Ju He
StarCitrus reticulata Blanco
Traditionally used for
- Digestion
☯ TCM Properties
Moves Qi; Dissipates Nodules and Softens Hardness; Alleviates Pain
Traditional Chinese Uses
Ju He (tangerine or mandarin seed) is a neutral, bitter herb used in Chinese medicine to move Qi and disperse lumps in the Liver channel — particularly in the lower abdominal and genital region. Its primary applications are testicular pain and swelling, inguinal hernia pain, and the distension and nodular formations associated with Liver Qi stagnation in the lower body. As a Liver-channel Qi-mover, it complements other Qi-regulating herbs for lower abdominal stagnation patterns.
Western Herbalism Properties
Relationships
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Botanical Description
Citrus reticulata, the mandarin orange, is a small evergreen tree in the family Rutaceae, native to southern China and Southeast Asia and widely cultivated in subtropical regions. It typically grows 4-8 meters tall, with slender, often spiny branches and a rounded crown. The alternate, lanceolate to elliptic leaves are glossy dark green, leathery, and aromatic when crushed, with narrowly winged petioles. Small, fragrant, white five-petaled flowers are borne singly or in small axillary clusters. The fruit is an oblate hesperidium, 4-8 cm across, with a thin, loose, easily separable orange rind and segmented juicy orange pulp containing several small, ovoid, pointed seeds with smooth pale yellowish-white coats. Ju He refers specifically to these dried mandarin seeds.
Active Constituents
Limonin
Limonoid (triterpenoid) aglyconeConcentration: the predominant limonoid aglycone across Citrus seeds
Limonin is the principal bitter limonoid of the seed and the compound most responsible for its taste and for the class of activity attributed to the drug. Limonoids isolated from C. reticulata seeds inhibit proliferation of HepG2 liver cancer cells in vitro, with the most active member of a 15-limonoid panel reaching an IC50 of 18.24 micromolar. All efficacy data is cell-line data.
Nomilin
Limonoid (triterpenoid) aglyconeA second major seed limonoid, present both as the aglycone and, in the glucoside pool, as its most abundant member. It is reported across all Citrus seeds studied and is part of the anti-inflammatory and antiproliferative fraction attributed to the drug.
Limonoid glucosides (limonin 17-beta-D-glucopyranoside, nomilin glucoside, obacunone glucoside)
Limonoid glycosidesConcentration: total limonoid glucosides 0.31 to 0.87% of Citrus seed dry weight, nomilin glucoside the most abundant
The water-soluble, non-bitter storage forms of the seed limonoids. Because they are the fraction that actually enters a decoction, they matter more for oral dosing than the aglycone content that most analytical papers report.
Obacunone
Limonoid (triterpenoid) aglyconeOne of the neutral limonoid aglycones consistently found in Citrus seeds alongside limonin, nomilin, deacetylnomilin and ichangin. It has no separately established clinical role in this drug.
Hesperetin 7-O-beta-D-glucopyranoside
Flavanone glycosideIsolated from C. reticulata seeds and shown, in human ovarian granulosa-like KGN cells, to suppress estrogen biosynthesis by selectively regulating the aromatase PI.3 and P2 promoters through the PI3K/AKT pathway, reducing aromatase mRNA and protein. This is the clearest mechanistic finding for the seed and it is the basis of the theoretical endocrine interaction below.
Fixed oil and fatty acids
Triacylglycerols and free fatty acidsFatty acids are one of the three principal constituent classes of the seed alongside limonoids and flavonoids. They contribute bulk rather than characteristic activity and are the fraction most likely to go rancid in poorly stored material.
⚠ Drug Interactions
Aromatase inhibitors (anastrozole, letrozole) and estrogen therapy including HRT and combined contraceptives
Two compounds isolated from C. reticulata seeds, callyspongidipeptide A and hesperetin 7-O-beta-D-glucopyranoside, significantly inhibited estrogen biosynthesis in human ovarian granulosa-like KGN cells by selectively regulating the aromatase PI.3 and P2 promoters via the PI3K/AKT pathway, reducing aromatase mRNA and protein. This is cell-culture work with isolated compounds; no plasma concentration, no animal endocrine data and no human data exist, and Ju He is traditionally prescribed for exactly the breast conditions where aromatase inhibitors are also used, so the two are realistically likely to be co-prescribed.
Clinical note: Not a reason to withhold the herb, but record it if the patient is on an aromatase inhibitor, and do not present Ju He to the patient as an alternative to endocrine therapy. If a patient on HRT reports return of menopausal symptoms after starting the herb, consider this before adjusting the HRT dose.
Chen Pi, Qing Pi, Ju Hong, Ju Luo and Ju Ye (other Citrus reticulata drugs)
Six separate Chinese Pharmacopoeia drugs come from Citrus reticulata Blanco and its cultivars, and they are not interchangeable. This record is Ju He, the dried ripe seed (Semen Citri Reticulatae), which is bitter and neutral, enters Liver and Kidney, and is used for hernial pain, testicular pain and breast nodules. Chen Pi is the aged mature peel, Qing Pi the immature peel, Ju Hong the red outer layer of the peel, Ju Luo the fibrovascular bundles and Ju Ye the leaf. The chemistry diverges sharply: the peel drugs carry the volatile oil, polymethoxyflavones such as nobiletin and tangeretin, and hesperidin, whereas the seed is dominated by limonoids and fixed oil and contains essentially none of the peel's volatile fraction. Any interaction reasoning built on the peel's flavonoid chemistry does not transfer to the seed, and vice versa.
Clinical note: Confirm which Citrus drug the prescription intends before dispensing, and label stock by both pinyin and Latin part name rather than by the binomial alone. A pharmacy that files all Citrus reticulata material under one heading will eventually send out the wrong one.
CYP3A4 substrates (simvastatin, felodipine, ciclosporin, tacrolimus)
Practitioners and patients routinely generalise the grapefruit-juice interaction to anything labelled Citrus. That interaction is driven by furanocoumarins, chiefly bergamottin and 6,7-dihydroxybergamottin, in Citrus paradisi juice and peel, and it inactivates intestinal CYP3A4. The published constituent profile of C. reticulata seeds is limonoids, flavonoids and fatty acids; no furanocoumarin content and no CYP3A4 inhibition has been demonstrated for the seed, and the 2026 review of the drug explicitly notes that research on Ju He remains limited and lacks depth. This entry exists to record the absence of evidence rather than to assert an interaction.
Clinical note: Do not tell a patient on a statin or a calcium channel blocker to avoid Ju He on grapefruit grounds; the evidence is not there. Equally, do not affirmatively reassure that no interaction exists, because the drug has not been studied for it. Advise on grapefruit juice itself separately, since that interaction is real and unrelated.
Salt-processed Ju He (yan ju he) versus raw Ju He
Ju He processing evolved from stir-frying and wine-processing to the modern standard of crude and salt-processed forms, and the 2026 Journal of Ethnopharmacology review states specifically that salt-processing markedly alters the profile of the bioactive constituents. The traditional rationale is that salt guides the drug to the Kidney, which is where the classical hernial and testicular indications sit, so most clinical prescribing of Ju He means the salt-processed drug. The review notes that the transformation pathways of the constituents during processing have not been characterised and that standardised processing protocols remain to be established.
Clinical note: Specify raw or salt-processed on the prescription rather than writing Ju He alone. For the classical shan qi and testicular indications, the salt-processed form is the intended drug; do not assume the supplier will infer this.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 3–9 g | Daily | — | — | 中国药典 2020 【用法与用量】3～9g。 【性味与归经】苦，平。归肝、肾经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Evidence Tier
Moderate evidence · 3 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
3
0 verified · 3 unverified
Show 3 studies
- Two natural products from the seeds of Citrus reticulata Blanco (Rutaceae) inhibit estrogen biosynthesis by regulating the PI3K-aromatase pathway
- Chemical constituents of the seeds of Citrus reticulata and their bioactivity
- Identification and quantification of limonoid aglycones content of Citrus seeds
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
Two natural products from the seeds of Citrus reticulata Blanco (Rutaceae) inhibit estrogen biosynthesis by regulating the PI3K-aromatase pathway
Twenty-six compounds were isolated from the seeds and tested for effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Callyspongidipeptide A and hesperetin 7-O-beta-D-glucopyranoside significantly inhibited estrogen biosynthesis, selectively regulating the aromatase PI.3 and P2 promoters through the PI3K/AKT pathway and reducing aromatase mRNA and protein. Network pharmacology pointed to the same pathway. This is the strongest mechanistic support for the traditional use in breast nodules, but it is entirely cell-based.
Chemical constituents of the seeds of Citrus reticulata and their bioactivity
Four new limonoids (reticulactone A, 21,23-dihydro-23-ethoxy-21-oxolimonin, tetrahydro-20,22-dihydroxy-21,23-diethoxy-nomilin and dasycarinone B) plus 11 known limonoids and a carbolic acid were isolated from an ethanol extract of C. reticulata seeds. All 15 limonoids were tested against HepG2 liver cancer cells by CCK-8 assay; typical limonoid structures were the more cytotoxic, and the strongest, compound 2, gave an IC50 of 18.24 plus or minus 2.78 micromolar. Cell-line data only.
Identification and quantification of limonoid aglycones content of Citrus seeds
Quantified the neutral limonoid aglycones across Citrus seeds, confirming that limonin is the predominant aglycone and that nomilin, deacetylnomilin, obacunone and ichangin are consistently present. Tangerine seeds were among the highest for total glycosidic free limonoids at around 0.75% of total dry weight. Useful as the quantitative baseline for what a seed drug actually contains, though it is a Citrus-wide survey rather than a study of the Chinese Pharmacopoeia drug.
Historical Texts
Ri Hua Zi Ben Cao
Five Dynasties to early SongBen Cao Jing Shu
Ming dynastyYan Shi Ji Sheng Fang
Southern Song dynastyReferences
- Yang X, Su S, Xie J, Wang T, Zhang Q, Zhao L, Dong F, Zhang Y. The seeds of Citrus reticulata Blanco: A comprehensive review of the traditional uses, phytochemistry, pharmacology, quality control and clinical applications . Journal of Ethnopharmacology (2026) [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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