Phyllanthin

Phyllanthin at a Glance

Phyllanthin is the major lipophilic dibenzylbutane lignan of chanca piedra (Phyllanthus niruri) and the closely related P. amarus. Together with its congener hypophyllanthin it is the pair of compounds routinely quantified to identify and standardize the herb — the “marker lignans” of the Phyllanthus fingerprint ^{15Reference 15Murugaiyah V · 2007Analysis of lignans from Phyllanthus niruri in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic studyView study →}.

It matters to read this molecule at the right altitude. Phyllanthus’s clinical reputation — chronic hepatitis B, kidney stones — belongs to the whole extract, in which phyllanthin is a marker, not the tested agent; and because the lignans partition into alcohol, a water tea or decoction is low in phyllanthin while a tincture or standardized extract is enriched ^{13Reference 13Colombo R et al. · 2009Validated HPLC method for the standardization of Phyllanthus niruri (herb and commercial extracts) using corilagin as a phytochemical markerView study →}. What distinguishes phyllanthin from the thinner hypophyllanthin file is that it carries genuine isolated-molecule data: a dedicated hepatoprotective/antifibrotic signal in a mammalian liver-injury model, a standalone anti-inflammatory study, and its own P-glycoprotein herb-drug-interaction paper.

All of that evidence is preclinical. There are no human trials of isolated phyllanthin, and the molecule’s poor aqueous solubility and low oral bioavailability are a real constraint on translating in-vitro potency. Its toxicity flag is low — but that reflects sparse dedicated data, not a demonstrated clean bill.

What It's Used For

Phyllanthin’s evidence base splits cleanly by whether the isolated molecule or the whole Phyllanthus extract was tested. The isolate has a real hepatoprotective and anti-inflammatory signal and a distinctive efflux-pump / drug-interaction throughline; the metabolic and clinical claims mostly ride on the extract.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. No human isolate data exist, so scores stay low by design.

01Hepatoprotective / AntifibroticShaky40%Dedicated isolate CCl₄ fibrosis studies ^{1,2Reference 1Krithika R et al. · 2015AnimalMechanism of protective effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and experimental liver fibrosis in miceView study →Reference 2Krithika R et al. · 2016Phyllanthin inhibits CCl₄-mediated oxidative stress and hepatic fibrosis by down-regulating TNF-α/NF-κB and the pro-fibrotic factor TGF-β1View study →}

02Anti-InflammatoryShaky32%Isolate NF-κB/MAPK/PI3K-Akt + asthma pair ^{3,4,5Reference 3Harikrishnan H et al. · 2018Phyllanthin from Phyllanthus amarus inhibits LPS-induced proinflammatory responses in U937 macrophages via downregulation of NF-κB/MAPK/PI3K-Akt signaling pathwaysView study →Reference 4Harikrishnan H et al. · 2018Anti-inflammatory effects of Phyllanthus amarus through inhibition of NF-κB, MAPK and PI3K-Akt signaling pathways in LPS-induced human macrophagesView study →Reference 5Wu W et al. · 2019Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthmaView study →}

03Bioavailability / P-GlycoproteinShaky28%Caco-2 efflux + own interaction paper ^{6,7Reference 6Sukhaphirom N et al. · 2013Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cellsView study →Reference 7Dunkoksung W et al. · 2019Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrierView study →}

04Anticancer / MDR ReversalShaky20%Lignan MDR-reversal + doxorubicin synergy ^{8,9Reference 8Leite DF et al. · 2006The cytotoxic effect and the multidrug resistance reversing action of lignans from Phyllanthus amarusView study →Reference 9Abdel-Sattar OE et al. · 2023Hypophyllanthin and phyllanthin from Phyllanthus niruri synergize doxorubicin anticancer properties against resistant breast cancer cellsView study →}

05Metabolic (Lipid / Uricosuric)Shaky16%Extract NAFLD + isolate uricosuric assay ^{12,14Reference 12Al Zarzour RH et al. · 2017AnimalPhyllanthus niruri standardized extract alleviates the progression of non-alcoholic fatty liver disease and decreases atherosclerotic risk in Sprague-Dawley ratsView study →Reference 14Murugaiyah V · 2009Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituentsView study →}

Mechanisms

Pharmacokinetics

Phyllanthin is a lipophilic dibenzylbutane lignan with poor aqueous solubility and low oral bioavailability — it partitions into alcohol, so it is enriched in tinctures and standardized extracts and scarce in aqueous tea. Validated bioanalysis exists (an HPLC-with-fluorescence-detection method quantifies P. niruri lignans in plasma for PK work ^{15Reference 15Murugaiyah V · 2007Analysis of lignans from Phyllanthus niruri in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic studyView study →}), and formulation research directly targets the solubility problem — for instance a phyllanthin-loaded self-microemulsifying drug-delivery system (SMEDDS) developed to enhance oral bioavailability ^{17Reference 17Duc Hanh N et al. · 2015Development of phyllanthin-loaded self-microemulsifying drug delivery system for oral bioavailability enhancementView study →}. Because phyllanthin is itself a P-gp inhibitor ^{6,7Reference 6Sukhaphirom N et al. · 2013Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cellsView study →Reference 7Dunkoksung W et al. · 2019Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrierView study →}, it may increase absorption of itself and of co-administered P-gp substrates — a two-way herb-drug-interaction signal, characterized only in-vitro / at the intestinal barrier. No human PK data exist for the isolate.

Clinical Trials

There are no robust trials of isolated phyllanthin. Human Phyllanthus trials (chronic hepatitis B; kidney stones) use the whole extract, in which phyllanthin serves only as a standardization/identity marker — not the studied agent — and the best-conducted hepatitis-B trials are negative ^{16Reference 16Srirama R et al. · 2012Hepatoprotective activity of Indian PhyllanthusView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

Phyllanthin sits in an unusually clear position on the isolate-vs-plant axis. The mechanistic depth is on the isolate: the CCl₄ hepatoprotection/antifibrosis series ^{1,2Reference 1Krithika R et al. · 2015AnimalMechanism of protective effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and experimental liver fibrosis in miceView study →Reference 2Krithika R et al. · 2016Phyllanthin inhibits CCl₄-mediated oxidative stress and hepatic fibrosis by down-regulating TNF-α/NF-κB and the pro-fibrotic factor TGF-β1View study →}, the U937-macrophage anti-inflammatory study ^{3Reference 3Harikrishnan H et al. · 2018Phyllanthin from Phyllanthus amarus inhibits LPS-induced proinflammatory responses in U937 macrophages via downregulation of NF-κB/MAPK/PI3K-Akt signaling pathwaysView study →}, and the Caco-2 / intestinal-barrier P-gp work ^{6,7Reference 6Sukhaphirom N et al. · 2013Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cellsView study →Reference 7Dunkoksung W et al. · 2019Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrierView study →} all test purified phyllanthin — a real strength, because the molecule’s own pharmacology is characterized rather than inferred. The human and metabolic claims are on the plant: the hepatitis-B and kidney-stone trials are whole-extract ^{16Reference 16Srirama R et al. · 2012Hepatoprotective activity of Indian PhyllanthusView study →}, the NAFLD/lipid effect is an extract result with phyllanthin only as a marker ^{12Reference 12Al Zarzour RH et al. · 2017AnimalPhyllanthus niruri standardized extract alleviates the progression of non-alcoholic fatty liver disease and decreases atherosclerotic risk in Sprague-Dawley ratsView study →}, and even the anti-inflammatory and asthma work is partly whole-extract or a lignan pair ^{4,5Reference 4Harikrishnan H et al. · 2018Anti-inflammatory effects of Phyllanthus amarus through inhibition of NF-κB, MAPK and PI3K-Akt signaling pathways in LPS-induced human macrophagesView study →Reference 5Wu W et al. · 2019Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthmaView study →}. The two do not transfer cleanly, and the preparation caveat sharpens the point: since phyllanthin is alcohol-soluble and low in a water tea ^{13Reference 13Colombo R et al. · 2009Validated HPLC method for the standardization of Phyllanthus niruri (herb and commercial extracts) using corilagin as a phytochemical markerView study →}, isolate results obtained at concentration say little about what a traditional decoction delivers.

Prevalence in Nature

Phyllanthin is a genus-restricted lignan, essentially a Phyllanthus compound rather than a widespread plant metabolite. It is the principal lipophilic lignan of chanca piedra (Phyllanthus niruri) and P. amarus, and is reported from other members of the genus such as P. urinaria and P. tenellus. In the herb it travels with its co-marker hypophyllanthin and the minor lignan phyltetralin, alongside a large pool of water-soluble hydrolysable tannins — the ellagitannins corilagin and geraniin and their breakdown phenolics ellagic acid and gallic acid — plus flavonoids like quercetin ^{12,13Reference 12Al Zarzour RH et al. · 2017AnimalPhyllanthus niruri standardized extract alleviates the progression of non-alcoholic fatty liver disease and decreases atherosclerotic risk in Sprague-Dawley ratsView study →Reference 13Colombo R et al. · 2009Validated HPLC method for the standardization of Phyllanthus niruri (herb and commercial extracts) using corilagin as a phytochemical markerView study →}.

Reported concentrations are modest and swing widely with plant source and, above all, extraction solvent: phyllanthin runs at roughly 0.33–3.1 mg/g of extract, higher in ethanolic than aqueous preparations because the lignans favor alcohol ^{13,15Reference 13Colombo R et al. · 2009Validated HPLC method for the standardization of Phyllanthus niruri (herb and commercial extracts) using corilagin as a phytochemical markerView study →Reference 15Murugaiyah V · 2007Analysis of lignans from Phyllanthus niruri in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic studyView study →}. As a dibenzylbutane lignan, phyllanthin is structurally distinct from the furofuran lignans sesamin, pinoresinol and syringaresinol and from the flavonolignan silybin — different plant lineages arriving at the same broad “lignan” label by different skeletons.

Discovery & Synthesis

Phyllanthin was reported from Phyllanthus niruri in the mid-20th century, and its constitution (structure) was elucidated by L. Ramachandra Row and colleagues in 1966, in the fifth paper of their “Crystalline constituents of Euphorbiaceae” series — establishing it as a dihydroxy-dimethoxy dibenzylbutane lignan ^{18Reference 18Row LR et al. · 1966Crystalline constituents of euphorbiaceae—V: New lignans from Phyllanthus niruri Linn — the constitution of phyllanthinView study →}. The name simply follows the genus (Phyllanthus → phyllanthin), and its partner lignan was named hypophyllanthin.

There is no commercial total-synthesis route in use: phyllanthin is obtained by extraction and chromatographic isolation from Phyllanthus biomass (leaf and aerial parts), the same material used to make standardized herbal extracts. Because supply is agronomic, work on the molecule has focused less on synthesis than on improving its poor solubility/bioavailability through formulation (e.g. self-microemulsifying delivery systems) ^{17Reference 17Duc Hanh N et al. · 2015Development of phyllanthin-loaded self-microemulsifying drug delivery system for oral bioavailability enhancementView study →}. As a preclinical marker compound rather than a manufactured drug, it has no established industrial-scale production.

Patents: not yet researched.

Toxicity & Safety

Phyllanthin shows no toxicity signal of its own, but the low flag reflects sparse data rather than demonstrated safety — and the mechanism worth watching is drug absorption, not intrinsic toxicity.

Safety at a Glance

✅ Low / no toxicityDrug interactions

• No isolate toxicity signal identified. Studied doses are preclinical; no adverse-effect pattern emerged for the pure compound in the available work.
• P-glycoprotein inhibition (drug-interaction flag). Phyllanthin inhibits intestinal P-gp in vitro, so it could in principle raise the absorption of narrow-therapeutic-index P-gp substrates — theoretical, not clinically documented ^{6,7Reference 6Sukhaphirom N et al. · 2013Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cellsView study →Reference 7Dunkoksung W et al. · 2019Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrierView study →}.
• The low flag means sparse data. No isolate toxicity was ruled in, but none was affirmatively ruled out either; there is no isolate genotoxicity, repeat-dose or reproductive dataset.

Full Safety & Interactions Detail

Phyllanthin has a low-concern profile: no isolate toxicity signal was identified across the hepatoprotective, anti-inflammatory and efflux-pump studies above, so the low flag encodes sparse dedicated data rather than a demonstrated clean profile. The one caution warranted on mechanistic grounds is a herb-drug interaction: its in-vitro P-glycoprotein inhibition ^{6,7Reference 6Sukhaphirom N et al. · 2013Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cellsView study →Reference 7Dunkoksung W et al. · 2019Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrierView study →} could raise the absorption of P-gp substrates with a narrow therapeutic index — but this is an in-vitro / intestinal-barrier finding, not a clinically documented interaction.

Reproductive/developmental data (prose only): there is no reproductive-toxicity dataset for isolated phyllanthin, and Phyllanthus species carry a traditional pregnancy caution at the herb level. Consistent with site policy, the pregnancy/lactation decision belongs to the chanca piedra herb page, where intake is decided — not to this molecule page; the finding here is simply that the isolate is unstudied.

Dosage

There is no human dose established for phyllanthin. It is a marker / standardization constituent, not a standalone supplement; all data are preclinical, and the molecule is poorly water-soluble. Human exposure is indirect — via Phyllanthus extracts standardized to lignan content — and figures such as the ~0.33–3.1 mg/g extract range are analytical descriptors, not doses ^{13,15Reference 13Colombo R et al. · 2009Validated HPLC method for the standardization of Phyllanthus niruri (herb and commercial extracts) using corilagin as a phytochemical markerView study →Reference 15Murugaiyah V · 2007Analysis of lignans from Phyllanthus niruri in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic studyView study →}. Nothing here is a personal recommendation.

References

1. Krithika R, et al. (2015). Mechanism of protective effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and experimental liver fibrosis in mice. Toxicology Mechanisms and Methods. https://pubmed.ncbi.nlm.nih.gov/26337812/
2. Krithika R, et al. (2016). Phyllanthin inhibits CCl₄-mediated oxidative stress and hepatic fibrosis by down-regulating TNF-α/NF-κB and the pro-fibrotic factor TGF-β1. Toxicology and Industrial Health. https://pubmed.ncbi.nlm.nih.gov/24817434/
3. Harikrishnan H, et al. (2018). Phyllanthin from Phyllanthus amarus inhibits LPS-induced proinflammatory responses in U937 macrophages via downregulation of NF-κB/MAPK/PI3K-Akt signaling pathways. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/30238535/
4. Harikrishnan H, et al. (2018). Anti-inflammatory effects of Phyllanthus amarus through inhibition of NF-κB, MAPK and PI3K-Akt signaling pathways in LPS-induced human macrophages. BMC Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/30045725/
5. Wu W, et al. (2019). Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma. Immunopharmacology and Immunotoxicology. https://pubmed.ncbi.nlm.nih.gov/30541359/
6. Sukhaphirom N, et al. (2013). Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cells. The Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/23278697/
7. Dunkoksung W, et al. (2019). Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrier. The Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/30251430/
8. Leite DF, et al. (2006). The cytotoxic effect and the multidrug resistance reversing action of lignans from Phyllanthus amarus. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/17054045/
9. Abdel-Sattar OE, et al. (2023). Hypophyllanthin and phyllanthin from Phyllanthus niruri synergize doxorubicin anticancer properties against resistant breast cancer cells. ACS Omega. https://pubmed.ncbi.nlm.nih.gov/37576627/
10. Braga Ribeiro AM, et al. (2019). Antimicrobial activity of Phyllanthus amarus and inhibition of the NorA efflux pump of Staphylococcus aureus by phyllanthin. Microbial Pathogenesis. https://pubmed.ncbi.nlm.nih.gov/30876871/
11. Conrado GG, et al. (2020). Prospecting and identifying Phyllanthus amarus lignans with antileishmanial and antitrypanosomal activity. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/32512613/
12. Al Zarzour RH, et al. (2017). Phyllanthus niruri standardized extract alleviates the progression of non-alcoholic fatty liver disease and decreases atherosclerotic risk in Sprague-Dawley rats. Nutrients. https://pubmed.ncbi.nlm.nih.gov/28718838/
13. Colombo R, et al. (2009). Validated HPLC method for the standardization of Phyllanthus niruri (herb and commercial extracts) using corilagin as a phytochemical marker. Biomedical Chromatography. https://pubmed.ncbi.nlm.nih.gov/19277954/
14. Murugaiyah V, Chan KL (2009). Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/19397979/
15. Murugaiyah V, Chan KL (2007). Analysis of lignans from Phyllanthus niruri in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic study. Journal of Chromatography B. https://pubmed.ncbi.nlm.nih.gov/17261384/
16. Srirama R, et al. (2012). Hepatoprotective activity of Indian Phyllanthus. Pharmaceutical Biology. https://pubmed.ncbi.nlm.nih.gov/22480277/
17. Duc Hanh N, et al. (2015). Development of phyllanthin-loaded self-microemulsifying drug delivery system for oral bioavailability enhancement. Drug Development and Industrial Pharmacy. https://pubmed.ncbi.nlm.nih.gov/24237327/
18. Row LR, Srinivasulu C, Smith M (1966). Crystalline constituents of euphorbiaceae—V: New lignans from Phyllanthus niruri Linn — the constitution of phyllanthin. Tetrahedron. https://doi.org/10.1016/S0040-4020%2801%2999083-0

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