Compound Monograph
Hypophyllanthin
Hypophyllanthin is a lipophilic lignan that, with phyllanthin, standardizes Phyllanthus niruri/amarus (chanca piedra). Preclinical only — an anti-inflammatory (NF-κB/MAPK/PI3K-Akt) and a distinctive in-vitro P-glycoprotein inhibitor / permeation enhancer — with no human isolate trials and poor aqueous solubility.
Sources · 2
Where Does It Come From?
Hypophyllanthin is a naturally occurring lignan, found in Chanca Piedra and 1 other source. It is well tolerated orally (low toxicity).
Concentration
Content by Source
Concentrations not reported. No percent-dry-weight or mg/g figures have been published for this compound in its source plants.
Hypophyllanthin at a Glance
Hypophyllanthin is a lipophilic lignan that, together with phyllanthin, is used to standardise Phyllanthus niruri — chanca piedra.
Its preclinical work covers anti-inflammatory signalling through NF-kB, MAPK and PI3K-Akt, plus a distinctive in-vitro P-glycoprotein inhibition — a drug-transporter effect that is theoretically relevant to interactions, since blocking P-gp raises absorption of drugs that rely on it for efflux.
What It's Used For
Hypophyllanthin is a lipophilic lignan that, with phyllanthin, serves as the species/standardization marker of chanca piedra (Phyllanthus niruri/amarus). Two framing points. First, it partitions into alcohol, so it is enriched in tinctures/standardized extracts and scarce in aqueous tea — a preparation-discipline detail. Second, Phyllanthus’s hepatoprotective/kidney-stone reputation is the whole extract (and the phyllanthin marker), not isolated hypophyllanthin. Its own literature is preclinical and thin, with two genuine isolate signals: an anti-inflammatory action and — more distinctively — in-vitro P-glycoprotein inhibition, making it a candidate permeation enhancer and a drug-interaction concern.
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, so scores stay low by design.
Hypophyllanthin (with niranthin) downregulated NF-κB, the MAPKs (ERK/JNK/p38) and PI3K-Akt in LPS-stimulated macrophages 3Reference 3Anti-inflammatory effects of hypophyllanthin and niranthin through downregulation of NF-κB/MAPK/PI3K-Akt signallingView study →, and the phyllanthin+hypophyllanthin pair reduced IgE/iNOS/TNF-α and raised Nrf2 in ovalbumin-induced asthma 4Reference 4Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorate the immune-inflammatory response in ovalbumin-induced asthmaView study →, consolidated in a 2022 review 1Reference 1ReviewPharmacological activities and mechanisms of action of hypophyllanthin: a reviewView study →.
Gap: each study pairs it with a second lignan or uses different models, with no single target replicated for hypophyllanthin alone and only downstream readouts 3,
The distinctive detail: phyllanthin and hypophyllanthin inhibited P-glycoprotein efflux (but not MRP2) in Caco-2 cells 2Reference 2Phyllanthin and hypophyllanthin inhibit the function of P-gp but not MRP2 in Caco-2 cellsView study →, and consistent with this, the pair sensitized doxorubicin-resistant breast-cancer cells 5Reference 5Hypophyllanthin and phyllanthin from Phyllanthus niruri synergise doxorubicin’s anticancer properties against resistant breast-cancer cellsView study → — making hypophyllanthin a candidate absorption/permeation enhancer and a drug-interaction concern 7Reference 7Implication of formulation strategies on the bioavailability of selected plant-derived hepatoprotectantsView study →.
Gap: in-vitro only, with no in-vivo interaction or human pharmacokinetic confirmation 2,
Liver protection is the traditional Phyllanthus indication, but the evidence is for the whole extract/genus (and, as a marker, phyllanthin), including NAFLD 9Reference 9Phyllanthus niruri standardised extract alleviates the progression of non-alcoholic fatty liver diseaseView study → and broader hepatoprotection 10Reference 10Hepatoprotective activity of Indian PhyllanthusView study →.
Gap: there is no isolated-hypophyllanthin hepatoprotection study — it rides on marker/extract co-attribution 9,
Hypophyllanthin is a weak xanthine-oxidase inhibitor and a uricosuric lignan 6Reference 6Mechanisms of the antihyperuricemic effect of Phyllanthus niruri and its lignan constituentsView study →.
Gap: a weak effect resting on a single mechanistic paper for the isolate 6Reference 6Mechanisms of the antihyperuricemic effect of Phyllanthus niruri and its lignan constituentsView study →.
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| NF-κB / MAPK (ERK, JNK, p38) / PI3K-Akt | downregulated → ↓ iNOS, COX-2, cytokines | anti-inflammatory |
| Nrf2 ↑; IgE, iNOS, TNF-α ↓ | immune-inflammatory modulation | anti-allergic / asthma |
| P-glycoprotein (ABCB1) efflux | inhibited (MRP2 unaffected) → ↑ intracellular substrate | bioavailability / permeationMDR reversal |
| Xanthine oxidase | weak inhibition; uricosuric | antihyperuricemic |
Pharmacokinetics
Hypophyllanthin is a lipophilic aryltetralin-type lignan with poor aqueous solubility and low oral bioavailability — it partitions into alcohol, so it is enriched in tinctures/standardized extracts and scarce in aqueous tea. Formulation strategies to raise solubility/absorption have been reviewed for this hepatoprotectant class 7Reference 7Implication of formulation strategies on the bioavailability of selected plant-derived hepatoprotectantsView study →, and a validated LC-MS/MS method quantifies it (with co-lignans) in rat plasma 8Reference 8AnimalHPLC-MS/MS method for the determination of four lignans from Phyllanthus urinaria in rat plasmaView study →. As a P-gp inhibitor 2Reference 2Phyllanthin and hypophyllanthin inhibit the function of P-gp but not MRP2 in Caco-2 cellsView study →, hypophyllanthin may increase absorption of itself and of co-administered P-gp substrates — a two-way drug-interaction signal, in-vitro only — and there is no human pharmacokinetic data.
Clinical trials
There are no trials of isolated hypophyllanthin. Human Phyllanthus trials (kidney stones; chronic hepatitis B) use the whole extract, where hypophyllanthin serves only as a standardization/identity marker, not as the studied agent.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| —(none, isolate) | — | — | Thin(mostly paired with a co-lignan) |
Last checked: July 2026.
Toxicity & Safety
There is no toxicity signal for hypophyllanthin, but that reflects how little has been looked at rather than demonstrated safety — and its one mechanistic flag is a theoretical drug interaction.
- Avoid in pregnancy and lactation. No data on the isolate.
- Theoretical P-glycoprotein interaction. In-vitro P-gp inhibition could raise absorption of narrow-therapeutic-index substrates; not clinically documented.
- Sparse dedicated data. No isolate toxicity signal has been identified, but little has been studied.
Full Safety & Interactions Detail
Hypophyllanthin has a low-concern profile with no isolate toxicity signal identified, so the low flag reflects sparse dedicated data rather than demonstrated safety. A drug-interaction caution is warranted on mechanistic grounds — its in-vitro P-glycoprotein inhibition 2Reference 2Phyllanthin and hypophyllanthin inhibit the function of P-gp but not MRP2 in Caco-2 cellsView study → could raise the absorption of narrow-therapeutic-index P-gp substrates — but this is in-vitro/theoretical, not clinically documented.
Dosage
There is no human dose established — hypophyllanthin is a marker/standardization constituent, not a standalone supplement, and all data are preclinical, so nothing here is a recommendation.
References
- Wan Saidin WA, et al. (2022). Pharmacological activities and mechanisms of action of hypophyllanthin: a review. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/36699081/
- Sukhaphirom N, et al. (2013). Phyllanthin and hypophyllanthin inhibit the function of P-gp but not MRP2 in Caco-2 cells. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/23278697/
- Harikrishnan H, et al. (2018). Anti-inflammatory effects of hypophyllanthin and niranthin through downregulation of NF-κB/MAPK/PI3K-Akt signalling. Inflammation. https://pubmed.ncbi.nlm.nih.gov/29427163/
- Wu W, et al. (2019). Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorate the immune-inflammatory response in ovalbumin-induced asthma. Immunopharmacology and Immunotoxicology. https://pubmed.ncbi.nlm.nih.gov/30541359/
- Abdel-Sattar OE, et al. (2023). Hypophyllanthin and phyllanthin from Phyllanthus niruri synergise doxorubicin’s anticancer properties against resistant breast-cancer cells. ACS Omega. https://pubmed.ncbi.nlm.nih.gov/37576627/
- Murugaiyah V, Chan KL (2009). Mechanisms of the antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/19397979/
- Dash RP, et al. (2017). Implication of formulation strategies on the bioavailability of selected plant-derived hepatoprotectants. Critical Reviews in Therapeutic Drug Carrier Systems. https://pubmed.ncbi.nlm.nih.gov/29256835/
- Fan H, et al. (2015). HPLC-MS/MS method for the determination of four lignans from Phyllanthus urinaria in rat plasma. Bioanalysis. https://pubmed.ncbi.nlm.nih.gov/25871587/
- Al Zarzour RH, et al. (2017). Phyllanthus niruri standardised extract alleviates the progression of non-alcoholic fatty liver disease. Nutrients. https://pubmed.ncbi.nlm.nih.gov/28718838/
- Srirama R, et al. (2012). Hepatoprotective activity of Indian Phyllanthus. Pharmaceutical Biology. https://pubmed.ncbi.nlm.nih.gov/22480277/
