Du Huo
StarAngelica pubescens Maxim. f. biserrata Shan et Yuan
Traditionally used for
- Colds & fever
- Pain & joints
Cautions & contraindications
- Bleeding disorders
- Seizure disorders
☯ TCM Properties
Dispels Wind-Dampness; Relieves Painful Obstruction; Releases the Exterior; Disperses Cold
Traditional Chinese Uses
Du Huo (angelica root, pubescent angelica) is a warm, pungent herb used in Chinese medicine primarily to expel Wind-Cold-Damp from the lower body. It is the principal herb for lower back and leg pain, weakness, and stiffness from Wind-Damp bi obstruction, particularly when symptoms are more pronounced in the lower limbs. It is commonly paired with Sang Ji Sheng in formulas for lower body Wind-Damp on a background of Kidney and Liver deficiency.
Western Herbalism Properties
Pharmacological Effects
- Analgesic, antiinflammatory and sedative: Decoction 2 g/kg i.p. was analgesic in mice (hot plate); methanolic/ethyl acetate extracts were analgesic (writhing) and anti-inflammatory (carrageenin edema), osthol being the active principle; several coumarins active at 10 mg/kg; extracts sedative in mice and rats.
- Cardiovascular: I.v. decoction or tincture lowered blood pressure in anesthetized dogs (atropine-sensitive); high doses arrested isolated frog heart; byakangelicin and isopimpinellin dilated coronaries, weaker than khellin.
- Antispasmodic: Bergapten, xanthotoxin, isopimpinellin and pimpinellin relaxed intestinal smooth muscle; scopoletin inhibited uterine spasm.
- Other: Xanthotoxin and bergapten are photosensitizers used for vitiligo; bergapten/pimpinellin moderately antiulcer; decoction and xanthotoxin inhibited M. tuberculosis; umbelliferone inhibited Brucella.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 251.
Relationships
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Botanical Description
Angelica pubescens (Du Huo, pubescent angelica) is a robust perennial herb in the Apiaceae family, growing 1 to 2 meters tall from a stout, fleshy, conical taproot 10 to 30 centimeters long, externally grayish-brown with prominent ringed scars and short rootlets, internally pale yellowish with brownish oil canals visible on cross section. The hollow purple-tinged stems are erect, finely pubescent in the upper portion, and bear large bi- to tri-pinnately compound leaves 30 to 50 centimeters long with broadly ovate ultimate leaflets coarsely serrate at the margins; the leaf sheaths are conspicuously inflated. From mid to late summer, large compound umbels 10 to 20 centimeters across bear numerous small white flowers. The schizocarp fruits are oblong-elliptic, 6 to 8 millimeters long, with broadly winged lateral ribs. Native to central China, particularly Sichuan, Hubei, and Anhui provinces, growing on damp shaded slopes and in forest understory. The aromatic, sweet-bitter roots are harvested in autumn and dried.
Active Constituents
Osthole
Prenylated simple coumarinConcentration: Chinese Pharmacopoeia assay marker: not less than 0.50 per cent of the dried root
The principal quality marker and one of the two coumarins the drug is assayed on. In mice it reduced oxaliplatin-induced mechanical and cold hypersensitivity and preferentially inhibited T-type and L-type voltage-gated calcium currents in small dorsal root ganglion neurons, which is a plausible mechanism for the analgesic reputation of the root.
Columbianadin
Angular dihydrofuranocoumarin ester (columbianetin angelate)Concentration: Chinese Pharmacopoeia assay marker: not less than 0.080 per cent of the dried root
The second pharmacopoeial marker and the most studied anti-inflammatory constituent of the root. It inhibited neuropathic pain behaviour and T-type and L-type calcium currents in the same mouse model as osthole, and is under study in its own right as an anti-arthritic lead.
Columbianetin acetate
Angular dihydrofuranocoumarin esterConcentration: One of eight coumarins measured in rat plasma after oral dosing of the root extract
A close congener of columbianadin that is absorbed after oral administration of the root extract. The angular dihydrofuranocoumarins as a group lack the planar furan ring that makes the linear furanocoumarins photoreactive.
Bergapten (5-methoxypsoralen)
Linear furanocoumarinConcentration: Minor constituent, detected in rat plasma after oral administration of the root extract
A photoreactive linear furanocoumarin that intercalates DNA and forms cyclobutane adducts under UVA, the basis of phytophotodermatitis. It is also a potent cytochrome P450 inhibitor: it inhibited melatonin metabolism through CYP1A2, 1A1 and 1B1 with a Ki of 5.34 nM, and pretreatment raised macitentan exposure in rats through CYP3A4 inhibition.
Xanthotoxin (8-methoxypsoralen, methoxsalen)
Linear furanocoumarinConcentration: Minor constituent, detected in rat plasma after oral administration of the root extract
The same molecule licensed as the drug methoxsalen and given deliberately with ultraviolet A in PUVA photochemotherapy, so its photosensitising potency in humans is not in doubt. It inhibited melatonin metabolism with a Ki of 18 nM via CYP1A2, 1A1 and 1B1.
Psoralen
Linear furanocoumarinConcentration: Minor constituent, detected in rat plasma after oral administration of the root extract
The parent linear furanocoumarin and the archetypal plant photosensitiser. Its presence, together with bergapten and xanthotoxin, is what places this root in the phototoxic Apiaceae rather than among the harmless simple coumarins.
Imperatorin
Linear furanocoumarinConcentration: Quantified alongside osthole, columbianadin, isoimperatorin and oxypeucedanin in root from twelve Chinese production areas
Inhibited CYP3A4-mediated macitentan metabolism with IC50 values of 6.58 micromolar in rat and 6.97 micromolar in human liver microsomes, mixed-type inhibition, with molecular docking placing it in the CYP3A4 active site and raised macitentan exposure in rats. It also inhibited melatonin metabolism with a Ki of 14.5 nM.
Isoimperatorin
Linear furanocoumarinConcentration: Quantified alongside osthole, columbianadin, imperatorin and oxypeucedanin in root from twelve Chinese production areas
A further linear furanocoumarin of the root, inhibiting melatonin metabolism with a Ki of 38.8 nM. It contributes to the cumulative cytochrome P450 and photosensitising load of the drug rather than carrying a distinct activity of its own.
Oxypeucedanin
Linear furanocoumarinConcentration: One of five coumarins quantified by HPTLC in root from twelve Chinese production areas
Another linear furanocoumarin of the root. Its content, like that of the other four markers, varies enough between production areas that samples cluster into distinct quality groups.
⚠ Drug Interactions
Photosensitising drugs and phototherapy (methoxsalen and PUVA, amiodarone, tetracyclines, fluoroquinolones, voriconazole, thiazide diuretics, piroxicam, St John's wort)
The root contains psoralen, bergapten and xanthotoxin, all three of which were quantified in rat plasma after oral administration of the extract, so they reach the circulation rather than acting only on contact. Xanthotoxin is methoxsalen, the drug deliberately combined with ultraviolet A in PUVA therapy. Adding an oral source of the same photosensitisers to another photosensitising drug, or to phototherapy, stacks the same photochemical mechanism. The angular dihydrofuranocoumarins that dominate the root by mass are not photoreactive, but the linear furanocoumarins present alongside them are.
Clinical note: Warn patients to use sun protection while taking the herb, particularly at higher doses or in prolonged courses. Do not co-prescribe with PUVA or narrowband UVB phototherapy, and take extra care in patients already on amiodarone, a tetracycline or a fluoroquinolone.
CYP3A4 substrates with a narrow therapeutic index (ciclosporin, tacrolimus, simvastatin, midazolam, apixaban, rivaroxaban, macitentan)
Two of the root's linear furanocoumarins have been tested directly against a CYP3A4 substrate. Imperatorin inhibited macitentan metabolism with IC50 values of 6.58 micromolar in rat and 6.97 micromolar in human liver microsomes and raised macitentan exposure in rats, and bergapten pretreatment did the same in a companion study using rat and human microsomes and recombinant CYP3A4. This is the mechanism behind the grapefruit juice effect, which is carried by the same chemical class. The gap in the evidence is that the whole root has not itself been given with a CYP3A4 substrate in humans, so the size of the effect at ordinary decoction doses is unknown.
Clinical note: Avoid in transplant recipients and in anyone on a narrow-therapeutic-index CYP3A4 substrate unless levels can be monitored. If the herb is started or stopped during such therapy, check drug levels or the relevant clinical marker.
CYP1A2 substrates (theophylline, clozapine, olanzapine, tizanidine, duloxetine, ramelteon, melatonin, caffeine)
Bergapten and xanthotoxin inhibit CYP1A2, CYP1A1 and CYP1B1 with Ki values of 5.34 nM and 18 nM in human liver microsomes, and imperatorin and isoimperatorin at 14.5 nM and 38.8 nM. In the same study a coumarin-rich Angelica extract raised melatonin area under the curve about twelvefold and peak concentration about fourfold in twelve healthy volunteers. That human work used Angelica dahurica, not Angelicae Pubescentis Radix, but the four inhibitory coumarins responsible are all present in this root and are all orally absorbed, so the mechanism transfers even though the magnitude has not been measured for this drug.
Clinical note: Treat as a probable CYP1A2 inhibitor. Avoid with theophylline, clozapine and tizanidine, and be alert for excess sedation with olanzapine or melatonin. Nanomolar Ki values mean the effect does not require a large herb dose.
Warfarin and other oral anticoagulants
The plant coumarins of this root are simple, angular and linear furanocoumarins, not 4-hydroxycoumarins, and they have no vitamin K antagonist activity: the recurring assumption that a coumarin-rich herb thins the blood is a naming error, not a pharmacological finding. The real concern runs the other way, through the furanocoumarin inhibition of cytochrome P450 enzymes that clear warfarin, and it has not been measured for this herb.
Clinical note: Do not stop an anticoagulant on the mistaken ground that the herb is itself anticoagulant. Do check the international normalised ratio more often for the first few weeks after the herb is started or stopped.
Aralia continentalis and Aralia cordata (Korean Dok-Hwal)
The Korean drug Dok-Hwal and the Chinese drug Du-Huo carry the same name in the two traditions but are defined differently in the two national pharmacopoeias: Araliae Continentalis Radix in Korea, Angelicae Pubescentis Radix in China. A multiplex SCAR and ITS2 assay built to separate them also identified inauthentic and adulterated commercial samples from both Korea and China. Aralia is Araliaceae and carries no furanocoumarins, so the photosensitivity and cytochrome P450 concerns of the Apiaceae drug do not transfer to it, and neither do the pharmacopoeial osthole and columbianadin assays.
Clinical note: Establish which pharmacopoeia the material was sourced under before applying either the dosing or the interaction profile. A Korean-sourced Dok-Hwal is a different drug and should be researched as Aralia.
Levisticum officinale and Heracleum moellendorffii roots
Dried Levisticum officinale and Heracleum moellendorffii roots are distributed under the same drug name and are morphologically hard to separate from the authentic root, which is why the multiplex molecular assay was developed. Both substitutes are Apiaceae and Heracleum in particular is a notoriously furanocoumarin-rich, phototoxic genus, so the substitution does not remove the photosensitivity risk and may raise it.
Clinical note: Buy from suppliers who authenticate species. Unexplained phototoxic reactions on this herb are a reason to question the identity of the batch as well as the dose.
Notopterygium incisum and Notopterygium franchetii (Qiang Huo)
The Shen Nong Ben Cao Jing lists Qiang Huo as an alternative name for Du Huo, treating them as one drug; Tao Hongjing was the first to separate them on morphology, aroma and provenance, and they have been two distinct drugs ever since. They remain separate Chinese Pharmacopoeia entries with different botanical sources, different assay markers and different families of coumarin, and Qiang Huo is itself heavily adulterated. Classical citations under either name from before that separation cannot safely be assigned to one species.
Clinical note: Do not treat the two as interchangeable, and do not carry the constituent, dose or interaction profile of one across to the other. When reading a classical source, check whether it predates the separation.
Calcium channel blockers and gabapentinoids
Osthole and columbianadin, the two pharmacopoeial markers of the root, preferentially inhibited T-type and L-type voltage-gated calcium currents in mouse dorsal root ganglion neurons, and gabapentin prevented their effect on oxaliplatin-induced allodynia, indicating a shared target. Whether this reaches systemic significance at oral doses in humans is untested, and no cardiovascular calcium channel effect has been demonstrated.
Clinical note: No action needed for most patients. Note the possibility if a patient on a gabapentinoid reports an unexpected change in neuropathic pain control after starting the herb.
Sedatives and hypnotics
Sedative and hypnotic activity is listed among the reproducible pharmacological effects of the root in both recent reviews of Angelicae Pubescentis Radix, alongside its anti-inflammatory and analgesic actions. The relevant animal work has not been followed into humans and no specific interacting agent has been identified, so this is a class-level caution rather than a documented interaction.
Clinical note: Mention the possibility of drowsiness to patients driving or operating machinery, particularly when the herb is combined with a benzodiazepine, a Z-drug or an antihistamine.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 3–10 g | Daily | — | — | 中国药典 2020 【用法与用量】3～10g。 【性味与归经】辛、苦，微温。归肾、膀胱经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Dui Yao — Herb Pairs
The classical two-herb combinations this herb appears in, each with an action neither herb has alone.
Together they dispel wind-damp from the whole body: one acts mainly on the upper body and exterior, the other on the lower back and legs, so the pair treats generalized painful obstruction.
Classic for wind-damp in the exterior with headache, stiff neck and generalized body aches.
Core pair of a classical formula — Qiang Huo Sheng Shi Tang, Nei Wai Shang Bian Huo Lun (Li Dongyuan)
The pair dispels wind-damp while tonifying the liver and kidneys and strengthening sinew and bone, treating chronic painful obstruction on a background of deficiency.
Chronic lower back and knee pain with weakness in liver-kidney deficiency.
Core pair of a classical formula — Du Huo Ji Sheng Tang, Bei Ji Qian Jin Yao Fang (Sun Simiao)
Evidence Tier
Strong evidence · 10 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
2
0 verified · 2 unverified
Other clinical trial
0
Observational / case report
0
In vitro / animal
4
1 verified · 3 unverified
Show 4 studies
- Simultaneous determination of scopoletin, psoralen, bergapten, xanthotoxin, columbianetin acetate, imperatorin, osthole and isoimperatorin in rat plasma by LC-MS/MS for pharmacokinetic studies following oral administration of Radix Angelicae Pubescentis extract
- Drug Interactions of Imperatorin and Curcumin on Macitentan in vitro and in vivo
- Effects of bergapten on the pharmacokinetics of macitentan in rats both in vitro and in vivo
- Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice
Other / unclassified
3
1 verified · 2 unverified
Show 3 studies
- Efficacy and Safety of Duhuo Jisheng Decoction for Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis
- Rapid Authentication of the Herbal Medicine Plant Species Aralia continentalis Kitag. and Angelica biserrata C.Q. Yuan and R.H. Shan Using ITS2 Sequences and Multiplex-SCAR Markers
- Determination of Five Coumarins in Angelicae Pubescentis Radix from Different Origins by HPTLC-Scanning
Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description
Clinical Studies
Evidence of Chinese herbal medicine Duhuo Jisheng decoction for knee osteoarthritis: a systematic review of randomised clinical trials
Twelve randomised trials with 982 participants were pooled. Duhuo Jisheng decoction combined with glucosamine improved total WOMAC score by a mean difference of 4.20 (95 per cent CI 1.72 to 6.69), and with meloxicam plus glucosamine by 3.48 (1.59 to 5.37); pain improved when it was added to sodium hyaluronate injection. The authors rated the included trials at high risk of bias, found safety reporting insufficient, and concluded that effectiveness and safety remain uncertain. This is evidence for a multi-herb formula in which Du Huo is the lead ingredient, not for the single root.
Therapeutic effect of Duhuo Jisheng Decoction add-on Tui-na manipulation on osteoarthritis of knee: a randomized controlled trial
Seventy patients with knee osteoarthritis were randomised to eight sessions of tuina over four weeks with or without added oral Duhuo Jisheng decoction. The primary outcome, total WOMAC at four weeks, did not differ between groups. Secondary analyses favoured the decoction on the WOMAC pain subscale at eight-week follow-up (mean difference -1.8, 95 per cent CI -3.5 to -0.02) and on stiffness at weeks two and eight. The honest reading is a negative primary endpoint with modest secondary signals in a small trial of a formula, not of Du Huo alone.
Efficacy and Safety of Duhuo Jisheng Decoction for Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis
Eight randomised trials with 650 participants were pooled. Duhuo Jisheng decoction alone or added to conventional therapy improved lumbar spine bone mineral density (mean difference 0.46, 95 per cent CI 0.24 to 0.68) and clinical effectiveness (odds ratio 5.07, 95 per cent CI 3.07 to 8.35), with no effect on bone gla protein. The authors judge trial quality unsatisfactory. Again this is formula-level evidence, and the very large effectiveness odds ratio is characteristic of small unblinded Chinese trials rather than of a large true effect.
Inhibition of melatonin metabolism in humans induced by chemical components from herbs and effective prediction of this risk using a computational model
Sixty-six common herbs were screened in human liver microsomes; the Angelica coumarins were the most potent inhibitors of melatonin metabolism. Imperatorin, isoimperatorin, phellopterin, 5-methoxypsoralen and 8-methoxypsoralen inhibited CYP1A2, 1A1 and 1B1 with Ki values of 14.5, 38.8, 6.34, 5.34 and 18 nM. In twelve healthy volunteers the herb raised melatonin area under the curve roughly twelvefold and peak concentration roughly fourfold. The herb dosed in humans was Angelica dahurica, not Angelicae Pubescentis Radix, but four of the five inhibitory coumarins are constituents of Du Huo and are orally absorbed from it.
Simultaneous determination of scopoletin, psoralen, bergapten, xanthotoxin, columbianetin acetate, imperatorin, osthole and isoimperatorin in rat plasma by LC-MS/MS for pharmacokinetic studies following oral administration of Radix Angelicae Pubescentis extract
A validated LC-MS/MS assay measured eight coumarins in rat plasma after oral dosing of the root extract, with lower limits of quantitation below 2.16 ng/mL. The finding that matters clinically is not the method but the list: psoralen, bergapten and xanthotoxin are systemically absorbed from an oral preparation of this root, which is what makes the phototoxicity and cytochrome P450 questions real rather than notional.
Drug Interactions of Imperatorin and Curcumin on Macitentan in vitro and in vivo
Imperatorin inhibited the metabolism of the CYP3A4 substrate macitentan with IC50 values of 6.58 micromolar in rat and 6.97 micromolar in human liver microsomes, by mixed-type inhibition, and molecular docking placed it in the CYP3A4 active site. Oral macitentan exposure rose significantly in rats given imperatorin. Imperatorin is a constituent of Angelicae Pubescentis Radix, so this is constituent-level rather than whole-herb evidence.
Effects of bergapten on the pharmacokinetics of macitentan in rats both in vitro and in vivo
Bergapten was tested against macitentan in rat and human liver microsomes and recombinant CYP3A4, and rats were pretreated with bergapten 10 mg/kg for seven days before an oral 20 mg/kg dose of macitentan. Bergapten inhibited the CYP3A4-mediated metabolism and altered macitentan pharmacokinetics in vivo, with molecular docking supporting active-site binding. Bergapten is one of the linear furanocoumarins absorbed from Du Huo.
Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice
Columbianadin and osthole, the two pharmacopoeial markers of the root, both reduced oxaliplatin-induced mechanical and cold hypersensitivity in mice and preferentially inhibited T-type and L-type calcium currents in small dorsal root ganglion neurons. Gabapentin prevented their effect on mechanical allodynia, implying a shared target. This gives the traditional analgesic indication a defined ion-channel mechanism, at constituent level and in rodents.
Rapid Authentication of the Herbal Medicine Plant Species Aralia continentalis Kitag. and Angelica biserrata C.Q. Yuan and R.H. Shan Using ITS2 Sequences and Multiplex-SCAR Markers
ITS2 sequences were used to design species-specific primers for Aralia continentalis, Angelica biserrata, Levisticum officinale and Heracleum moellendorffii, combined into a single multiplex PCR. Applied to commercial samples bought in Korea and China, the assay confirmed authentic material and identified inauthentic or adulterated samples. The paper documents that Dok-Hwal and Du-Huo are the same drug name over two different pharmacopoeial species, with two further Apiaceae roots circulating under it.
Determination of Five Coumarins in Angelicae Pubescentis Radix from Different Origins by HPTLC-Scanning
Osthole, columbianadin, isoimperatorin, oxypeucedanin and imperatorin were quantified by HPTLC in root from twelve Chinese production areas. Cluster analysis split the samples into two quality groups, with material from Dazhou in Sichuan and Huating in Gansu scoring best. The practical point for a dispensary is that both the marker coumarins and the furanocoumarins that drive the interaction profile vary substantially with provenance.
⚠ Safety & Contraindications
- Bleeding disorders
- Seizure disorders
Contraindications
Its use is cautious in patients with yin deficiency and blood dryness.
Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, pp. 105–112.
Side Effects
- Decoction caused nausea, vomiting and stomach discomfort in some cases
- Xanthotoxin 200-300 mg/kg in guinea pigs caused liver cloudy swelling, fatty degeneration and acute hemorrhagic necrosis, severe renal congestion and hematuria; 400 mg/kg was lethal
- Xanthotoxin 1-2 mg/kg for 5 months caused liver necrosis in young rats
- Photosensitizing furocoumarins (xanthotoxin, bergapten)
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 251.
Historical Texts
Shen Nong Ben Cao Jing (Divine Husbandman's Classic of Materia Medica)
Han dynasty, compiled by the second century CEBen Cao Jing Ji Zhu (Collected Commentaries on the Classic of Materia Medica), Tao Hongjing
Southern and Northern Dynasties, about 500 CEBei Ji Qian Jin Yao Fang (Essential Formulas for Emergencies Worth a Thousand Gold Pieces), Sun Simiao
Tang dynasty, 652 CEBen Cao Gang Mu (Compendium of Materia Medica), Li Shizhen
Ming dynasty, completed 1578, published 1596Pharmacopoeia of the People's Republic of China
Modern, twentieth to twenty-first centuryReferences
- Yang L; Hou A; Wang S; Zhang J; Man W; Guo X; Yang B; Jiang H. A Review of the Botany, Traditional Use, Phytochemistry, Analytical Methods, Pharmacological Effects, and Toxicity of Angelicae Pubescentis Radix . Evidence-Based Complementary and Alternative Medicine (2020) [DOI]
- Lu Y; Wu H; Yu X; Zhang X; Luo H; Tang L; Wang Z. Traditional Chinese Medicine of Angelicae Pubescentis Radix: A Review of Phytochemistry, Pharmacology and Pharmacokinetics . Frontiers in Pharmacology (2020) [DOI]
- Ge Y; Chen S; Luo Q; Wang CP; Hao J; He J; Chen X; Yang X. The Tissue Distribution of Four Major Coumarins after Oral Administration of Angelicae Pubescentis Radix Extract to Rats Using Ultra-High-Performance Liquid Chromatography . Evidence-Based Complementary and Alternative Medicine (2019) [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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