Di Long
StarPheretima aspergillum (E. Perrier)
Traditionally used for
- Cough & breathing
- Colds & fever
- Urinary & fluids
- Nerves & recovery
- Pain & joints
Cautions & contraindications
- Pregnancy
- Bleeding disorders
☯ TCM Properties
Settles Fright and Calms Convulsions; Calms the Liver and Extinguishes Wind; Unblocks the Channels and Collaterals; Calms Wheezing; Promotes Urination
Traditional Chinese Uses
Di Long (earthworm, pheretima) is a cold, salty substance used in Chinese medicine to clear Heat, calm Wind, unblock the channels, and promote urination. It addresses convulsions and high fever with muscle spasm from extreme Heat generating Wind, chronic joint pain and paralysis from Heat-Bi obstruction in the channels, and urinary difficulty from Heat accumulation. Its channel-opening properties make it useful in formulas for stroke sequelae, upper motor neuron conditions, and long-standing joint disease with Heat involvement.
Pharmacological Effects
- Antiasthmatic: 90% alcoholic extract dilated bronchi in rat/rabbit trachea-lung perfusion and antagonized histamine/pilocarpine constriction; nitrogenous fraction (20 mg i.v.) protected 50% of guinea pigs from lethal histamine; aqueous extract antiasthmatic in guinea pigs.
- Hypotensive: Aqueous or alcoholic extract (100 mg/kg i.v.) lowered blood pressure in anesthetized dogs for 2-3 h, peaking at 90 min; two weeks oral dosing lowered pressure in normal and renal hypertensive rats.
- Sedative and anticonvulsant: Alcoholic extract (20 g/kg i.p.) countered electroconvulsions in mice comparably to 20 mg/kg pentobarbital, but not strychnine convulsions.
- Antipyretic: Aqueous extract or lumbrifebrine reduced endotoxin- or heat-induced fever in rabbits, more mildly than aminopyrine; enhanced aminopyrine's onset and duration.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 534.
Relationships
Full-screen graph →Click a node for details · double-click to expand it · Ctrl/⌘ + scroll or two fingers to zoom and pan.
Botanical Description
Di Long is the dried body of the earthworm, principally Pheretima aspergillum (formerly Amynthas aspergillus) and several related Pheretima species, large terrestrial oligochaete annelids in the family Megascolecidae widely distributed across southern China and Southeast Asia. Adult worms reach 12-30 cm in length and about 6-12 mm in diameter, with a smooth pinkish-grey to reddish-brown elongated cylindrical body composed of approximately 100-180 segments separated by transverse grooves, and a prominent saddle-like glandular clitellum near the anterior third. For medicinal use the worms are collected, slit longitudinally, washed clean of soil and gut contents, flattened, and dried, yielding thin curled strips with the cleaned body wall visible as a fine ringed texture. This is an animal product, not a plant.
Active Constituents
Lumbrokinase and related earthworm fibrinolytic serine proteases
Fibrinolytic serine protease (enzyme)Concentration: not standardised in crude Di Long; among 509 components catalogued for Pheretima, 47 are enzymes and 117 are proteins and peptides, and proteins and enzymes are described as the main active constituents
These enzymes dissolve fibrin directly and also activate plasminogen to plasmin, which is the mechanistic basis for the drug's anticoagulant and antithrombotic reputation. Note the species question: the best-characterised individual fibrinolytic proteins have been purified from Pheretima vulgaris and Pheretima guillelmi rather than from P. aspergillum. For P. aspergillum specifically, Feng et al. (2022) identified marker peptides associated with fibrinolytic efficacy by parallel reaction monitoring. Crude decoction is not standardised for enzyme activity, and enzyme content will vary with drying, processing and storage.
Hypoxanthine
Purine baseConcentration: one of six HPLC-DAD quality markers determined across 40 batches; content correlated with anticoagulation activity
Hypoxanthine is the constituent most often invoked for the antiasthmatic action of Di Long. Shang et al. (2022) selected hypoxanthine, uridine, phenylalanine, inosine, guanosine and tryptophan as efficacy-related quality markers of Pheretima after grey relational analysis showed their contents were strongly related to the drug's anticoagulation activity.
Inosine, uridine and guanosine
NucleosidesConcentration: quantified as quality markers by HPLC-DAD across 40 batches; 28 nucleoside compounds are catalogued for the genus
Nucleoside markers used for authentication and batch quality control, and correlated with in vitro anticoagulant activity. They are markers of quality rather than proven single actives.
Lysoglycerophospholipids
LipidsConcentration: 57 of the 124 compounds detected by molecular networking in P. aspergillum were lysoglycerophospholipids; 117 lipid compounds are catalogued for the genus
The largest single chemical class detected in Pheretima aspergillum by mass spectral molecular networking. Their pharmacological contribution has not been separately established, though the 2025 systematic review attributes part of the drug's cardiovascular effect to its lipid, protein and enzyme fractions acting through inhibition of coagulation, inhibition of platelet aggregation and promotion of fibrinolysis.
Free amino acids and oligopeptides
Amino acids and peptidesConcentration: 52 amino acid components catalogued for the genus; 20 oligopeptides first characterised in the active fraction of a P. aspergillum decoction
Water-extractable peptides carry part of the anti-asthmatic activity of the decoction in animal models. Because these are proteins and peptides of animal origin, they are also the most likely basis for the allergic reactions seen with Pheretima-containing injectable products.
⚠ Drug Interactions
Warfarin, direct oral anticoagulants (apixaban, rivaroxaban, dabigatran) and heparins
This is a real pharmacodynamic interaction, not a theoretical one. Pheretima contains fibrinolytic serine proteases (the lumbrokinase group) that cleave fibrin directly and convert plasminogen to plasmin, and the 2025 systematic review of the genus states plainly that its lipids, proteins and enzymes act on cardiovascular disease by inhibiting coagulation, preventing platelet aggregation and promoting fibrinolysis. Shang et al. (2022) demonstrated that the contents of six quality markers in 40 batches correlate closely with measured anticoagulation activity, which means potency varies batch to batch and is not declared on the packet. Adding an unstandardised fibrinolytic to a patient already anticoagulated stacks two mechanisms on the same endpoint.
Clinical note: Avoid combining with therapeutic anticoagulation unless the prescriber is monitoring. If Di Long is added to a formula for a patient on warfarin, check INR within one to two weeks and again after any change of herb supplier or batch, since enzyme content is not standardised. Stop Di Long ahead of surgery, dental extraction or neuraxial anaesthesia on the same timetable as any other antithrombotic. Report unexplained bruising, epistaxis, haematuria or black stools.
Aspirin, clopidogrel, ticagrelor and other antiplatelet agents
Inhibition of platelet aggregation is one of the mechanisms attributed to Pheretima proteins and enzymes in the 2025 systematic review of the genus. The effect is in the same direction as the antiplatelet drugs and there is no reason to expect the combination to be neutral. There are no human interaction studies.
Clinical note: Use with caution on dual antiplatelet therapy after stenting. Counsel the patient on bleeding signs and record the herb in the medication list so that any bleeding episode is attributed correctly.
Thrombolytics (alteplase, tenecteplase, urokinase)
Earthworm fibrinolytic enzymes act partly by inducing endogenous tissue plasminogen activator activity and converting plasminogen to plasmin - the same final pathway as pharmacological thrombolysis. No clinical study has examined the combination, but the mechanistic overlap is direct.
Clinical note: Disclose recent Di Long use before thrombolysis for stroke or myocardial infarction. Do not start or continue Di Long during a thrombolysis admission.
Injectable Pheretima-containing products (Shuxuetong injection and similar animal-protein TCM injections)
Shuxuetong injection is an extract of leech and earthworm and is therefore a parenterally administered animal-protein product. A prospective multicentre hospital monitoring study of 32,546 patients across 54 institutions recorded 64 adverse reactions, a rate of 0.197%, characterised mainly by skin itching, rash, flu-like symptoms, dyspnoea, palpitations, headache and chest tightness - that is, predominantly allergic-type reactions, concentrated in elderly patients. Some of these reactions are infusion-rate dependent and reverse on slowing the infusion. Anaphylactic shock has been reported for animal-protein traditional Chinese medicine injections used in cardiovascular and cerebrovascular indications, and the allogeneic protein content is the accepted explanation.
The distinction that matters clinically is route. An oral decoction of Di Long carries a very different immunological risk from an intravenous protein extract of the same animal, and safety data from one cannot be read across to the other.
Clinical note: Injectable earthworm-derived products must be given only in a setting with resuscitation facilities, with observation during the first infusion and a slow initial rate. They are not something a herbal practitioner administers. Ask about prior reactions to leech- or earthworm-derived injections and about known allergy to insect, shellfish or other invertebrate proteins before any oral Di Long in an atopic patient.
Antihypertensives
Di Long is described in the pharmacological literature as an antihypertensive as well as an antiasthmatic and anticoagulant drug, and it is prescribed in TCM largely in cardiovascular and cerebrovascular indications. Controlled human blood pressure data for the isolated herb are lacking, so the size of any additive effect is unknown.
Clinical note: Check blood pressure when Di Long is added to or removed from the formula of a treated hypertensive, particularly in an older patient at risk of postural hypotension.
Pheretima vulgaris, Pheretima guillelmi and Pheretima pectinifera sold as Di Long
Four Megascolecidae species are traded as Di Long - Pheretima aspergillum (Guang Di Long), P. vulgaris, P. guillelmi and P. pectinifera (together Hu Di Long). The best-characterised fibrinolytic proteins in the literature were purified from P. vulgaris and P. guillelmi, not from P. aspergillum, so evidence cited for Di Long is frequently evidence for a different species from the one on the prescription. DNA-barcoding and metabolomic methods have been developed specifically to distinguish P. aspergillum from P. vulgaris, which is itself an indication that the substitution is common enough to need policing.
Clinical note: Specify P. aspergillum on the order if the formula requires Guang Di Long, and expect potency to vary between species and batches. Do not treat published enzyme activity figures from P. vulgaris as applying to the material in your dispensary.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 5–10 g | Daily | — | — | 中国药典 2020 【用法与用量】5～10g。 【性味与归经】咸，寒。归肝、脾、膀胱经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Evidence Tier
Strong evidence · 5 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
1
1 verified · 0 unverified
Randomized controlled trial
0
Other clinical trial
0
Observational / case report
1
0 verified · 1 unverified
In vitro / animal
3
2 verified · 1 unverified
Show 3 studies
- Pheretima aspergillum decoction suppresses inflammation and relieves asthma in a mouse model of bronchial asthma by NF-κB inhibition
- A Strategy for Rapid Discovery of Marker Peptides Associated with Fibrinolytic Efficacy of Pheretima aspergillum Based on Bioinformatics Combined with Parallel Reaction Monitoring
- A Novel Fibrinolytic Protein From Pheretima vulgaris: Purification, Identification, Antithrombotic Evaluation, and Mechanisms Investigation
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
32 546 intensive hospital monitoring cases of Shuxuetong injection
A prospective multicentre hospital monitoring study of Shuxuetong injection, a leech and earthworm extract, across 54 medical institutions. 64 adverse reactions were recorded in 32,546 monitored patients, a rate of 0.197%, mainly skin itching, rash, flu-like symptoms, dyspnoea, palpitations, headache and chest tightness - that is, allergic-type reactions - and concentrated in elderly patients. The authors judged clinical safety acceptable. The study is the best available denominator for how often parenteral earthworm protein causes a reaction, and confirms that the reactions that do occur are predominantly hypersensitivity.
Effect of Pheretima aspergillum on reducing fibrosis: A systematic review and meta-analysis
Thirteen randomised controlled animal experiments, selected from 325 records, pooling rat and mouse models of renal fibrosis (unilateral ureteral obstruction), pulmonary fibrosis (paraquat) and hepatic fibrosis (carbon tetrachloride). Dilong extract significantly reduced transforming growth factor beta 1 (SMD -3.16, 95% CI -4.18 to -2.14) and alpha-smooth muscle actin (SMD -2.57, 95% CI -3.47 to -1.66). This is an animal-only synthesis; no human antifibrotic trial of Pheretima exists, and the effect sizes should not be read as clinical.
Pheretima aspergillum decoction suppresses inflammation and relieves asthma in a mouse model of bronchial asthma by NF-κB inhibition
Pheretima aspergillum decoction was tested against ovalbumin-induced asthma in BALB/c mice. The decoction reduced airway inflammation, with the effect attributed to inhibition of NF-κB signalling. This is the species named in the batch record, and it is the decoction rather than an isolated constituent, which makes it more directly relevant to the dispensed drug than the enzyme-purification literature. It remains an animal model.
A Strategy for Rapid Discovery of Marker Peptides Associated with Fibrinolytic Efficacy of Pheretima aspergillum Based on Bioinformatics Combined with Parallel Reaction Monitoring
Bioinformatics combined with parallel reaction monitoring mass spectrometry was used to find peptide markers linked to the fibrinolytic activity of Pheretima aspergillum specifically. The work establishes measurable, species-attributable markers for the fibrinolytic fraction, which matters because most purified earthworm fibrinolytic proteins in the literature come from other Pheretima species.
A Novel Fibrinolytic Protein From Pheretima vulgaris: Purification, Identification, Antithrombotic Evaluation, and Mechanisms Investigation
Purification and characterisation of a fibrinolytic protein from Pheretima vulgaris, with antithrombotic evaluation and mechanism work. Cited here for the mechanism of the earthworm fibrinolytic fraction, with the explicit caveat that the source species is P. vulgaris and not the P. aspergillum of this monograph - the two are traded under the same pinyin name but are different animals.
⚠ Safety & Contraindications
- Pregnancy
- Bleeding disorders
Contraindications
- Use with caution during pregnancy (uterine stimulant).
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 534.
Side Effects
- Stimulates the uterus.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 534.
Historical Texts
Shen Nong Ben Cao Jing
Han dynastyBen Cao Gang Mu
Ming dynasty (1596)References
- Fu-Hui Luo, Fen-Fen Zeng, Xu Ren, Xing-Li Lu, Bin-Bin Rong, Zhong-Qiao Zhao, Xia Yang, Feng-Xiang Zhang, Wei Shi. Pheretima: A system review of zoology, traditional applications, processing technology, chemical composition, pharmacologic activities, quality control and toxicity . Journal of Ethnopharmacology (2025) [DOI]
- Tao-Fang Cheng, Yu-Hao Zhang, Ji Ye, Hui-Zi Jin, Wei-Dong Zhang. Investigation of the chemical compounds in Pheretima aspergillum (E. Perrier) using a combination of mass spectral molecular networking and unsupervised substructure annotation topic modeling together with in silico fragmentation prediction . Journal of Pharmaceutical and Biomedical Analysis (2020) [DOI]
- Ye Shang, Suyi Liu, Chunxiao Liang, Kunze Du, Shujing Chen, Jin Li, Hua Jin, Yanxu Chang. An Integrated Strategy of Chemical Fingerprint and Network Pharmacology for the Discovery of Efficacy-Related Q-Markers of Pheretima . International Journal of Analytical Chemistry (2022) [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.
📝 Notes
Public notes from the community and your own private notes on Di Long.
No notes yet.