Tie Shu Ye

Star

Cycas revoluta Thunb.

Not yet clinically reviewed

Pinyin: Tie Shu Ye
Fruticose Dracaena Leaf

Traditionally used for

  • Cough & breathing
  • Digestion
  • Menstrual & women's health
  • Skin

Cautions & contraindications

  • Pregnancy
  • Liver conditions
  • Toxic — professional use only
Limited evidence · 2 studies

☯ TCM Properties

Category: regulating blood
Temperature: cool
Taste: sweet, bland
Meridians: liver, stomach
Functions:

Clears Heat, stops bleeding and dissipates Blood Stasis

Traditional Chinese Uses

Tie Shu Ye (Folium Cycadis) is the leaf of Cycas revoluta, the sago cycad or 'iron tree', a sweet-bland, cool blood-regulating substance. It clears Heat, stops bleeding, and dissipates Blood stasis to relieve pain. In folk use the leaves are decocted for coughing or vomiting of blood, blood in the stool, painful menstruation and stasis-type abdominal pain, and are applied to swellings and sores; the related seeds and flowers have their own hemostatic and channel-unblocking uses.

Caution is essential: cycads contain cycasin, a glucoside converted by gut bacteria into a carcinogenic, neurotoxic, and hepatotoxic metabolite (methylazoxymethanol). All parts are toxic, seeds most of all. Internal use should be limited, properly processed, and avoided in pregnancy; this material is best regarded as toxic and used with great care.

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Botanical Description

Cycas revoluta, the sago cycad or 'king sago palm', is not a true palm but a gymnosperm of the ancient Cycadaceae, native to southern Japan (notably Kyushu and the Ryukyus) and southeastern China and widely cultivated as an ornamental. It grows extremely slowly to 2–3 m, forming a stout, columnar, persistent-leaf-base-clothed trunk crowned by a symmetrical rosette of stiff, dark green, pinnate fronds 60–150 cm long. The narrow, leathery pinnae are sharply pointed, with strongly revolute margins — the source of the specific epithet. The species is dioecious: male cones are large, narrow, yellow, and pollen-bearing; female plants produce a low, rounded dome of woolly megasporophylls bearing bright orange seeds. The medicinal organ is the dried leaf (pinna), cut from mature fronds. All parts contain the toxins cycasin, methylazoxymethanol, and BMAA.

Active Constituents

Cycasin (methylazoxymethanol beta-D-glucoside)

Azoxyglycoside

Concentration: highest in the seed, where cycad seeds have been reported at up to about 4% w/w; leaf content is far lower and variable, and azoxyglycosides were undetectable in mature leaves of some Cycas species analysed by HPLC. No reliable published figure exists for the cycasin content of commercial Tie Shu Ye.

This is the toxicologically decisive constituent of the drug. Cycasin is itself inert; it is hydrolysed by beta-glucosidase, either from the damaged plant or from gut microbiota, to methylazoxymethanol. What is established specifically for C. revoluta is that the species contains cycasin and that all parts of the plant, leaves included, are regarded as toxic. What is not established for C. revoluta is a quantitative leaf figure, and practitioners should not assume a leaf preparation is cycasin-free.

Methylazoxymethanol (MAM)

Azoxy aglycone (alkylating agent)

The active aglycone. MAM decomposes spontaneously to methyldiazonium ions and carbon-centred radicals that methylate DNA at the O6, N7 and C8 positions of guanine. These lesions underlie the hepatotoxic, carcinogenic, mutagenic and teratogenic properties of cycasin. Old-world monkeys given cycasin or MAM acetate over years developed hepatocellular carcinoma and, in nearly every treated animal, toxic hepatitis or cirrhosis. This is genus-wide cycad chemistry demonstrated with the isolated compound, not an experiment on C. revoluta leaf.

beta-N-Methylamino-L-alanine (BMAA)

Non-protein amino acid (neurotoxic)

Concentration: reported in Cycas revoluta seed at low microgram-per-gram levels; genus-wide leaf figures vary by orders of magnitude between laboratories and analytical methods

BMAA is produced by cyanobacteria symbiotic in cycad coralloid roots and is found through the genus. It is the compound at the centre of the contested cycad hypothesis for the Western Pacific ALS-parkinsonism-dementia complex. Its presence in Cycas revoluta is documented; its causal role in human neurodegenerative disease is not established, and the quantitative literature is unreliable enough that no dose statement can honestly be made.

Amentoflavone

Biflavonoid

Amentoflavone and related biflavonoids are the characteristic non-toxic chemistry of cycad leaves and are the constituents to which the reported antioxidant and antimicrobial activity of leaf extracts is usually attributed. Note that amentoflavone is a known inhibitor of several CYP isoforms in vitro, which is a more plausible route to a pharmacokinetic interaction than the azoxyglycosides.

2,3-Dihydroamentoflavone

Biflavonoid

Reported from C. revoluta leaf and female cone extracts; a methylated derivative, 2,3-dihydro-4'-O-methylamentoflavone, was isolated from chloroform extracts of leaves and cones during antimicrobial screening.

Hinokiflavone

Biflavonoid

Another leaf biflavonoid of C. revoluta. The 2026 review of the species cautions that the reproducibility and authenticity of several reported leaf constituents remain uncertain because analytical verification has been inconsistent across studies.

Naringenin

Flavanone

Reported from methylene chloride extracts of the leaf alongside amentoflavone. As with the other flavonoids of this drug, the reports are isolation studies rather than validated quantitative assays.

⚠ Drug Interactions

Hepatotoxic drugs (e.g. paracetamol/acetaminophen, methotrexate, isoniazid)

Major Evidence: Probable

Cycasin is metabolised to methylazoxymethanol, an established hepatotoxin. In old-world monkeys given cycasin or MAM acetate for an average of 57 months, all but one animal developed hepatic lesions including toxic hepatitis and cirrhosis, and hepatocellular carcinoma occurred (Sieber 1980). Cycad poisoning in animals is dominated by acute hepatic failure and carries a case fatality around 30% in dogs. The species-specific gap is that these data come from cycasin and from cycad seed, not from measured doses of C. revoluta leaf, but the leaf is not established to be free of the toxin.

Clinical note: Do not combine with drugs that carry a hepatotoxicity signal, and do not use this herb at all in anyone with existing liver disease, alcohol use disorder, or on long-term paracetamol. Check liver enzymes if it has been used.

Alkylating cytotoxic chemotherapy and prior radiotherapy

Major Evidence: Probable

Methylazoxymethanol is a direct-acting DNA methylating agent producing O6- and N7-methylguanine adducts, the same lesion class produced by nitrosourea and other methylating cytotoxics, and cycasin is a proven animal carcinogen including in primates. Adding an unmeasured dose of a genotoxin to a regimen whose toxicity is itself genotoxic has no defensible risk-benefit case.

Clinical note: Contraindicated in patients receiving or recovering from cytotoxic chemotherapy or radiotherapy, and in anyone with a personal history of hepatic or colorectal malignancy.

Cordyline fruticosa leaf (Zhu Jiao, sold as red-leaved Tie Shu) as a substituted drug

Moderate Evidence: Probable

The Chinese name Tie Shu (iron tree) is applied both to Cycas revoluta and to Cordyline fruticosa, which carries the vernacular names hong ye tie shu and tie shu; Cycas siamensis is also traded under the name in parts of the south. Cordyline leaf has none of the azoxyglycoside chemistry of a cycad. A prescription written for Tie Shu Ye can therefore be filled with either a genotoxic cycad leaf or an unrelated monocot leaf, and the substitution runs in the dangerous direction as well as the harmless one.

Clinical note: Order and verify by binomial. Cycad leaf is a stiff pinnate frond with revolute leaflet margins; Cordyline leaf is a simple broad, often red-purple, strap. Do not accept material identified only by the Chinese name.

Broad-spectrum oral antibiotics

Theoretical Evidence: Theoretical

Oral cycasin requires beta-glucosidase from intestinal microflora to release methylazoxymethanol; this microbial step is why the route of administration changes cycasin's toxicity so markedly in animal work. Suppressing or altering the gut flora would be expected to change how much aglycone is released, though no study has measured this in a person taking a cycad preparation. The practical point is that the toxicity of this drug is not a fixed quantity but depends on gut metabolism.

Clinical note: Do not treat this as a reason to consider the herb safer on antibiotics. It is a reason to regard the dose-toxicity relationship of any cycad preparation as unpredictable between individuals.

Evidence Tier

Limited evidence · 2 studies

Recorded 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

0

Randomized controlled trial

0

Other clinical trial

0

Observational / case report

1

0 verified · 1 unverified

Show the study

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

Cycas revoluta (sago cycad) exposures reported to Texas poison centers

Forrester MB, Layton GM, Varney SM (2020) The American Journal of Emergency Medicine cohort

192 C. revoluta exposures reported to Texas poison centres over 2000-2018. Ingestion accounted for 55.7% and dermal contact for 34.4%; 92.2% were unintentional and 94.8% occurred at home. The commonest reported effects were dermal (23.4%, mostly puncture wounds and irritation from the stiff leaflets) followed by gastrointestinal (13.0%, chiefly vomiting and nausea), and 78.6% of cases were managed on site. This is the largest human exposure series specific to C. revoluta. It describes mostly small accidental exposures in an ornamental-plant setting, so it should not be read as evidence that repeated therapeutic dosing is safe.

Carcinogenicity and hepatotoxicity of cycasin and its aglycone methylazoxymethanol acetate in nonhuman primates.

Sieber SM, Correa P, Dalgard DW, McIntire KR, Adamson RH (1980) Journal of the National Cancer Institute animal

Rhesus, cynomolgus and African green monkeys received cycasin (50-75 mg/kg) or methylazoxymethanol acetate (1.5-3.0 mg/kg) orally five days a week, or MAM acetate by weekly intraperitoneal injection, for up to 11 years. One orally dosed monkey developed well-differentiated hepatocellular carcinoma and a second developed hepatocellular carcinoma, intrahepatic bile-duct adenocarcinoma, renal carcinoma and adenomas, and adenomatous colonic polyps. All but one of the orally dosed monkeys had hepatic lesions such as toxic hepatitis and cirrhosis. Six of ten monkeys given MAM acetate intraperitoneally developed tumours. This is the primate evidence that cycasin is a hepatotoxin and carcinogen; it used the isolated compound, not Cycas revoluta leaf.

Historical Texts

Ben Cao Gang Mu Shi Yi

Qing dynasty
Zhao Xuemin gives the first materia medica record of this leaf, under the name Feng Wei Jiao Ye, listing Tie Shu among its synonyms and stating that it calms the liver and treats all liver-qi pain. The drug is a late folk addition to the materia medica, not a classical one.

Lu Chuan Ben Cao

Modern (20th century)
A Guangxi local materia medica recording the leaf as anti-inflammatory and haemostatic, for cough with copious phlegm, dysentery, knife wounds and traumatic injury. This is the source closest to the blood-cooling and haemostatic functions recorded for this record.

Fujian Min Jian Cao Yao

Modern (20th century)
Records the leaf as invigorating blood and moving stasis, dispelling wind and resolving toxin. Together with the Zhejiang folk-herb literature it is the basis for the modern folk use; none of these sources reports the plant's cycasin content or its toxicity.

References

  1. Du Q, Xing N, Guo S, Li R, Meng X, Wang S. Cycads: A comprehensive review of its botany, traditional uses, phytochemistry, pharmacology and toxicology . Phytochemistry (2024) [DOI]
  2. Abdul Jaleel K, Prakash PS, Nakshathra KV, Devika V. Ethnobotany, Phytochemistry, Pharmacology, and Toxicology of Cycas revoluta Thunb.: An Updated Review . Sciences of Phytochemistry (2026) [DOI]
  3. Spencer PS, Palmer VS, Kisby GE. Western Pacific ALS-PDC: Evidence implicating cycad genotoxins . Journal of the Neurological Sciences (2020) [DOI]
  4. Kokubo Y, Morimoto S, Yoshida M. Questioning the cycad theory of Kii ALS–PDC causation . Nature Reviews Neurology (2024) [DOI]
  5. Chernoff N, Hill DJ, Diggs DL, Faison BD, Francis BM, Lang JR, Larue MM, Le T-T. A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans . Journal of Toxicology and Environmental Health, Part B (2017) [DOI]
  6. Kisby GE, Ellison M, Spencer PS. Content of the neurotoxins cycasin (methylazoxymethanol β‐D‐glucoside) and BNLAA (β‐ N ‐methylamino‐L‐alanine) in cycad flour prepared by Guam Chamorros . Neurology (1992) [DOI]
  7. Charlton TS, Marini AM, Markey SP, Norstog K, Duncan MW. Quantification of the neurotoxin 2-amino-3-(methylamino)-propanoic acid (BMAA) in cycadales . Phytochemistry (1992) [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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