Anemarrhena asphodeloides (Zhi Mu)

Anemarrhena asphodeloides
Evidence Level
Preliminary
2 Clinical Trials
5 Documented Benefits
1/5 Evidence Score

Anemarrhena asphodeloides, known in Traditional Chinese Medicine as Zhi Mu, is a rhizomatous herb classically used to clear 'heat' and nourish 'yin.' The dried rhizome contains a distinctive family of steroidal saponins (timosaponins, especially timosaponin AIII and BII), the aglycone sarsasapogenin, xanthones (mangiferin and neomangiferin), and polysaccharides. In TCM it is paired with herbs like Phellodendron to address symptoms attributed to kidney yin deficiency, including hot flashes, night sweats, irritability, and excessive thirst. Modern preclinical research has examined timosaponins and sarsasapogenin for effects on cognitive function, blood glucose regulation, and inflammation. No published trial has given the rhizome or a standardized extract of it to people on its own. Human data exist only for multi-herb formulas that contain it and for two isolated constituents, and the constituent trial that measured memory found no benefit over placebo.

Studied Dose Traditional TCM decoctions use 6 to 12 g of dried rhizome daily, the usual traditional range. No published human trial has tested a standardized Anemarrhena extract at any milligram dose. The only oral doses ever given to people are isolated constituents: sarsasapogenin 200 mg/day for 8 weeks and mangiferin 150 mg/day for 12 weeks. Neither is the whole rhizome, and a concentrated extract is not interchangeable with a decoction of raw rhizome.
Active Compound Steroidal saponins (timosaponin AIII, BII, BIII), aglycones (sarsasapogenin), xanthones (mangiferin, neomangiferin), and polysaccharides.

Benefits

Hot flashes: tested only inside multi-herb formulas

Zhi Mu on its own has never been tested for hot flashes in a published human trial. It is one of six herbs in Er-Xian decoction, which beat placebo over 12 weeks in 108 Hong Kong perimenopausal women, though the placebo group improved almost as much: the hot flush score fell from 16.6 to 7.0 on placebo versus 19.6 to 4.9 on the formula (P = 0.02). A four-arm pilot trial of a formula named Zhi Mu 14, with about 10 women per arm, found no difference from placebo on hot flush frequency, severity or Menopause Rating Scale score. The 2016 Cochrane review of Chinese herbal medicine for menopausal symptoms (22 trials, 2,902 women) pooled the placebo-controlled trials that counted hot flushes per day and found little or no difference (mean difference 0.00 per day, 95% CI -0.88 to 0.89, from 2 trials in 199 women). Nothing measured for a multi-herb formula can be credited to Anemarrhena alone.

Cognition: the one human trial of its aglycone found no benefit

Sarsasapogenin, the aglycone from this rhizome, was tested at 200 mg/day for 8 weeks against placebo in 80 patients already taking risperidone. Memory (Wechsler Memory Scale) and intelligence (modified Chinese Wechsler Adult Intelligence Scale) scores did not differ from placebo. Improved maze performance in aged and scopolamine-treated rodents is the whole basis for the cognitive interest in this herb, and it did not carry over to the one human test that has been run.

Blood glucose: rodent data only, never tested in people

Mangiferin and timosaponins lower blood glucose in diabetic rodents. No trial has given Anemarrhena rhizome or its extract to people to see whether glucose changes at all. The closest human data come from isolated mangiferin at 150 mg/day for 12 weeks in 97 overweight adults with high blood lipids: triglycerides and free fatty acids fell and the insulin resistance index improved, but fasting glucose and insulin themselves did not differ from placebo. Mangiferin also occurs in mango leaf and other plants, so that trial is not a test of this rhizome.

Inflammatory signaling: cell and animal models only

Timosaponins and mangiferin suppress NF-κB activation and lower TNF-alpha and IL-6 output in cultured cells and in rodents. No inflammatory marker has been measured in people taking Anemarrhena, so this remains a laboratory finding. The traditional use for 'clearing heat' is a TCM concept, not an inflammation measurement.

Antioxidant activity in laboratory assays

Mangiferin is a well-characterized antioxidant xanthone in test-tube assays and raises antioxidant enzyme activity in animals. It is also the main xanthone in mango leaf and several other plants, so most of the antioxidant literature attached to this rhizome is really literature on mangiferin. No antioxidant or oxidative-stress marker has been measured in people taking Anemarrhena.

Mechanism of action

1

Cholinergic and BDNF modulation

Preclinical studies suggest sarsasapogenin enhances cholinergic neurotransmission and supports brain-derived neurotrophic factor (BDNF) expression. These are rodent and cell-culture findings. The one human trial of sarsasapogenin measured memory directly and found no difference from placebo.

2

Insulin sensitivity and glucose handling

Mangiferin from Anemarrhena has been shown to activate AMPK signaling and modulate PPARγ in animal models, contributing to improved insulin sensitivity and reduced hepatic glucose output, supporting balanced glucose metabolism.

3

NF-κB and cytokine modulation

Timosaponins suppress NF-κB activation and reduce production of pro-inflammatory cytokines such as TNF-α and IL-6 in cell models, contributing to the herb's traditional reputation for 'cooling' inflammatory conditions.

4

Thermoregulatory and HPA-axis effects

Animal research suggests Anemarrhena extracts may modulate hypothalamic temperature regulation and HPA-axis activity, providing a plausible mechanism for traditional use in addressing hot flashes and stress-related heat symptoms.

Clinical trials

1
Er-Xian decoction, a six-herb formula and not Anemarrhena alone, for menopausal symptoms
PubMed

Randomized, double-blind, placebo-controlled trial, 12 weeks, of Er-Xian decoction, a six-herb formula whose ingredients include Rhizoma Anemarrhenae and Cortex Phellodendri alongside Rhizoma Curculiginis, Herba Epimedii, Radix Morindae Officinalis and Radix Angelicae Sinensis. Zhong LL et al., Menopause 2013;20(7):767-76 (PMID 23793167).

108 Hong Kong PERImenopausal women with a Menopause Rating Scale total score of 28 or higher; 101 completed the study.

Hot flush frequency fell from 5.8 to 2.2 per day on the formula and from 5.0 to 2.4 on placebo (P = 0.04). The hot flush score fell from 19.6 to 4.9 versus 16.6 to 7.0 on placebo (P = 0.02). Menopause Rating Scale and menopause-specific quality-of-life scores also favored the formula, serum hormone levels did not change, and blood counts, liver and kidney tests stayed normal. Most of the improvement happened in the placebo group too, and five of the six herbs were not Anemarrhena, so nothing here can be attributed to this rhizome.

2
Sarsasapogenin, one constituent of the rhizome, 200 mg/day in people: no cognitive benefit
PubMed

Double-blind, placebo-controlled, parallel-group trial of sarsasapogenin, the aglycone from Anemarrhena, at 200 mg/day for 8 weeks added to risperidone 2 to 4 mg/day. Xiao SF et al., Neuroscience Bulletin 2011;27(4):258-68 (PMID 21788997).

80 adults with negative-symptom-dominant schizophrenia (41 on sarsasapogenin, 39 on placebo).

Sarsasapogenin produced no significant difference from placebo on the Positive and Negative Syndrome Scale, the Wechsler Memory Scale or the modified Chinese Wechsler Adult Intelligence Scale at 8 weeks. Adverse events matched placebo, so 200 mg/day was safe and well tolerated but did not improve memory, intelligence or symptoms. Sarsasapogenin is one isolated aglycone, not the whole rhizome.

Side effects and drug interactions

Common Potential side effects

Mild gastrointestinal upset such as loose stools or diarrhea.
Possible abdominal cramping at higher doses.
Nausea in sensitive individuals.
Cooling effects considered contraindicated in 'cold' TCM patterns.
Rare allergic reactions to plant constituents. Liver caution: timosaponin A3 (timosaponin AIII), a saponin tied to this rhizome, injured the liver in rats given 100 mg/kg/day by oral gavage for 14 days, raising serum ALT and total bile acids and producing ballooning degeneration in liver tissue; in cultured rat liver cells it raised reactive oxygen species, shut down the bile acid transporters Ntcp, Bsep and Mrp2, and killed the cells at an IC50 of 15.2 micromolar. Pharmacokinetic work in rats shows gut bacteria generate this saponin from timosaponins B2 and B3 and that the liver clears it slowly after an oral Zhimu decoction, while the herb's own mangiferin blocks the oxidative damage. Short courses at the traditional 6 to 12 g have a long safety record; prolonged use or concentrated extracts have not been shown to be safe in people.

Important Drug interactions

May potentiate blood-glucose-lowering medications.
Possible interactions with hormone replacement therapy.
Could affect drugs metabolized by CYP enzymes.
Use cautiously alongside immunomodulating medications. Bleeding risk is theoretical but plausible: timosaponin B-II inhibited ADP-induced platelet aggregation in laboratory assays and, at 1 to 6 mg/kg in animals, prolonged activated partial thromboplastin time by 9% to 26% and reduced thrombus weight, with no effect on prothrombin time. In a rabbit shunt model given intravenously it had no effect on thrombus formation at all. All of this is animal and test-tube work, none of it oral dosing in a person. Pair this herb carefully with warfarin, clopidogrel, aspirin or other blood thinners.

Frequently asked questions about Anemarrhena asphodeloides (Zhi Mu)

What is Anemarrhena asphodeloides (zhi mu) used for?

Anemarrhena asphodeloides, known as zhi mu, is a Chinese herb used as a cooling, moistening tonic to clear heat and nourish fluids, traditionally for feverish conditions, dryness, and irritability. Its blood-sugar effects have been shown in rodents, not in people.

What is zhi mu good for?

Traditionally it is used to clear heat and moisten dryness (for night sweats, hot flashes, dry cough), and modern research has looked at its compounds for blood sugar and antioxidant effects. It is usually used within formulas.

How much Anemarrhena should I take?

It is used within traditional formulas or as a decoction or extract; follow product or practitioner guidance.

Is Anemarrhena asphodeloides safe?

At the traditional 6 to 12 g and for short courses it has a long safety record. It is cooling and can be harsh on digestion for some, so it is usually balanced within a formula. One of its saponins, timosaponin A3, injured the liver in rats at high doses and builds up in rat liver after oral dosing, so long-term use or concentrated extracts have not been shown to be safe. Those with medical conditions should consult a practitioner or doctor.

What is Anemarrhena asphodeloides?

Anemarrhena asphodeloides, known in Traditional Chinese Medicine as Zhi Mu, is a rhizomatous herb classically used to clear 'heat' and nourish 'yin.' The dried rhizome contains a distinctive family of steroidal saponins (timosaponins, especially timosaponin AIII and BII), the aglycone sarsasapogenin, xanthones (mangife…

What is Anemarrhena asphodeloides used for?

Anemarrhena asphodeloides is researched primarily for Menopause Support. Zhi Mu on its own has never been tested for hot flashes in a published human trial. It is one of six herbs in Er-Xian decoction, which beat placebo over 12 weeks in 108 Hong Kong perimenopausal women, though the placebo group improved almos…

What is the recommended dosage of Anemarrhena asphodeloides?

The clinically studied dose is Traditional TCM decoctions use 6 to 12 g of dried rhizome daily, the usual traditional range. No published human trial has tested a standardized Anemarrhena extract at any milligram dose. Always follow the product label and check with a healthcare provider for personal advice.

Is Anemarrhena asphodeloides safe, and does it have side effects?

For most healthy adults, Anemarrhena asphodeloides is well tolerated at studied doses. Reported effects can include: Mild gastrointestinal upset such as loose stools or diarrhea. Possible abdominal cramping at higher doses. It may also interact with some medications. Anemarrhena asphodeloides is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Anemarrhena asphodeloides interact with any medications?

Possible interactions include: May potentiate blood-glucose-lowering medications. Possible interactions with hormone replacement therapy. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Anemarrhena asphodeloides?

NutraSmarts rates the evidence for Anemarrhena asphodeloides as Preliminary (1 out of 5). It is backed by 2 clinical trials and 11 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(11 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Wang Y, Dan Y, Yang D, Hu Y, Zhang L, Zhang C, Zhu H, Cui Z, Li M, Liu Y. The genus Anemarrhena Bunge: A review on ethnopharmacology, phytochemistry and pharmacology. J Ethnopharmacol. 2014;153(1):42-60. doi: 10.1016/j.jep.2014.02.013.PubMedUsed to support: Review of the Anemarrhena genus covering its steroidal saponin and xanthone chemistry, its recorded uses in China, Japan and Korea, and its pharmacology. Every activity the review catalogues is from extracts or isolated compounds in cells and animals, and the authors close by noting that clinical studies and toxicity work on the herb still need to be done.
  2. King FW, Fong S, Griffin C, Shoemaker M, Staub R, Zhang YL, Cohen I, Shtivelman E. Timosaponin AIII is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress. PLoS One. 2009;4(9):e7283. doi: 10.1371/journal.pone.0007283.PubMedUsed to support: Laboratory cell-culture work. An aqueous Anemarrhena extract and its minor saponin timosaponin AIII killed cultured cancer cell lines while sparing non-transformed cells, by blocking mTORC1 and triggering endoplasmic reticulum stress. The abundant saponin timosaponin BII showed little activity until enzymes stripped a sugar from it. No animals and no people were studied, and all the authors were paid employees and shareholders of the company developing the compound as a drug candidate, which also funded the work.
  3. MarElia CB, Sharp AE, Shemwell TA, Zhang YC, Burkhardt BR. Anemarrhena asphodeloides Bunge and its constituent timosaponin-AIII induce cell cycle arrest and apoptosis in pancreatic cancer cells. FEBS Open Bio. 2018;8(7):1155-1166. doi: 10.1002/2211-5463.12457.PubMedUsed to support: Laboratory cell-culture work. Anemarrhena extract and timosaponin AIII slowed the growth of cultured pancreatic cancer cell lines, arrested the cell cycle, and triggered caspase-dependent apoptosis. The comparison with gemcitabine was made in the same dishes of cells. No animals and no people were studied.
  4. Lu WQ, Qiu Y, Li TJ, Tao X, Sun LN, Chen WS. Antiplatelet and antithrombotic activities of timosaponin B-II, an extract of Anemarrhena asphodeloides. Clin Exp Pharmacol Physiol. 2011;38(7):430-4. doi: 10.1111/j.1440-1681.2011.05530.x.PubMedUsed to support: Laboratory and animal study. Timosaponin B-II inhibited ADP-induced platelet aggregation in vitro and, at 1 to 6 mg/kg in animals, prolonged activated partial thromboplastin time by 9.3% to 25.5% and reduced thrombus wet weight by 13.6% to 24.7%, with no effect on prothrombin time. In a rabbit arteriovenous shunt model given intravenously it did not reduce thrombus formation. No oral dosing in people has been studied, so this is grounds for caution alongside blood thinners rather than a demonstrated interaction.
  5. Xiao SF, Xue HB, Li X, Chen C, Li GJ, Yuan CM, Zhang MY. A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia. Neurosci Bull. 2011;27(4):258-68. doi: 10.1007/s12264-011-1417-6.PubMedUsed to support: Randomized, double-blind, placebo-controlled trial in 80 adults. Sarsasapogenin, the aglycone from Anemarrhena, at 200 mg/day for 8 weeks added nothing over placebo on memory (Wechsler Memory Scale), intelligence (modified Chinese Wechsler Adult Intelligence Scale) or symptom scales. Adverse events matched placebo. This is the only published human trial of an Anemarrhena constituent taken by mouth with a cognitive endpoint, and it was negative.
  6. Nedeljkovic M, Tian L, Ji P, Deglon-Fischer A, Stute P, Ocon E, Birkhauser M, Ausfeld-Hafter B. Effects of acupuncture and Chinese herbal medicine (Zhi Mu 14) on hot flushes and quality of life in postmenopausal women: results of a four-arm randomized controlled pilot trial. Menopause. 2014;21(1):15-24. doi: 10.1097/GME.0b013e31829374e8.PubMedUsed to support: Four-arm randomized pilot trial in 40 postmenopausal women reporting at least 20 hot flushes a week, roughly 10 women per arm. The Chinese herbal formula named Zhi Mu 14 showed no significant improvement in hot flush frequency, hot flush severity or Menopause Rating Scale score compared with a matching placebo formula over 12 weeks; only the acupuncture arm separated from its sham. The trial was designed to test feasibility and is too small to rule out a modest effect.
  7. Zhong LL, Tong Y, Tang GW, Zhang ZJ, Choi WK, Cheng KL, Sze SC, Wai K, Liu Q, Yu BX. A randomized, double-blind, controlled trial of a Chinese herbal formula (Er-Xian decoction) for menopausal symptoms in Hong Kong perimenopausal women. Menopause. 2013;20(7):767-76. doi: 10.1097/GME.0b013e31827cd3dd.PubMedUsed to support: Randomized, double-blind, placebo-controlled trial over 12 weeks in 108 Hong Kong perimenopausal women of Er-Xian decoction, a six-herb formula containing Rhizoma Anemarrhenae and Cortex Phellodendri. Hot flush frequency fell from 5.8 to 2.2 per day on the formula versus 5.0 to 2.4 on placebo (P = 0.04), and the hot flush score from 19.6 to 4.9 versus 16.6 to 7.0 (P = 0.02). Serum hormones did not change. The placebo group improved substantially as well, and the result belongs to the whole formula, not to Anemarrhena.
  8. Wu ZT, Qi XM, Sheng JJ, Ma LL, Ni X, Ren J, Huang CG, Pan GY. Timosaponin A3 induces hepatotoxicity in rats through inducing oxidative stress and down-regulating bile acid transporters. Acta Pharmacol Sin. 2014;35(9):1188-98. doi: 10.1038/aps.2014.65.PubMedUsed to support: Rat and cell study. Timosaponin A3, a steroidal saponin from Anemarrhena, given by oral gavage at 100 mg/kg/day for 14 days raised serum ALT and total bile acids in rats, lowered bile acid concentrations in bile, and produced ballooning degeneration in liver tissue. In cultured rat hepatocytes it lowered the bile acid transporters Ntcp, Bsep and Mrp2, increased reactive oxygen species, dropped cellular ATP, and killed the cells at an IC50 of 15.2 micromolar; mangiferin, another constituent of the same herb, almost completely blocked that oxidative damage. Animal and cell data only, and the clearest signal that this saponin can injure the liver.
  9. Na L, Zhang Q, Jiang S, Du S, Zhang W, Li Y, Sun C, Niu Y. Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial. Sci Rep. 2015;5:10344. doi: 10.1038/srep10344.PubMedUsed to support: Double-blind randomized trial in overweight adults with high blood lipids; 97 completed. Isolated mangiferin at 150 mg/day for 12 weeks lowered serum triglycerides and free fatty acids, raised HDL cholesterol and improved the insulin resistance index, but total cholesterol, LDL cholesterol, fasting glucose and insulin did not differ from placebo. Mangiferin is one of several constituents of Anemarrhena and also occurs in mango and other plants, so this is a trial of the isolated compound and not of the rhizome.
  10. Zhu X, Liew Y, Liu ZL. Chinese herbal medicine for menopausal symptoms. Cochrane Database Syst Rev. 2016;3(3):CD009023. doi: 10.1002/14651858.CD009023.pub2.PubMedUsed to support: Cochrane review of Chinese herbal medicine for menopausal symptoms: 22 randomized trials in 2,902 women, eight of them placebo controlled. Pooling the placebo-controlled trials that counted hot flushes per day showed little or no difference (mean difference 0.00 per day, 95% CI -0.88 to 0.89, from 2 trials in 199 women, moderate quality evidence), and pooled hot flush scores and MENQOL vasomotor scores also showed no difference. One small trial using the Kupperman Index did favor the herbal arm. The authors concluded there was insufficient evidence that Chinese herbal medicines were any more or less effective than placebo or hormone therapy for vasomotor symptoms.
  11. Xie Y, Zhou X, Pei H, Chen MC, Sun ZL, Xue YR, Tian XT, Huang CG. Metabolism, pharmacokinetics, and hepatic disposition of xanthones and saponins on Zhimu treatments for exploratively interpreting the discrepancy between the herbal safety and timosaponin A3-induced hepatotoxicity. Acta Pharmacol Sin. 2018;39(12):1923-1934. doi: 10.1038/s41401-018-0012-z.PubMedUsed to support: Pharmacokinetic study in rats given oral Zhimu decoction. Timosaponin A3 is barely present in the raw herb but is produced by gut bacteria from timosaponins B2 and B3, and it reaches sizeable, slowly cleared concentrations in the liver, while mangiferin and other xanthones in the herb appear to offset the oxidative damage. This is the current explanation for why traditional short-course Zhimu has a good safety record despite the toxicity of one of its metabolites, and the authors call for attention to safety with continued use.