Chuan Lian Zi
StarMelia toosendan Sieb. et Zucc.
Traditionally used for
- Digestion
- Pain & joints
Cautions & contraindications
- Liver conditions
- Toxic — professional use only
☯ TCM Properties
Courses the Liver and Drains Heat; Moves Qi and Alleviates Pain; Expels Parasites; Clears Damp-Heat from the Lower Burner
Traditional Chinese Uses
Chuan Lian Zi (Sichuan chinaberry fruit, toosendan fruit) is a cold, bitter herb used in Chinese medicine to move Liver Qi, relieve pain, dry Dampness, and kill intestinal parasites. It is the principal herb for Liver Qi stagnation with heat — addressing the hypochondriac pain, epigastric discomfort, and hernia pain of Liver Fire patterns. It also relieves intestinal parasite infections and associated abdominal pain. Its cold nature specifically addresses Liver Qi patterns with heat signs, distinguishing it from warming Liver-Qi herbs.
Western Herbalism Properties
Used In Formulas (2)
Relationships
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Botanical Description
Melia toosendan, the Sichuan chinaberry or Chuan Lian Zi tree, is a deciduous tree in the Meliaceae family, native to central, southern, and southwestern China. It reaches 10-20 m with a straight trunk and spreading crown; bark is gray-brown and longitudinally fissured. Leaves are large, bipinnately compound, 30-70 cm long, with numerous ovate-lanceolate, finely serrated leaflets. Fragrant pale purple to lilac flowers 1-1.5 cm across appear in axillary panicles in spring. The drupaceous fruit is globose to ovoid, 2-3 cm in diameter, ripening yellow with a leathery, glossy pericarp. All parts, especially the fruit, are notably toxic.
Active Constituents
Toosendanin
Limonoid (tetranortriterpenoid)Concentration: the Chinese Pharmacopoeia assay requires 0.060-0.20% of the dried fruit (0.040-0.20% for the stir-fried form)
Both the Pharmacopoeia quality marker and the principal toxic constituent. It carries the analgesic and anthelmintic activity for which the fruit is prescribed, and it is also the compound responsible for the drug's documented hepatotoxicity. In HepG2 cells and in zebrafish it raises reactive oxygen species, blocks autophagic flux and lysosomal function, causes unrepaired DNA damage with G1/S arrest, and sensitises hepatocytes to ferroptosis; in mice it raises serum ALT and AST and produces histological liver lesions.
Isotoosendanin
Limonoid (tetranortriterpenoid)A close structural congener of toosendanin reported from the fruit, along with its delta-5,6 isomer. Limonoids are the predominant and characteristic phytochemical class of the drug, with over 100 catalogued from the fruit.
Nimbolinin B
Limonoid (tetranortriterpenoid)One of the nimbolinin-type limonoids of the fruit, reported together with 1-deacetylnimbolinin B. Limonoids of this genus are studied mainly for insecticidal and antitumour activity.
Meliatoosenins
Limonoids (tetranortriterpenoids)A series of limonoids (meliatoosenin E, N, P, R and others) isolated specifically from Fructus Meliae Toosendan. They contribute to the chemical fingerprint that distinguishes this fruit from that of the related Melia azedarach.
Vanillic acid
Phenolic acidA minor phenolic constituent of the fruit, reported alongside syringic acid and p-hydroxybenzoic acid. It is not thought to contribute meaningfully to either the analgesic effect or the hepatotoxicity.
p-Hydroxybenzoic acid
Phenolic acidA common phenolic acid identified in the fruit; used chiefly as a chromatographic reference peak rather than as an active principle.
Rutin
Flavonol glycosideQuercetin-3-O-rutinoside, present as a minor flavonoid of the fruit. It carries the usual antioxidant activity of the class but is not a marker for this drug.
⚠ Drug Interactions
Hepatotoxic drugs (e.g. paracetamol/acetaminophen, methotrexate, isoniazid, azole antifungals)
Chuan Lian Zi is a Pharmacopoeia-graded toxic herb and its hepatotoxicity is well documented rather than theoretical. Toosendanin injures hepatocytes by at least four converging mechanisms shown in vitro and in vivo: inhibition of the STAT3/CTSC axis with consequent blockade of autophagy and lysosomal function; TFEB-mediated lysosomal dysfunction; irreparable DNA damage with cell-cycle arrest; and ALOX5-driven lipid peroxidation that sensitises cells to ferroptosis. In mice, toosendanin raises serum ALT and AST and produces liver lesions, and Stat3-knockout mice suffer worse injury. Any co-administered drug that loads the same hepatocellular and lipid-peroxidation pathways can be expected to add to that injury.
Clinical note: Do not combine with other hepatotoxic drugs. Do not prescribe in existing liver disease, alcohol-related liver injury or hepatitis B/C. Keep to Pharmacopoeia dose and short courses, and obtain baseline and follow-up liver function tests if the course exceeds a few weeks or if the patient takes any drug with a hepatic warning. Stop immediately on nausea, right-upper-quadrant pain, dark urine or jaundice.
Alcohol
Toosendanin hepatotoxicity is driven by reactive oxygen species, mitochondrial damage and lipid peroxidation. Chronic ethanol exposure depletes glutathione and induces the same oxidative injury pathways, so the two insults plausibly compound. This is a mechanistic extrapolation - no controlled human co-exposure study exists.
Clinical note: Advise abstinence for the duration of treatment, and avoid the herb entirely in patients with a heavy drinking history.
Fructus Foeniculi (Xiao Hui Xiang, fennel fruit) - herb-herb pairing
The classical Chuan Lian Zi / Xiao Hui Xiang pair has a measured pharmacokinetic basis. In rats, co-administration of fennel significantly reduced the Cmax, AUC(0-t), AUC(0-inf) and mean residence time of toosendanin and increased its apparent volume of distribution, that is, it lowered absorption and bioavailability and accelerated elimination of the toxic constituent; hepatotoxicity was correspondingly reduced. In the opposite direction, Chuan Lian Zi increased the Cmax, AUC and half-life of trans-anethole from fennel and lowered its clearance.
Clinical note: This supports the traditional practice of never using Chuan Lian Zi as a single herb. The corollary is also worth stating: a patient taking the herb alone, or in a formula stripped of the fennel pairing, is exposed to higher toosendanin levels than the classical prescription intends.
Neuromuscular blocking agents (e.g. vecuronium, rocuronium)
Toosendanin is characterised in the experimental pharmacology literature as a presynaptic blocker of neuromuscular transmission - the property behind its investigation as an anti-botulism agent. Whether oral doses of the crude fruit reach concentrations relevant to neuromuscular junction function in humans has not been studied, and no clinical case of potentiated blockade has been reported. The concern is mechanistic only.
Clinical note: Include the herb when taking a pre-anaesthetic medication history and stop it, as with other herbs, in the week before elective surgery.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 5–10 g | — | — | — | ChP 2025.. Corrected from a generic 3-9g decoction filler value generated from tcm_category. |
| topical | Appropriate amount | — | — | — | ChP 2025. 外用适量，研末调涂。 |
Dui Yao — Herb Pairs
The classical two-herb combinations this herb appears in, each with an action neither herb has alone.
Together they spread constrained Liver qi, drain Liver heat and move blood, giving a strong analgesic effect for pain from qi stagnation transforming into heat.
Hypochondriac, epigastric, hernial and menstrual pain from Liver qi stagnation with heat. Chuan Lian Zi is mildly toxic.
Core pair of a classical formula — Jin Ling Zi San, Tai Ping Sheng Hui Fang (recorded in Xiu Zhen Fang)
Evidence Tier
Moderate evidence · 5 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
0
Randomized controlled trial
0
Other clinical trial
0
Observational / case report
0
In vitro / animal
5
2 verified · 3 unverified
Show 5 studies
- Toosendanin induces hepatotoxicity by restraining autophagy and lysosomal function through inhibiting STAT3/CTSC axis
- Toosendanin-induced liver damage through irreparable DNA damage and autophagy flow blockade
- Toosendanin Induces Hepatotoxicity by Facilitating ALOX5-Mediated Lipid Peroxidation and Sensitizing Cells to Ferroptosis
- Toosendanin Induces Hepatocyte Damage by Inhibiting Autophagic Flux via TFEB-Mediated Lysosomal Dysfunction
- Determination of toosendanin and trans‐anethole in Fructus Meliae Toosendan and Fructus Foeniculi by HPLC–MS/MS and GC–MS/MS in rat plasma and their potential herb–herb interactions
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
Toosendanin induces hepatotoxicity by restraining autophagy and lysosomal function through inhibiting STAT3/CTSC axis
In HepG2 cells and in Stat3-knockout and wild-type C57BL/6 mice, toosendanin reduced cell viability, raised lactate dehydrogenase release, and elevated serum AST and ALT with histological liver lesions. It inhibited the JAK2/STAT3 pathway and cathepsin C expression; suppressing STAT3 worsened the autophagy blockade and liver injury while activating STAT3 attenuated it, and Stat3-knockout mice showed markedly worse hepatotoxicity.
Toosendanin-induced liver damage through irreparable DNA damage and autophagy flow blockade
Toosendanin at 50, 100 and 200 microM in HepG2 cells over 48 h and at 50, 75 and 100 microM in zebrafish over 72 h disrupted the balance between reactive oxygen species and antioxidant defence, damaged mitochondria and repressed DNA-dependent protein kinase catalytic subunit. The resulting DNA damage could not be repaired, producing G1/S cell-cycle arrest, and simultaneous blockade of autophagic flow prevented clearance of damaged organelles, leading to hepatocyte death.
Toosendanin Induces Hepatotoxicity by Facilitating ALOX5-Mediated Lipid Peroxidation and Sensitizing Cells to Ferroptosis
Toosendanin triggered ferroptosis both in vitro and in vivo, with raised expression of 5-lipoxygenase (ALOX5) and its downstream metabolites driving lipid peroxidation in hepatocytes. The work adds ferroptosis to the autophagy and DNA-damage mechanisms already described for this compound.
Toosendanin Induces Hepatocyte Damage by Inhibiting Autophagic Flux via TFEB-Mediated Lysosomal Dysfunction
Toosendanin blocked autophagic flux in hepatocytes by impairing lysosomal function through the transcription factor TFEB, establishing lysosomal dysfunction as an early step in the hepatocellular injury caused by this constituent.
Determination of toosendanin and trans‐anethole in Fructus Meliae Toosendan and Fructus Foeniculi by HPLC–MS/MS and GC–MS/MS in rat plasma and their potential herb–herb interactions
Validated LC-MS/MS and GC-MS/MS assays were used to compare rats given Fructus Meliae Toosendan alone with rats given the classical Fructus Meliae Toosendan / Fructus Foeniculi pair. Fennel significantly lowered the Cmax, AUC and mean residence time of toosendanin and raised its apparent volume of distribution, reducing accumulation of the toxic constituent and reducing hepatotoxicity; conversely the Melia fruit increased absorption and slowed elimination of trans-anethole.
⚠ Safety & Contraindications
- Liver conditions
- Toxic — professional use only
Contraindications
Use with caution in hepatic impairment and in the weak or depleted.
Safety Warnings
- Not for prolonged use — the hepatotoxicity is cumulative.
- Liver function should be checked on an extended course.
⚠ Toxicity Information
Nausea, abdominal discomfort and dizziness at higher doses; hepatotoxicity on prolonged use.
Historical Texts
Shen Nong Ben Cao Jing
Han dynastyBen Cao Tu Jing
Song dynasty (1061)References
- Hui Chang, Chao Wang, Lili Gong, Yinghan Zhang, Conglian Liang, Hongyan Liu. An overview of Fructus Meliae Toosendan: Botany, traditional uses, phytochemistry, pharmacology and toxicology . Biomedicine & Pharmacotherapy (2023) [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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