Cockspur orange
StarZanthoxylum asiaticum
Synonyms: Toddalia angustifolia, Cranzia willdenowii, Cranzia aculeata, Limonia oligandra, Scopolia angustifolia, Scopolia rubicaulis, Scopolia aculeata, Cranzia nitida, Toddalia rubicaulis, Scopolia micracantha, Toddalia schmidelioides, Toddalia ambigua, Cranzia schmidelioides, Toddalia aculeata, Zanthoxylum floribundum, Cranzia asiatica, Toddalia tonkinensis, Toddalia asiatica var. gracilis, Scopolia nitida, Toddalia asiatica var. floribunda, Toddalia floribunda, Toddalia asiatica var. obtusifolia, Toddalia willdenowii, Toddalia micrantha, Toddalia effusa, Cranzia micrantha, Paullinia asiatica, Toddalia asiatica var. parva, Toddalia asiatica
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
- Digestion
Cautions & contraindications
- Bleeding disorders
Western Herbalism Properties
Gallery
Botanical Description
Zanthoxylum asiaticum (cockspur orange, Asian prickly-ash) is a scandent shrub or small woody climber in the Rutaceae, native to tropical and subtropical Asia, including India, Sri Lanka, southern China, Indo-China, the Malay Peninsula, the Philippines, and Indonesia. Plants reach 3-10 m, climbing through neighbouring vegetation by recurved, woody prickles on the stems, branches, leaf rachises, and even leaflet midribs. The leaves are alternate and odd-pinnate, 10-30 cm long, with 5-13 ovate to elliptic leaflets 3-7 cm long, with a translucent crenate margin and distinct pellucid oil glands; crushed foliage gives off a strong, citrus-pepper aroma. The flowers are small, greenish-yellow, unisexual, and borne in axillary or terminal panicles. The fruit is a small reddish-brown follicle 4-6 mm in diameter, splitting to reveal a single shiny black seed; both the pericarp and seed contain pungent aromatic oils similar to Sichuan pepper.
Active Constituents
Toddalolactone
Prenyl-derived dihydroxyisopentyl coumarinConcentration: The principal coumarin of the root and root bark; the dominant single coumarin in root-bark extracts
The compound most often taken as the chemical marker of this drug. In vitro it is turned over mainly by CYP1A1 and CYP3A5, and at 50 microM it raised CYP1A1 protein expression by roughly 50 percent over control, so it is a plausible route by which the root could disturb the handling of co-administered drugs. Reported activities include anti-inflammatory, antifungal, antihypertensive and antitumour effects, all preclinical.
Nitidine
Benzo[c]phenanthridine alkaloidConcentration: Isolated from root bark; not routinely quantified in commercial material
The alkaloid that carries much of the antiplasmodial activity of the root bark, isolated together with dihydronitidine from Kenyan root-bark material. Nitidine chloride also inhibited proliferation of primary human T cells with an IC50 of 0.4 microM, and nitidine is a topoisomerase I poison, so it is a cytotoxic rather than a benign constituent.
Dihydronitidine
Dihydrobenzo[c]phenanthridine alkaloidCo-occurs with nitidine in the root bark and shares its antiplasmodial activity in Plasmodium falciparum assays.
Chelerythrine
Benzo[c]phenanthridine alkaloidOne of seven benzophenanthridine alkaloids characterised from the root bark, alongside des-N-methylchelerythrine, oxychelerythrine, oxyavicine, avicine and arnottianamide. Chelerythrine is a potent protein kinase C inhibitor and is cytotoxic at low micromolar concentrations; it is the same alkaloid class that makes Chelidonium and Sanguinaria preparations a toxicological concern, and it argues against casual high-dose or long-term use of the root.
Isopimpinellin
Linear furanocoumarinConcentration: One of the four main coumarins isolated from the root bark
A furanocoumarin identified as one of the four principal coumarins of the root bark in bioassay-guided work on the drug's haemostatic fraction. Furanocoumarins as a class interact with cytochrome P450 enzymes, which is the main reason this constituent matters clinically.
Pimpinellin
Angular furanocoumarinConcentration: One of the four main coumarins isolated from the root bark
Isomeric with isopimpinellin and isolated alongside it from the root bark; contributes to the drug's coumarin load and to its furanocoumarin-related P450 liability.
Phellopterin
Prenylated linear furanocoumarinConcentration: One of the four main coumarins isolated from the root bark
A prenylated furanocoumarin characterised from the root bark in the haemostatic-fraction work; prenylated furanocoumarins of this type are among the more active P450 inhibitors in the class.
Coumurrayin
Prenylated simple coumarinConcentration: One of the four main coumarins isolated from the root bark
Completes the set of four main coumarins identified from the root bark by LC-ESI Q-TOF with reference-standard confirmation.
Toddanol
CoumarinOne of a large series of coumarins described from this species; of chemotaxonomic rather than established clinical significance.
Toddanone
CoumarinIsolated with toddanol from the same material; no independent clinical evidence.
Toddalidimerine
Dimeric benzophenanthridine alkaloidA dimeric alkaloid reported from this species and essentially unique to it; no pharmacological or safety data of clinical relevance.
⚠ Drug Interactions
Zanthoxylum nitidum (Liang Mian Zhen) root
Zanthoxylum asiaticum (the plant long known as Toddalia asiatica, Chinese Fei Long Zhang Xue) is a documented market confusable of Zanthoxylum nitidum, the Chinese Pharmacopoeia drug Liang Mian Zhen. Quality-control work that built a UPLC plus near-infrared discriminant model for Z. nitidum treated Z. asiaticum, Z. avicennae and Z. scandens explicitly as the related Rutaceae roots appearing in herb markets and needing to be separated from authentic Z. nitidum. The confusion is easy to make because both are spiny Rutaceae roots used for wind-damp pain and both contain nitidine; the classical macroscopic discriminator is that the Z. asiaticum root surface is blackish-brown with small whitish lenticels in vertical lines and the cut surface lacks the bright yellow of Z. nitidum.
Clinical note: Do not treat these as interchangeable. If a prescription calls for Liang Mian Zhen, insist on material authenticated as Zanthoxylum nitidum, and vice versa; ask the supplier which binomial the lot was identified to, not which pinyin name it was sold under.
Warfarin and other oral anticoagulants
The root bark is used in Chinese and minority medicine specifically to stop bleeding, and that use has a measured chemical basis: bioassay-guided fractionation with LC-ESI Q-TOF characterised 31 compounds in the haemostatic fraction of the root bark, and a follow-up chemical-fingerprint pharmacokinetic-pharmacodynamic study in rats linked those constituents to a haemostatic effect in vivo. A drug that shortens bleeding time is a plausible antagonist of warfarin, heparin or a direct oral anticoagulant. No human interaction study exists. Note that although the drug is coumarin-rich, these are simple and furano-coumarins, not 4-hydroxycoumarin anticoagulants, so the expected direction is antagonism of anticoagulation, not additive bleeding.
Clinical note: Avoid in anticoagulated patients, or if it is used, monitor INR or the relevant coagulation parameter on starting and stopping. Do not assume a coumarin-containing herb will increase bleeding here; the traditional and experimental evidence points the other way.
CYP1A2 and CYP1A1 substrates (theophylline, clozapine, tizanidine, olanzapine)
Toddalolactone, the main coumarin of the root, is metabolised chiefly by CYP1A1 and CYP3A5 in human liver microsomes, and at 50 microM it induced CYP1A1 protein expression by about 50 percent over control in vitro. Induction of a CYP1A enzyme by a herb constituent is the mechanism by which a co-administered CYP1A2 substrate could lose effect. This is an in vitro observation at a concentration well above the rat plasma Cmax of 0.42 microg/mL seen after 10 mg/kg, so it should be treated as a signal to watch, not a demonstrated clinical interaction.
Clinical note: Where a patient is on theophylline, clozapine or tizanidine, prefer another herb, or monitor clinically and by drug level where levels are available.
Ciclosporin, methotrexate, azathioprine and other immunosuppressants
A methanol extract of this species inhibited proliferation of human primary T cells with an IC50 of 25.8 microg/mL in an activity-guided screen, and the activity tracked to nitidine chloride, which inhibited primary human T-cell proliferation with an IC50 of 0.4 microM. Additive suppression of T-cell proliferation is the mechanism of concern in a transplant or autoimmune patient already on an immunosuppressant. No in vivo or human data.
Clinical note: Avoid in transplant recipients and in patients on biologic or conventional immunosuppression unless there is a specific reason to use it and the prescribing specialist is aware.
Hexane and other lipophilic concentrated root extracts
In a systematic antimalarial and safety evaluation, aqueous, ethyl acetate, hexane and methanol extracts of root bark, fruit and leaf were tested for acute toxicity in mice and for cytotoxicity in Vero cells. Every extract except the hexane extract of the root gave an LD50 above 1000 mg/kg and a CC50 above 100 microg/mL; the hexane root extract was the exception, and did not clear those thresholds. Chinese materia medica records the drug as xiao du, slightly toxic. The safety of a decoction therefore does not transfer to a concentrated lipophilic extract of the same root.
Clinical note: Restrict use to traditional aqueous decoctions of authenticated root or root bark at customary doses. Do not substitute a concentrated non-polar extract, tincture percolated in high-strength alcohol or an essential-oil-type preparation on the assumption that it is equivalent.
Dosage Calculator
⚖ Dosage Calculator
A weight-based mathematical estimate for Cockspur orange. Not a prescription.
Evidence Tier
6 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
0
Other clinical trial
0
Observational / case report
0
In vitro / animal
6
2 verified · 4 unverified
Show 6 studies
- Antimalarial and safety evaluation of extracts from Toddalia asiatica (L) Lam. (Rutaceae)
- Antinocieptive and anti-inflammatory effects of Toddalia asiatica (L) Lam. (Rutaceae) root extract in Swiss albino mice
- Compounds from Toddalia asiatica: Immunosuppressant Activity and Absolute Configurations
- In vitro differences in toddalolactone metabolism in various species and its effect on cytochrome P450 expression
- Antiplasmodial and larvicidal compounds of Toddalia asiatica root bark
- Determination of quality markers for quality control of Zanthoxylum nitidum using ultra-performance liquid chromatography coupled with near infrared spectroscopy
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
Antimalarial and safety evaluation of extracts from Toddalia asiatica (L) Lam. (Rutaceae)
Aqueous, ethyl acetate, hexane and methanol extracts of root bark, fruit and leaf were screened against chloroquine-sensitive (D6) and chloroquine-resistant (W2) Plasmodium falciparum and in the Peters four-day suppressive test in Plasmodium berghei-infected mice. The ethyl acetate fruit extract was most active in vitro against W2 (IC50 1.87 microg/mL), followed by the aqueous root-bark extract (IC50 2.43 microg/mL). In vivo the fruit ethyl acetate extract at 500 mg/kg and the aqueous root-bark extract at 250 mg/kg suppressed parasitaemia by 81.34 percent and 56.8 percent; higher doses were less effective. All extracts except the hexane root extract had LD50 above 1000 mg/kg and Vero-cell CC50 above 100 microg/mL. Published under the synonym Toddalia asiatica.
Antinocieptive and anti-inflammatory effects of Toddalia asiatica (L) Lam. (Rutaceae) root extract in Swiss albino mice
Root extract was tested in the formalin pain test and the carrageenan paw-oedema model in mice at 100 and 200 mg/kg. The response was not dose-ordered: 200 mg/kg was active in the early formalin phase while 100 mg/kg was not, and 100 mg/kg was active in the late phase and in reducing carrageenan oedema while 200 mg/kg was not. This supports the traditional use for pain and inflammation but gives no usable dose-response, and the non-monotonic result should temper any claim that more of this root is better.
Compounds from Toddalia asiatica: Immunosuppressant Activity and Absolute Configurations
A methanol extract of the species inhibited proliferation of human primary T cells with an IC50 of 25.8 microg/mL in an extract-library screen. HPLC activity profiling characterised fifteen compounds, including three new natural products (toddalic acid and both enantiomers of toddanolic acid). Nitidine chloride was the most potent constituent, inhibiting primary human T-cell proliferation with an IC50 of 0.4 microM. This is the basis for treating the drug as immunosuppressive as well as analgesic.
In vitro differences in toddalolactone metabolism in various species and its effect on cytochrome P450 expression
Toddalolactone was incubated with liver microsomes from seven species. Human CYP-mediated half-life was 673 min and UGT-mediated half-life 83 min, with monkeys clearing it fastest. Chemical inhibition and screening assays identified CYP1A1 and CYP3A5 as the major isoforms involved, and immunoblotting showed 50 microM toddalolactone induced CYP1A1 protein by about 50 percent over control. Rat pharmacokinetics after 10 mg/kg gave Cmax 0.42 microg/mL at 0.25 h and elimination half-life 1.05 h. The species differences are large enough that animal interaction data on this compound should not be read across to humans.
Antiplasmodial and larvicidal compounds of Toddalia asiatica root bark
Bioassay-guided isolation from root bark collected in western Kenya yielded coumarin and benzophenanthridine constituents with antiplasmodial and mosquito-larvicidal activity, with nitidine and dihydronitidine among the active alkaloids. It is the phytochemical counterpart to the ethnobotanical claim that the root bark is the most potent part.
Determination of quality markers for quality control of Zanthoxylum nitidum using ultra-performance liquid chromatography coupled with near infrared spectroscopy
Not a study of this herb as a medicine but the authentication evidence that matters for it. A UPLC plus near-infrared discriminant model built for the Chinese Pharmacopoeia drug Zanthoxylum nitidum (Liang Mian Zhen) had to separate it from three related Rutaceae roots circulating in herb markets, of which Toddalia asiatica, that is Zanthoxylum asiaticum, was one. It documents this species as a market confusable of Liang Mian Zhen.
Historical Texts
Zhi Wu Ming Shi Tu Kao (Illustrated Investigation of the Names and Natures of Plants), Wu Qijun
Qing dynasty, 1848Zhong Hua Ben Cao (Chinese Materia Medica)
Modern compilation, 1999, ChinaQuan Guo Zhong Cao Yao Hui Bian (National Compendium of Chinese Herbal Medicine)
Modern compilation, 1975-1978, ChinaEast African traditional practice, recorded by ethnobotanical survey in the Lake Victoria Basin (Kenya, Uganda, Tanzania)
Documented by fieldwork in 2006; oral tradition of unknown antiquityReferences
- Hisashi Ishii; Junichi Kobayashi; Munekazu Ishikawa; Joju Haginiwa; Tsutomu Ishikawa. Studies on the Chemical Constituents of Rutaceous Plants. LXVI. The Chemical Constituents of Toddalia asiatica (L.) LAM. (T. aculeata PERS.). (1). Chemical Constituents of the Root Bark . YAKUGAKU ZASSHI (1991) [DOI]
- Xiaoyan Zhang; Wenbo Sun; Zhou Yang; Yan Liang; Wei Zhou; Lei Tang. Hemostatic chemical constituents from natural medicine Toddalia asiatica root bark by LC-ESI Q-TOF MSE . Chemistry Central Journal (2017) [DOI]
- Xiaoyan Zhang; Jie Liu; Wenbo Sun; Xiangchun Shen; Xiaojian Gong; Cong Wang; Yan Liang; Wei Zhou. CF-PK-PD analysis of natural hemostatic compounds from Toddalia asiatica (Linn) Lam root bark in rats . Acta Chromatographica (2021) [DOI]
- Cairong Luo; Jie Liu; Yan Liang; Xiangchun Shen; Xiaoyan Zhang; Wei Zhou. Antitumor chemical constituents of Toddalia asiatica (Linn) Lam root bark and its rational alternative medicinal parts by multivariate statistical analysis . Acta Chromatographica (2021) [DOI]
- J.A. Orwa; I.J.O. Jondiko; R.J.A. Minja; M. Bekunda. The use of Toddalia asiatica (L) Lam. (Rutaceae) in traditional medicine practice in East Africa . Journal of Ethnopharmacology (2008) [DOI]
- Haoxuan He; Niping Li; Yunqi Fan; Qian Huang; Jianguo Song; Lixia Lv; Fen Liu; Lei Wang; Qi Wang; Jihong Gu. Six new coumarins from the roots of Toddalia asiatica and their anti-inflammatory activities . Chinese Journal of Natural Medicines (2023) [DOI]
- Sanwat Sukieum; Wichien Sang-aroon; Chavi Yenjai. Coumarins and alkaloids from the roots of Toddalia asiatica . Natural Product Research (2017) [DOI]
- Padam N. Sharma; Aboo Shoeb; Randhir S. Kapil; Satya P. Popli. Toddalidimerine, a dimeric benzophenanthridine alkaloid from Toddalia asiatica . Phytochemistry (1981) [DOI]
- Padam N. Sharma; Aboo Shoeb; Randhir S. Kapil; Satya P. Popli. Toddanol and toddanone, two coumarins from Toddalia asiatica . Phytochemistry (1981) [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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