Zhu Sha Lian
StarAristolochia cinnabarina C.Y.Cheng & J.L.Wu
Traditionally used for
- Nose & throat
- Digestion
- Bowel health
- Skin
☯ TCM Properties
Clears Heat and removes toxicity; Regulates Qi, invigorates the Blood, breaks up Blood Stasis and alleviates pain
Traditional Chinese Uses
Zhu Sha Lian (朱砂莲, "cinnabar lotus") is the tuberous root of Aristolochia cinnabarina and related Aristolochia species, used in southwestern China. Bitter, acrid and cold, it was traditionally described as clearing heat and resolving toxicity, and as regulating qi and invigorating the blood to break up stasis and stop pain. Historically it was taken for enteritis, dysentery, sore throat, and stomach and abdominal pain, and applied to snakebite and sores.
Safety: as an Aristolochia, this root contains aristolochic acid, which is nephrotoxic and carcinogenic and causes irreversible kidney failure and urothelial cancer. It is banned or restricted in many countries. This information is provided for historical and reference purposes only; the herb must not be used medicinally, and any product containing Aristolochia should be avoided.
Relationships
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Botanical Description
Zhu Sha Lian (朱砂莲), literally "cinnabar lotus," is a regional folk-name applied in southwestern China most commonly to the tuberous root of certain Aristolochia species (notably Aristolochia tuberosa C. F. Liang & S. M. Hwang or A. cinnabarina), and in some sources to Loropetalum chinense red-leaved cultivars or particular Polygala species. The candidate Aristolochia identification is clinically significant because plants in that genus contain aristolochic acids, which are nephrotoxic and carcinogenic and are banned or strictly restricted in many jurisdictions. Without a corroborating Latin name on the source record the identification cannot be confirmed, and the safety implications make speculative assignment inappropriate. The entry follows the unidentifiable null-pattern and should be flagged for source-record verification and toxicological review.
Active Constituents
Aristolochic acid I (aristolochic acid A)
Nitrophenanthrene carboxylic acidConcentration: the principal aristolochic acid of this species. In a 52-batch comparative survey, 21 batches of A. cinnabarina root tuber from Sichuan and Yunnan carried total aristolochic acid contents considerably higher than either A. mollissima or A. debilis, with AA I, AA II, AA IIIa and AA IVa all present in large amounts; AA I, AA II, AA IIIa and aristolactam I in A. cinnabarina exceeded those in A. mollissima by roughly 30-400%.
Aristolochic acid I is a proven human nephrotoxin and is classified by IARC in Group 1, carcinogenic to humans. After reductive activation, principally by NAD(P)H:quinone oxidoreductase and by sulfotransferases in renal tissue, it forms aristolactam-DNA adducts that persist in kidney and urothelium for decades and generate the characteristic A:T to T:A transversion mutational signature seen in aristolochic-acid-associated upper urinary tract, renal and hepatocellular cancers. The renal lesion is a rapidly progressive hypocellular interstitial fibrosis that does not reverse on withdrawal. No threshold below which exposure is safe has been demonstrated.
Aristolochic acid II
Nitrophenanthrene carboxylic acidConcentration: present in this species; isolated from methanolic extracts of fresh A. cinnabarina root in 1994 and confirmed among the 45 aristolochic-acid-type analogues detected in 21 batches of the root tuber by UPLC-QTOF-MS/MS
Shares the nitrophenanthrene core and the aristolactam-adduct pathway of AA I. It was less cytotoxic than AA I to HepG2 cells and caused less comet-assay DNA damage in the same experiments, but it is not a safe congener: it is bioactivated by the same reductive route and is covered by the same regulatory prohibitions.
Aristolochic acid IIIa (AA C) and aristolochic acid IVa (AA D)
Hydroxylated and methoxylated nitrophenanthrene carboxylic acidsConcentration: both reported in large amounts in A. cinnabarina root tuber, alongside AA I and AA II
Hydroxy and methoxy analogues of the parent acids. They are reduced to the corresponding aristolactams and contribute to the total aristolactam-adduct burden. Their presence is the main reason that assays limited to AA I and AA II understate the true exposure from an Aristolochia root.
Aristolactams (aristolactam I and 15 further aristolactams)
Phenanthrene lactam alkaloidsConcentration: 16 aristolactams were among the 45 aristolochic-acid-type analogues identified in A. cinnabarina; aristolactam I in this species exceeded that in A. mollissima by roughly 30-400%
Aristolactams are both natural constituents and the reductive metabolites through which aristolochic acids bind DNA. Aristolactam-DNA adducts recovered from renal cortex are the accepted biomarker of aristolochic acid exposure. Aristolactam BII was the most cytotoxic single compound tested against HepG2 cells in the comparative study, with an IC50 of 0.2 micromolar, although that particular congener was detected only in A. mollissima.
Aristolochic acid IIIa-6-O-beta-D-glucoside, cepharanone-A N-beta-D-glucoside and 2-hydroxy-8-methyloxycepharanone-A
Aristolochic acid and aristolactam glycosidesConcentration: three compounds first described from methanolic extracts of fresh A. cinnabarina roots, isolated together with eight known aristolochic acid derivatives
Glycosylated forms of the aristolochic acid and aristolactam skeletons. They are relevant because they are not measured by routine free-AA-I assays and can be hydrolysed to the aglycones, so a batch reported as low in free aristolochic acid may still carry a substantial conjugated reservoir.
Cinnabarin, aristoliukine C, aristophyllides C, aristchamic A, 7-hydroxy-aristolochic acid I and aristolochic acid I methyl ester
Aristolochic acid analogues (species-characteristic markers)Concentration: detected only in A. cinnabarina among the three Aristolochia herbs compared; used as chemometric markers distinguishing this species from A. mollissima and A. debilis
A group of analogues that appear to be characteristic of this species. Their toxicology has not been studied individually, but they belong to the same nitrophenanthrene and aristolactam families and there is no basis for treating them as inert.
⚠ Drug Interactions
Any nephrotoxic drug (NSAIDs, aminoglycosides, cisplatin, calcineurin inhibitors, tenofovir, iodinated contrast media)
Aristolochic acid nephropathy is a hypocellular interstitial fibrosis with tubular atrophy that continues to progress after the herb is stopped; in the Belgian cohort the rate of progression tracked the cumulative Aristolochia dose ingested. Anything that adds a further tubular insult, or that reduces renal perfusion, compounds a lesion that has no recovery phase. Rats with pre-existing chronic renal failure have been shown to be markedly more sensitive to aristolochic acids than animals with normal kidneys.
Clinical note: This is not a manageable interaction. Aristolochia-derived material should not be dispensed at all; if exposure has occurred, monitor eGFR and arrange long-term urothelial surveillance rather than adjusting co-medication.
Stephania tetrandra (Han Fang Ji), Akebia/Clematis Mu Tong and Aucklandia lappa (Mu Xiang), for which Aristolochia species are documented substitutes
The Belgian slimming-clinic outbreak arose when Stephania tetrandra (Han Fang Ji) in a compounded preparation was replaced by Aristolochia fangchi (Guang Fang Ji); of 39 patients from that cohort who underwent prophylactic nephroureterectomy, 18 had urothelial carcinoma and 19 more had mild to moderate urothelial dysplasia, and the risk rose with cumulative dose. Aristolochia manshuriensis (Guan Mu Tong) has similarly been supplied for Mu Tong and Aristolochia debilis (Qing Mu Xiang) for Mu Xiang. Zhu Sha Lian is exposed to the same hazard in reverse: it is a regional Sichuan and Yunnan folk drug with no Chinese Pharmacopoeia monograph, and the pinyin name gives no hint that the material is an Aristolochia. The name is also applied in some sources to Aristolochia tuberosa, another aristolochic-acid-bearing species, so the pinyin does not even fix a single binomial.
Clinical note: Verify the botanical identity of any Fang Ji, Mu Tong or Mu Xiang from a supply chain that also handles Aristolochia, and treat any material identified as Zhu Sha Lian, by whichever binomial, as unusable.
NQO1 and sulfotransferase substrates and modulators
Cytosolic NAD(P)H:quinone oxidoreductase is the principal enzyme reducing aristolochic acid I to the reactive N-hydroxyaristolactam, and human sulfotransferases, which are expressed in the renal target tissue, further activate the hydroxylamine to the DNA-binding species. In principle, agents that induce these enzymes would increase adduct formation. No clinical interaction study exists, and the theoretical nature of the interaction is not a reason to regard any level of exposure as acceptable.
Clinical note: Of mechanistic interest only. It does not create a safe co-prescribing strategy, because there is no exposure level at which the herb becomes acceptable.
Cytochrome P450 1A1 and 1A2 substrates, inducers and inhibitors (tobacco smoke, omeprazole, fluvoxamine, ciprofloxacin)
Human CYP1A1 and CYP1A2 chiefly detoxify aristolochic acid I by O-demethylation to aristolochic acid Ia under aerobic conditions, but the same enzymes reductively activate it under low oxygen tension, so their net contribution depends on tissue oxygenation. This has been demonstrated in human recombinant enzyme and knockout-mouse systems, not in patients.
Clinical note: Mechanistic background only; it does not translate into a dose adjustment or a safe combination.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| not recommended | Not established — see note | — | — | — | No Chinese Pharmacopoeia 2025 monograph for this drug, so no pharmacopoeial dose is given here. **This drug should not be dispensed.** Zhu Sha Lian is *Aristolochia cinnabarina*, and *Aristolochia* species contain aristolochic acid, which is nephrotoxic and a Group 1 human carcinogen; it causes irreversible interstitial fibrosis (aristolochic acid nephropathy) and urothelial carcinoma, and is implicated in Balkan endemic nephropathy. Aristolochic-acid-containing herbs are banned or restricted in the EU, UK, USA, Canada and elsewhere, and China removed the *Aristolochia* species Guan Mu Tong, Guang Fang Ji and Qing Mu Xiang from the Pharmacopoeia for this reason. No dose is given because no dose is defensible. The previous value was generic filler generated from tcm_category and has been removed rather than replaced with an estimate. |
Evidence Tier
Moderate evidence · 4 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
2
0 verified · 2 unverified
In vitro / animal
2
0 verified · 2 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
Comparative Analysis of Aristolochic Acids in Aristolochia Medicinal Herbs and Evaluation of Their Toxicities
The only substantial quantitative work located on this species. Fifty-two batches of three Aristolochia drugs were profiled by UPLC-QTOF-MS/MS, including 21 batches of A. cinnabarina root tuber (abbreviated ACY) from Sichuan and Yunnan. Forty-five aristolochic-acid-type analogues were identified in A. cinnabarina, comprising 29 aristolochic acids and 16 aristolactams, more than in A. mollissima (44) or A. debilis (41). Total aristolochic acid content in A. cinnabarina was considerably higher than in either comparator; AA I was the principal component; AA I, AA II, AA IIIa and aristolactam I exceeded the levels in A. mollissima by roughly 30-400%; and cinnabarin, aristoliukine C, aristophyllides C, aristchamic A, 7-hydroxy-AA I and AA I methyl ester were detected only in this species. The authors concluded that A. cinnabarina is the most toxic of the three. Cytotoxicity and comet-assay genotoxicity were run on isolated compounds and on the A. mollissima and A. debilis extracts, with aristolactam BII, AA I and the A. mollissima extract giving IC50 values of 0.2, 9.7 and 50.2 micromolar against HepG2 cells; the A. cinnabarina extract itself was not put through the cell assays, so the toxicity conclusion for this species rests on its chemistry rather than on direct cell testing.
Eleven aristolochic acid derivatives from Aristolochia cinnabarina
The original phytochemical study of this species. Three new compounds, aristolochic acid IIIa-6-O-beta-D-glucoside, cepharanone-A N-beta-D-glucoside and 2-hydroxy-8-methyloxycepharanone-A, were isolated from methanolic extracts of fresh Aristolochia cinnabarina roots together with eight known aristolochic acid derivatives. It establishes that the aristolochic acid and aristolactam chemistry of the genus is present in this species, and that part of it circulates as glycosides that free-aglycone assays would miss.
Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi)
The defining human evidence, obtained with Aristolochia fangchi rather than A. cinnabarina. Thirty-nine patients from the Belgian nephropathy cohort underwent prophylactic nephroureterectomy; 18 had urothelial carcinoma of the upper urinary tract and 19 of the remainder had mild to moderate urothelial dysplasia. Aristolactam-DNA adducts were detected in the urothelial tissue, and the cancer risk rose with the cumulative dose of Aristolochia ingested. The finding is cited here because the mechanism is a property of aristolochic acid, which A. cinnabarina carries at higher total levels than the better-studied Aristolochia drugs.
Increased risks of chronic kidney disease associated with prescribed Chinese herbal products suspected to contain aristolochic acid
A population-based cohort study using Taiwan's National Health Insurance prescription records, in which prescribed Chinese herbal products suspected of containing aristolochic acid were associated with an increased risk of chronic kidney disease, with a dose-response relationship. The exposure was to aristolochic-acid-containing herbal products generally, not to Aristolochia cinnabarina specifically.
References
- Michl J, Ingrouille MJ, Simmonds MSJ, Heinrich M. Naturally occurring aristolochic acid analogues and their toxicities . Natural Product Reports (2014) [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]
- Debelle FD, Vanherweghem JL, Nortier JL. Aristolochic acid nephropathy: A worldwide problem . Kidney International (2008) [DOI]
- Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Suzuki N, Fernandes A, Rosenquist T, Medverec Z, Jakovina K, Brdar B, Slade N, Turesky RJ, Goodenough AK, Rieger R, Vukelic M, Jelakovic B. Aristolochic acid and the etiology of endemic (Balkan) nephropathy . Proceedings of the National Academy of Sciences (2007) [DOI]
- Jelakovic B, Karanovic S, Vukovic-Lela I, Miller F, Edwards KL, Nikolic J, Tomic K, Slade N, Brdar B, Turesky RJ, Stipancic Z, Dittrich D, Grollman AP, Dickman KG. Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid . Kidney International (2012) [DOI]
- Chen CH, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL, Gnatenko DV, Wu L, Turesky RJ, Wu XR, Pu YS, Grollman AP. Aristolochic acid-associated urothelial cancer in Taiwan . Proceedings of the National Academy of Sciences (2012) [DOI]
- Ng AWT, Poon SL, Huang MN, Lim JQ, Boot A, Yu W, Suzuki Y, Thangaraju S, Ng CCY, Tan P, Pang ST, Huang HY, Yu MC, Lee PH, Hsieh SY, Chang AY, Teh BT, Rozen SG. Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia . Science Translational Medicine (2017) [DOI]
- Lai MN, Wang SM, Chen PC, Chen YY, Wang JD. Population-Based Case-Control Study of Chinese Herbal Products Containing Aristolochic Acid and Urinary Tract Cancer Risk . JNCI Journal of the National Cancer Institute (2009) [DOI]
- Stiborova M, Levova K, Barta F, Shi Z, Frei E, Schmeiser HH, Nebert DW, Phillips DH, Arlt VM. Bioactivation versus Detoxication of the Urothelial Carcinogen Aristolochic Acid I by Human Cytochrome P450 1A1 and 1A2 . Toxicological Sciences (2011) [DOI]
- Meinl W, Pabel U, Osterloh-Quiroz M, Hengstler JG, Glatt H. Human sulphotransferases are involved in the activation of aristolochic acids and are expressed in renal target tissue . International Journal of Cancer (2005) [DOI]
- de Souza VV, De Andrade LR, da Silva Souza T. Beyond Tradition: An Integrated Toxicological, Ecological, and Public Health Perspective on Aristolochic Acids . Journal of Applied Toxicology (2026) [DOI]
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Aristolochic acids and plants containing them . IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 100A: Pharmaceuticals (2012)
- National Toxicology Program. Aristolochic Acids . Report on Carcinogens, Fifteenth Edition, U.S. Department of Health and Human Services (2021)
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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