Long Dan Cao
StarGentiana scabra Bge.
Traditionally used for
- Headaches
- Eye health
- Ears & hearing
- Colds & fever
- Urinary & fluids
- Mood & calm
- Nerves & recovery
- Energy & fatigue
- Liver & jaundice
Cautions & contraindications
- Liver conditions
- Toxic — professional use only
☯ TCM Properties
Clears Heat and dries Dampness; Drains Liver and Gallbladder Fire; Clears Damp-Heat from the Lower Burner; Arrests Convulsions
Traditional Chinese Uses
Long Dan Cao (gentiana root, Chinese gentian) is one of the most bitter and cold herbs in Chinese medicine, with an intense ability to drain Liver and Gallbladder Fire and clear Damp-Heat from the Lower Burner. It is used for febrile conditions with jaundice, acute hepatitis, gallbladder inflammation, urinary tract infections with burning from Damp-Heat, as well as for headache, red eyes, tinnitus, and irritability from Liver Fire. Due to its intense bitterness and cold nature, it is used briefly and in controlled doses.
Western Herbalism Properties
Pharmacological Effects
- Stomachic: Gentiopicroside via gastric catheter increased gastric juice and free HCl in dogs (not sublingually or i.v.); no gain in food intake or body weight in rats.
- Hepatoprotective and choleretic: Injection solution reduced CCl4 hepatic necrosis in mice and increased liver glycogen; increased bile flow in normal and liver-injured rats and in dogs.
- Hypotensive and diuretic: I.v. 20% tincture lowered rabbit blood pressure from 70 to 40 mmHg for about 15 min; slowed and weakened isolated toad heart; i.v. injection increased urine output in rabbits.
- Antibacterial and antiinflammatory: Decoction inhibited P. aeruginosa, Proteus, S. typhi, S. aureus and some fungi in vitro; gentiopicroside antiinflammatory in carrageenin paw edema in rats.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 146.
Used In Formulas (17)
Relationships
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Botanical Description
Gentiana scabra Bunge (Gentianaceae) is a perennial herb 30-60 cm tall native to northeast China, Korea, Japan, and the Russian Far East, with erect simple stems, opposite ovate to lanceolate leaves with three prominent veins and rough margins, and terminal or upper axillary clusters of large funnel-shaped deep blue to violet flowers in late summer and autumn. The rhizome bears numerous slender pale yellow roots which are harvested in autumn after the aerial parts wither, washed, and sun-dried. In TCM, Long Dan Cao is bitter in flavor and cold in nature, entering the Liver and Gallbladder channels; it drains damp-heat from the lower burner, clears Liver fire, and is used for jaundice, eczema, and red eyes. The bitter glycosides are also recognized as classical Western bitters.
Active Constituents
Gentiopicroside (gentiopicrin)
Secoiridoid glycosideConcentration: The official assay marker. The Chinese Pharmacopoeia requires not less than 2% of the dried root and rhizome; HPLC surveys of commercial Long Dan from different growing regions found 0.89-6.47%, mean about 2.97%.
The dominant constituent and the compound that carries most of the studied activity. It is hepatoprotective in chemical- and alcohol-induced liver injury models, anti-inflammatory, and in diet-induced obese mice at 50 mg/kg orally it reduced body weight and visceral fat by downregulating PPAR-gamma, C/EBP-alpha and SREBP-1c. It is also the source of the herb's one well-characterised metabolic interaction risk, through potent inhibition of human CYP2A6.
Swertiamarin
Secoiridoid glycosideConcentration: A minor secoiridoid relative to gentiopicroside; content varies with species and provenance and is not subject to a Pharmacopoeia limit.
One of the four secoiridoid and iridoid glycosides common to all the Gentiana species admitted as Long Dan. In hepatocyte experiments it alleviated cell injury alongside gentiopicroside and sweroside, and it is one of the markers used to separate genuine Long Dan from substitute Gentiana material.
Sweroside
Secoiridoid glycosideConcentration: Minor constituent; not subject to a Pharmacopoeia limit.
Contributes to the hepatoprotective activity of the drug in cell models and, with gentiopicroside, swertiamarin and loganic acid, forms the chemical signature used to authenticate Gentianae Radix et Rhizoma.
Loganic acid
Iridoid glycosideConcentration: Minor constituent; not subject to a Pharmacopoeia limit.
One of the four common iridoid and secoiridoid glucosides of Long Dan and part of the chromatographic fingerprint used in quality control. It has little independent pharmacology attributed to it.
Triterpenoids (oleanane and ursane type)
TriterpenoidConcentration: A large but individually minor group; a recent survey of Gentianae Radix et Rhizoma catalogued 47 triterpenoids among 172 constituents.
Repeatedly isolated from the rhizome and root of Gentiana scabra specifically, including compounds with reported cytotoxic activity. They are a substantial fraction of the drug's chemistry but are not covered by the official assay, which looks only at gentiopicroside.
Flavonoids, chiefly luteolin and its glycosides
Flavone and flavone glycosidesConcentration: About 30 flavonoids catalogued in Gentianae Radix et Rhizoma; individual contents are low.
Contribute anti-inflammatory and antioxidant activity. Phenolic profiling has been proposed as a chemotaxonomic tool for distinguishing the several Gentiana species that may be dispensed as Long Dan.
⚠ Drug Interactions
Guan Mu Tong (Aristolochia manshuriensis), as a historical adulterant of the Long Dan Xie Gan Wan formula
This is a supply-chain hazard of the patent formula, not a property of Gentiana scabra. Gentiana scabra contains no aristolochic acid. But Long Dan Xie Gan Tang and its patent form Long Dan Xie Gan Wan contain Mu Tong, and through the twentieth century the cheaper Guan Mu Tong, the stem of Aristolochia manshuriensis, was widely marketed as a substitute for genuine Akebia Mu Tong. Aristolochic acids form covalent DNA adducts, cause a rapidly progressive interstitial nephropathy and are carcinogenic to the urothelium. Cases of renal failure from Mu Tong were reported from 1964 onward, and the same confusion (Mokutsu, Akebia quinata, versus Kan-Mokutsu, Aristolochia manshuriensis) is documented in Japanese and United Kingdom poisoning cases. China's drug regulator banned Guan Mu Tong in 2003. The problem is not entirely closed: DNA-barcode sequencing and species-specific qPCR of commercial Long Dan Xie Gan Wan from three manufacturers detected Clematidis Armandii Caulis and the counterfeit Clematis peterae in every sample rather than the labelled Akebiae Caulis.
Clinical note: Record it explicitly whenever a patient reports past use of Long Dan Xie Gan Wan, especially product obtained before 2004 or outside a regulated market. Patients with documented aristolochic acid exposure need long-term urothelial cancer surveillance, not just renal monitoring. Do not dispense any Mu Tong-containing formula from an unverified supply chain. Note also that Long Dan Cao itself is unaffected by this and should not be avoided on these grounds.
CYP2A6 substrates (e.g. nicotine, coumarin, letrozole, tegafur, efavirenz)
In human liver microsomes gentiopicroside inhibited CYP2A6 concentration-dependently with an IC50 of 21.8 micrograms/mL, a figure the investigators noted is close to the clinically observed Cmax of gentiopicroside injection. Inhibition was non-competitive at lower and competitive at higher concentrations. CYP2E1 was inhibited only weakly (IC50 594 micrograms/mL), and CYP2C9, CYP2D6, CYP1A2 and CYP3A4 were not inhibited; in cultured human hepatocytes no induction of CYP1A2, CYP3A4 or CYP2B6 occurred. This is the only human-enzyme interaction signal for the herb, and it is in vitro.
Clinical note: Relevant mainly for concentrated gentiopicroside preparations rather than a decoction dose. Where tegafur is used, its conversion to fluorouracil depends on CYP2A6, so a clinically meaningful inhibition would reduce efficacy; avoid pairing concentrated Gentiana extracts with tegafur-based chemotherapy without oncology input.
Gardenia jasminoides (Zhi Zi) and other geniposide-containing herbs within Long Dan Xie Gan Tang
Long Dan Xie Gan Tang is used clinically for liver conditions and attenuates liver injury at ordinary doses, but at 600 mg/kg in rats with D-galactosamine-induced liver injury it made the injury worse. The mechanism traced was not Gentiana: overdosed decoction shifted the gut microbiota so that geniposide, contributed by the Gardenia in the formula, was biotransformed to genipin, which raised reactive oxygen species and activated TLR4/MyD88/NF-kB signalling in hepatic stellate cells. Hepatotoxicity attached to this formula therefore belongs to the geniposide component and to overdosing, and should not be recorded against Gentiana scabra itself, for which acute toxicity is low (LD50 above 5 g/kg in mice).
Clinical note: Do not exceed conventional dosing of Long Dan Xie Gan Tang in a patient with active hepatocellular injury, and do not assume that because the formula is indicated for Liver heat it is hepatically safe at any dose. Baseline and follow-up transaminases are reasonable for prolonged courses.
Other Gentianae Radix et Rhizoma source species (Gentiana manshurica, Gentiana triflora, Gentiana rigescens)
Long Dan is not a single-species drug. The Chinese Pharmacopoeia admits Gentiana manshurica, Gentiana scabra and Gentiana triflora as Long Dan and Gentiana rigescens separately as Jian Long Dan. Metabolomic profiling with multivariate analysis has identified chemical markers that separate Gentiana scabra from Gentiana rigescens, confirming the material is not chemically interchangeable even though all four share gentiopicroside, swertiamarin, sweroside and loganic acid. Studies reported on Long Dan may have used any of these species; much of the alcoholic and non-alcoholic liver disease work, for example, was done on Gentiana scabra, while the acetaminophen hepatoprotection literature is largely Gentiana manshurica.
Clinical note: When reproducing a published result, check which species the study used rather than relying on the pinyin name. Where a monograph specifies Gentiana scabra, request species-verified material.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 3–6 g | Daily | — | — | 中国药典 2020 monograph 【龙胆】【用法与用量】3～6g。 【性味与归经】苦，寒。归肝、胆经。 — Matched by hand: Gentiana scabra is a ChP source species of 龙胆. Chinese Pharmacopoeia 2020, quoted verbatim. |
Dui Yao — Herb Pairs
The classical two-herb combinations this herb appears in, each with an action neither herb has alone.
Together they drain excess fire from the liver and gallbladder and clear damp-heat, extending the bitter-cold draining action upward and downward along the channel.
Core of the formula for liver-gallbladder fire (headache, red eyes, bitter taste, hypochondriac pain) or damp-heat pouring downward. Very bitter and cold; not for prolonged use or spleen deficiency.
Core pair of a classical formula — Long Dan Xie Gan Tang, Yi Fang Ji Jie (Wang Ang)
Evidence Tier
Strong 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
1
1 verified · 0 unverified
Randomized controlled trial
0
Other clinical trial
0
Observational / case report
0
In vitro / animal
5
2 verified · 3 unverified
Show 5 studies
- In Vitro Inhibition and Induction of Human Liver Cytochrome P450 Enzymes by Gentiopicroside: Potent Effect on CYP2A6
- Gentiana scabra Restrains Hepatic Pro-Inflammatory Macrophages to Ameliorate Non-Alcoholic Fatty Liver Disease
- Gentiana scabra Bunge roots alleviates skin lesions of contact dermatitis in mice
- Mechanisms of Longdan Xiegan decoction–aggravated D-Galactosamine–induced liver injury: Gut microbiota–mediated geniposide biotransformation and TLR4/NF-κB pathway activation
- Gentiopicroside isolated from Gentiana scabra Bge. inhibits adipogenesis in 3T3-L1 cells and reduces body weight in diet-induced obese mice
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
Gentiana scabra Bunge. Formula for Herpes Zoster: Biological Actions of Key Herbs and Systematic Review of Efficacy and Safety
Systematic review and meta-analysis of 26 clinical studies involving 2955 participants using oral modified Gentiana formula for herpes zoster, searched across nine English and Chinese databases. Modified Gentiana formula resolved pain earlier than pharmacotherapy alone or combined with topical Chinese herbal medicine, and the incidence of postherpetic neuralgia was lower with modified Gentiana formula plus topical herbal medicine (risk ratio 0.14, 95% CI 0.03 to 0.74). Only mild adverse events were reported. The authors caution that findings were limited by study quality and by diversity in intervention and comparator dosing.
In Vitro Inhibition and Induction of Human Liver Cytochrome P450 Enzymes by Gentiopicroside: Potent Effect on CYP2A6
Human liver microsome and cultured human hepatocyte study of gentiopicroside, the compound developed in China as gentiopicroside injection for acute jaundice and chronic active hepatitis. Gentiopicroside inhibited CYP2A6 (IC50 21.8 micrograms/mL, close to the clinical Cmax) and weakly CYP2E1 (IC50 594 micrograms/mL), with no inhibition of CYP2C9, CYP2D6, CYP1A2 or CYP3A4 and no induction of CYP1A2, CYP3A4 or CYP2B6 in hepatocytes. The authors concluded the CYP2A6 effect deserves in vivo follow-up and that the compound's hepatoprotection is unrelated to P450 modulation.
Gentiana scabra Restrains Hepatic Pro-Inflammatory Macrophages to Ameliorate Non-Alcoholic Fatty Liver Disease
In vitro and in vivo study using shTBK1 plasmid vectors, the TBK1 inhibitor amlexanox and a hepatocyte/bone-marrow-derived-macrophage co-culture system. Metabolic load raised TBK1 phosphorylation, activating NF-kB and raising MCP1, which recruited pro-inflammatory macrophages. Gentiana scabra inhibited TBK1 phosphorylation and MCP1 expression and so restrained macrophage recruitment. Species is explicitly Gentiana scabra.
Gentiana scabra Bunge roots alleviates skin lesions of contact dermatitis in mice
Ethanol extract of Gentiana scabra root and rhizome, with gentiopicrin confirmed present by TLC and HPLC, applied topically in DNFB-induced contact dermatitis in mice. It reduced surface roughness, excoriation and scab formation, prevented skin thickening, lowered erythema and melanin index, prevented hyperkeratosis, epidermal hyperplasia and immune cell infiltration, and inhibited TNF-alpha, IFN-gamma, IL-6 and MCP-1 in inflamed tissue. Unlike dexamethasone it did not alter body weight or spleen-to-body-weight ratio.
Mechanisms of Longdan Xiegan decoction–aggravated D-Galactosamine–induced liver injury: Gut microbiota–mediated geniposide biotransformation and TLR4/NF-κB pathway activation
Dose-ranging study (150, 300, 600 mg/kg) of Long Dan Xie Gan decoction in D-galactosamine-induced liver injury, combining histopathology, ALT/AST, serum LPS, 16S rRNA sequencing, untargeted faecal metabolomics and an LPS-stimulated LX-2 stellate cell model. Only the 600 mg/kg overdose aggravated injury, by shifting gut microbiota so that geniposide was converted to genipin, which reduced cell viability, raised ROS and activated TLR4, MyD88 and NF-kB p65. Locates the formula's hepatic risk in the Gardenia component and in overdosing rather than in Gentiana.
Gentiopicroside isolated from Gentiana scabra Bge. inhibits adipogenesis in 3T3-L1 cells and reduces body weight in diet-induced obese mice
Gentiopicroside downregulated PPAR-gamma, C/EBP-alpha and SREBP-1c in 3T3-L1 adipocytes and dose-dependently inhibited LPL, FABP4, DGAT2, FAS and SCD1, reducing lipid droplet accumulation and triglyceride content, while also lowering NF-kB1, TNF-alpha and IL6 expression. Oral gentiopicroside at 50 mg/kg for 12 weeks reduced body weight and visceral fat mass in high-fat-diet mice.
⚠ Safety & Contraindications
- Liver conditions
- Toxic — professional use only
Contraindications
It is not suitable for patients with deficiency-cold of the spleen and stomach. Its use is cautious in patients with yin deficiency and fluid consumption.
Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, pp. 46–50.
Side Effects
- May impair digestive function and occasionally cause headache, facial flushing and vertigo when taken after meals or in overdose.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 146.
Historical Texts
Shen Nong Ben Cao Jing
Han dynastyYi Fang Ji Jie
Qing dynasty, 1682Chinese Pharmacopoeia (Zhonghua Renmin Gongheguo Yaodian)
Modern, 2020 editionReferences
- Song Y, Yang Z, Wang P, Song K, Zhang S, Fan T. Next-generation sequencing and targeted quantitative real-time polymerase chain reaction for detection of Akebiae Caulis in the traditional Chinese medical formula Longdan Xiegan Wan . Annals of Translational Medicine (2022) [DOI]
- Zhu YP. Toxicity of the Chinese Herb Mu Tong (Aristolochia manshuriensis) . Adverse Drug Reactions and Toxicological Reviews (2002) [DOI]
- Yang B, Xie Y, Guo M, Rosner MH, Yang H, Ronco C. Nephrotoxicity and Chinese Herbal Medicine . Clinical Journal of the American Society of Nephrology (2018) [DOI]
- Zhang G, Li Y, Wei W, Li J, Li H, Huang Y, Guo DA. Metabolomics Combined with Multivariate Statistical Analysis for Screening of Chemical Markers between Gentiana scabra and Gentiana rigescens . Molecules (2020) [DOI]
- Antoniadi L, Bartnik M, Angelis A, Wawruszak A, Halabalaki M, Kukula-Koch W, Skaltsounis LA. Gentiopicroside—An Insight into Its Pharmacological Significance and Future Perspectives . Cells (2023) [DOI]
- Liu GK, Zhang BY, Niu Z, Chen JQ, Fan CY, Deng XY, Ye FQ, Cao SJ. Triterpenoids from the rhizomes and roots of Gentiana scabra Bge. and their cytotoxic activities . Fitoterapia (2025) [DOI]
- Yu H, Gachmaa B, Yu J, Tian-Liang, Uranghai X, Guo G, Xu W, Wang P. A comprehensive and systemic review of the Gentiana: Ethnobotany, traditional applications, phytochemistry, pharmacology, and toxicology in the Mongolian Plateau . Journal of Ethnopharmacology (2025) [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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