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Traditional Chinese medicine

Evodia (wu zhu yu)Tetradium ruticarpum (syn. Evodia rutaecarpa)

A hot, bitter fruit the texts call slightly toxic; the one human gut study we found is 14 patients on Zuo Jin Wan, and the lab record includes liver injury.

Botanical name
Tetradium ruticarpum (syn. Evodia rutaecarpa)
Part used
nearly ripe fruit, processed before use
Also called
pinyin Wu zhu yu (吴茱萸); Evodia fruit, Euodiae fructus, Tetradii fructus
Used in
Traditional Chinese medicine
Taken for
Nausea, Reflux and heartburn, Cramping and pain, Loose stools and diarrhea
Sold as
dried fruit, pills in formulas, decoction, granules

What evodia (wu zhu yu) is

Evodia is the fruit of Tetradium ruticarpum, long known in the literature as Evodia rutaecarpa, a small tree of the citrus family. The Chinese name is wu zhu yu and the pharmacopoeia name is Euodiae Fructus. A review calls it a versatile medicine prescribed in Chinese herbal formulas and recognized in Japanese Kampo, clinically used to treat headache, vomiting, diarrhea, abdominal pain, dysmenorrhea and pelvic inflammation. The same review reports 165 chemical compounds isolated from it, chiefly alkaloids, terpenoids, flavonoids, phenolic acids, steroids and phenylpropanoids.

The fruit is not used raw in the same way as a kitchen spice. Chinese pharmacy processes it before use, and a chemistry paper examines how processing and combining it with other herbs reduces its toxicity. For the gut it appears chiefly as the small partner in Zuo Jin Wan, a pill of coptis and evodia in a 6 to 1 ratio, where the tradition pairs the cold, bitter coptis with the hot evodia. It is also the main herb of Wu Zhu Yu Tang, a decoction the texts use for cold in the stomach with vomiting and headache.

What the traditions use it for

Traditional Chinese medicine (about TCM)

Wu zhu yu is classed in the Chinese materia medica as pungent, bitter and hot, and slightly toxic, entering the liver, spleen, stomach and kidney channels. The tradition says it warms the middle, disperses cold, relieves pain and directs rebellious qi downward, and uses it for what the texts call cold in the stomach and liver with epigastric and abdominal pain, vomiting, acid regurgitation and diarrhea at dawn. In Zuo Jin Wan, which the tradition uses for what it calls liver fire invading the stomach with acid regurgitation, flank pain and a bitter taste, a small amount of evodia is paired with coptis to temper coptis’s cold. The texts’ own warning that it is slightly toxic matches the toxicity work reviewed below. These are the tradition’s own classifications and not findings about the body.

The constituents

The fruit’s best-known alkaloids are evodiamine and rutaecarpine, and a review of 165 isolated compounds lists alkaloids, terpenoids, flavonoids, phenolic acids, steroids and phenylpropanoids. In the laboratory the extracts and pure components show anti-inflammatory, antitumor, antibacterial, anti-obesity and cardiovascular activity. The same review states that bioactive components of the fruit can induce drug interaction and hepatic injury, and rutaecarpine is a selective inhibitor of the cytochrome P450 1A enzymes in mouse and human liver microsomes. A study ties the fruit’s liver toxicity in the laboratory to a dichloromethane extract. These are laboratory findings.

The human evidence

We found no controlled trial of evodia alone or of Zuo Jin Wan in a gut disease. The human data we could find are one pilot study. Fourteen patients with chronic nonatrophic gastritis took Zuo Jin Wan (coptis root and evodia fruit combined in a 6 to 1 ratio) at 6.0 g a day for two weeks. Endoscopy and biopsy showed less erosion and bile reflux, though not less red plaques or hemorrhage, and less active chronic inflammation. The inflammatory markers COX-2, IL-4 and IL-17 fell in the gastric mucosa and the serum. The abstract does not describe a control group, so the findings are before-and-after changes in a small group.

Animal work backs the formula’s traditional gut use. In a rat model of gastroesophageal reflux disease, Zuo Jin Wan at three doses reduced esophageal tissue damage and pro-inflammatory cytokines and strengthened the esophageal mucosal barrier, with effects through the MAPK/NF-kB pathway. Other laboratory papers study the formula in gastritis, ulcerative colitis and several cancers.

A published review of the fruit sums up the clinical use as traditional and the pharmacology as laboratory-based, and flags drug interaction and liver injury. What has not been tested: evodia alone in people, Zuo Jin Wan against placebo in any gut disease, and Wu Zhu Yu Tang in nausea or vomiting.

StudyDoseWhat it found
Pilot study, 14 patients with chronic nonatrophic gastritis (Zuo Jin Wan; abstract describes no control group) PMID 35899115Coptis and evodia 6:1, 6.0 g a day for 2 weeksLess erosion, bile reflux and active chronic inflammation on endoscopy and biopsy; COX-2, IL-4, IL-17 lower
Rat model of gastroesophageal reflux disease, Zuo Jin Wan at three doses PMID 39662861Three animal dosesLess esophageal damage and cytokine release; esophageal mucosal barrier strengthened
Review: traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of Tetradium ruticarpum fruit PMID 32758577Not applicable165 compounds isolated; laboratory activities listed; bioactive components can induce drug interaction and hepatic injury
Liver microsome study of rutaecarpine PMID 11854157Laboratory concentrationsSelective inhibitor of cytochrome P450 1A enzymes in mouse and human liver microsomes

Doses, in trials and in practice

The only human dose we found is the pilot study’s: Zuo Jin Wan at 6.0 g a day for two weeks, made of coptis root and evodia fruit in a 6 to 1 ratio. Because the ratio is 6 to 1, evodia is the smaller share of that daily amount. In the tradition the fruit is processed first, and the processing and the pairing with other herbs are studied in a paper as ways of reducing its toxicity. Wu Zhu Yu Tang and other decoctions are made with the fruit as the main herb. We found no single-herb gram dose for a gut outcome that we could tie to a primary source.

The amounts above are what trials and pharmacopoeias record, not a dose for you; your medicines and conditions change the answer, and a clinician or pharmacist who knows them is the person to ask.

What is known about safety

The fruit is the most safety-flagged herb in this group. The tradition calls it slightly toxic, a review of the fruit lists hepatic injury among its toxicology findings, and a paper finds a dichloromethane extract responsible for the fruit’s liver toxicity in the laboratory. The abstract of the 14-patient pilot study of Zuo Jin Wan does not report adverse events, and the study was small and short. We found no pregnancy or breastfeeding data in the sources. For patent-medicine pills, reviews of Asian herbal medicines have reported toxic heavy metals and undeclared prescription drugs in some Chinese preparations, mostly as anecdotal reports; this concerns the products reviewed and not every product containing evodia.

Where it meets prescription medicines

The documented interaction mechanism is enzyme inhibition. Rutaecarpine, an alkaloid of evodia, was a selective inhibitor of the cytochrome P450 1A enzymes in mouse and human liver microsomes, and a review of the fruit states that its components can cause drug interactions. CYP1A2, one of that family, is the enzyme used as the caffeine probe in a human enzyme study, so caffeine and other medicines cleared by that route are the ones pharmacologists would look at; this is a laboratory signal and no human interaction trial of the fruit is reported in the sources we read. Zuo Jin Wan also contains coptis, which carries its own interaction record.

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Herbs that sit beside it

TCM Coptis Coptis chinensis Ayurvedic / TCM / Western Ginger Zingiber officinale Ayurvedic / TCM / Western Cardamom Elettaria cardamomum (small or green cardamom); Amomum species in Chinese medicine Ayurvedic / TCM / Western Licorice Glycyrrhiza glabra

Common questions

What is Zuo Jin Wan?

A Chinese pill made of coptis root and evodia fruit in a 6 to 1 ratio. The tradition uses it for acid regurgitation, flank pain and a bitter taste, which it calls liver fire invading the stomach. A pilot study gave it to 14 patients with gastritis for two weeks.

Has evodia been tested in people for the gut?

We found one small pilot of the formula Zuo Jin Wan in 14 patients and no trial of evodia alone. Animal and laboratory work is more extensive.

Is it toxic?

The tradition classes it as slightly toxic, and a review of the fruit lists hepatic injury among its toxicology findings. Chinese pharmacy processes the fruit before use, and a recent paper studies how processing reduces toxicity.

Can it interact with medicines?

Rutaecarpine, an alkaloid of evodia, selectively inhibited the cytochrome P450 1A enzymes in mouse and human liver microsomes. That is a laboratory finding, and no human interaction study is reported in the sources we read.

Sources