Guang Fang Ji
StarAristolochia fangchi Y.C.Wu ex L.D.Chow & S.M.Hwang
Traditionally used for
- Cough & breathing
- Urinary & fluids
Cautions & contraindications
- Kidney conditions
- Toxic — professional use only
☯ TCM Properties
Expels Wind-Dampness and clears Heat; Promotes urination and reduces edema
Traditional Chinese Uses
Safety warning: Guang Fang Ji is the root of Aristolochia fangchi and contains aristolochic acid, a nephrotoxin and carcinogen responsible for aristolochic acid nephropathy (notably the 1990s Belgian slimming-clinic cases) and urothelial carcinoma. Its medicinal standard was removed from the Chinese Pharmacopoeia in 2004 and it is banned in many countries; the description below is historical only and it must not be used.
It was formerly classed among the Dampness-dispelling herbs: pungent, bitter and cold, entering the Bladder, Lung, Spleen and Kidney channels, and used to expel Wind-Dampness while clearing Heat, and to promote urination and reduce edema. Because it shares the name element “Fang Ji,” it was dangerously confused with and substituted for Han Fang Ji (Stephania tetrandra), the intended safe herb for these indications.
Relationships
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Botanical Description
Aristolochia fangchi is a woody, deciduous climbing vine of the Aristolochiaceae, native to subtropical broadleaf forests of southern China (notably Guangdong and Guangxi) and northern Vietnam. The slender twining stems may reach 5–10 m. Alternate, long-petioled leaves are oblong-ovate to narrowly cordate, 8–18 cm long, glabrous and dull green above with paler pubescence beneath. The bilaterally symmetrical pipe-shaped flowers, characteristic of the genus, are yellow-green flushed with purple-brown markings. The cylindrical, longitudinally six-ribbed capsule splits at maturity. The medicinal organ is the dried root, cylindrical or somewhat tortuous, with a thick yellow-brown bark and pale yellow woody centre. The species contains nephrotoxic aristolochic acids and is the documented causative agent of the Belgian 'Chinese-herb nephropathy' outbreak; it is now banned or withdrawn from medicinal use in most jurisdictions.
Active Constituents
Aristolochic acid I
Nitrophenanthrene carboxylic acid (aristolochic acid)Concentration: Principal aristolochic acid of the root; content varies widely between batches and commercial sources, so no batch can be assumed low
The compound responsible for the injury attributed to this drug. It is reduced by NQO1 and CYP1A1/1A2 to a cyclic N-acylnitrenium ion that forms persistent 7-(deoxyadenosin-N6-yl)-aristolactam I adducts in DNA, driving the A:T to T:A transversion signature found in aristolochic acid associated urothelial and hepatic tumours, and it is directly toxic to the renal proximal tubule, producing hypocellular interstitial fibrosis. The International Agency for Research on Cancer classifies aristolochic acid, and plants containing it, as carcinogenic to humans (Group 1). No threshold below which exposure is safe has been demonstrated.
Aristolochic acid II
Nitrophenanthrene carboxylic acid (aristolochic acid)Concentration: Second most abundant aristolochic acid in the root, generally below aristolochic acid I
Shares the nitroreduction and DNA-adduct pathway of aristolochic acid I and contributes to the total genotoxic burden of the drug. Analytical methods that quantify only aristolochic acid I therefore understate exposure.
Aristolochic acid IIIa
Nitrophenanthrene carboxylic acid (aristolochic acid)Concentration: Minor component of the root
A hydroxylated aristolochic acid recorded in this species by the IARC review of Aristolochia constituents. It is one reason total aristolochic acid content, rather than a single marker, is the relevant exposure measure.
Aristolactam I
Aristolactam (phenanthrene lactam) alkaloidConcentration: Present in the root
Both a native constituent and the reductive metabolite of aristolochic acid I. Its presence is used analytically as a marker of Aristolochia material, and aristolactam-DNA adducts are the biomarker used to establish past exposure in patients decades after ingestion.
Magnoflorine
Aporphine quaternary alkaloidConcentration: Present in the root
A quaternary aporphine alkaloid shared with several unrelated medicinal roots. It is of analytical rather than therapeutic interest here, because it is one of the fifteen alkaloids used to separate Aristolochia fangchi from Stephania tetrandra chromatographically.
Mufongchins A, B, C and D
Sesquiterpene-type constituents characteristic of the speciesConcentration: Minor constituents of the root
Constituents recorded specifically from Aristolochia fangchi in the IARC review of the species. They have no established pharmacology and are noted here only as species-characteristic markers.
Allantoin
Purine metabolite (imidazolidinyl urea derivative)Concentration: Minor constituent of the root
A widely distributed plant purine metabolite recorded in this root. It carries no clinical significance relative to the aristolochic acid content.
Beta-sitosterol
PhytosterolConcentration: Minor constituent of the root
A ubiquitous plant sterol recorded among the neutral constituents of the root, of no clinical relevance in this drug.
Tetrandrine
Bisbenzylisoquinoline alkaloidConcentration: Absent from Aristolochia fangchi; the marker of Stephania tetrandra, the drug this one is confused with
Listed here as a negative marker. Tetrandrine and fangchinoline are the characteristic alkaloids of Han Fang Ji (Stephania tetrandra); their absence, together with detectable aristolochic acid I, is what identifies a sample as Aristolochia fangchi. Analysis of twelve powder batches supplied to Belgian clinics as Stephania tetrandra found ten containing aristolochic acids only, one containing both, and one containing tetrandrine only.
⚠ Drug Interactions
Han Fang Ji (Stephania tetrandra)
This is the substitution that caused the Belgian slimming-clinic epidemic and is the principal route by which patients are exposed to this drug. Both roots are sold under the shared trade name fang ji, and they are morphologically similar in sliced form. Between 1990 and 1992 Belgian clinics dispensing a weight-loss regimen received consignments labelled Stephania tetrandra that were in fact Aristolochia fangchi; chemical analysis of the powders confirmed aristolochic acid where tetrandrine should have been. Roughly 100 patients developed rapidly progressive hypocellular interstitial renal fibrosis, about 70 percent of them reaching end-stage renal disease. Of 39 patients who went on to prophylactic nephroureterectomy, 18 were found to have urothelial carcinoma, with a positive dose-response relationship to the cumulative amount of the herb consumed. Renal function decline was proportional to the estimated ingested dose of the substituted material. The confusion runs in both directions: material sold as Han Fang Ji may be Aristolochia fangchi, and material sold as Guang Fang Ji may be Stephania tetrandra.
Clinical note: Do not treat these as interchangeable and do not accept a supplier's fang ji label. Aristolochia fangchi must not be dispensed at all. Where Stephania tetrandra is intended, require certificate-of-analysis evidence of tetrandrine and fangchinoline and of the absence of aristolochic acid I; the United Kingdom prohibition order bans Stephania tetrandra alongside Aristolochia precisely because the label cannot be trusted. Any patient with a history of fang ji or slimming-preparation use in the 1990s warrants renal function testing and lifelong urothelial surveillance regardless of current symptoms.
Mu Fang Ji (Cocculus orbiculatus and Cocculus trilobus)
The name fang ji is shared by three unrelated drugs: Han Fang Ji from Stephania tetrandra (Menispermaceae), Mu Fang Ji from Cocculus orbiculatus or Cocculus trilobus (Menispermaceae), and Guang Fang Ji from Aristolochia fangchi (Aristolochiaceae). The three-way ambiguity is the mechanism of exposure, because a prescription or a supplier invoice reading simply fang ji does not determine which botanical source arrives. The United Kingdom prohibition order lists Cocculus laurifolius, Cocculus orbiculatus and Cocculus trilobus alongside Aristolochia and Stephania tetrandra for this reason.
Clinical note: Prescribe and purchase by binomial, never by the bare pinyin fang ji. Treat any consignment identified only as fang ji as of unknown botanical origin and unsuitable for dispensing until assayed for aristolochic acid I.
Guan Mu Tong (Aristolochia manshuriensis), Qing Mu Xiang (Aristolochia debilis) and Xi Xin (Asarum species)
Injury from aristolochic acid tracks cumulative lifetime dose, and every additional aristolochic-acid-bearing drug adds to it. Aristolochia manshuriensis substituted for Mu Tong caused a separate large series of end-stage renal disease in China, and Aristolochia debilis was used as Qing Mu Xiang; Asarum species contain lower but non-zero amounts. The Chinese regulator cancelled the drug standards for Guan Mu Tong in 2003 and for Guang Fang Ji and Qing Mu Xiang in 2004, and in the same 2004 notice required aristolochic acid warnings on preparations containing Aristolochia debilis fruit, Aristolochia mollissima, Aristolochia contorta stem and Aristolochia tuberosa. Aristolochia and Asarum species are also documented adulterants of one another and of unrelated drugs, so exposure may be unrecorded on any prescription.
Clinical note: Take a cumulative exposure history rather than asking about a single herb, and include Chinese proprietary medicines taken before the 2003 and 2004 standard cancellations. There is no dose at which co-administration becomes acceptable; the correct total exposure is zero.
Nonsteroidal anti-inflammatory drugs
Aristolochic acid nephropathy produces a hypocellular interstitial fibrosis with severe loss of proximal tubule mass and reduced renal reserve. Nonsteroidal anti-inflammatory drugs reduce prostaglandin-dependent afferent arteriolar vasodilatation and are an established cause of acute-on-chronic decline in patients with existing tubulointerstitial disease. Concomitant analgesic use was also examined as a confounder in the Belgian cohort and could not account for the lesion, which was attributed to aristolochic acid, but it remains an avoidable additional insult in exposed patients.
Clinical note: In any patient with known or suspected aristolochic acid exposure, avoid nonsteroidal anti-inflammatory drugs and other nephrotoxic agents including aminoglycosides, cisplatin, iodinated contrast and calcineurin inhibitors where alternatives exist, and monitor serum creatinine and estimated glomerular filtration rate.
Fenfluramine, diethylpropion, acetazolamide and meprobamate
The Belgian slimming preparation combined the substituted Chinese herb powders with appetite suppressants and other synthetic agents, and these were examined as possible contributors when the epidemic was first described in 1993. Subsequent identification of aristolochic acid in the powders, detection of aristolactam-DNA adducts in patient tissue, reproduction of the nephropathy in animals and the appearance of the same lesion in unrelated populations exposed to Aristolochia without any of these drugs established aristolochic acid as the cause. They are recorded here so that a patient history mentioning appetite suppressants is recognised as a marker of possible aristolochic acid exposure.
Clinical note: Treat a history of 1990s slimming-clinic preparations, particularly Belgian ones, as presumptive aristolochic acid exposure and investigate renal function and urothelium accordingly, even if the patient recalls only the synthetic drugs.
Ciclosporin and tacrolimus
Many patients injured by this drug progress to renal transplantation and then receive calcineurin inhibitors, which are themselves nephrotoxic to the graft. Independently, aristolactam-DNA adducts persist in urothelium for decades after exposure ends, so the risk of urothelial carcinoma continues in the transplanted patient while under immunosuppression. Urothelial tumours were found in 18 of 39 exposed Belgian patients undergoing prophylactic nephroureterectomy at the time of, or in preparation for, transplantation.
Clinical note: In transplant candidates with documented aristolochic acid exposure, urothelial assessment of the native urinary tract belongs in the pre-transplant workup, and surveillance must continue after grafting.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| not recommended | Not established — should not be dispensed | — | — | — | **This drug should not be dispensed.** Guang Fang Ji (广防己) is the root of Aristolochia fangchi. All Aristolochia species contain aristolochic acid, which causes irreversible aristolochic acid nephropathy and urothelial carcinoma, and is an IARC Group 1 human carcinogen. This is the drug behind the Belgian slimming-clinic nephropathy cluster of the 1990s, in which more than 100 patients developed renal failure and many later urothelial cancer. It has no monograph in the Chinese Pharmacopoeia 2020 — the aristolochic-acid drugs were delisted — so no dose is given here and none is defensible. Safe substitutes that ARE in ChP 2020: Mu Tong (Akebiae Caulis, 3–6 g) replaces the Aristolochia 'mu tong' drugs, and Fang Ji (Stephaniae Tetrandrae Radix, 5–10 g) replaces the Aristolochia 'fang ji' drugs. |
Evidence Tier
Moderate evidence · 9 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
9
1 verified · 8 unverified
Show 9 studies
- Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs
- Urothelial lesions in Chinese-herb nephropathy
- Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi)
- Progression rate of Chinese herb nephropathy: impact of Aristolochia fangchi ingested dose
- Aristolochic acid and the etiology of endemic (Balkan) nephropathy
- Aristolochic acid-associated urothelial cancer in Taiwan
- Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing
- Genome-Wide Mutational Signatures of Aristolochic Acid and Its Application as a Screening Tool
- Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia
In vitro / animal
0
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
Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs
The index report of the Belgian epidemic. Nine young women attending a Brussels slimming clinic developed rapidly progressive interstitial renal fibrosis; the regimen had been altered in 1990 to include powdered Chinese herbs nominally Stephania tetrandra and Magnolia officinalis. Renal biopsy showed extensive hypocellular interstitial fibrosis with tubular atrophy and relative sparing of glomeruli. The paper identified the herbal component of the regimen as the suspect exposure before the responsible compound was known.
Urothelial lesions in Chinese-herb nephropathy
Examination of the urinary tract in Belgian patients with end-stage Chinese-herb nephropathy found multifocal, high-grade atypia and carcinoma of the urothelium extending along the whole urinary tract, not confined to the kidney. This established that the lesion was a field change of the entire urothelium and provided the rationale for prophylactic removal of the native kidneys and ureters rather than surveillance alone.
Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi)
The decisive human study. Thirty-nine patients with end-stage Chinese-herb nephropathy who had taken the substituted preparation underwent prophylactic nephroureterectomy; 18 had urothelial carcinoma and a further 19 had mild to moderate urothelial dysplasia, so only 2 specimens were normal. The cumulative dose of Aristolochia fangchi ingested predicted the presence of carcinoma. Aristolactam-DNA adducts were detected in the tissue of the majority of patients tested, linking the tumours directly to aristolochic acid rather than to any other component of the regimen.
Progression rate of Chinese herb nephropathy: impact of Aristolochia fangchi ingested dose
Analysis of the Belgian cohort showed that the rate of decline in renal function was determined by the cumulative dose of the substituted Aristolochia fangchi material rather than by the duration of the slimming regimen or the other drugs it contained. This dose-dependence is the basis for treating any quantified exposure as clinically meaningful and for the absence of a demonstrated safe intake.
Aristolochic acid and the etiology of endemic (Balkan) nephropathy
In Croatian patients with endemic nephropathy and upper urinary tract cancer, aristolactam-DNA adducts were found in renal tissue and A:T to T:A transversions were found in TP53 in tumours, matching the mutational fingerprint of aristolochic acid. The exposure route here was dietary contamination of wheat by Aristolochia clematitis seed, a different species from Aristolochia fangchi, which is important because it shows the same lesion arises from the aristolochic acid itself rather than from anything peculiar to the Belgian preparation.
Aristolochic acid-associated urothelial cancer in Taiwan
In 151 Taiwanese patients with upper urinary tract urothelial carcinoma, aristolactam-DNA adducts were detected in 83 percent of renal tissue samples and the A:T to T:A TP53 signature in 44 of 60 tumours sequenced, in a population with exceptionally high prescribed use of aristolochic-acid-containing herbs. The study extends the risk from a single contaminated slimming regimen to routine prescribing of Aristolochia drugs.
Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing
Whole-exome sequencing of upper urinary tract tumours from patients with documented aristolochic acid exposure found a very high somatic mutation burden dominated by A:T to T:A transversions at the sequence context characteristic of aristolactam-adenine adducts. The signature is specific enough to identify past aristolochic acid exposure from tumour DNA alone, which is how exposure is confirmed in patients who cannot recall what they took.
Genome-Wide Mutational Signatures of Aristolochic Acid and Its Application as a Screening Tool
Whole-genome sequencing of upper tract urothelial carcinomas defined the genome-wide aristolochic acid signature and showed it could be used to screen tumour series for unrecognised exposure. Applying it revealed aristolochic acid exposure in cases where no herbal history had been recorded, indicating that the exposed population is larger than clinical reporting suggests.
Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia
Screening 1400 hepatocellular carcinoma genomes across Asia found the aristolochic acid mutational signature in 78 percent of Taiwanese cases and substantial proportions elsewhere in Asia, versus about 5 percent in Europe and North America. This extends the organ risk beyond the urinary tract to the liver and shows the exposure is not historical or confined to one country.
⚠ Safety & Contraindications
- Kidney conditions
- Toxic — professional use only
Safety Warnings
- Aristolochic acid — nephrotoxic and carcinogenic (aristolochic-acid nephropathy, urothelial cancer). Not for internal use; illegal to dispense.
Regulatory Status
- Banned in China (removed from the Pharmacopoeia in 2004); prohibited or restricted in the US/EU. Contains aristolochic acid.
⚠ Toxicity Information
Historical Texts
Shen Nong Ben Cao Jing
Eastern Han dynasty, compiled by the 2nd century CEBen Cao Gang Mu, Li Shizhen
Ming dynasty, 1596Pharmacopoeia of the People's Republic of China
Editions from 1963 to 2000State Food and Drug Administration of China, document Guo Shi Yao Jian Zhu (2004) No. 379
2004Belgian slimming-clinic case series, Brussels
1990 to 1992, reported from 1993The Medicines (Aristolochia and Mu Tong etc.) (Prohibition) Order 2001, United Kingdom
2001, in force 1 July 2001References
- Vanhaelen M, Vanhaelen-Fastre R, But P, Vanherweghem JL. Identification of aristolochic acid in Chinese herbs . The Lancet (1994) [DOI]
- Lord GM, Cook T, Arlt VM, Schmeiser HH, Williams G, Pusey CD. Urothelial malignant disease and Chinese herbal nephropathy . The Lancet (2001) [DOI]
- Schaneberg BT, Khan IA. Analysis of products suspected of containing Aristolochia or Asarum species . Journal of Ethnopharmacology (2004) [DOI]
- Koh HL, Wang H, Zhou S, Chan E, Woo SO. Detection of aristolochic acid I, tetrandrine and fangchinoline in medicinal plants by high performance liquid chromatography and liquid chromatography/mass spectrometry . Journal of Pharmaceutical and Biomedical Analysis (2006) [DOI]
- Yuan J, Liu Q, Wei G, Tang F, Ding L, Yao S. Characterization and determination of six aristolochic acids and three aristololactams in medicinal plants and their preparations by high-performance liquid chromatography-photodiode array detection/electrospray ionization mass spectrometry . Rapid Communications in Mass Spectrometry (2007) [DOI]
- Debelle FD, Vanherweghem JL, Nortier JL. Aristolochic acid nephropathy: A worldwide problem . Kidney International (2008) [DOI]
- Gokmen MR, Cosyns JP, Arlt VM, Stiborova M, Phillips DH, Schmeiser HH, Simmonds MSJ, Cook HT, Vanherweghem JL, Nortier JL, Lord GM. The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy . Annals of Internal Medicine (2013) [DOI]
- Tankeu S, Vermaak I, Chen W, Sandasi M, Viljoen A. Differentiation between two "fang ji" herbal medicines, Stephania tetrandra and the nephrotoxic Aristolochia fangchi, using hyperspectral imaging . Phytochemistry (2016) [DOI]
- Jadot I, Decleves AE, Nortier J, Caron N. An Integrated View of Aristolochic Acid Nephropathy: Update of the Literature . International Journal of Molecular Sciences (2017) [DOI]
- Das S, Thakur S, Korenjak M, Sidorenko VS, Chung FFL, Zavadil J. Aristolochic acid-associated cancers: a public health risk in need of global action . Nature Reviews Cancer (2022) [DOI]
- International Agency for Research on Cancer. Plants Containing Aristolochic Acid . IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 100A: Pharmaceuticals (2012)
- International Agency for Research on Cancer. Aristolochia species and aristolochic acids . IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 82: Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene (2002)
- United Kingdom Secretary of State for Health. The Medicines (Aristolochia and Mu Tong etc.) (Prohibition) Order 2001 . UK Statutory Instruments 2001 No. 1841 (2001)
- State Food and Drug Administration of China. Notice on strengthening the supervision and administration of Guang Fang Ji and five other medicinal materials and their preparations . State Food and Drug Administration document Guo Shi Yao Jian Zhu (2004) No. 379 (2004)
- United States Food and Drug Administration. Import Alert 54-10: Detention Without Physical Examination of Bulk/Finished Dietary Supplement Products Containing Aristolochic Acid . US Food and Drug Administration Import Alerts (2020)
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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