Gou Ju Ye
StarPoncirus trifoliata (L.) Raf.
Synonyms: Citrus trifoliata L., Aegle sepiaria DC.
Also known as: Kou Chü Yeh · Wade–Giles
Safety at a glance
No rule in our tables for this herb: pregnancy, breastfeeding, incompatible pairs (十八反 / 十九畏), herb–drug, dose ceiling. This is not a safety clearance.
Not graded — No toxicity grade is recorded. Most herbs in the catalogue carry none.
Traditionally used for
- Nose & throat
- Cough & breathing
- Digestion
- Heart & circulation
- Skin
☯ TCM Properties
Promotes the circulation of Qi, dissipates nodulation and stops vomiting
Traditional Chinese Uses
Gou Ju Ye (枸橘叶) is the leaf of the trifoliate orange, Poncirus trifoliata (Rutaceae), and should not be confused with tangerine leaf (Ju Ye) from Citrus. Pungent and warm, it enters the Lung, Stomach and Large Intestine channels. Its principal action is to move and regulate Qi, and by directing rebellious Stomach Qi downward it harmonizes the middle and stops vomiting.
Traditionally it is used for Qi stagnation with epigastric and abdominal distension, belching, regurgitation, hiccups and vomiting. Its dispersing, Qi-moving nature also allows it to dissipate nodulation, so it has been applied to swellings and to mouth and throat sores (aphtha). It is typically decocted, and its warm pungency makes it suited to cold-type or stagnant patterns rather than to Heat from Yin deficiency.
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Botanical Description
Gou Ju Ye, Folium Ponciri, is the leaf of the trifoliate orange, Poncirus trifoliata (L.) Raf. (syn. Citrus trifoliata L.; Rutaceae), a deciduous, densely branched, thorny shrub or small tree 1-5 m tall native to China and Korea. The green, flattened young stems bear stout axillary spines and distinctive trifoliolate compound leaves with narrowly winged petioles; the three leaflets are obovate to elliptic, 1.5-5 cm long, with finely crenulate margins. Fragrant white five-petalled flowers open before or with the leaves and are followed by small, downy, aromatic yellow fruits. The leaves are gathered in spring and summer and dried for use. Pungent and warm, they promote the circulation of Qi, dissipate nodulation and stop vomiting.
Cultivated as hedging and citrus rootstock; also on slopes, roadsides and forest margins.
Active Constituents
Poncirin
Flavanone glycoside (isosakuranetin 7-O-neohesperidoside)Concentration: A principal flavonoid of the dried immature fruit (Ponciri Fructus); no validated figure exists for the leaf, which is the part the name Gou Ju Ye designates
The species-characteristic flavanone glycoside, named for the genus. It carries much of the anti-inflammatory and antiallergic activity attributed to the immature fruit in cell and animal models, and it is the marker most useful for distinguishing this drug from genuine Citrus material.
Naringin
Flavanone glycoside (naringenin 7-O-neohesperidoside)Concentration: A major flavonoid of the immature fruit
The prokinetic constituent. Naringin and its aglycone naringenin activate the ghrelin receptor, producing a transient rise in intracellular calcium that is blocked by the ghrelin receptor antagonist cortistatin-8, and naringin shows prokinetic activity in vivo in rats with gastrointestinal motility dysfunction. Neither compound activated the motilin receptor.
Neohesperidin
Flavanone glycosideConcentration: 0.03-0.14% in Poncirus trifoliata material analysed as an adulterant of Zhi Shi, against 9.38-21.93% in genuine Citrus aurantium
Analytically the single most useful discriminator between this species and genuine Zhi Shi. Poncirus material contains two to three orders of magnitude less neohesperidin than Citrus aurantium and lacks hesperetin and tangeretin entirely, so a Zhi Shi prescription filled with Poncirus delivers a fundamentally different flavonoid dose.
Synephrine
Phenylethylamine protoalkaloidConcentration: Present, but below the Chinese Pharmacopoeia specification for Aurantii Fructus Immaturus - which is precisely how Poncirus adulteration of Zhi Shi is detected
The adrenergic constituent that gives genuine Zhi Shi its cardiovascular and metabolic profile. Because Poncirus fails the pharmacopoeial synephrine specification, material substituted for Zhi Shi under-delivers on this constituent, which matters for both the intended effect and any assumption about adrenergic drug interactions.
Methoxsalen (8-methoxypsoralen, xanthotoxin)
Linear furanocoumarinConcentration: Identified as the constituent of the crude extract responsible for its acetylcholinesterase inhibition; not quantified as a percentage of the drug
The same molecule licensed as the photosensitiser in PUVA phototherapy. Isolated from Poncirus trifoliata, it inhibits acetylcholinesterase and improved trimethyltin-induced learning and memory impairment in mice at dietary doses over four weeks. Its identity as a clinical photosensitising agent is the reason phototoxicity, rather than a grapefruit-type CYP3A4 effect, is the furanocoumarin concern that is actually documented for this species.
Imperatorin and isoimperatorin
Linear furanocoumarinsConcentration: Isolated from the fruit and seeds; not quantified as a percentage of the crude drug
Furanocoumarins of the fruit and seed with reported antibacterial and cytotoxic activity in vitro. Isoimperatorin has been shown to act on glutathione S-transferase and CYP1A rather than on CYP3A4, which matters when judging whether a grapefruit-type interaction should be assumed for this species.
Auraptene
Prenyloxycoumarin (7-geranyloxycoumarin)Concentration: Isolated from the seeds of the fruit
A geranyloxycoumarin with anti-inflammatory and chemopreventive activity in laboratory models. It is a coumarin rather than a furanocoumarin and is not one of the compounds responsible for the grapefruit interaction.
Limonin
Limonoid (triterpenoid)Concentration: Isolated from the seeds
The bitter limonoid characteristic of Rutaceae seeds, reported to contribute to the antibacterial and cytotoxic activity of seed extracts and part of the drug's marked bitterness.
⚠ Drug Interactions
Zhi Shi (Aurantii Fructus Immaturus, Citrus aurantium) for which Poncirus trifoliata is substituted
Poncirus trifoliata is a documented adulterant of Aurantii Fructus Immaturus in the Chinese market. A quality-control study of Zhi Shi and its adulterants found that the pulp-capsule to cross-section ratio separates Poncirus material from genuine Citrus aurantium, that synephrine content in Poncirus adulterant samples failed the Chinese Pharmacopoeia specification which all genuine samples met, and that Poncirus material carries neohesperidin at only 0.03-0.14% against 9.38-21.93% in Citrus aurantium while lacking hesperetin and tangeretin altogether. The two drugs are not chemically interchangeable, and the substitution runs in the direction of a cheaper, hardier tree standing in for the pharmacopoeial species.
Clinical note: If Zhi Shi is intended, specify Citrus aurantium and require a certificate of analysis showing the synephrine specification is met. Conversely, when Poncirus is what is wanted, do not carry Zhi Shi dosing across to it. Note that this record's own latin_name field conflates two unrelated drugs and should not be used to identify the material.
CYP3A4 substrates (e.g. simvastatin, midazolam, ciclosporin) - grapefruit-type interaction NOT demonstrated for this species
Poncirus trifoliata is a Rutaceae close relative of Citrus and is used as a citrus rootstock, so a grapefruit-type interaction is often assumed. The published chemistry does not support that assumption. The grapefruit effect is caused by mechanism-based inactivation of intestinal CYP3A4 by bergamottin and 6',7'-dihydroxybergamottin, and neither compound is an established constituent of this species. The furanocoumarins actually reported from Poncirus trifoliata are imperatorin, isoimperatorin and methoxsalen, and the one CYP study on an isolate from this plant found isoimperatorin acting on glutathione S-transferase and CYP1A, not CYP3A4. No study has measured CYP3A4 inhibition by Poncirus trifoliata extract or reported a clinical interaction. Screening work on citrus furanocoumarins likewise attributes CYP3A4 inhibition mainly to bergaptol and its derivatives.
Clinical note: Do not counsel patients as though this were grapefruit. Record it as an unstudied gap rather than an interaction: if a patient on a narrow-therapeutic-index CYP3A4 substrate takes the drug long term, monitor the substrate as you normally would, but no dose adjustment is indicated on current evidence.
Photosensitising drugs (doxycycline, amiodarone, voriconazole, methoxsalen for PUVA) and UV exposure
Methoxsalen isolated from this species is 8-methoxypsoralen, the licensed photosensitiser used in PUVA phototherapy, and linear furanocoumarins as a class intercalate DNA and form cyclobutane adducts on UVA exposure. Imperatorin and isoimperatorin are also present. What is not established is how much methoxsalen an ordinary decoction or extract delivers systemically, which has never been quantified, so the size of the risk is unknown while its mechanism is not in doubt.
Clinical note: Advise sun protection during courses of this herb, particularly in patients already on a photosensitising drug or undergoing phototherapy, and avoid it entirely in patients receiving PUVA. Handling large quantities of fresh plant material in sunlight is a separate phytophotodermatitis risk.
Prokinetic drugs acting at 5-HT4 or the ghrelin receptor (mosapride, prucalopride, ghrelin agonists)
The aqueous extract of the dried immature fruit raises intracellular cAMP in 5-HT4 receptor-expressing cells, an effect blocked by the 5-HT4 antagonist GR125487, and GR125487 pretreatment also blocked the extract's acceleration of intestinal transit in rats, establishing that the prokinetic action is 5-HT4-mediated. Separately, naringin and naringenin from the same drug activate the ghrelin receptor. Combining it with a prescribed prokinetic is therefore additive at two identified targets. One reassuring finding: the same extract showed no interaction with the hERG potassium channel in either an astemizole binding assay or electrophysiology, so it does not carry the QT liability that removed cisapride from the market.
Clinical note: Expect additive effect rather than a hazard - watch for cramping and diarrhoea and reduce one agent if it occurs. Conversely, expect the herb to work against antimuscarinics, opioids and other agents that slow transit.
Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine)
Methoxsalen was identified as the constituent responsible for the acetylcholinesterase inhibition produced by crude Poncirus trifoliata extract, and dietary methoxsalen over four weeks improved trimethyltin-induced learning and memory impairment in mice. The enzymatic target is the same one the anticholinesterase drugs act on. No human exposure or interaction data exist and the systemic methoxsalen dose from the crude drug has not been quantified.
Clinical note: Mention it in dementia patients on an anticholinesterase and watch for cholinergic excess - nausea, bradycardia, cramping - but do not adjust drug dosing on the basis of a mouse dietary study.
Dosage Calculator
⚖ Dosage Calculator
A weight-based mathematical estimate for Gou Ju Ye. Not a prescription.
Evidence Tier
3 studies on recordRecorded 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
3
1 verified · 2 unverified
Show 3 studies
- An aqueous extract of Poncirus fructus activates the prokinetic activity of 5-HT receptor subtype 4 without hERG interaction
- Ghrelin receptor is activated by naringin and naringenin, constituents of a prokinetic agent Poncirus fructus
- Effects of Methoxsalen fromPoncirus trifoliataon Acetylcholinesterase and Trimethyltin-Induced Learning and Memory Impairment
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
An aqueous extract of Poncirus fructus activates the prokinetic activity of 5-HT receptor subtype 4 without hERG interaction
The aqueous extract of the dried immature fruit of Poncirus trifoliata raised intracellular cAMP in 5-HT4 receptor-expressing HEK293T cells, an effect abolished by the antagonist GR125487; the same antagonist blocked the extract's elevation of intestinal transit rate in rats, showing the prokinetic effect is 5-HT4-mediated. Astemizole binding and electrophysiology showed no interaction with the hERG channel, indicating the extract does not carry the cardiac liability of earlier 5-HT4 prokinetics.
Ghrelin receptor is activated by naringin and naringenin, constituents of a prokinetic agent Poncirus fructus
Calcium imaging and whole-cell patch clamp showed that the aqueous extract of the dried immature fruit activates the ghrelin receptor but not the motilin receptor. Of the constituents tested, only naringin and naringenin evoked the calcium rise, which the ghrelin receptor inhibitor cortistatin-8 specifically blocked, and both induced inward currents in ghrelin receptor-expressing cells. This identifies a second molecular target, alongside 5-HT4, for the drug's prokinetic action.
Effects of Methoxsalen fromPoncirus trifoliataon Acetylcholinesterase and Trimethyltin-Induced Learning and Memory Impairment
Methoxsalen, previously identified as the compound responsible for the acetylcholinesterase inhibition of crude Poncirus trifoliata extract, was fed to ICR mice for four weeks before assessment of trimethyltin-induced neurotoxicity. Learning and memory performance improved relative to control diet, with supporting biochemical analysis of dissected brain tissue. The finding matters clinically less for its nootropic claim than for confirming that this species contains the licensed PUVA photosensitiser at biologically active levels.
Historical Texts
Ben Cao Gang Mu
Ming dynasty (1596)Ju Lu
Southern Song dynasty (1178, Han Yanzhi)References
- Lamichhane G, Pandey J, Devkota HP. Bioactive Chemical Constituents and Pharmacological Activities of Ponciri Fructus . Molecules (2022) [DOI]
- Jang Y, Kim EK, Shim WS. Phytotherapeutic effects of the fruits of Poncirus trifoliata (L.) Raf. on cancer, inflammation, and digestive dysfunction . Phytotherapy Research (2018) [DOI]
- Liu HY, Xue BX, Li C, Ou ZM, Wang ZM, Yi H, Liu XQ. [Quality identification of Aurantii Fructus Immaturus from different origins and their adulterants]. . Zhongguo Zhong Yao Za Zhi (China Journal of Chinese Materia Medica), 2024;49(16):4477-4487, PMID 39307784 (2024) [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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