IngredientsGentiana manshurica Kitagawa is a perennial herb belonging to the family Gentianaceae. It is classified within the genus Gentiana, family Gentianaceae. The species epithet manshurica refers to its primary native range in Manchuria (northeastern China) and neighboring regions of East Asia. It is a perennial herb used in traditional Chinese medicine (TCM) as Gentianae Radix et Rhizoma — the dried roots and rhizomes — and is widely used in Europe and Asia.
The plant is known by a range of synonyms and common names. In Chinese it is called Long Dan Cao (龙胆草) or simply Long Dan (龙胆). In traditional Chinese medicine, "Long-Dan" and "Qin-Jiao" are two important TCM herbs recognized since ancient times in China. In China, Longdan and Qinjiao are two major representative herbal medicines from the Gentiana genus; the commodities of Longdan are divided into Guanlongdan (Gentiana scabra Bunge, Gentiana manshurica Kitag., and Gentiana triflora Pall.) and Dianlongdan (Gentiana rigescens Franch.).
The 2020 edition of the Chinese Pharmacopoeia stipulates that Gentiana is the dried root and rhizome of Gentiana manshurica Kitag., G. scabra Bge., Gentiana triflora Pall., or G. rigescens Franch., which belong to the Gentianaceae family; these plants are perennial herbs, and their roots and rhizomes are used medicinally.
Among the approved source species, G. manshurica is the mainstream of excellent-quality commercial products; however, in recent decades wild resources have been severely damaged due to the biological characteristics and the destruction of grasslands caused by human disturbance.
Long Dan Cao (Gentiana manshurica) is a perennial herb, 1 to 2 feet in height; its leaves are opposite, with lower leaves small and scaly, and middle and upper leaves lanceolate with dark green upper surfaces, pale green lower surfaces, and three distinct veins. Tubular bell-shaped blue flowers grow at the tips of branches or at axillae close to the branch. Fruits are oblong, slightly flat, and two-lobed when ripe, with numerous small seeds. The rhizome is short, yellowish brown or pale yellow, and clustered with many slender roots.
The medicinal material is commercially available in several forms: as dried root and rhizome (raw herb), as standardized dry extract powders, as alcohol or water-alcohol tinctures, as encapsulated powders, and as a component of multi-herb traditional decoctions. Gentiopicroside (GPS), the principal marker compound, is a secoiridoid glucoside isolated from the ethanol extract of Gentianae Radix, with a content of approximately 13% in that extract.
Gentianae Radix et Rhizoma was first recorded in the Shen nong Bencaojing (Divine Farmer's Classic of Materia Medica) during the Han Dynasty (202 B.C.–220 A.D.) and is categorized as a moderate herb. The earliest pharmaceutical records of Longdan and Qinjiao are found in Shennong's Classic of Materia Medica.
In early texts it is described as efficacious in treating cold and heat within the bones, convulsions, expelling noxious qi, healing severe injuries, and stabilizing the functions of the five viscera and detoxifying; prolonged use is believed to enhance memory, invigorate the body, and delay aging.
In TCM, its roots are known as "Long Dan Cao" and are utilized to "clear heat" and "dry dampness," addressing issues such as jaundice, hepatitis, conjunctivitis, and swelling due to inflammation. The section Gentiana, represented by the traditional Chinese medicinal herb Gentianae Radix et Rhizoma, is known for its bitter taste and cold nature, possessing the effects of purging excess fire in the liver and gallbladder as well as clearing damp-heat in the lower jiao; it is used in the treatment of diseases such as excessive heat in the liver meridian, convulsions, mania, jaundice, dysentery, Japanese encephalitis, sore throat, red eyes, scrotal swelling and pain, and damp itchiness in the genital area.
Gentiana manshurica and its root, known as gentianae radix, were also used in traditional Chinese medicine as a treatment for individuals with liver diseases. In China, "Long-Dan" is typically used for protecting the liver and is commonly used for curing inflammation, hepatitis, rheumatism, cholecystitis, and tuberculosis as a well-known traditional Chinese medicinal herb.
The most prominent traditional formula incorporating G. manshurica as a principal ingredient is Long Dan Xie Gan Tang (Gentiana Decoction to Drain the Liver). The LDXGT decoction originates from the Formulae of the Bureau of People's Welfare Pharmacies (Taiping Huimin Hejiju Fang in Chinese) from the period of 960–1127 C.E., and is composed of ten Chinese herbal medicines including Chaihu (Radix Bupleuri), Huangqin (Scutellaria baicalensis), Longdancao (Radix Gentianae), Zhizi (Gardenia jasminoides Ellis), ZeXie (Rhizoma Alismatis), Mutong (Caulis Akebiae), Cheqianzi (Semen Plantaginis), Danggui (Radix Angelicae Sinensis), Shengdi (Radix Rehmanniae Recens), and Gancao (Radix Glycyrrhizae).
Long Dan Xie Gan Tang (LDXGT) is one of the best-known traditional Chinese herbal prescriptions for the treatment of chronic hepatitis, jaundice, cystitis, conjunctival congestion, earache, as well as scrotal and extremitas inferior eczema. The ancient Chinese herbal formula Longdan Xiegan Tang has been used in clinical practice for insulin resistance- and inflammation-associated liver injuries, such as chronic hepatitis B, icteric hepatitis, fatty liver, and drug- or alcohol-induced liver diseases.
Herbs of the Gentianaceae family were used centuries ago as part of traditional medicine in China and Tibet. The dried roots and rhizomes, which contain bitter-tasting secoiridoid glucosides, have been used in the Chinese system of traditional medicine for over 2,000 years as an analgesic, anti-inflammatory, antipyretic, antirheumatic, diuretic, febrifuge, and hypoglycaemic agent, and for treating rheumatic pains, fevers, and allergic inflammations. The use of G. manshurica is documented in traditional Korean and Japanese herbal practices as well, paralleling its Chinese applications.
Across the Gentianae Radix et Rhizoma source species (including G. manshurica Kitag.), 172 constituents have been compiled from literature from 2004–2024 and traditional sources, comprising terpenoids (66 iridoids, 47 triterpenoids, and others), flavonoids, lignans, and alkaloids. Iridoids (e.g., gentiopicroside, swertiamarin) and triterpenoids are the key bioactive agents.
Among the phytochemicals of Gentiana species, iridoids and secoiridoids are the major constituents; iridoids have an iridoid alcohol as their core chemical structure, forming secoiridoids via C7–C8 bond breaking; these compounds, having a hemiacetal structure, are highly unstable.
The medicinal properties of the crude herbal drug are attributed to bitter glycosides, flavonoids, and xanthones, the main plant secondary metabolites; these plant-derived molecules, especially naturally occurring xanthones, possess a broad spectrum of bioactivity, being anticarcinogenic, antimicrobial, neuroprotective, antidiabetic, and cardioprotective.
Modern pharmacological research indicates that Gentianae Radix et Rhizoma possesses hepatoprotective, choleretic, anti-inflammatory, analgesic, antimicrobial, antiviral, antiallergic, antitumor, neuroprotective, and stomachic activities; these diverse pharmacological effects are associated with its complex chemical structure, particularly with compounds such as gentiopicroside, swertiamarin, amarogentin, linarin, oleanolic acid, gentianine, and polysaccharides.
Though iridoid and secoiridoid glucosides were reported as the main constituents in "Long-Dan," these four different species also produce different minor components, which may be related to their pharmacological activities. Additionally, globuloside A, cornusoside A, cornolactone A, 6,9-epi-8-O-acetylshanziside methyl ester, and polar extracts (petroleum ether, ethyl acetate) from Gentiana manshurica exhibit potent inhibition of HepG2 cell viability.
Pharmacologically, Gentiana extracts target NF-κB and MAPK pathways to suppress inflammation and oxidative liver injury via Nrf2 activation, while inducing tumor cell apoptosis (Bax/Bcl-2) and S/G2-M phase arrest to inhibit lung and liver cancer proliferation.
At the molecular level, gentiopicroside directly inhibits the phosphorylation of IKKβ, which prevents the degradation of IκB and subsequent nuclear translocation of the NF-κB p65 subunit; this blockade leads to the downregulation of key inflammatory mediators, including COX-2, TNF-α, and IL-6.
GPS modulates key signaling pathways, such as NF-κB and MAPK, to suppress pro-inflammatory cytokines and oxidative stress, and it activates the Keap1-Nrf2 pathway to enhance cellular antioxidant defenses and exhibits direct free radical scavenging capabilities.
Gentiana manshurica attenuated the nuclear translocation of sterol regulatory element-binding protein-1 (nSREBP-1) and suppressed CYP2E1 induction, suggesting it prevents ethanol-induced liver damage by reducing fatty acid synthesis and oxidative stress; in vivo models of acute and chronic alcoholic hepatosteatosis showed that gentiopicroside upregulates the LKB1 and AMPK pathways and downregulates SREBP1 and PPARα, leading to attenuation of lipogenesis and increased lipid oxidation in ethanol-exposed cells.
Gentiopicroside can modulate the LKB1/AMPK pathway by suppressing the activation of the P2X7 receptor-NLRP3 inflammasome, thereby inhibiting IL-1β production; its anti-inflammatory properties and regulation of lipid metabolism highlight its hepatoprotective pharmacological potential for treating alcoholic hepatosteatosis.
Crude Gentianae Radix et Rhizoma extracts and gentiopicroside significantly reduce ALT and AST levels in acute liver injury models induced by CCl4 or D-galactosamine, while enhancing glutathione peroxidase and superoxide dismutase (SOD) activity, reducing malondialdehyde (MDA) accumulation, directly scavenging free radicals, and reinforcing hepatic antioxidant defenses.
Gentiana extracts enhance gastrointestinal repair, regulate motility, and mitigate chronic pain through central-peripheral analgesic synergy. The intensely bitter taste of the secoiridoid compounds such as gentiopicroside stimulates bitter taste receptors in the oral cavity and gastrointestinal tract, reflexively increasing gastric secretion and digestive enzyme output — the classic "bitter tonic" mechanism documented across bitter-herb pharmacology.
In neurodegenerative diseases like Alzheimer's and Parkinson's, GPS reduces amyloid-β accumulation and dopaminergic neuron loss, respectively; its hepatoprotective effects include mitigating chemical- and alcohol-induced liver damage by regulating lipid metabolism and reducing fibrosis.
GPS possesses a wide spectrum of pharmacological properties, including hepatoprotective, anti-arthritic, analgesic, antidiabetic, anticancer, and neuropsychopharmacological activities; specifically, GPS can alleviate liver injury caused by alcohol, D-galactosamine, or lipopolysaccharide by reducing liver function impairment, improving hepatic lipid disorders, and inhibiting oxidative stress and inflammation; GPS also has antitumor activity by inducing apoptosis and inhibiting the proliferation of cancer cells.
Preclinical / Animal Evidence: One study demonstrated that the methanolic extract of Gentiana manshurica roots significantly reduced the elevated levels of serum AST and ALT, as well as serum and hepatic triglycerides, in ethanol-treated C57BL/6 mice; additionally, it showed the ability to prevent alcohol-induced acute liver steatosis by inhibiting CYP2E1-mediated free radical production and suppressing the synthesis of SREBP-1.
A separate preclinical study directly examined protection from acetaminophen (APAP)-induced liver injury. The investigators examined in vivo hepatoprotective effects and mechanisms of G. manshurica Kitagawa (GM) in acetaminophen-induced liver injury in mice; GM (200, 150, or 50 mg/kg body weight) or N-acetyl-L-cysteine (NAC; 300 mg/kg body weight) was administered orally with a single dose 2 hours prior to APAP (300 mg/kg body weight) injection; APAP treatment significantly depleted hepatic glutathione (GSH), increased serum AST, ALT, and malonyldialdehyde (MDA) and 4-hydroxynonenal levels, and decreased hepatic activity of glutathione peroxidase and superoxide dismutase; however, pretreatment with GM significantly alleviated APAP-induced oxidative stress by increasing GSH content, decreasing serum ALT, AST, and MDA, and retaining the activity of GSH-px and SOD in the liver. These results were published in the World Journal of Gastroenterology (2010) and represent a mechanistic study in an animal model.
In neurodegenerative and liver disease models, gentiopicroside reduces amyloid-β accumulation and dopaminergic neuron loss; its hepatoprotective effects include mitigating chemical- and alcohol-induced liver damage by regulating lipid metabolism and reducing fibrosis.
Evidence Strength: Evidence for hepatoprotection is substantial at the preclinical (in vitro and animal) level, with several independent studies demonstrating consistent effects on liver enzyme markers, oxidative stress, and fatty acid metabolism pathways. No large-scale randomized clinical trials in humans evaluating G. manshurica specifically for liver disease could be identified in the available peer-reviewed literature.
In Vitro / Animal Evidence: Gentiopicroside, one of the main active ingredients from Gentiana manshurica Kitag., attenuates acute pancreatitis in rats; experimental acute pancreatitis was induced by retrograde injection of sodium taurocholate into the biliopancreatic duct; gentiopicroside given orally markedly reduced the pancreatitis-evoked increase of serum amylase and lipase activity, decreased the pancreas mass/body mass index, tissue water content, TNF-α and IL-1β concentrations, and attenuated the histopathological changes and NF-κB p65 protein expression in pancreatic tissue; the results indicate that the function of gentiopicroside on acute pancreatitis may be related to inhibiting the release of inflammatory mediators and NF-κB p65 protein expression.
Evidence Strength: Evidence for anti-inflammatory effects is preliminary and largely limited to in vitro cell-culture experiments and animal models. Specific human clinical trial data for G. manshurica isolates in inflammatory conditions are not available in the identified literature.
Preclinical Evidence: Gentiopicroside (GPS), a natural iridoid glycoside isolated from G. manshurica Kitagawa, has demonstrated anti-inflammatory, anti-hepatotoxic, and antioxidant activities in animal experiments; recent research has revealed that GPS regulates the NF-κB signaling pathway to prevent kidney inflammation in diabetes mice, and GPS intensified trimetazidine-mediated inhibition of oxidative injury and inflammation in myocardial ischemia-reperfusion injury rats.
Evidence Strength: Cardiovascular evidence is exclusively preclinical (animal studies). No human clinical trial data were identified for this indication.
The most clinically evaluated preparation involving G. manshurica is the traditional formula Long Dan Xie Gan Tang (LDXGT). Clinically, LDXGT is widely employed in managing herpes zoster, hypertension, sudden deafness, and inflammatory conditions, with Longdan Xiegan Tang remaining a cornerstone therapy for damp-heat liver disorders.
A systematic review and meta-analysis of randomized controlled trials (RCTs) examined LDXGT in insomnia. Long Dan Xie Gan Tang (LDXGT) is a representative Chinese herbal medicine for the treatment of insomnia, especially in patients with irritability symptoms, and its effectiveness and safety have been validated clinically. The search covered multiple databases including PubMed, Chinese Biomedicine Database (CBM), CNKI, VIP, and Wan-fang; randomized-controlled trials were identified for insomnia treatment involving LDXGT and LDXGT combined with ordinary Western medicine.
In the domain of ear, nose, and throat disorders: Longdan Xiegan Capsules with tympanocentesis reduced middle ear effusion and TGF-β1/β2 levels via TLR4/MyD88/NF-κB pathway inhibition; and in chronic rhinosinusitis, LDXGT corrects Th17/Treg imbalance by suppressing IL-17A/IL-22 and improving Lund-Kennedy endoscopic scores.
For kidney-related conditions: Gentiana extracts attenuate renal fibrosis via TGR5 receptor activation, inhibiting tubular epithelial-mesenchymal transition (EMT) and NF-κB-driven inflammation in diabetic nephropathy models; in chronic kidney disease, diuretic effects of Gentiana roots were reported to match furosemide in sodium excretion but with reduced potassium loss, offering potentially safer edema management.
For hepatitis in Taiwan: Among the top 10 Chinese herbal formulas prescribed for chronic hepatitis in Taiwan, Long-dan-xie-gan-tang, which consists of Gentiana scabra and other plants, was the most common; the herbal drugs in this formula were reported to have multiple effects including antiviral, anti-inflammatory, antioxidant, and immune-modulation properties; a Chinese herbal preparation including Gentiana manshurica as one of 19 medicinal plants was also shown to provide protection from hepatocyte necrosis in an animal model.
Evidence Strength: Clinical evidence for LDXGT is predominantly from Chinese-language RCTs of variable methodological quality. Most are single-center studies, frequently without adequate blinding, and are primarily conducted in China. The formula contains ten herbs, making it impossible to attribute effects specifically to G. manshurica alone. Systematic reviews note a general paucity of high-quality clinical trials meeting international standards for G. manshurica as a standalone supplement.
Pharmacologically, Gentiana extracts target NF-κB and MAPK pathways to suppress inflammation and oxidative liver injury via Nrf2 activation, while inducing tumor cell apoptosis (Bax/Bcl-2) and S/G2-M phase arrest to inhibit lung and liver cancer proliferation. Globuloside A, cornusoside A, cornolactone A, 6,9-epi-8-O-acetylshanziside methyl ester, and polar extracts from Gentiana manshurica exhibit potent inhibition of HepG2 cell viability.
Evidence Strength: All identified evidence for antitumor activity from G. manshurica is from in vitro cell-line studies. No human clinical trials on anticancer use were identified.
Clinically, gentiopicroside demonstrates hepatoprotective, antiviral, and neuroprotective effects, with applications in herpes zoster, non-alcoholic fatty liver disease, and metabolic disorders. Mechanistically, in preclinical models of Alzheimer's disease and Parkinson's disease, GPS has been reported to reduce amyloid-β accumulation and protect dopaminergic neurons respectively, though all such data derive from animal experiments.
Evidence Strength: Preliminary; exclusively preclinical data available for neuroprotective applications attributable to G. manshurica.
Based on the available literature, Gentiana manshurica and its principal constituents have been pharmacologically investigated in the following body systems:
Modern pharmacological research indicates that Gentianae Radix et Rhizoma possesses hepatoprotective, choleretic, anti-inflammatory, analgesic, antimicrobial, antiviral, antiallergic, antitumor, neuroprotective, and stomachic activities.
Dosages reported in scientific studies are as follows:
All dosages above are from animal studies and are provided for scientific context only; they do not represent established human doses. No human clinical dosing regimens specific to G. manshurica as a single-herb preparation could be confirmed from peer-reviewed clinical trial sources.
Gentiana manshurica Kitagawa is a high-quality original species of Gentianae Radix et Rhizoma with significant medicinal value; however, wild resources have experienced a sharp decline due to human excavation, habitat destruction, and other factors; consequently, it has been classified as an Endangered (EN) species on the IUCN Red List and is considered a third-level national key-protected medicinal material in China. Some scholars have suggested changing it to the second level of protection considering the exhausted wild resources. This has practical implications for supplement quality, as commercial products sourced from wild-harvested material may face supply chain inconsistency, adulteration with related species, or involve ecologically unsustainable procurement.
Direct inhibition of CYP2A6 and CYP2E1 activity by GPS was observed in a concentration-dependent manner; the enzyme most potently inhibited by GPS in vitro was CYP2A6 (activity of the enzyme decreased by 80% compared to the control); the evaluated IC50 was 21.80 µg/mL, which was close to the value observed in clinical studies (19.50 µg/mL), indicating CYP2A6 inhibition by pharmacologically relevant concentrations of GPS, while GPS had little effect on CYP2E1 or CYP3A4.
It is reported that gentiopicroside acted as a CYP2A6 non-competitive inhibitor at low concentration and a competitive inhibitor at high concentration, and gentiopicroside only had little effect on CYP2E1 or CYP3A4.
CYP2A6 is involved in the metabolism of several pharmaceuticals, including coumarin, nicotine, and certain cancer chemotherapy agents. The clinical significance of this inhibition at doses encountered in typical herbal supplement use has not been formally established in human pharmacokinetic studies.
Swertiamarin, another active constituent, accelerates toxicant metabolism by activating CYP3A4 and CYP2E1 enzymes, thereby attenuating CCl4-induced hepatotoxicity. This differential effect — one constituent inhibiting CYP2A6 while another activates CYP3A4 — means that the net herb-drug interaction profile of whole-root preparations is complex and not fully characterized.
Though iridoid and secoiridoid glucosides are reported as the main constituents in "Long-Dan," the four different pharmacopeial species also produce different minor components, which may be related to their pharmacological activities. Products that do not specify the exact source species among the four permitted pharmacopeial origins may vary significantly in active constituent profiles.
The scientific literature consistently acknowledges that evidence for the clinical safety and efficacy of G. manshurica as a standalone supplement is limited. There is a paucity of large-scale, high-quality clinical trials in humans evaluating the efficacy and safety of Gentiana manshurica as a nutritional supplement; existing evidence is primarily preliminary, indicating a need for further research to confirm its health benefits, elucidate mechanisms, and establish optimal dosing.
The TCM tradition characterizes the herb as having a bitter, cold nature, and classical texts caution against long-term use or use in constitutionally deficient individuals. These traditional safety parameters have not been systematically examined in controlled clinical studies.
Health conditions that Gentiana manshurica may help support.
Body systems that Gentiana manshurica may help support.
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