Zhu Ya Zao
StarGleditsia sinensis Lam.
Traditionally used for
- Cough & breathing
- Skin
Cautions & contraindications
- Pregnancy
- Breastfeeding
- Toxic — professional use only
☯ TCM Properties
Expels Phlegm and Opens the Orifices; Disperses Swelling and Dissipates Nodules; Opens the Orifices and Revives Consciousness; Disperses Wind; Expels Parasites
Traditional Chinese Uses
Zhu Ya Zao (honeylocust thorn) is a warm, acrid herb used to promote the discharge and rupture of deep-seated abscesses and carbuncles in the suppurative stage, facilitating drainage and healing. It also expels Wind, kills parasites, and is applied for skin conditions involving Wind-type itching, scabies, and similar parasitic disorders. Due to its strong dispersing action, it is used cautiously and contraindicated in pregnancy.
Relationships
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Botanical Description
Gleditsia sinensis Lam. (Fabaceae) is a deciduous tree native to China, reaching 15-30 m, with stout branched thorns on the trunk and pinnately compound leaves. It produces large, dark brown leguminous pods, but the medicinal Zhu Ya Zao (literally 'pig-tooth pod') consists of the small, abortive, sickle-shaped underdeveloped pods, only 5-10 cm long, used in traditional Chinese medicine. The pods are rich in triterpenoid saponins (gleditsia saponins), which are strongly irritant and surface-active. In TCM, Zhu Ya Zao is acrid, warm, and slightly toxic; it enters the lung and large intestine channels to forcefully dispel phlegm, open the orifices, and induce sneezing or vomiting in patients with phlegm obstruction, sudden loss of consciousness, or wind-stroke. It is used cautiously and rarely in modern practice due to its strong action.
Active Constituents
Gleditsia saponin C
Oleanane-type triterpenoid saponinConcentration: A principal saponin of the abortive pod; the saponin fraction is what the drug is standardised and assayed on.
Isolated specifically from Gleditsiae Fructus Abnormalis, gleditsia saponin C kills A549 lung carcinoma cells through a caspase-dependent cascade with a raised Bax to Bcl-2 ratio and inhibition of ERK and Akt signalling, and it suppressed tumour growth in a mouse xenograft. This is preclinical oncology work, not a basis for prescribing the pod as a cancer treatment.
Triterpenoid saponin fraction (gleditsiosides)
Triterpenoid saponin mixtureConcentration: Dominant active and toxic fraction; thirteen saponins were isolated from the abnormal fruit in one bioassay-guided study alone.
The saponins are simultaneously the therapeutic and the toxic principle. They irritate mucous membranes, which is how powdered pod insufflated into the nose provokes sneezing and expectoration, and how it loosens phlegm when swallowed. Absorbed in quantity the same saponins are haemolytic and act on the central nervous system, with convulsion followed by paralysis and death from respiratory centre failure described in overdose. Structure-activity work on thirteen saponins from the abnormal fruit mapped the features required for cytotoxicity and apoptosis induction.
Echinocystic acid and oleanolic acid
Triterpene saponin aglyconesConcentration: Quantified by HPLC with diode array detection; content did not differ significantly between the abortive pod and the mature pod.
The two aglycones released on hydrolysis of the pod saponins, used as quantitative markers. Their near-identical levels in the abortive and the mature pod, against clearly different full fingerprints, is the reason the two drugs cannot be told apart on aglycone assay alone.
Volatile oil (paeonol, linalool, citral, methyleugenol, palmitate)
Essential oilConcentration: Forty components resolved by GC-MS, with paeonol about 5.2 percent, palmitate about 4.69 percent, linalool about 3.31 percent and citral about 2.65 percent of the oil.
The volatile fraction, given intranasally, reduced infarct volume, brain water content, inflammatory cytokines and apoptotic markers in high-fat-diet and middle cerebral artery occlusion rats, which is the modern reading of the drug's traditional use for stroke from phlegm and blood stasis. Methyleugenol is among the identified components and is a genotoxic rodent carcinogen classified by IARC as possibly carcinogenic to humans, which argues against long-term or high-dose use of the oil.
Flavonoids and phenolic glycosides (saikachinoside A, locustoside A, vitexin, orientin, isoquercitrin, luteolin, quercetin, apigenin, taxifolin, quercitrin)
Flavonoid and phenolic glycosideConcentration: Quantified together with two alkaloids across the three Gleditsia drugs; alkaloid content in the abortive pod, 0.03 to 10.41 micrograms per gram, is far below that of the mature pod at 2.03 to 834.75 micrograms per gram.
A minor fraction relative to the saponins, and the basis on which the abortive pod, the mature pod and the thorn can be told apart analytically. The large alkaloid gap between the abortive and the mature pod is the clearest single chemical argument against treating them as interchangeable.
⚠ Drug Interactions
Zao Jiao, the mature pod (Gleditsiae Sinensis Fructus)
Zhu Ya Zao is the small, curved, sterile pod set by an aged or wounded Gleditsia sinensis tree, and in cultivation it is deliberately induced by cutting or driving nails into the trunk. Zao Jiao is the full mature pod of the same species. HPLC with diode array detection showed that the saponin aglycone content of the two is not significantly different but their full chromatographic fingerprints are distinctly different, and the authors concluded that interchangeable use must be approached with specific precaution. Targeted mass spectrometry across the three Gleditsia drugs found alkaloid content in the abortive pod of 0.03 to 10.41 micrograms per gram against 2.03 to 834.75 micrograms per gram in the mature pod. Classically the two were also assigned different jobs, the tooth pod for Wind-phlegm and the large pod for Damp-phlegm.
Clinical note: Dispense the drug the prescription names. Both are toxic and dosed at roughly 1 to 1.5 g, so a swap is not covered by any safety margin, and neither should be substituted on price or availability.
Zao Jiao Ci, the thorn (Gleditsiae Spina)
The thorn of the same tree is a separate Pharmacopoeia drug used to discharge pus and disperse swelling in sores, not to open the orifices or expel phlegm. Its chemistry and its literature are separate, and the thorn's most cited modern activity does not even belong to the plant. Activity-guided fractionation of the thorn's antiangiogenic effect isolated cytochalasin H, a fungal secondary metabolite, which the authors attributed to the endophytic fungus Chaetomium globosum populating the plant. That is a warning against reading thorn data as pod data, and against assuming a stated Gleditsia activity is even of plant origin.
Clinical note: Do not substitute thorn for pod or the reverse, and do not cite antiangiogenic or antitumour claims made for the thorn when discussing this drug with a patient.
Pregnancy, and any uterotonic or abortifacient drug
The Chinese Pharmacopoeia classifies the abortive pod as slightly toxic and lists pregnancy as a contraindication. The traditional grounds are the drug's strong downward-driving and orifice-opening action; the pharmacological grounds are that triterpenoid saponins of this class are mucosal irritants and haemolytic agents with no reproductive safety data in humans. Related Gleditsia material has shown dose-dependent reductions in fetal weight and length in rodent developmental testing, although that work was on the processed seed perisperm rather than on the pod.
Clinical note: Do not prescribe in pregnancy or when pregnancy is possible, and do not use while breastfeeding in the absence of any data. The contraindication is absolute, not a caution.
NSAIDs, aspirin and oral corticosteroids
The saponins that make this drug work are direct mucosal irritants: excess oral use causes vomiting and diarrhoea by that route, and classical practice already excludes patients with haematemesis or haemoptysis. Adding a drug that independently impairs gastric mucosal defence is a plausible additive injury, particularly given the drug's narrow 1 to 1.5 g dose range. There is no formal interaction study, so the grade rests on the shared mechanism rather than on trial data.
Clinical note: Avoid in patients on regular NSAIDs, aspirin or systemic corticosteroids, and in anyone with active or recent peptic ulcer. If it must be used, keep to the low end of the dose range and stop at the first sign of epigastric pain or dark stool.
Drugs and conditions that predispose to haemolysis (dapsone, primaquine, nitrofurantoin, glucose-6-phosphate dehydrogenase deficiency)
Gleditsia triterpenoid saponins are haemolytic, and systemic toxicity from overdose is described as haemolysis with central nervous system involvement. Whether a therapeutic 1 to 1.5 g oral dose delivers enough intact saponin to the circulation to matter is not established, since saponins are poorly absorbed intact. The concern is therefore an additive one in a patient whose red cells are already stressed, not a demonstrated interaction.
Clinical note: Avoid in known glucose-6-phosphate dehydrogenase deficiency and in patients on oxidant haemolytic drugs. Any dark urine, jaundice or unexplained fall in haemoglobin during use should stop the herb and be investigated.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction, or powder/pills | 1–1.5 g | Daily | — | — | 中国药典 2020 【用法与用量】1～1.5g，多入丸散用。外用适量，研末吹鼻取嚏或研末调敷患处。 【注意】孕妇及咯血、吐血患者禁用。 【性味与归经】辛、咸，温；有小毒。归肺、大肠经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Evidence Tier
Moderate evidence · 6 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
6
1 verified · 5 unverified
Show 6 studies
- Chemical fingerprinting and quantitative analysis of two common Gleditsia sinensis fruits using HPLC-DAD
- Structure-Activity Relationships of Saponins from Gleditsia sinensis in Cytotoxicity and Induction of Apoptosis
- Gleditsia Saponin C Induces A549 Cell Apoptosis via Caspase-Dependent Cascade and Suppresses Tumor Growth on Xenografts Tumor Animal Model
- Chemical Composition, Protective Effects, and Mechanisms of Volatile Oil from Fructus Gleditsiae Abnormalis with Nasal Administration against Ischemic Injury in HFD and MCAO-Induced Rats
- Gleditsiae sinensis fructus Pills combined with Jujubae fructus attenuate chronic bronchitis via regulation of AGE-RAGE signaling pathway
- Cytochalasin H, an Active Anti-angiogenic Constituent of the Ethanol Extract of Gleditsia sinensis Thorns
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 fingerprinting and quantitative analysis of two common Gleditsia sinensis fruits using HPLC-DAD
Analytical comparison of Gleditsiae Fructus Abnormalis, the abortive pod that is Zhu Ya Zao, with Gleditsiae Sinensis Fructus, the mature pod, both from Gleditsia sinensis. Echinocystic acid and oleanolic acid contents did not differ significantly, but the chromatographic fingerprints were distinctly different, and the authors concluded that interchangeable use of the two fruits requires specific precaution. This is the clearest published basis for keeping the two drugs apart.
Structure-Activity Relationships of Saponins from Gleditsia sinensis in Cytotoxicity and Induction of Apoptosis
Thirteen saponins were isolated from the anomalous fruits of Gleditsia sinensis, the drug of this record, by bioassay-guided fractionation, then tested with six analogues against six tumour cell lines by MTT and for apoptosis induction in HL-60 cells by flow cytometry. The work identified the structural features required for activity and built a predictive model. It is the most direct chemical characterisation of the abortive pod's saponin fraction.
Gleditsia Saponin C Induces A549 Cell Apoptosis via Caspase-Dependent Cascade and Suppresses Tumor Growth on Xenografts Tumor Animal Model
Gleditsia saponin C extracted from gleditsiae fructus abnormalis induced caspase-dependent apoptosis in A549 lung carcinoma cells, an effect blocked by caspase inhibitors, with a raised Bax to Bcl-2 ratio and inhibition of ERK and Akt signalling, and it sensitised the cells to tumour necrosis factor alpha by suppressing nuclear factor kappa B activation. In a mouse xenograft the compound suppressed tumour growth and induced apoptosis in the tumour.
Chemical Composition, Protective Effects, and Mechanisms of Volatile Oil from Fructus Gleditsiae Abnormalis with Nasal Administration against Ischemic Injury in HFD and MCAO-Induced Rats
Forty components of the volatile oil of the abortive pod were resolved by GC-MS, with paeonol at 5.2 percent, palmitate at 4.69 percent, violetone at 3.56 percent, linalool at 3.31 percent, citral at 2.65 percent and salpinol at 2.42 percent. Nasal administration in rats on a high-fat diet subjected to middle cerebral artery occlusion reduced cerebral infarct volume, brain water content, blood lipids, inflammatory factors and oxidative stress markers, and shifted Bax, Bcl-2 and cleaved caspase 3. The nasal route mirrors the traditional practice of insufflating the powdered pod.
Gleditsiae sinensis fructus Pills combined with Jujubae fructus attenuate chronic bronchitis via regulation of AGE-RAGE signaling pathway
A Gleditsia sinensis fruit pill preparation given with jujube reduced chronic bronchitis pathology in an animal model, with the AGE-RAGE pathway implicated. Note that the preparation studied is built on the fruit of Gleditsia sinensis in the classical pill form paired with jujube, which is the traditional way the toxic pod is buffered; it is not the abortive pod given alone.
Cytochalasin H, an Active Anti-angiogenic Constituent of the Ethanol Extract of Gleditsia sinensis Thorns
Activity-guided fractionation of the ethanol extract of Gleditsia sinensis thorns in human umbilical vein endothelial cells isolated cytochalasin H as the potent antiangiogenic constituent. Cytochalasin H is a fungal secondary metabolite, and the authors attributed it to the endophytic fungus Chaetomium globosum populating the plant. Included here as a caution rather than as evidence for the pod: the thorn is a different drug, and even its headline activity was not of plant origin.
⚠ Safety & Contraindications
- Pregnancy
- Breastfeeding
- Toxic — professional use only
Contraindications
Contraindicated in pregnancy and in the weak or depleted.
Safety Warnings
- Irritant to mucous membrane; small doses only.
⚠ Toxicity Information
Mucosal irritation, nausea and vomiting; haemolysis in overdose.
Historical Texts
Shen Nong Ben Cao Jing (Divine Husbandman's Classic of the Materia Medica)
Han dynasty, compiled c. 200 CEBen Cao Gang Mu, Li Shizhen
Ming dynasty, 1596Pharmacopoeia of the People's Republic of China, monograph for Zhu Ya Zao (Gleditsiae Fructus Abnormalis)
Modern, editions from 1963 to 2020References
- Xia Yufeng; Gao Zhengzhen; Dai Yue; Wang Qiang. Analysis of Bioactive Saponins in Fructus Gleditsiae abnormalis and Fructus Gleditsiae sinensis by LC-ELSD . Chromatographia (2009) [DOI]
- Xie HM; Mi YG; Xu XY; Sun MX; Liu EW; Gao XM; Li X; Yang WZ. [Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina]. . China Journal of Chinese Materia Medica (2023) [DOI]
- Ding Qin; Wang Xiang-Pei; Xu Feng; Zhang Mei; Fang Rong-Zhe; Qin Ping; Wu Hong-Mei. Exploring the anti-inflammatory effect of Fructus Gleditsia sinensis Lam., Fructus Gleditsiae abnormalis, and Gymnocladus chinensis Baill. using SPME-GC-MS, network pharmacology, and molecular docking . Arabian Journal of Chemistry (2022) [DOI]
- Wang Shuang; Wang Qi; Qiao Xue; Song Wei; Zhong Lei; Guo De-an; Ye Min. Separation and Characterization of Triterpenoid Saponins in Gleditsia sinensis by Comprehensive Two-Dimensional Liquid Chromatography Coupled with Mass Spectrometry . Planta Medica (2016) [DOI]
- Lian Xiao-Yuan; Zhang Zhizhen. Quantitive analysis of gleditsia saponins in the fruits of Gleditsia sinensis Lam. by high performance liquid chromatography . Journal of Pharmaceutical and Biomedical Analysis (2013) [DOI]
- Yang Zhongqin; Ding Qin; Li Jiaxin; Xu Feng; Zhang Yanyan; Wu Hongmei; Wang Xiangpei. Gleditsia sinensis perisperm ameliorates DSS-induced ulcerative colitis via the TLR4/NF-κB/NLRP3 signaling pathway: Safety evaluation and bioactive amino acid profiling . 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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