Citrus grandis
StarCitrus grandis
Synonyms: Citrus maxima
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
- Cough & breathing
- Digestion
Cautions & contraindications
- Kidney conditions
Western Herbalism Properties
Traditional Uses
The pomelo is grown above all for its large edible fruit, a major food across tropical Asia. In Chinese medicine the dried, mature peel of Citrus grandis is the drug Hua Ju Hong, classed as acrid, bitter and warm and entering the lung, spleen and stomach; it is used to regulate the qi, dry dampness and transform phlegm, easing productive cough, chest congestion, indigestion and food stagnation. The aromatic leaves and flowers are likewise used in folk practice as carminative, digestive remedies (TCM Wiki; Liu et al., 2014).
Botanical Description
Citrus grandis, also treated as Citrus maxima and known as the pomelo or shaddock, is a large evergreen tree of the family Rutaceae, native to Southeast Asia and the largest of the citrus fruits. It grows 5 to 15 metres tall, with a spreading, somewhat irregular crown, often spiny twigs, and young shoots and flower buds that are downy. The glossy dark green leaves are large and leathery, with broadly winged petioles characteristic of the genus, and are dotted with aromatic oil glands. The large, fragrant white flowers are borne singly or in small clusters in the leaf axils. The fruit is very large, 15 to 30 centimetres across, more or less round to pear-shaped, with a thick pale-green to yellow rind and a thick spongy white albedo enclosing pale yellow, pink or red segments of large, firm, mildly sweet to tart juice vesicles. The peel, leaves and flowers are all strongly aromatic owing to abundant essential oils and flavonoids such as naringin. The species is widely cultivated throughout the tropics and subtropics for its edible fruit.
Active Constituents
Naringin
Flavanone 7-O-neohesperidoside (flavonoid glycoside)Concentration: The pharmacopoeial marker and assay compound for the peel drug. The Chinese Pharmacopoeia (2020 and 2025 editions) requires not less than 3.5% naringin, calculated on the dried basis, determined by HPLC; the Guangdong provincial standard for Huazhou-grown material sets the higher bar of not less than 5.0%. The white bloom that forms on the surface of dried peel during curing has been shown by multi-technique analysis to be roughly 80% crystalline naringin by mass.
Naringin is the compound that makes pomelo peel and pulp bitter, and it is the single constituent the Chinese Pharmacopoeia uses to decide whether a batch of the peel drug is genuine. It is a poor substrate for absorption as the intact glycoside; gut microbial rhamnosidases cleave it to naringenin, which is what mostly reaches the circulation, so activity attributed to naringin in a cell assay may in the body belong to its aglycone. Anti-inflammatory effects in rodent lung and liver injury models, running through TLR4/NF-kappaB and Nrf2/HO-1 signalling, are the best-replicated preclinical finding.
Naringenin
Flavanone aglyconeConcentration: Present natively in small amounts and generated in much larger amounts from naringin by gut bacterial rhamnosidase and glucosidase after oral dosing.
The absorbed form of the drug's principal flavonoid. In the mouse polystyrene-microplastic and lipopolysaccharide liver-injury models naringenin reproduces much of the whole-extract effect on oxidative stress and epithelial tight-junction integrity, which is the usual argument that it, rather than naringin itself, is the active species in vivo.
Bergapten (5-methoxypsoralen) and related linear furanocoumarins, including bergamottin
Linear furanocoumarin (psoralen-type)Concentration: Not assayed by the pharmacopoeial monograph and not limited by it. Furanocoumarin load in Citrus varies widely with cultivar, maturity and tissue, and concentrates in the flavedo and peel oil rather than the pulp, so a peel drug is the tissue where it would be expected to be highest.
This is the constituent class that makes the species pharmacologically dangerous around prescription drugs rather than merely bitter. Bergamottin and its 6',7'-dihydroxy metabolite are mechanism-based (suicide) inactivators of intestinal CYP3A4: they are turned over by the enzyme into a reactive intermediate that covalently modifies it, so the enzyme is destroyed rather than reversibly blocked and activity returns only as new enzyme is synthesised over one to three days. Bergapten is additionally phototoxic, being the same molecule used clinically as 5-MOP in photochemotherapy. Because the interaction outlasts the meal by days, separating the herb from the drug by a few hours does not avoid it.
Narirutin
Flavanone 7-O-rutinoside (flavonoid glycoside)Concentration: A consistent minor flavanone of the peel, reported alongside naringin in HPLC and UPLC-Q-TOF-MS profiles of the drug.
The rutinoside isomer of naringin, differing only in the linkage of the terminal rhamnose. It is not bitter, which is why the naringin-to-narirutin ratio is informative about cultivar and substitution: peel from species with high narirutin and low naringin will fail the pharmacopoeial assay even though it looks similar.
Limonene
Monocyclic monoterpene (volatile oil)Concentration: Dominant component of the peel essential oil. Regional surveys of Citri Grandis Exocarpium volatiles across southern China find limonene as the leading volatile in essentially all provenances, with the absolute figure varying by ecology and drying method.
The oil, not the flavonoids, is what a practitioner smells and what the traditional aromatic qi-rectifying and dampness-drying description rests on. Limonene is a mild gastrointestinal motility stimulant and carminative; it is also volatile, so prolonged decoction drives most of it off, and a short late addition retains more of it than a long boil.
Limonin and related limonoids
Highly oxygenated triterpenoid (limonoid)Concentration: A minor but reliably detected fraction of the peel; comparative UPLC-Q-TOF-MS/MS profiling of medicinal citrus drugs identifies limonin among the differentiating metabolites of this drug.
Limonoids account for part of the delayed bitterness of citrus peel preparations. Their pharmacological contribution at achievable decoction concentrations is not established, and they should be read as chemotaxonomic markers rather than as an active principle.
⚠ Drug Interactions
Ciclosporin (cyclosporine)
Demonstrated in humans, not inferred. In an open-label randomised three-way crossover trial, twelve healthy male volunteers took single 200 mg oral doses of ciclosporin with 240 mL of pomelo juice, cranberry juice or water, with 14-day washouts. Pomelo juice raised ciclosporin AUC to the last measurable concentration to 119.4% of the water arm (95% CI 113.4 to 125.8), AUC to infinity to 118.9% (95% CI 113.8 to 124.3) and Cmax to 112.1% (95% CI 102.3 to 122.8). The AUCt increase fell outside the 80 to 125% bioequivalence bounds and was judged clinically significant; cranberry juice in the same subjects did nothing. The authors attribute it to inhibition of gut-wall CYP3A and/or P-glycoprotein, which is the furanocoumarin mechanism. Note that the trial used pomelo juice while the TCM drug is the immature peel, the tissue in which citrus furanocoumarins are most concentrated, so the peel is unlikely to be safer than the juice on this axis.
Clinical note: Do not add this herb, or pomelo fruit and juice, to the diet of a transplant recipient or anyone on ciclosporin without arranging trough-level monitoring. Because furanocoumarin inhibition of CYP3A4 is mechanism-based and enzyme activity recovers only as new protein is made, dose separation does not help; the exposure must be either avoided or held constant and dosed around.
Tacrolimus
A renal transplant recipient developed a rise in whole-blood tacrolimus attributed to pomelo intake, reported in Transplantation in 2003. Tacrolimus is a CYP3A4 and P-glycoprotein substrate with an even narrower window than ciclosporin, and the same intestinal furanocoumarin mechanism applies. The evidence here is a single case rather than a controlled trial, so the size of the effect is not quantified, but it is mechanistically coherent with the controlled ciclosporin data in the same species.
Clinical note: Treat as equivalent in risk to the ciclosporin interaction and manage the same way. If a patient on tacrolimus reports eating pomelo or taking a pomelo-peel preparation and presents with tremor, headache or a creatinine rise, check a tacrolimus level before adjusting anything else.
Sildenafil
This one runs the opposite way to the expected CYP3A4 story and is worth stating precisely for that reason. In a randomised two-period two-treatment crossover study, six healthy Jordanian men took 50 mg sildenafil with pummelo juice or with water. Pummelo juice reduced both the rate and the extent of absorption to about 60% of control: Cmax fell from 212.44 to 134.07 ng/mL and AUC to infinity from 564.51 to 336.87 ng.h/mL. The authors state the direction was opposite to what they expected and speculate about a transporter effect or a physicochemical interaction in the gut lumen rather than enzyme inhibition. The sample is small, so this is a signal rather than a settled figure, but it is a controlled human crossover and it should not be reported as if pomelo raised sildenafil exposure.
Clinical note: Advise patients not to take pomelo juice or a pomelo-peel preparation with sildenafil. The practical failure mode is an apparently ineffective dose, which can lead to inappropriate dose escalation.
Oral CYP3A4 substrates with high first-pass metabolism, including felodipine, nifedipine, simvastatin, atorvastatin and midazolam
Extrapolated from the confirmed furanocoumarin content and from the two controlled human studies above, not measured drug by drug for this species. Citrus furanocoumarins inactivate enterocyte CYP3A4; the drugs whose exposure changes most are those that lose the largest fraction of an oral dose to gut-wall metabolism. The grapefruit literature, where this has been mapped drug by drug since the 1990s, is the closest available guide, but grapefruit is Citrus x paradisi, a pomelo by sweet orange hybrid, so its furanocoumarin profile is related to but not identical with the pomelo's, and the magnitudes should not be transferred quantitatively.
Clinical note: Ask specifically about pomelo, pomelo-peel preparations and Huajuhong lozenges and syrups in any patient on a CYP3A4-dependent drug with a narrow margin. Where the drug's own label carries a grapefruit warning, apply the same warning to this herb until species-specific data exist.
Photosensitising drugs and UV phototherapy
Bergapten is 5-methoxypsoralen, the agent used deliberately in photochemotherapy to sensitise skin to ultraviolet A. Its presence in citrus peel is established and phototoxic reactions to citrus peel oil on skin are well documented occupationally. What is not established is whether oral doses of the dried peel drug at pharmacopoeial amounts deliver enough systemic bergapten to matter. The interaction is recorded here because absence of an assay in the monograph is not evidence that the compound is absent.
Clinical note: Reasonable caution in patients already on PUVA, on other photosensitising drugs such as tetracyclines, amiodarone or voriconazole, or with a photosensitive dermatosis. Avoid applying the fresh peel or its oil directly to skin that will then be exposed to sun.
Substituted or adulterated Huajuhong (peel of other Citrus species sold as Huazhou juhong)
Substitution of this drug is not a modern supply-chain problem but a documented two-hundred-year-old one. Zhao Xuemin already complains of it in the Bencao Gangmu Shiyi, writing that what passes for Huazhou juhong is all counterfeited with the peel of Zengcheng fragrant pomelo. The commercial pressure is the large price premium on genuine Huazhou-grown Citrus grandis 'Tomentosa', whose peel is densely pubescent and carries the highest naringin. Cheaper Citrus peels substituted into the trade have a different flavanone profile, which is precisely why the pharmacopoeia sets a naringin floor rather than relying on morphology.
Clinical note: Buy on assay, not on appearance. Material meeting the 3.5% naringin floor is what the pharmacopoeial evidence base refers to; peel below it is a different drug. Note also that the substitute is itself a pomelo peel, so the CYP3A4 caution above still applies to adulterated material.
Dosage Calculator
⚖ Dosage Calculator
A weight-based mathematical estimate for Citrus grandis. Not a prescription.
Evidence Tier
2 RCTs · 5 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
2
2 verified · 0 unverified
Other clinical trial
0
Observational / case report
1
1 verified · 0 unverified
In vitro / animal
2
1 verified · 1 unverified
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
Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans
Open-label randomised three-way crossover in 12 healthy men, single 200 mg oral ciclosporin doses given with 240 mL pomelo juice, cranberry juice or water, 14-day washouts, blood sampled to 36 hours by LC-MS/MS. Pomelo juice raised ciclosporin AUCt to 119.4% of control (95% CI 113.4 to 125.8), AUCinf to 118.9% and Cmax to 112.1%; the AUCt increase lay outside the 80 to 125% bioequivalence interval and was called clinically significant. Cranberry juice had no meaningful effect. This is the strongest human evidence that Citrus grandis interacts with CYP3A4 and P-glycoprotein substrates. It used the juice, not the medicinal peel.
The effects of pummelo juice on pharmacokinetics of sildenafil in healthy adult male Jordanian volunteers
Randomised two-period, two-treatment, two-sequence single-dose crossover in six healthy men given 50 mg sildenafil with pummelo juice or water while fasting. Pummelo juice cut both the rate and the extent of sildenafil absorption to roughly 60% of control, with Cmax falling from 212.44 to 134.07 ng/mL and AUCinf from 564.51 to 336.87 ng.h/mL. The direction is opposite to the CYP3A4 inhibition the authors anticipated, and they attribute it tentatively to a transporter effect or a physicochemical interaction in the gut. Small sample, so treat the magnitude as provisional, but the direction matters: this is a loss-of-effect interaction.
Pomelo-induced increase in the blood level of tacrolimus in a renal transplant patient
A single-patient case report, filed here under the nearest available observational category: a renal transplant recipient's whole-blood tacrolimus rose after pomelo consumption. It is the index human report for the tacrolimus arm of this interaction and is mechanistically consistent with the controlled ciclosporin crossover, but it quantifies nothing and cannot exclude confounding by adherence or by other diet.
Exocarpium Citri Grandis alleviates the aggravation of NAFLD by mitigating lipid accumulation and iron metabolism disorders
Rodent and cell work on the medicinal peel itself rather than the juice, reporting that the extract reduces hepatic lipid accumulation and corrects iron-handling disturbance in a non-alcoholic fatty liver model. Relevant because it is one of the few studies that uses the pharmacopoeial drug, but it is preclinical: no human trial of the peel for liver disease exists, and the traditional indication is cough and phlegm, not hepatic steatosis.
Characterization of White Frost on Exocarpium Citri Grandis: Flavonoid Crystallization Enhances Anti-Inflammatory Activities
Settles a practical quality question. The white bloom that appears on dried peel is not mould: multi-technique analysis shows it is about 80% crystalline naringin by mass, formed when drying ruptures the oil glands and drives metabolites to the surface. Fungal and bacterial communities did not differ between frosted and unfrosted material and none of eight common mycotoxins was detected. Frosted extract suppressed lipopolysaccharide-induced nitric oxide, TNF-alpha, IL-6 and IL-1beta in RAW264.7 macrophages somewhat more strongly than unfrosted. Thirty minutes of boiling extracted naringin efficiently.
Historical Texts
Bencao Gangmu Shiyi (Gleanings from the Compendium of Materia Medica), Zhao Xuemin
Qing dynasty, preface dated 1765; printed 1871Bencao Gangmu (Compendium of Materia Medica), Li Shizhen
Ming dynasty, completed 1578, first printed 1596References
- Liu J, Zeng D, Hu B, Wang W, Hu S, Li H, Zhao X, Zhao H, Dai C, Lu W. Huajuhong (Citri grandis Exocarpium): Phytochemistry, bioactivities, functional food development, and artificial intelligence-driven strategies . Trends in Food Science & Technology (2026) [DOI]
- Li PF, Du YY, Zheng SL, Qian ZM, Zhou JL, Huang ZS, Hu YJ. Citri Grandis Exocarpium with medicine and food homology: A review regarding its potential anti-obesity effects and future applications . Journal of Ethnopharmacology (2026) [DOI]
- Zhang G, Li J, Xu Z, Zhou K, Zhao X, Wu X, Liang C, Lai Z, Cheng Y, Meng C, Huang J, Deng Z. Exocarpium Citri Grandis Attenuates Lipopolysaccharide-Induced Acute Liver Injury Through Suppression of Inflammatory, Apoptotic, Oxidative, and Ferroptotic Pathways . Food Science & Nutrition (2025) [DOI]
- Lin HL, Kenaan C, Hollenberg PF. Identification of the Residue in Human CYP3A4 That Is Covalently Modified by Bergamottin and the Reactive Intermediate That Contributes to the Grapefruit Juice Effect . Drug Metabolism and Disposition (2012) [DOI]
- Fuhr U. Drug Interactions with Grapefruit Juice . Drug Safety (1998) [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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