Zhi Mu
StarAnemarrhena asphodeloides Bunge
Traditionally used for
- Cough & breathing
- Colds & fever
- Digestion
Cautions & contraindications
- Diabetes
☯ TCM Properties
Clears Heat and Drains Fire; Nourishes Yin and Moistens Dryness; Generates Fluids and Relieves Thirst; Clears Lung Heat; Drains Kidney Fire; Clears Stomach Heat
Traditional Chinese Uses
Zhi Mu (anemarrhena rhizome) is a bitter, cold herb with complementary actions of clearing Heat and nourishing Yin. It clears both Qi-level Heat — addressing high fever with thirst — and Kidney Fire from deficiency, making it one of the few herbs bridging excess and deficiency heat patterns. It moistens Lung and Kidney to relieve dry cough from Lung dryness and bone-steaming fever from Yin deficiency. Its combination with Huang Bai in Zhi Bai Di Huang Wan represents a cornerstone of Kidney Yin deficiency with Fire treatment.
Western Herbalism Properties
Pharmacological Effects
- Antipyretic: S.c. aqueous extract (4 g/kg) lowered temperature in E. coli-inoculated rabbits; saponin fraction and sarsasapogenin inhibited Na+/K+-ATPase (including human RBC in vitro), possibly underlying the antipyretic action.
- Hypoglycemic: Aqueous extract lowered blood sugar in normal and alloxan-diabetic rabbits and mice (i.p. 0.15 g/kg reduced glucose by 200 mg% in 5 h); anemarans A–D hypoglycemic; hot water extract increased saliva flow in diabetic animals.
- Adrenocortical hormones: Oral extract raised plasma corticosterone in dexamethasone-treated rabbits and retarded hepatic catabolism of cortisol in vitro.
- Antimicrobial: Decoction inhibited many bacteria, Candida albicans and dermatophytes in vitro; ethanol and ether extracts more active.
- Other: Hinokiresinol and derivatives inhibited cAMP phosphodiesterase; hinokiresinol 25–100 mg/kg prolonged hexobarbital sleep in mice.
Source: Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic, 1998, p. 111.
Used In Formulas (66)
Relationships
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Botanical Description
Anemarrhena asphodeloides is a tufted herbaceous perennial in the Asparagaceae (subfamily Agavoideae), the sole species of its genus, native to northern China, Mongolia and Korea, where it grows on dry sunny slopes, sandy grasslands and rocky open ground. Plants form dense clumps 60-100 cm tall, arising from a stout, creeping, knotty, yellow-brown rhizome covered with persistent leaf-base fibres. The basal leaves are very long and narrow, linear and grass-like, 20-70 cm long and 3-7 mm wide, with a tough, leathery texture and parallel venation. In summer the species sends up a tall, slender, leafless flowering scape ending in a long, sparse, spike-like raceme of small, six-tepalled flowers that are pale pink to greenish-white, opening in the late afternoon and evening and emitting a delicate fragrance. The fruits are small ovoid capsules containing a few black, three-angled seeds.
Active Constituents
Timosaponin BII
Steroidal saponin (furostanol glycoside)Concentration: the Chinese Pharmacopoeia assay marker for the rhizome; not less than 3.0% in the 2015 edition
The most abundant saponin of the drug and the official quantitative marker for it. It is the furostanol precursor from which timosaponin AIII is formed by loss of the C-26 glucose, a conversion carried out both by processing and by gut bacteria after ingestion, so the saponin the patient is actually exposed to is not necessarily the one assayed in the raw herb.
Timosaponin AIII
Steroidal saponin (spirostanol glycoside, sarsasapogenin glycoside)Concentration: a minor constituent relative to timosaponin BII; content varies widely between production regions
The most pharmacologically studied constituent of the drug, with reported anti-inflammatory, antiplatelet and antitumour activity. Its oral pharmacokinetics are poor: after 6.8 mg/kg in rats the peak blood level was only 18.2 +/- 3.1 ng/mL at 2.3 hours with a half-life of 4.9 hours, and its hydrophobicity and low bioavailability are the stated limits on its use. It is also the toxicologically important constituent, being eliminated slowly from the liver and causing hepatotoxicity attributed to intracellular reactive oxygen species and downregulation of bile acid transporters.
Mangiferin
Xanthone C-glucosideConcentration: the second Chinese Pharmacopoeia assay marker; not less than 0.50% in the 2015 edition, and reported to vary several-fold between production regions
The constituent responsible for the drug's hypoglycaemic action, and the reason Zhi Mu is a genuine interaction risk in diabetic patients rather than a theoretical one. In KK-Ay mice, a genetic model of type 2 diabetes, mangiferin lowered blood glucose after three weeks of oral dosing, improved hyperinsulinaemia and improved the insulin tolerance test, while having no effect on glucose in normal mice, indicating that it works by reducing insulin resistance rather than by driving insulin release. It also protects the liver against timosaponin AIII induced injury, so the whole drug is less hepatotoxic than its isolated saponin.
Mangiferin-7-O-beta-glucoside (neomangiferin)
Xanthone C-glucoside glycosideConfirmed alongside mangiferin as one of the two active antidiabetic components of the water extract of the rhizome. It is deglycosylated to mangiferin in the gut, so it behaves largely as a prodrug of it.
Sarsasapogenin
Spirostanol steroidal sapogeninThe aglycone shared by the timosaponin series, released by hydrolysis of the glycosides. It is the scaffold behind most of the neuropharmacological and antitumour work on this drug, but it is a metabolite and processing product rather than an abundant native constituent.
Timosaponin BIII
Steroidal saponin (furostanol glycoside)One of the four saponin and xanthone constituents routinely tracked together in pharmacokinetic and processing studies of the rhizome, alongside timosaponins AIII and BII and mangiferin. Its levels shift measurably with salt-processing, which is the standard preparation of Zhi Mu for draining Kidney fire.
Glucomannans of the rhizome
Polysaccharide (glucomannan)Immunomodulating polysaccharides isolated from the rhizome that act on intestinal Peyer's patches. They are extracted into a water decoction but are absent from ethanolic extracts and from most standardised products, which is one reason a decoction and a capsule of this herb are not equivalent preparations.
⚠ Drug Interactions
Insulin, sulfonylureas (gliclazide, glibenclamide), metformin and other glucose-lowering drugs
This is the best-documented interaction of the drug and rests on several independent lines of animal and cellular work. The water extract of the rhizome at 90 mg/kg lowered blood glucose in KK-Ay diabetic mice from 570 to 401 mg/dL within seven hours, tended to lower serum insulin, and improved the insulin tolerance test, indicating reduced insulin resistance; the active components were confirmed as mangiferin and its glucoside. Isolated mangiferin reproduced the glucose lowering in the same model without affecting normal mice. Separately, an ethanol extract of the rhizome directly stimulated insulin secretion from isolated islets of both normal Wistar and diabetic Goto-Kakizaki rats, up to 11.9-fold at 8 mg/mL, through a pertussis toxin sensitive G-protein effect on the exocytotic machinery, an action that mangiferin itself did not have. So the herb has at least two distinct glucose-lowering mechanisms, one insulin-sensitising and one insulin-releasing. Mangiferin has also been tested explicitly in combination with metformin and with gliclazide in high-fat-diet plus streptozotocin diabetic rats and in HepG2 cells, where both combinations showed positive interaction on glucose uptake and potent antidiabetic effect, with the metformin combination acting through Akt and the gliclazide combination through AMPK.
Clinical note: Ask every patient prescribed Zhi Mu whether they take glucose-lowering medication. This herb is routinely used in diabetic patients precisely because it treats xiao ke, so the exposure is common. Advise home glucose monitoring when starting or stopping the herb and be prepared to reduce insulin or sulfonylurea dose; the insulin-releasing action means the risk is not confined to insulin-resistant patients.
Warfarin, aspirin, clopidogrel and other antiplatelet or anticoagulant drugs
Timosaponin AIII inhibited U46619-induced platelet aggregation in vitro by reducing ADP secretion and prevented thrombus formation in mice in vivo, through suppression of thromboxane A2 receptor signalling. That is the same pathway aspirin acts on upstream, so the effects are mechanistically additive rather than independent. The constituent's poor oral bioavailability makes the size of any clinical effect uncertain, and no human study has been done.
Clinical note: Monitor for bruising or bleeding in patients on antiplatelet drugs or warfarin taking this herb long term. Consider stopping a week before elective surgery, as for other antiplatelet-active herbs.
Hepatotoxic and cholestatic drugs (e.g. methotrexate, isoniazid, flucloxacillin, high-dose paracetamol)
Timosaponin AIII is eliminated slowly from the liver and causes hepatotoxicity attributed to induction of intracellular reactive oxygen species and downregulation of bile acid transporter expression, which is a cholestatic mechanism. Mangiferin from the same plant is protective against this injury, so the whole drug carries a lower risk than the isolated saponin and concentrated saponin extracts are the greater concern. Adding a drug that independently impairs bile acid handling is the plausible route to a clinically visible event.
Clinical note: Prefer the whole decocted herb over saponin-enriched extracts in patients on hepatotoxic drug regimens, and check liver function if the herb is used at high dose or for extended periods alongside them.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 6–12 g | Daily | — | — | 中国药典 2020 【用法与用量】6～12g。 【性味与归经】苦、甘，寒。归肺、胃、肾经。 — 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.
Yin is nourished and heat cleared, calming the spirit in lily disease after mistaken sweating.
Core pair of a classical formula — Bai He Zhi Mu Tang, Jin Gui Yao Lue (Zhang Zhongjing)
The warm drying action that disperses turbid dampness and interrupts malarial disorders is balanced by a cool herb that clears heat and protects yin.
Malarial disorders and membrane-source patterns with alternating chills and fever.
Named pairing — Lü Jingshan, Shi Jinmo Dui Yao
Clearing and moistening the lung is combined with transforming phlegm, relieving dry or heat cough with scanty sticky sputum.
Er Mu San is recorded in several texts with differing attributions.
Named pairing — Zhongyaoxue national textbook; the pair forms Er Mu San
Together they drain Kidney fire and nourish yin, treating steaming bone fever, night sweats and deficiency-fire signs.
The pair is the core addition in Zhi Bai Di Huang Wan and appears in Da Bu Yin Wan.
Named pairing — Lu Jingshan, Shi Jinmo Dui Yao
Qi is tonified and raised while heat is cleared and yin moistened, so the warmth of one is tempered by the coolness of the other.
Used by Zhang Xichun in many formulas, e.g. Sheng Xian Tang for sinking of the great qi.
Named pairing — Lü Jingshan, Shi Jinmo Dui Yao
Acrid-cold and bitter-cold together clear qi-level and yangming heat strongly while protecting fluids, so high fever and thirst are cleared without drying yin.
Classic for yangming channel or qi-level heat with high fever, sweating, thirst and a surging pulse.
Core pair of a classical formula — Bai Hu Tang, Shang Han Lun (Zhang Zhongjing)
Nourishing Liver blood and calming the spirit combined with clearing deficiency heat and moistening, which relieves irritability and insomnia from Liver blood deficiency with heat.
Deficiency irritability with inability to sleep.
Core pair of a classical formula — Suan Zao Ren Tang, Jin Gui Yao Lue (Zhang Zhongjing)
Evidence Tier
Moderate evidence · 4 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
0
Randomized controlled trial
0
Other clinical trial
0
Observational / case report
0
In vitro / animal
4
3 verified · 1 unverified
Show 4 studies
- Antidiabetic Activity of the Rhizoma of Anemarrhena asphodeloides and Active Components, Mangiferin and Its Glucoside.
- Antidiabetic activity of a xanthone compound, mangiferin
- Insulin Secretion is Stimulated by Ethanol Extract of Anemarrhena asphodeloides in Isolated Islet of Healthy Wistar and Diabetic Goto-Kakizaki Rats
- Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide
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
Antidiabetic Activity of the Rhizoma of Anemarrhena asphodeloides and Active Components, Mangiferin and Its Glucoside.
A water extract of the rhizome at 90 mg/kg orally reduced blood glucose in KK-Ay mice, a genetic model of type 2 diabetes, from 570 +/- 29 to 401 +/- 59 mg/dL within seven hours, and tended to reduce serum insulin. Treated mice showed significantly lower glucose on insulin tolerance testing, so the authors concluded the mechanism is a reduction in insulin resistance. The active components were confirmed as mangiferin and its glucoside. This is the primary source for the clinically important hypoglycaemic interaction of Zhi Mu.
Antidiabetic activity of a xanthone compound, mangiferin
Mangiferin isolated from Anemarrhena asphodeloides rhizome lowered blood glucose in KK-Ay mice three weeks after oral administration and improved hyperinsulinaemia, while having no effect on blood glucose in normal mice. On insulin tolerance testing it reduced glucose levels, from which the authors concluded it acts by decreasing insulin resistance. The absence of any effect in normal animals is the reason this is characterised as an antidiabetic rather than a generally hypoglycaemic action.
Insulin Secretion is Stimulated by Ethanol Extract of Anemarrhena asphodeloides in Isolated Islet of Healthy Wistar and Diabetic Goto-Kakizaki Rats
An ethanol extract of the rhizome directly stimulated insulin release from isolated pancreatic islets of normal Wistar rats and of spontaneously diabetic Goto-Kakizaki rats. At 3.3 mM glucose, 2, 4 and 8 mg/mL raised insulin release 2.5, 4.1 and 5.7-fold in Wistar islets and 1.7, 3.0 and 6.3-fold in GK islets; at 16.7 mM glucose the GK islet response reached 11.9-fold. The effect was reversible on washout, persisted in depolarised islets with K-ATP channels held open by diazoxide, and was suppressed 35-47% by pertussis toxin, indicating an action on the beta cell exocytotic machinery through Gi or Ge proteins. Mangiferin itself had no effect on insulin secretion, so this is a second and separate hypoglycaemic mechanism in the same herb.
Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide
The one study that tests the interaction directly. Mangiferin was combined with metformin and with gliclazide in HepG2 cells and in high-fat-diet plus streptozotocin diabetic Sprague Dawley rats, with combination indices calculated by CompuSyn. Both combinations showed positive interaction on glucose uptake at specific concentrations and potent antidiabetic effect in vivo, confirmed by hepatic enzyme, oxidative stress and carbohydrate-metabolising enzyme markers and by AMPK, Akt, ACC beta, Glut-2, PPARalpha and PPARgamma expression. The metformin combination was insulin dependent, acting through Akt, while the gliclazide combination was insulin independent, acting through AMPK. The authors frame this positively, as dose sparing, but for a practitioner it is direct evidence that the herb's main antidiabetic constituent adds to the effect of both drug classes.
⚠ Safety & Contraindications
- Diabetes
Contraindications
Since it is cold, moistening, and laxative, it is not suitable for patients with thin, unformed stool due to spleen deficiency.
Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, pp. 37–43.
Historical Texts
Shen Nong Ben Cao Jing
Han dynastyReferences
- Liu Congying, Cong Zhufeng, Wang Shengguang, Zhang Xin, Song Huaying, Xu Tianren, Kong Hongwei, Gao Peng, Liu Xiaonan. A review of the botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality of Anemarrhena asphodeloides Bunge . Journal of Ethnopharmacology (2023) [DOI]
- Lin Yan, Zhao Wai-Rong, Shi Wen-Ting, Zhang Jing, Zhang Kai-Yu, Ding Qian, Chen Xin-Lin, Tang Jing-Yi. Pharmacological Activity, Pharmacokinetics, and Toxicity of Timosaponin AIII, a Natural Product Isolated From Anemarrhena asphodeloides Bunge: A Review . Frontiers in Pharmacology (2020) [DOI]
- Ji De, Huang Zi-yan, Fei Cheng-hao, Xue Wei-wei, Lu Tu-lin. Comprehensive profiling and characterization of chemical constituents of rhizome of Anemarrhena asphodeloides Bge. . Journal of Chromatography B (2017) [DOI]
- Kiyohara Hiroaki, Matsuzaki Toshiake, Yamada Haruki. Intestinal Peyer's patch-immunomodulating glucomannans from rhizomes of Anemarrhena asphodeloides Bunge . Phytochemistry (2013) [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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