-apoptotic, and anti-inflammatory activities in vitro.
Riccardin D — studied for anticancer properties.
Isoriccardin C — isolated from Vietnamese specimens of M. polymorpha with documented cytotoxic activity.
Plagiochin E — an antifungal macrocyclic bisbibenzyl isolated from M. polymorpha.
Perrottetin E — an acyclic bisbibenzyl found in Indian and Chinese specimens. Perrottetin E is an acyclic bisbibenzyl found in Indian and Chinese specimens of common liverwort. It can be used as a precursor for the synthesis of marchantin- and riccardin-type compounds.

LC-MS and GC-MS analysis of methanolic extract revealed the presence of numerous phytochemicals responsible for its antibacterial and anti-inflammatory potential, such as Pentadecanal, 3-β-Hydroxy-5-cholen-24-oic acid, Stigmasterol, Phytol, n-Hexadecanoic acid, Ergosterol, Caryophyllene, some important bis-bibenzyls like Marchantin A, Marchantin M, Riccardin D, Plagiochin E and some flavonoids like Rutin, Kaempferol 3-O-glucosyl-rhamnosyl-glucoside and Luteolin 7-O-diglucuronide.

3.3 Terpenoids

Marchantia polymorpha is a rich source of terpenoids, in particular those belonging to the sesquiterpene group. Forty-eight sesquiterpenoids belonging to twenty different classes are included in the known literature.

A review of the literature shows that the major compounds in this species are undoubtedly sesquiterpenoids and bisbibenzyls. Among the sesquiterpenoids, it is worth mentioning cuparenes, chamigranes, and thujopsanes. Compounds belonging to these classes were found in specimens from Japan, China, Poland, Germany, and India and could be the chemical markers of this liverwort species.

Most sesqui- and di-terpenoids obtained from liverworts are enantiomers of those found in higher plants. This mirror-image chirality is considered biochemically significant and may partly explain the unique pharmacological profiles of liverwort extracts.

3.4 Flavonoids and Polyphenols

The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Specific flavonoids identified include rutin, luteolin, apigenin, and various glycosylated kaempferol derivatives. The total flavonoids content in the archegoniophore was about 10 times higher than that of the gametophyte.

One study isolated five phenolic compounds from Vietnamese M. polymorpha: Lunularin, marchantin A, isoriccardin C, luteolin, and apigenin were isolated from the ethyl acetate extract of Marchantia polymorpha collected at Lam Dong province, Vietnam.

3.5 Cannabinoid-Type Bibenzyls in the Radula Genus

A distinct and pharmacologically notable group of compounds occurs in the leafy liverwort genus Radula:

Phytochemical studies on the liverwort Radula genus have previously identified the bibenzyl (-)-cis-perrottetinene (cis-PET), which structurally resembles (-)-Δ9-trans-tetrahydrocannabinol (Δ9-trans-THC) from Cannabis sativa L.

The ether extract of the New Zealand liverwort Radula marginata afforded a new cannabinoid type bibenzyl compound named perrottetinenic acid, and two new bibenzyls, together with a known cannabinoid, perrottetinene.

These compounds of liverworts are in fact bisbenzyls that are accumulated in oil bodies and their biosynthesis evolved in a completely different fashion to that of cannabinoids in vascular plants.

3.6 Oil Bodies as the Cellular Repository of Secondary Metabolites

It has been assumed that the specialized metabolites in M. polymorpha specifically accumulate in the oil bodies in oil body cells. Direct evidence was obtained using micromanipulation techniques coupled with MS analysis that demonstrated the specific accumulation of sesquiterpenoids and marchantin A in the oil body cells of M. polymorpha thalli.

Regarding biosynthesis of the characteristic marchantins, marchantins are potentially biosynthesized from phenylalanine via the phenylpropanoid pathway. The condensation of dihydro-p-coumaroyl-CoA with three molecules of malonyl-CoA produces prelunularic acid, which is subsequently converted into bibenzyl lunularic acid. A putative cytochrome P450 enzyme catalyzes the oxidative coupling of two lunularic acid molecules to form marchantin C in an NADPH-dependent manner.

4. Mechanisms of Action

4.1 Anti-Inflammatory Mechanisms

To evaluate the anti-inflammatory effect of liverwort, the levels of nitric oxide (NO) production and the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 and IL-1β in LPS-induced HaCaT cells were measured. This in vitro experimental framework represents the primary mechanistic model through which anti-inflammatory activity of liverwort extracts has been characterized.

Especially the bis-bibenzyls exhibited significant antibacterial, antifungal, anti-inflammatory, and antioxidant properties.

4.2 Antioxidant Mechanisms

Antioxidant activity has been assessed through multiple in vitro assays: radical scavenging assay methods (DPPH, ABTS, O²⁻), reducing power assay, and acetylcholinesterase inhibition assay. The flavonoid fraction is primarily responsible for free radical scavenging capacity.

4.3 Cytotoxic and Pro-Apoptotic Mechanisms

The study on marchantin C showed pro-apoptotic effect on human glioma A172 cells. The results demonstrated that marchantin C conferred dose-dependent inhibitory effects onto cell growth, viability, and colony formation ability of A172 cells. Other than triggering apoptosis of human tumor cells, marchantin C could induce cell cycle arrest at G(2)/M phase in A172 and HeLa cells. In addition, marchantin C decreased the quantity of microtubules in a time- and dose-dependent manner in these cells. Exposure of purified bovine brain tubulin to marchantin C inhibited polymerization of gross tubulin in vitro.

Marchantin M was reported as an active agent to induce apoptosis in human prostate cancer (PCa). It is believed that marchantin M inhibits 20S proteasome both in in vitro and intracellular systems.

4.4 Antifungal Mechanism of Plagiochin E

Plagiochin E (PLE) obtained from Marchantia polymorpha L. is an antifungal macrocyclic bis(bibenzyl). Studies examined the effects of PLE on Candida albicans. It was observed through Transmission Electron Microscopy (TEM) that the mechanism involved F0F1-ATPase. This demonstrated the antifungal mechanism of action of PLE.

4.5 Cannabinoid Receptor Mechanism of Perrottetinene (cis-PET)

Both molecules (cis-PET and its trans diastereoisomer) readily penetrate the brain and induce hypothermia, catalepsy, hypolocomotion, and analgesia in a CB1 receptor–dependent manner in mice. The natural product cis-PET was profiled on major brain receptors, showing a selective cannabinoid pharmacology.

Most notably, cis-PET and trans-PET significantly reduced basal brain prostaglandin levels associated with Δ9-trans-THC side effects in a CB1 receptor–dependent manner.

5. Scientific Evidence by Area of Use

5.1 Anti-Inflammatory Activity

Evidence Level: Preclinical (in vitro only; no human or animal clinical data identified)

Bryophytes contain a variety of bioactive metabolites, but studies about the anti-inflammatory effect of bryophytes are meager. A key study aimed to compare the anti-inflammatory effect of methanol extract of Marchantia polymorpha L. (liverwort) and Racomitrium canescens (Racomitrium moss) in lipopolysaccharide (LPS)-induced HaCaT cells.

This study (published in PMC, 2021) used LPS-stimulated keratinocyte (HaCaT) cell lines. Parameters measured included NO production and pro-inflammatory cytokine mRNA expression (iNOS, COX-2, TNF-α, IL-6, IL-1β). No human or animal in vivo data accompanied these in vitro findings. The extracts and compounds isolated from liverwort exhibited various biological activities such as antimicrobial, antioxidant, anti-inflammatory activities, and cytotoxic potential against cancer cell lines. All these characterizations derive from cell-culture or chemical assay systems; no clinical evidence in humans exists.

5.2 Antioxidant Activity

Evidence Level: Preclinical (in vitro); chemistry-based assays only

The flavonoid profiles, antioxidant potential, and acetylcholinesterase inhibition activity of the extracts from the gametophyte and archegoniophore of M. polymorpha L. were compared. Results demonstrated measurable DPPH and ABTS radical scavenging activity attributable principally to the flavonoid fraction. No clinical antioxidant trials in humans have been identified.

5.3 Antimicrobial and Antifungal Activity

Evidence Level: Preclinical (in vitro); confirmed for specific isolated compounds against specific organisms

The extracts of M. polymorpha L. exhibited antifungal activity, antibacterial and antioxidant activities.

Marchantin A displayed significant antibacterial activity against Acinetobacter calcoaceticus.

A 2024 study in ScienceDirect characterized antifungal activity of M. polymorpha extracts against the plant pathogen Rhizoctonia solani. The compounds identified belong to diverse subclasses such as phenolic, flavonoids, cyclic bisbenzyls, alkaloids, amines, terpenoids and phytosterol esters.

All antimicrobial evidence is confined to in vitro microbiology studies; no human clinical trials for infection treatment or prevention have been identified.

5.4 Hepatoprotective (Liver-Protective) Activity

Evidence Level: Preclinical (rodent animal models); no human clinical trials identified

Chloroform extract of M. polymorpha was postulated to have hepatoprotective properties. When mice were administered with paracetamol in liver-damaging quantities along with marchantin A, the amount of markers of liver damage in mice blood (aspartate transaminase and alanine transaminase) was significantly lower than in the control group administered with paracetamol only, and on par with the group in which paracetamol was administered along with silymarin.

Another study showed that flavonoids of M. polymorpha can protect liver cells from injuries caused by administration of carbon tetrachloride. As both compounds induce damage to liver cells with their oxidizing potential, the hepatoprotective effect was postulated to be due to antioxidant properties of M. polymorpha extracts.

The CCl₄-induced liver injury rat model was the basis for a study (PubMed, 2020): Marchantia polymorpha L. (MPL), a common type of liverwort, has been used as herbal medicine to improve liver function in China for many years. Although modern studies revealed that MPL contains various polyphenols, terpenoids, and bis[bibenzyls], its biological effects on liver function have never been systemically studied in any animal model. In this study, flavonoids were extracted from MPL and the components in the MPL flavonoids as well as the antioxidant capacity of MPL flavonoids were analyzed. A rat model of liver injury was induced by intraperitoneal injection of 10% carbon tetrachloride (CCl₄). The flavonoid fraction demonstrated hepatoprotective activity in this rodent model.

For Marchantia paleacea, a study using an acetaminophen-induced liver damage model in rats found: Findings suggest that 26 and 104 mg/kg bw have a potential protective effect on liver function against hepatotoxicity in rat livers. These animal model results have not been replicated or extended to human trials.

5.5 Anticancer / Cytotoxic Activity

Evidence Level: Preclinical (in vitro cell lines, limited in vivo rodent models); no human clinical evidence

Marchantia polymorpha L. is a kind of Chinese herbal medicine and has various biological activities including antioxidant and antifungal. It is not clear about the antitumor effect and mechanism of M. polymorpha. One study prepared M. polymorpha ethanol extract (MPEE) and investigated its antitumor effect on hepatocellular carcinoma cells both in vitro and in vivo.

Marchantin A has shown activity in breast cancer cell lines: Marchantin A was shown to induce a reduction in cell viability of breast cancer cell lines A256 (IC₅₀ = 5.5 µM), MCF7 (IC₅₀ = 11.5 µM), and T47D (IC₅₀ = 15.3 µM). The effect was considerably increased in all cell lines in a synergistic manner when the Aurora-A kinase inhibitor MLN8237 was added simultaneously.

Compound isolation studies from Vietnamese specimens showed: The evaluation of the cytotoxic activity against MCF-7, Hep G2, NCI-H460, and HeLa cancer cell lines of the ethyl acetate extract and compounds showed that lunularin was potent against MCF-7 cancer cell with the IC₅₀ value of 4.59±0.38 µg/mL.

Compounds such as Marchantin and Riccardin as well as extracts from Bazzania and Scapania species have been shown to have pronounced antitumour effects. All this evidence is derived from cell-culture experiments and, in a limited number of cases, tumor-bearing mouse models. No human oncology clinical data exists.

5.6 Psychoactive / Cannabinoid Activity (Radula spp.)

Evidence Level: Preclinical (animal pharmacology in mice); no human clinical evidence

A landmark 2018 study in Science Advances (Chicca et al.) showed that cis-PET is a moderately potent but efficacious psychoactive cannabinoid identified outside the Cannabis genus, in agreement with the reported recreational use of R. marginata, which is endemic to New Zealand and Tasmania. Like Δ9-trans-THC, cis-PET occurs in the plant as acid, which is progressively decarboxylated upon drying or smoking.

Both molecules readily penetrate the brain and induce hypothermia, catalepsy, hypolocomotion, and analgesia in a CB1 receptor-dependent manner in mice. The natural product cis-PET was profiled on major brain receptors, showing a selective cannabinoid pharmacology.

Therefore, the natural product cis-PET is a psychoactive cannabinoid from bryophytes, illustrating the existence of convergent evolution of bioactive cannabinoids in the plant kingdom. These findings may have implications for bioprospecting and drug discovery and provide a molecular rationale for the reported effects upon consumption of certain Radula preparations as moderately active legal highs.

The online community reporting about legal highs both affirms and refutes the anecdotes regarding the cannabis-like effects of smoked R. marginata. Given the uncertain amounts of cis-PET in the purchasable preparations and the lack of information on human pharmacokinetics, the actual potency in humans remains unknown.

5.7 Acetylcholinesterase Inhibition

Evidence Level: Preclinical (in vitro enzyme inhibition assay only)

One study compared acetylcholinesterase inhibition activity of extracts from the gametophyte and archegoniophore of M. polymorpha using in vitro enzyme assays. The flavonoid profiles, antioxidant potential, and acetylcholinesterase inhibition activity of the extracts from the gametophyte and archegoniophore of M. polymorpha L. were compared. No animal or human neurological studies have been conducted to date.

6. Body Systems and Health Areas

Based on the available preclinical research, liverwort extracts and isolated compounds have been studied in relation to the following body systems. All associations below are derived from laboratory and/or animal research only, unless otherwise stated:

Hepatic System: Traditional use for liver and gallbladder ailments reinforced by preclinical animal models demonstrating hepatoprotective effects via antioxidant mechanisms. It possesses antimicrobial, diuretic, cytotoxic, antipyretic, antifungal, anti-hepatic properties, 5-lipoxygenase, and cardiotonic activity.
Immune/Inflammatory System: Inhibition of pro-inflammatory mediators (TNF-α, IL-6, IL-1β, COX-2, iNOS, NO) demonstrated in vitro; attributed primarily to bisbibenzyl and flavonoid fractions.
Cutaneous/Dermatological System: Traditional use for wound healing, burns, and skin infections aligns with in vitro antimicrobial data. Certain sesquiterpenes in oil bodies are, however, also known contact allergens (see Safety section).
Oncological/Cytological: Multiple isolated bisbibenzyls (marchantin A, C, M; riccardin D) display in vitro cytotoxicity toward breast, hepatic, glioma, prostate, and cervical cancer cell lines.
Renal System: Traditional diuretic use documented in European ethnopharmacy; no controlled evidence.
Respiratory System: Grieve considered liverwort as an expectorant useful in bronchial conditions. This is a historical/traditional attribution with no supporting modern clinical or animal study data.
Central Nervous System: The CB1 receptor agonism of cis-perrottetinene (from Radula species) is established in murine models, producing hypothermia, analgesia, and hypolocomotion.
Cardiovascular/Musculoskeletal: Marchantin A in M. polymorpha was found to induce muscle relaxation. Cardiotonic activity has also been attributed to Marchantia extracts in ethnopharmacological reviews.

7. Dosage Forms and Reported Dosages

No standardized or regulatory-approved dosage exists for any liverwort-derived product as a dietary supplement. The following dosages are drawn exclusively from published experimental research:

Hepatoprotective animal study (M. paleacea, rat model, acetaminophen-induced hepatotoxicity): Doses of 26 and 104 mg/kg body weight demonstrated a potential protective effect on liver function against hepatotoxicity in rat livers.
Acute toxicity testing (M. paleacea ethanol extract, female mice): The acute toxicity test was carried out by giving ethanol extract of liverwort herb Marchantia paleacea Bertol. in single doses at 250, 500, 1000, and 2000 mg/kg bw orally for 14 days, while sub-acute toxicity tests were performed by administering test extracts at doses of 125, 250, 500, 1000, and 2000 mg/kg bw orally for 28 days.
In vitro cytotoxicity (marchantin A, breast cancer cell lines): Marchantin A was shown to induce a reduction in cell viability of breast cancer cell lines A256 (IC₅₀ = 5.5 µM), MCF7 (IC₅₀ = 11.5 µM), and T47D (IC₅₀ = 15.3 µM).
In vitro cytotoxicity (lunularin against MCF-7 cells): Lunularin was potent against MCF-7 cancer cell with the IC₅₀ value of 4.59±0.38 µg/mL.
In vitro apoptosis induction (M. polymorpha extract, HeLa cells): Cell apoptosis induction begins at a concentration of 50 µg/mL, whereas at a concentration of 250 µg/mL cell apoptotic phase approaches almost 100%. Methanolic extract of liverworts (M. polymorpha L.) inhibits growth of HeLa cell and induced cell apoptosis.

No human pharmacokinetic studies, dose-finding trials, or dosage guidelines for oral supplementation have been published in peer-reviewed literature. All dosages above apply to in vitro or animal experimental models and cannot be extrapolated to human use.

8. Safety Considerations and Interactions

8.1 Contact Allergenicity

The secondary metabolites of liverwort oil bodies have characteristic odor and taste properties — pungency or bitterness — as well as being responsible for allergenic contact dermatitis, and antimicrobial or insecticidal activities.

Liverwort terpenoids and lipophilic compounds have been observed to have significant biological activity, including cyto-toxicity, anti-obesity, anti-influenza, allergenic contact dermatitis, anti-HIV inhibitory, antimicrobial, and vasorelaxant effects.

This contact allergenicity is well-documented in the dermatology literature; certain sesquiterpene lactones in liverworts, particularly from the genus Frullania, are among the documented causes of occupational and woodland contact dermatitis. The responsible compounds belong to the sesquiterpene class that is broadly distributed across liverworts.

8.2 Genotoxic and Cytotoxic Potential of Isolated Compounds

The same bisbibenzyls and sesquiterpenes responsible for cytotoxic activity against cancer cell lines may pose safety concerns in non-target tissues at higher concentrations. All cytotoxic data are from in vitro models, and the therapeutic window in humans has not been established.

8.3 Toxicological Data: Limited and Predominantly Animal-Based

Information regarding oral acute and sub-acute toxicity data from ethanol extracts of Marchantia paleacea Bertol. liverwort herb is still very limited. The acute and sub-acute toxicity studies conducted in mice provide the only formal toxicological datasets available, and these are restricted to animal models.

Only about 8.8% of liverworts have been chemically investigated, and species such as Bryum, Marchantia, Sphagnum, Octeblepharum, Riccia, Barbula and Fontinalis have been tested for different diseases such as heart disease, fever, inflammation, lung disease, various infections, skin diseases and external wounds. The incomplete chemical characterization of the majority of liverwort species means that the full toxicological profile of commonly used species is not established.

8.4 Psychoactive Risk from Radula Preparations

In recent years, reports on Radula as a legal high have accumulated. The research shows that cis-PET is a moderately potent but efficacious psychoactive cannabinoid identified outside the Cannabis genus, in agreement with the reported recreational use of R. marginata.

The quantity of cannabinoid present is much less than in cannabis. However, given that the uncertain amounts of cis-PET in the purchasable preparations and the lack of information on pharmacokinetics remain uncharacterized, the risks associated with consuming dried Radula preparations — including variable potency and unknown interactions — cannot be quantified from published data.

8.5 Absence of Human Clinical Safety Data

Comprehensive clinical trials in humans are limited, and more rigorous research is needed to confirm liverwort's safety and efficacy as a nutritional supplement. No controlled human trials examining the safety of oral liverwort supplementation have been published in peer-reviewed sources to date. The pharmacokinetics of any liverwort-derived compound in humans have not been characterized in published research.

8.6 Phytochemical Variability by Geographical Origin

The phytochemistry of M. polymorpha varies depending on its place of origin. Specimens from European countries and Japan are characterized by the occurrence of only marchantin A derivatives. This geographic variability means that the chemical composition — and therefore the bioactive and potentially toxic compound profile — of any liverwort preparation will differ substantially depending on the source material, raising quality and standardization concerns relevant to supplement safety.

9. Current Status of Research and Evidence Gaps

Liverworts are a group of non-vascular plants that possess unique metabolism not found in other plants. Many liverwort metabolites have interesting structural and biochemical characteristics; however, the fluctuations of these metabolites in response to stressors is largely unknown.

The overall body of liverwort pharmacological research is dominated by in vitro cell culture studies and, to a lesser extent, rodent animal models. The greatest number of biochemical and pharmacological reports on European bryophytes concern Marchantia polymorpha. Despite this, no human clinical trials have been conducted for any health indication. Mechanistic evidence supports biological plausibility for anti-inflammatory, hepatoprotective, antimicrobial, and anticancer activities, but translation to clinical outcomes in humans remains unestablished. The cannabinoid activity of Radula-derived perrottetinene represents a scientifically characterized but clinically unvalidated pharmacological mechanism. The secondary metabolites of liverworts offer an under-characterised diversity of potentially pharmaceutically relevant compounds.

References

Health Conditions

Health conditions that Liverwort may help support.

No conditions available.

Body Systems

Body systems that Liverwort may help support.

No body systems available.