Zhen Zhu Cao
StarPhyllanthus urinaria L.
Traditionally used for
- Eye health
- Teeth & mouth
- Cough & breathing
- Bowel health
- Urinary & fluids
- Skin
- Liver & jaundice
☯ TCM Properties
Calms the Liver, clears Heat, promotes diuresis and removes toxicity
Traditional Chinese Uses
Zhen Zhu Cao ("pearl grass," also called Ye Xia Zhu) is the whole herb of Phyllanthus urinaria, used to clear Heat, calm the Liver, resolve toxicity, and promote urination. Sweet and bitter with a cool nature, it enters the Liver and Lung channels. Its best-known application is for Liver damp-heat: it is a common folk treatment for jaundice and infectious hepatitis, and for red, swollen, painful eyes ("Liver fire rising"). Its heat-clearing and detoxifying actions address summer-heat dysentery, enteritis with diarrhea, and sores or mouth ulcers.
Through promoting urination it drains damp-heat downward, treating painful urinary dysfunction and edema, and it is also used in southern China for childhood malnutrition (gan) with accumulation. It is typically decocted or the fresh plant is pounded for topical use on sores.
Western Herbalism Properties
Relationships
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Botanical Description
Zhen Zhu Cao (珍珠草), or pearl-grass, is Phyllanthus urinaria L., a small annual herb in the Phyllanthaceae (formerly Euphorbiaceae) widespread across tropical and subtropical Asia. The plant grows 10–60 cm tall with slender, often reddish, ribbed stems bearing two ranks of small oblong leaflets that close at night, giving a fern-like appearance. Tiny apetalous unisexual flowers and minute warty capsular fruits sit beneath the leaf axils in two neat rows along the underside of the branchlets, resembling rows of pearls. The whole plant is collected in summer and autumn, washed, and dried for medicinal use; it is widely employed in southern China and across Southeast Asia for liver and urinary conditions.
Active Constituents
Corilagin
Ellagitannin (hydrolysable tannin)Concentration: one of the three most abundant compounds of the herb; an Indonesian sample of P. urinaria assayed at 379.23 micrograms/mL of extract, the highest of the Phyllanthus samples compared, and preparative isolation has given yields around 25 mg/g
The best-characterised single constituent of this species and the one most consistently credited with its hepatoprotective and anti-inflammatory action. It strongly inhibits reactive oxygen species production by stimulated human neutrophils, more so than aspirin in the same assay. Corilagin content is markedly higher in P. urinaria than in the related P. amarus, which is one of the chemical grounds for keeping the two species apart.
Geraniin
DehydroellagitanninConcentration: one of the three most prevalent compounds of the herb
The most potent anti-inflammatory constituent identified in direct comparison, inhibiting chemotaxis of human neutrophils and monocytes with IC50 values of 1.09 and 1.69 micromolar, lower than ibuprofen tested alongside it. Geraniin is labile and hydrolyses to corilagin and further to gallic and ellagic acid, so assayed geraniin falls with heat, decoction and storage.
Gallic acid
Phenolic acidConcentration: the third of the three most prevalent compounds; reported at 354 +/- 27 mg/g in a methanol extract (an extract figure, not a content of the crude herb)
The terminal hydrolysis product of the herb's gallotannins and ellagitannins, so its measured amount rises with extraction severity rather than reflecting a fixed content of the raw plant. It contributes to the antioxidant capacity of the drug and is used as an assay handle for total phenolics.
Ellagic acid
Polyphenol (dilactone of hexahydroxydiphenic acid)Concentration: reported at about 10.2 mg/g by mechanochemically assisted extraction
Generated from the herb's ellagitannins during processing and decoction as well as being present as such. It is one of the routine marker constituents used to standardise Phyllanthus material.
Phyllanthin
Aryl-naphthalene lignanConcentration: present, but substantially lower in P. urinaria than in P. amarus, in which it reached 103.50 micrograms/mL of extract in the same comparison
The best-known Phyllanthus lignan and the one most often used as the marker for standardised extracts, although it is in truth more characteristic of P. amarus and P. niruri than of P. urinaria. At 50 micrograms/mL it was the strongest inhibitor of neutrophil and monocyte phagocytosis of the compounds compared, reducing engulfment to 14.2% and 27.1% respectively, which is an immunosuppressive rather than a merely anti-inflammatory action.
Hypophyllanthin
Aryl-naphthalene lignanThe usual companion lignan of phyllanthin. It matters clinically because, in Phyllanthus amarus, phyllanthin and hypophyllanthin are mechanism-based inhibitors of CYP3A4, which is the source of the herb-drug interaction concern attached to this genus.
Niranthin and phyltetralin
Aryl-naphthalene lignansFurther members of the lignan series catalogued from this species, twenty-two lignans in total in the standing review of its phytochemistry. They are studied mainly for antiviral and antitumour activity and have no established clinical role on their own.
Rutin, quercetin and kaempferol
Flavonol and flavonol glycosidesThe flavonoid fraction of the herb, twelve compounds in the standing review. They contribute to the antioxidant profile but are not the constituents that distinguish this species from its congeners.
Brevifolin carboxylic acid
Phenolic acid (ellagitannin degradation product)One of the twenty-one phenolics catalogued from the herb and a recognised chromatographic marker for Phyllanthus material. It arises from breakdown of the ellagitannin fraction.
⚠ Drug Interactions
Phyllanthus amarus and Phyllanthus niruri (traded and studied interchangeably with this species)
This is the central identity problem of the drug. The two Cochrane reviews of Phyllanthus in chronic hepatitis B pooled trials of the genus rather than of one species, and the great majority of the antiviral and pharmacokinetic literature was done on P. amarus or P. niruri. Direct chemical comparison shows the species are not equivalent: P. urinaria carried the highest corilagin and P. amarus the highest phyllanthin and ellagic acid of the samples compared, and geographical origin shifted the figures further. Because activity in this genus tracks these very compounds, a claim carried over from P. amarus to P. urinaria is not supported.
Clinical note: Require the binomial on any Phyllanthus material, and do not cite P. amarus or P. niruri trials as evidence for this drug. Where a standardised extract is used, ask which species it was standardised from and against which marker.
CYP3A4 substrates (e.g. midazolam, ciclosporin, tacrolimus, statins, many antivirals)
The evidence here belongs to a different species and is offered as a caution, not a finding. In human liver microsomes, ethanolic and aqueous extracts of Phyllanthus amarus inhibited CYP1A2, CYP2D6, CYP2E1 and CYP3A4 dose-dependently, and its lignans phyllanthin and hypophyllanthin were mechanism-based CYP3A4 inhibitors with KI values of 1.75 +/- 1.20 and 2.24 +/- 1.84 micromolar. Mechanism-based inhibition is not readily reversed on stopping the herb. P. urinaria contains the same two lignans but at lower levels than P. amarus, so the same inhibition is plausible and untested rather than demonstrated.
Clinical note: Relevant chiefly for transplant patients on ciclosporin or tacrolimus and for patients on antiretrovirals, where this genus is often taken for the liver. Check levels if the herb is started or stopped; prefer to avoid concurrent use in narrow-margin CYP3A4 substrates.
Nucleos(t)ide analogue antivirals (lamivudine, entecavir, tenofovir)
Chinese multicentre trials have added P. urinaria containing formulas to standard anti-HBV drug therapy: a 48-week randomised trial of Ruangan granules plus antiviral drugs in 240 patients with chronic hepatitis B and advanced fibrosis or cirrhosis reported improved liver histology and a lower incidence of hepatocellular carcinoma at two-year follow-up compared with antiviral drugs alone, without a signal of added adverse events. These trials tested multi-herb formulas, so the contribution of P. urinaria itself is not isolated, and no study has measured antiviral drug concentrations during co-administration.
Clinical note: Co-administration is common in Chinese hepatology practice and is not contraindicated, but it should not be presented to a patient as a reason to reduce or stop antiviral therapy. Monitor HBV DNA and liver enzymes as normal.
Insulin, sulfonylureas, metformin and other glucose-lowering drugs
Alpha-glucosidase inhibition and antidiabetic activity are reported for extracts of this species in vitro and in animals. No human pharmacodynamic study exists, and the magnitude of any clinical effect is unknown, so the concern is additive rather than demonstrated.
Clinical note: No action needed for most patients. Advise glucose self-monitoring if the herb is added at high dose to insulin or a sulfonylurea.
Immunosuppressants and immune-stimulating therapy
In isolated human neutrophils and monocytes, phyllanthin at 50 micrograms/mL suppressed phagocytic engulfment to 14.2% and 27.1% of control, and geraniin and corilagin strongly inhibited reactive oxygen species production. These are ex vivo cellular effects at concentrations that oral dosing may not reach, but they indicate the herb's anti-inflammatory action includes genuine suppression of innate immune effector function rather than only antioxidant scavenging.
Clinical note: Consider before prolonged high-dose use in patients who are already immunosuppressed or neutropenic. Not a reason to avoid ordinary short-course use.
Evidence Tier
Strong evidence · 4 studiesRecorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.
Systematic review / meta-analysis
2
0 verified · 2 unverified
Randomized controlled trial
1
0 verified · 1 unverified
Other clinical trial
0
Observational / case report
0
In vitro / animal
1
0 verified · 1 unverified
Other / unclassified
0
Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description
Clinical Studies
Double-blinded placebo-controlled study of Phyllanthus urinaris for the treatment of chronic hepatitis B
The only placebo-controlled trial of this species as a single drug. HBeAg-positive patients with HBV DNA above 500,000 copies/mL and raised ALT were randomised to Phyllanthus urinaria 1, 2 or 3 g three times daily or placebo for six months, with HBV DNA reduction as the primary endpoint and HBeAg seroconversion and ALT normalisation as secondary endpoints. The trial was small, with groups of twelve and only six placebo patients, and it did not demonstrate a significant reduction in HBV DNA against placebo at any dose. It is the key negative result behind the standing conclusion that clinical evidence for this herb in hepatitis B is limited. Note the species name is misspelled as urinaris in the published title.
Phyllanthus species for chronic hepatitis B virus infection
Cochrane review of Phyllanthus preparations versus placebo or no intervention in chronic hepatitis B. It found the included trials small and at high risk of bias, and did not establish a reliable benefit. Crucially for this monograph, the review pools the genus rather than one species, so its conclusions do not attach specifically to Phyllanthus urinaria.
Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection
Companion Cochrane review comparing Phyllanthus preparations with antiviral drugs, based on five randomised trials in 290 patients. Phyllanthus showed no significant effect on clearance of serum HBsAg, on serum HBV DNA or on HBeAg seroconversion when compared with antiviral drugs, and the evidence was judged of insufficient quality to support use. Again the unit of analysis is the genus, not this species.
Correlation between the major components of Phyllanthus amarus and Phyllanthus urinaria and their inhibitory effects on phagocytic activity of human neutrophils
Direct chemical and pharmacological comparison of P. amarus and P. urinaria from Malaysia and Indonesia. Malaysian P. amarus carried the most phyllanthin (103.50) and ellagic acid (601.29) while Indonesian P. urinaria carried the most corilagin (379.23), all in micrograms/mL of extract, with the authors attributing the spread to growing environment. Geraniin inhibited neutrophil and monocyte chemotaxis with IC50 values of 1.09 and 1.69 micromolar, below ibuprofen; geraniin and corilagin inhibited reactive oxygen species production more strongly than aspirin; and phyllanthin at 50 micrograms/mL was the strongest inhibitor of phagocytic engulfment. The paper is the clearest demonstration that these two species are not chemically interchangeable.
⚠ Safety & Contraindications
Contraindications
Due to its bitter and cool properties, its use should be cautious in the weak or patients with yang deficiency.
Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, pp. 153–155.
Historical Texts
Sheng Cao Yao Xing Bei Yao
Qing dynastyZhi Wu Ming Shi Tu Kao
Qing dynasty (1848)References
- Geethangili Madamanchi, Ding Shih-Torng. A Review of the Phytochemistry and Pharmacology of Phyllanthus urinaria L. . Frontiers in Pharmacology (2018) [DOI]
- Liu Linhua, Wang Bing, Ma Yibo, Sun Kunhui, Wang Ping, Li Meifang, Dong Junlin, Qin Meirong, Li Mingshun, Wei Chunshan. A review of Phyllanthus urinaria L. in the treatment of liver disease: viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma . Frontiers in Pharmacology (2024) [DOI]
- Taesotikul Theerada, Dumrongsakulchai Weeraya, Wattanachai Nitsupa, Navinpipat Vichien, Somanabandhu Aimon, Tassaneeyakul Wongwiwat, Tassaneeyakul Wichittra. Inhibitory Effects of Phyllanthus amarus and Its Major Lignans on Human Microsomal Cytochrome P450 Activities: Evidence for CYP3A4 Mechanism-Based Inhibition . Drug Metabolism and Pharmacokinetics (2011) [DOI]
This information is for educational purposes only and is not intended to replace professional medical advice. Always consult a qualified healthcare provider before using any herbal remedy, especially if you are pregnant, nursing, or taking medications.
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