Wu Zhu Yu

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Tetradium ruticarpum (A.Juss.) Hartley

Genus: Tetradium Species: ruticarpum Pinyin: Wu Zhu Yu
Evodia fruit吴茱萸

☯ TCM Properties

Category: warming interior
Temperature: hot
Taste: pungent, bitter
Meridians: liver, spleen, stomach, kidney
Functions:

Dispels Cold and Alleviates Pain; Directs Rebellious Qi Downward and Stops Vomiting; Assists Yang and stops diarrhea; Warms the Middle and Dries Dampness; Soothes the Liver and Regulates Qi

Traditional Chinese Uses

Wu Zhu Yu (evodia fruit) is a warm, toxic herb that warms the Liver and Stomach, disperses cold, descends rebellious Qi, and stops pain. It is the primary herb for the classical Liver-Stomach cold pattern presenting with vertex headache, flank pain, acid regurgitation, vomiting, and cold abdominal pain. It is also used topically for foot soaking in patients with hypertension where ascending Liver Fire needs to be drawn downward. Its warm, stimulating nature requires careful dosing, as it is toxic in excess.

Western Herbalism Properties

Actions:
analgesiccarminativestimulant

Used In Formulas (1)

Botanical Description

Tetradium ruticarpum (A.Juss.) T.G.Hartley (Rutaceae), formerly Evodia rutaecarpa, is a small dioecious deciduous tree 2.5-8 m tall native to China, with pinnately compound aromatic leaves of 5-11 ovate to elliptic leaflets dotted with translucent oil glands, and dense terminal corymbose panicles of small greenish-white flowers. The unripe to just-ripe fruits are five-lobed schizocarpic capsules 2-5 mm across, reddish-brown to purplish, that split into follicles containing shiny black seeds. For Wu Zhu Yu, fruits are harvested in August-October before fully ripening, sun-dried, and processed (often with licorice decoction) to reduce acrid intensity. In TCM, Wu Zhu Yu is acrid and bitter in flavor, hot in nature, and slightly toxic, entering the Liver, Spleen, Stomach, and Kidney channels; it warms the middle, dispels cold, descends rebellious qi, and stops pain and vomiting.

Active Constituents

Evodiamine

Indoloquinazoline (quinazolinocarboline) alkaloid

Concentration: Major indole alkaloid of the fruit

A principal bioactive alkaloid with analgesic, anti-inflammatory, thermogenic (TRPV1 agonist), anti-obesity and antitumor activity in experimental models; contributes to the warming and pain-relieving actions of the herb.

Rutaecarpine

Indoloquinazoline (quinazolinocarboline) alkaloid

Concentration: Major indole alkaloid of the fruit

Vasodilatory, anti-inflammatory and gastroprotective alkaloid. It is a potent modulator of cytochrome P450 1A2 (inhibition of the enzyme in vitro but induction on repeated dosing), the basis of important herb-drug interactions.

Dehydroevodiamine

Quinazolinocarboline alkaloid

Concentration: Minor-to-moderate alkaloid

Shows cardiovascular (antiarrhythmic, hypotensive) and neuroprotective activity, including acetylcholinesterase inhibition in experimental studies.

Evodin / limonin (limonoids)

Limonoid (triterpenoid)

Concentration: Bitter principle of the fruit

Bitter limonoids contributing to the characteristic taste and to anti-inflammatory and digestive effects.

Evocarpine

Quinolone alkaloid

Concentration: Minor alkaloid

A quinolone alkaloid with antimicrobial activity, including reported activity against Helicobacter pylori and other bacteria.

Evodol / synephrine and volatile oil components

Mixed (protoalkaloid / essential oil)

Concentration: Minor constituents of the essential oil fraction

The volatile oil (including evodene and ocimene-type terpenes) contributes the aromatic, warming, qi-descending quality used to stop vomiting and dispel cold.

⚠ Drug Interactions

Theophylline

Major Evidence: Probable

In rats, pretreatment with Evodia rutaecarpa extract and the formula Wu-Chu-Yu-Tang significantly and dose-dependently decreased theophylline blood levels, attributed to induction of CYP1A2/CYP2E1-mediated theophylline metabolism.

Clinical note: Given theophylline's narrow therapeutic index, avoid concurrent use or monitor theophylline levels closely.

Caffeine

Moderate Evidence: Probable

Rutaecarpine induces CYP1A2 (and CYP2E1) on repeated dosing, accelerating the metabolism of caffeine and shortening its half-life in animal studies.

Clinical note: May reduce caffeine effect; relevant for other CYP1A2 substrates as well.

CYP1A2 substrate drugs (e.g., clozapine, olanzapine, tizanidine, duloxetine)

Moderate Evidence: Theoretical

Because rutaecarpine both inhibits CYP1A2 acutely and induces it with repeated exposure, plasma levels of narrow-index CYP1A2 substrates could rise or fall depending on timing and duration of use.

Clinical note: Use caution and monitor for altered efficacy or toxicity of CYP1A2-metabolized drugs.

Dosage

FormAmount Frequency Duration Population Notes
decoction 3-9g Daily

Preparation Methods

Decoction (Tang), often processed

Parts: unripe fruit

Typical dose 1.5-4.5 g of the dried near-ripe fruit. It is toxic and harsh when raw, so it is usually processed (e.g., stir-fried, or soaked/boiled with licorice water) to reduce toxicity before decocting. Doses are kept low.

Prepared / stir-fried (paozhi)

Parts: fruit

Dry-fried or processed with licorice decoction to moderate its hot, drying and mildly toxic nature; used in formulas such as Wu Zhu Yu Tang for cold-type headache, vomiting and abdominal pain.

Clinical Studies

Herb-drug interaction of Evodia rutaecarpa extract on the pharmacokinetics of theophylline in rats

Jan WC, Lin LC, Chen CF, Tsai TH (2005) Journal of Ethnopharmacology Preclinical pharmacokinetic (animal) study

Three-day pretreatment of rats with Evodia rutaecarpa ethanol extract or Wu-Chu-Yu-Tang significantly and dose-dependently lowered intravenous theophylline blood levels measured by microdialysis-HPLC, indicating a herb-drug interaction via induction of theophylline metabolism.

Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats

Ueng YF, Wang JJ, Lin LC, Park SS, Chen CF (2005) Journal of Pharmacy and Pharmacology Preclinical pharmacokinetic (animal) study

Rutaecarpine, an alkaloid of Evodia rutaecarpa, altered theophylline pharmacokinetics in rats consistent with induction of CYP1A-mediated metabolism, supporting a mechanistic basis for evodia-theophylline interactions.

Historical Texts

Shen Nong Ben Cao Jing (Divine Farmer's Materia Medica)

c. 200 CE, Han Dynasty
Lists Wu Zhu Yu as a middle-grade herb for warming the interior, dispelling cold and directing rebellious qi downward.

Shang Han Lun (Treatise on Cold Damage), Zhang Zhongjing

c. 220 CE, Han Dynasty
Basis of Wu Zhu Yu Tang, a classic formula using the fruit for cold-type headache, vomiting and epigastric pain.

References

  1. Jan WC, Lin LC, Chen CF, Tsai TH. Herb-drug interaction of Evodia rutaecarpa extract on the pharmacokinetics of theophylline in rats . Journal of Ethnopharmacology (2005) [DOI]
  2. Tan Q, Zhang J. Evodiamine and Its Role in Chronic Diseases . Advances in Experimental Medicine and Biology (2016) [DOI]
  3. Bensky D, Clavey S, Stoger E. Chinese Herbal Medicine: Materia Medica, 3rd Edition (Wu Zhu Yu) . Eastland Press (2004) [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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