Ju Hong
StarCitrus reticulata Blanco
Traditionally used for
- Cough & breathing
- Digestion
☯ TCM Properties
Dries Dampness and Transforms Phlegm; Regulates Qi and Widens the Chest; Disperses Cold; Harmonizes the Middle Burner; Resolves Stagnation and Dissipates Masses
Traditional Chinese Uses
Ju Hong (red tangerine peel outer layer) is a warm, acrid herb made from the outermost red portion of the tangerine peel, concentrating the aromatic, Phlegm-drying, and Qi-moving properties of Chen Pi (whole aged tangerine peel). It is used for coughs with abundant white or sticky phlegm, bloating after meals, and nausea from Phlegm-Damp obstructing the Stomach. Its more concentrated aromatic and Phlegm-dispersing action compared to whole peel makes it preferred in formulas requiring stronger Phlegm dissolution and Qi movement.
Western Herbalism Properties
Relationships
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Botanical Description
Citrus reticulata is a small evergreen tree or shrub in the Rutaceae family reaching 4-8 m tall with a slender, often spiny-twigged crown and aromatic foliage. Native to southern China and Southeast Asia, it is one of the original true citrus species and has been cultivated for over two millennia. The leaves are simple, lanceolate, 4-8 cm long, glossy dark green above, with narrowly winged petioles and pellucid oil glands that release a characteristic fragrance when crushed. White star-shaped five-petalled flowers borne singly or in small axillary clusters give rise to the familiar oblate orange-red mandarin fruit 5-8 cm across with a loose easily-peeled rind. Ju Hong is specifically the dried outermost coloured layer (flavedo) of the peel, separated from the inner white spongy albedo, distinct from Chen Pi which uses the whole peel.
Active Constituents
Nobiletin
Polymethoxylated flavoneConcentration: 4.98 mg/g of the dried outer pericarp in a direct three-part comparison; 0.587-15.7 mg/g across ten commercial Ju Hong samples
Nobiletin is one of the two flavones that define Ju Hong as a distinct drug from the other mandarin peel medicines. Polymethoxyflavones sit in the oil glands of the coloured outer peel, so scraping away the white inner layer concentrates them: the outer pericarp carries about 4.98 mg/g nobiletin against 0.12 mg/g in the white middle pericarp and 0.15 mg/g in the vascular strands sold as Ju Luo. It is lipophilic, well absorbed, and is oxidatively demethylated in human liver by CYP1A2 and CYP3A4, which is also why it interferes with those enzymes.
Tangeretin
Polymethoxylated flavoneConcentration: 3.99 mg/g of the dried outer pericarp; 0.222-6.03 mg/g across ten commercial Ju Hong samples
Tangeretin follows the same steep gradient as nobiletin, at roughly 3.99 mg/g in the outer peel against 0.27 mg/g in the white middle pericarp and 0.05 mg/g in Ju Luo. It is the constituent behind the single most important caution attached to this drug, having abolished tamoxifen's tumour-suppressing benefit in tumour-bearing mice. It also activates PXR, inducing CYP3A4 and ABCB1 expression, while inhibiting CYP1A2.
3,5,6,7,8,3',4'-Heptamethoxyflavone
Polymethoxylated flavoneConcentration: 0.46 mg/g of the dried outer pericarp, against 0.01 mg/g in the white middle pericarp
A minor polymethoxyflavone that tracks nobiletin and tangeretin and is used analytically as part of the fingerprint that distinguishes true outer-peel Ju Hong from material that still carries the white albedo.
Total polymethoxyflavones
Polymethoxylated flavone fractionConcentration: 10.78 mg/g of the dried outer pericarp, against 0.37 mg/g in the white middle pericarp and 0.56 mg/g in Ju Luo
This roughly twenty- to thirty-fold enrichment over the inner peel layers is the chemical justification for dispensing Ju Hong separately from Chen Pi, Ju Bai and Ju Luo. A Ju Hong that assays low in total polymethoxyflavones has almost certainly been prepared with the white layer left on, or is not mandarin peel at all.
Hesperidin
Flavanone glycosideConcentration: 24.08 mg/g of the dried outer pericarp in a direct three-part comparison; 23.8-79.6 mg/g across ten commercial samples
Hesperidin runs in the opposite direction to the polymethoxyflavones across the fruit. The outer red peel is the hesperidin-poorest of the mandarin peel drugs at about 24 mg/g, against 54.47 mg/g for the white middle pericarp and 101.64 mg/g for Ju Luo. Ju Hong is therefore not interchangeable with Ju Luo on flavonoid grounds even though both come from the same fruit. Hesperidin is the constituent responsible for the transporter-mediated interactions citrus drugs carry.
d-Limonene
Monoterpene hydrocarbonConcentration: dominant component of the volatile oil held in the flavedo oil glands; oil yield and composition vary widely with cultivar and with how long the peel has been aged
The volatile oil is concentrated in the coloured outer layer, which is why Ju Hong is more acrid and drying than whole peel and why it is conventionally added late in a decoction. Ageing, which is prized for Chen Pi, progressively drives off the volatile fraction; a heavily aged peel is chemically a different preparation from a freshly dried one.
⚠ Drug Interactions
Tamoxifen
Tangeretin given in the drinking water of MCF-7/6 tumour-bearing mice neutralised the tumour-suppressing effect of tamoxifen, and median survival of the combination group fell to 14 weeks against 56 weeks on tamoxifen alone. The proposed mechanism is suppression of natural killer cell cytolysis rather than a pharmacokinetic effect: tangeretin at 1 micromolar and above inhibited murine NK cell killing of MCF-7/6 cells in vitro. Ju Hong is the most tangeretin-rich of the mandarin peel drugs, carrying roughly fifteen times more than the white inner pericarp, so this caution applies to it more strongly than to Chen Pi or Ju Luo. The evidence is animal and in vitro; no human outcome study exists, but the size of the effect and the seriousness of the endpoint make it unreasonable to wait for one.
Clinical note: Do not prescribe Ju Hong, or concentrated citrus polymethoxyflavone supplements, to a patient taking tamoxifen for breast cancer. If a citrus qi-regulator is needed, choose a low-polymethoxyflavone part such as Ju Luo and discuss it with the treating oncologist.
Hua Ju Hong (Exocarpium Citri Grandis, from Citrus grandis) supplied in place of Ju Hong
Hua Ju Hong is a separate Chinese Pharmacopoeia drug, the exocarp of Citrus grandis 'Tomentosa' or Citrus grandis (L.) Osbeck, and it is routinely supplied against orders for Ju Hong because the names overlap. The two are not chemically equivalent. Ju Hong is a polymethoxyflavone drug; Citri Grandis Exocarpium is described as a flavonoid, coumarin and volatile oil drug, and pomelo carries the furanocoumarins bergamottin and 6',7'-dihydroxybergamottin that act as mechanism-based, effectively irreversible inhibitors of intestinal CYP3A4. Pomelo juice raised cyclosporine exposure in humans, and pomelo has been shown to inhibit tacrolimus metabolism through CYP3A4 and P-glycoprotein. A patient stabilised on a CYP3A4 substrate who is dispensed pomelo peel under a mandarin peel name therefore inherits the grapefruit-juice interaction without anyone intending it.
Clinical note: Inspect the material. True Ju Hong is thin, orange-red, smooth and smells of tangerine; Hua Ju Hong is thicker, yellow-green, coarse and densely downy with a markedly more bitter taste. Confirm the botanical source with the supplier in writing when the patient takes ciclosporin, tacrolimus, a statin, a calcium-channel blocker or any other narrow-margin CYP3A4 substrate.
CYP1A2 substrates (e.g. theophylline, clozapine, olanzapine, tizanidine)
Nobiletin, sinensetin and tangeretin were profoundly inhibitory towards CYP1A2 in vitro, and were identified as the compounds chiefly responsible for the food-drug interaction potential of clementine (a Citrus reticulata hybrid). Because Ju Hong is the polymethoxyflavone-enriched fraction of the peel, it delivers more of these three compounds per gram than any other mandarin peel drug. The work is in vitro and no human pharmacokinetic study of Ju Hong exists, so the magnitude at decoction doses is unknown.
Clinical note: Watch for signs of accumulation in patients on narrow-margin CYP1A2 substrates, particularly theophylline and clozapine, if Ju Hong is used at the upper end of the range or for long periods. Separate doses where practical and monitor rather than assume the interaction is absent.
CYP3A4 and P-glycoprotein substrates
The direction of this interaction is genuinely ambiguous, which is itself the clinically useful point. In the clementine work, CYP3A4 inhibition appeared to arise from additive or synergistic effects of several polymethoxyflavones together, while tangeretin alone acted as a PXR activator and so induced CYP3A4 and ABCB1 expression. Nobiletin has separately been reported to increase vinblastine uptake in Caco-2 cells by inhibiting P-glycoprotein. Short exposure therefore tends towards inhibition and sustained exposure towards induction, and no human data resolve which dominates at herbal doses.
Clinical note: Avoid introducing or stopping Ju Hong abruptly during a period when a CYP3A4 or P-glycoprotein substrate is being titrated. Where the substrate is a transplant immunosuppressant or a direct oral anticoagulant, prefer a different qi-regulator.
OATP substrates (e.g. fexofenadine, aliskiren, some statins)
Citrus flavanone glycosides inhibit intestinal organic anion-transporting polypeptides, and this class of interaction reduces rather than increases drug exposure. Orange juice, in which hesperidin is the principal flavanone, cut fexofenadine AUC to about 31 percent of control in human studies, and hesperidin inhibits OATP1A2 in vitro at low micromolar concentrations. Ju Hong contains hesperidin at roughly 24 mg/g, so the constituent is certainly present, though the human data come from juice rather than from a peel decoction and the effective dose from a decoction has not been measured.
Clinical note: Where a patient depends on an orally absorbed OATP substrate, separate the herb from the drug by at least four hours and be alert to apparent loss of drug efficacy rather than to toxicity.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 3–10 g | Daily | — | — | 中国药典 2020 【用法与用量】3～10g。 【性味与归经】辛、苦，温。归肺、脾经 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
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
- Chemical compositions, chromatographic fingerprints and antioxidant activities of Citri Exocarpium Rubrum (Juhong)
- Comparative analysis of chemical constituents in Citri Exocarpium Rubrum, Citri Reticulatae Endocarpium Alba, and Citri Fructus Retinervus
- Influence of Tangeretin on Tamoxifen's Therapeutic Benefit in Mammary Cancer
- Inhibition of tamoxifen's therapeutic benefit by tangeretin in mammary cancer
- Nobiletin, sinensetin, and tangeretin are the main perpetrators in clementines provoking food-drug interactions in vitro
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
Chemical compositions, chromatographic fingerprints and antioxidant activities of Citri Exocarpium Rubrum (Juhong)
Ten commercial Ju Hong samples, defined as the dried exocarp of Citrus reticulata Blanco and its cultivars, were profiled by HPLC-UV-MS. Hesperidin ranged from 23.8 to 79.6 mg/g, nobiletin from 0.587 to 15.7 mg/g and tangeretin from 0.222 to 6.03 mg/g, with mainland Chinese samples markedly richer than Hong Kong material. Eleven further characteristic peaks including sinensetin were identified but not quantified. The spread across samples is wide enough that two batches of nominally the same drug can differ more than tenfold in polymethoxyflavone content.
Comparative analysis of chemical constituents in Citri Exocarpium Rubrum, Citri Reticulatae Endocarpium Alba, and Citri Fructus Retinervus
The three drugs taken from different layers of the same Citrus reticulata fruit were assayed side by side. The outer pericarp (Ju Hong) gave hesperidin 24.08 mg/g, nobiletin 4.98 mg/g, tangeretin 3.99 mg/g, heptamethoxyflavone 0.46 mg/g and total polymethoxyflavones 10.78 mg/g. The middle white pericarp gave hesperidin 54.47 mg/g with total polymethoxyflavones of only 0.37 mg/g, and the fruit-peel vascular strands (Ju Luo) gave hesperidin 101.64 mg/g with total polymethoxyflavones 0.56 mg/g. This is the cleanest published demonstration that the mandarin peel drugs are chemically distinct and not substitutable for one another.
Influence of Tangeretin on Tamoxifen's Therapeutic Benefit in Mammary Cancer
Tangeretin inhibited growth and invasion of human MCF-7/6 breast cancer cells in vitro, but when added to the drinking water of MCF-7/6 tumour-bearing mice it abolished the tumour-suppressing effect of tamoxifen. Median survival was 14 weeks on tamoxifen plus tangeretin against 56 weeks on tamoxifen alone. Tangeretin at 1 micromolar and above inhibited murine natural killer cell cytolysis of MCF-7/6 cells, offering a mechanism. The authors argued against heavy tangeretin intake by breast cancer patients on tamoxifen.
Inhibition of tamoxifen's therapeutic benefit by tangeretin in mammary cancer
A follow-up report from the same group restating that tangeretin, present in citrus and in some products marketed for menopausal symptoms, neutralises tamoxifen's benefit in the mouse mammary cancer model despite being an inhibitor of the same cells in culture.
Nobiletin, sinensetin, and tangeretin are the main perpetrators in clementines provoking food-drug interactions in vitro
Working with clementine, a Citrus reticulata hybrid, the authors identified polymethoxyflavones as the compounds chiefly responsible for the fruit's drug-interaction potential. CYP1A2 was profoundly inhibited by nobiletin, sinensetin and tangeretin. CYP3A4 inhibition appeared to arise from additive or synergistic action of several compounds together, whereas tangeretin alone activated PXR and thereby induced CYP3A4 and ABCB1. Because Ju Hong is the polymethoxyflavone-enriched layer of the mandarin peel, these findings bear on it more directly than on the other citrus drugs.
⚠ Safety & Contraindications
Contraindications
Its use is prohibited in patients with dry cough due to yin deficiency and chronic cough due to qi deficiency.
Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, pp. 183–185.
Historical Texts
Tai Ping Hui Min He Ji Ju Fang
Song dynastyBen Cao Gang Mu
Ming dynastyReferences
- Jintao Lü, Dan Zhang, Xiaomeng Zhang, Rina Sa, Xiaofang Wang, Huanzhang Wu, Zhijian Lin, Bing Zhang. Network Analysis of the Herb–Drug Interactions of Citrus Herbs Inspired by the “Grapefruit Juice Effect” . ACS Omega (2022) [DOI]
- J. Grenier, C. Fradette, G. Morelli, G. Merritt, M. Vranderick, M. Ducharme. Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans . Clinical Pharmacology & Therapeutics (2006) [DOI]
- David G. Bailey. Fruit juice inhibition of uptake transport: a new type of food–drug interaction . British Journal of Clinical Pharmacology (2010) [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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