IngredientsAnemarrhena asphodeloides Bunge is the only species in the genus Anemarrhena Bunge (family Asparagaceae) and is mainly distributed in China, Mongolia, and other eastern Asian countries. The plant is commonly classified under the family Liliaceae in older botanical literature, reflecting a historical classification that predates the current Asparagaceae assignment. The rhizome of A. asphodeloides, belonging to the family Liliaceae, is known as "Zhi-mu" in TCM and is mainly distributed in China, Mongolia, Korea, Japan, and other eastern Asian countries.
The rhizomes of Anemarrhena asphodeloides, known as Anemarrhenae Rhizoma, are called Zhimu (Chinese: 知母), Yanghuzi in vernacular Chinese usage, Chimo in Japanese Sino-medicine, and Jimo in Korean medicine.
Anemarrhena asphodeloides is a perennial erect and herbaceous plant with horizontal and thickened rhizomes, which is approximately 1 m tall, 0.5–1.5 cm wide, and covered by remaining leaf sheaths. The leaves are grasslike and all basal, up to 60 cm long and 2 cm wide, gradually narrowed into a filiform tip in the distal part. At the top of three-foot spikes, the plant bears small, fragrant, white six-petaled flowers that bloom at night.
Authentic Zhi Mu (Anemarrhena asphodeloides) is distinguished by its characteristic horizontal rhizome densely covered in golden-yellow fibrous hairs, basal grass-like leaves, and a distinctive long spike-like raceme. The cross-section should show a yellowish-white color with sticky mucilage.
The medicinal parts are the rhizomes (roots) and the stems. Rhizomes that are large, hard, and round with a pale-yellowish color inside are considered best for medicinal use. The root, or rhizome, is used medicinally and is often dried for use in decoctions. Anemarrhenae Rhizoma has a long history of use as a traditional medicine and is also used as an ingredient in healthy food, wine, tea, and biological toothpaste.
The rhizomes of Anemarrhena asphodeloides have been widely used in traditional Chinese medicine (TCM) for more than 2,000 years with remarkably therapeutic effects for the treatments of febrile diseases with high fever and thirst, heat in the lung with dry cough, consumptive fever, as well as diabetes due to internal heat and constipation.
Zhi Mu was first recorded in the Shen Nong Ben Cao Jing, where it was classified as a middle-grade (中品) herb. Written records of its use date from approximately 200 AD. Anemarrhena asphodeloides has been commonly used in traditional medicine in China, Japan, and Korea for thousands of years.
Its clinical features were aligned with those of "Lily disease" described in the ancient Chinese medicine text Synopsis of the Golden Chamber written by Zhang Zhongjing in the Han Dynasty. The Baihe Zhimu decoction (LBRAD) — consisting of lily bulb and Anemarrhena rhizome — is the first prescription recorded for "Lily Disease" in this text.
In TCM, Anemarrhena exerted its curative functions by clearing evil-heat and purging body-fire, generating body-fluids, and moistening dryness. Traditional Chinese medicine classifies this herb as cold (or yin) and bitter, reflecting the two complementary energies of yin and yang. Yin conditions are described as cold, damp, and deficient, while yang is characterized by heat, dry, and excess. Anemarrhena is used to treat heat disorders caused by excessive yang or insufficient yin.
Anemarrhenae Rhizoma has a long history of treating various ailments, including cold-induced febrile disease with arthralgia, hematochezia, tidal fever and night sweats due to Yin deficiency, bone-steaming, cough, and hemoptysis. Internally it has been used for congestive fever, high fever, chronic bronchitis, excessive sweating, dry throat, cough, dizziness, lumbago, and pneumonia. Externally, it has been used as a mouthwash to treat oral ulcers.
Based on phytochemical and pharmacological studies since the 1930s, Anemarrhena asphodeloides has been studied for potential use in conditions including Alzheimer's disease, Parkinson's disease, and schizophrenia.
The classic recipe LBRAD (Baihe Zhimu decoction) consists of two herbs: fresh lily bulbs and dried Rhizoma Anemarrhena slices, and has the effect of supplementing nutrition and clearing heat, nourishing Yin and moistening. Anemarrhena asphodeloides Bunge and Phellodendron chinense C.K. Schneid are a commonly used herb pair in clinical treatments of osteoporosis, including the formulae Zishen pill, Zhibai Dihuang pill, and Dabuyin pill.
Up to now, 108 compounds have been isolated from Anemarrhena asphodeloides, including steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, anthraquinones, and others. The chemical constituents of Rhizoma Anemarrhenae are complex and diverse, mainly including steroidal saponins, flavonoids, phenylpropanoids, benzophenones, and alkaloids.
Steroidal saponins are considered the primary bioactive compound class. The most pharmacologically investigated include:
Key flavonoid and xanthone constituents include mangiferin (PubChem CID: 5281647) and neomangiferin (PubChem CID: 6918448). Mangiferin is a C-glucoside xanthone and is one of the most studied phenolic constituents of the plant. The rhizome of Anemarrhena asphodeloides Bunge, used in TCM as a brain function-improving herb, is a promising source of neuroprotective substances, with its xanthone-enriched fraction being particularly significant.
The compounds isolated from Anemarrhena asphodeloides so far mainly include steroidal saponins, flavonoids, norlignans, and polysaccharides. Nyasol (PubChem CID: 12310493) is among the notable norlignan constituents. Additionally, novel phenolic compounds including anemarcoumarin A and anemarchalconyn have been isolated from ethyl acetate extracts of the rhizomes.
Anemarrhena asphodeloides Bunge (AA), a traditional Chinese medicine, is used clinically to treat inflammation, diabetes, osteoporosis, and tumors. Polysaccharides are the most abundant components in AA and have antioxidant, immunomodulatory, anti-inflammatory, hypoglycemic, anti-osteoporosis, and laxative effects. The specific polysaccharides from this plant are referred to as "Anemarans" (labelled A, B, C, D, etc.). AAP (Anemarrhena asphodeloides polysaccharide) is composed of mannose, galacturonic acid, galactose, glucose, and xylose in the molar ratio of 12:8.1:2.7:1.3:1, with an average molecular weight of 52.4 kDa.
The rhizome of Anemarrhena asphodeloides Bunge has been used as a traditional East Asian medicine for the treatment of various types of inflammatory disease. Studies have aimed to elucidate the anti-inflammatory effects and underlying mechanisms of ethanol extracts of the rhizome in murine macrophages. The anti-inflammatory activity of Timosaponin AIII (Timo AIII) is documented across many disease contexts. Key pharmacological targets identified for Timo AIII include VEGFR, XIAP, BMI1, thromboxane A2 receptor, mTOR, NF-κB, COX-2, MMPs, and acetylcholinesterase (AChE).
Timosaponin A-III (TA-III) has been identified as a potentially active component for anti-Alzheimer's disease (AD) activity, with BACE1 proven as a potential high-affinity target. Previous research has shown that Timosaponin-BII possesses a neuronal protective and anti-inflammatory effect, possibly by suppressing the production of pro-inflammatory factors IL-1, IL-6, and TNF-α.
Studies have investigated the effects of the total phenolic fraction of Anemarrhena asphodeloides on regulation of insulin sensitivity in adipocytes, given the plant's wide use for treatment of metabolic disorders in traditional Chinese medicine. It regulated serine/tyrosine phosphorylation of insulin receptor substrate-1 and subsequently restored Akt phosphorylation in response to insulin, thereby improving insulin-mediated glucose uptake. The total phenolic fraction of A. asphodeloides also enhanced AMP-activated protein kinase phosphorylation, which contributed to the inhibition of inflammation implicated in insulin resistance.
Anemarans A, B, C, and D from Anemarrhena asphodeloides displayed significant hypoglycemic bioactivities in normal and alloxan-produced hyperglycemic mice. Anemarans at 2 mg/kg and 20 mg/kg (intragastric) significantly reduced blood glucose in alloxan-induced diabetic rabbits, while at the dose of 200 mg/kg they reduced blood glucose of normal rabbits.
Timosaponin A-III (TAIII) isolated from the rhizome of Anemarrhena asphodeloides could effectively lower amyloid-beta (Aβ) production. Oral administration of sarsasapogenin (SSG), TAIII, and other timosaponins was shown to improve memory dysfunction in animal models of dementia.
A model has been proposed by which the timosaponins may bind to the steroid binding site of amyloid precursor protein (APP), possibly modulating the APP secretase properties. Sarsasapogenin-aglycone B (SAaB) was found to enhance the learning and memory abilities of aged rats by increasing cerebral nicotinic receptors.
Research has identified several novel features of TAIII-induced autophagy. TAIII induces a distinct form of autophagy with the involvement of multivesicular bodies, cholesterol biosynthesis, mTOR, and calcium signaling. The pharmacological significance of TAIII-induced autophagy is linked to degradation of ubiquitinated proteins and may play a role in the clearance of otherwise accumulated aggregation-prone proteins.
The effects of Anemarrhena asphodeloides (AA) and timosaponin-AIII (TAIII), a steroidal saponin present in AA, on pancreatic cancer cell proliferation have been examined. Viability assays and cell cycle analysis revealed that both AA and TAIII significantly inhibited pancreatic cancer cell proliferation and cell cycle progression compared to treatment with gemcitabine. A dose-dependent increase in caspase-dependent apoptosis and activation of pro-apoptotic PI3K/Akt pathway proteins, with subsequent downregulation of pro-survival PI3K/Akt pathway proteins, was identified.
TAIII from Anemarrhena asphodeloides induced autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells with IC50 values ranging from 8.5–10.1 μmol/L after 48 h incubation. TAIII could potentially inhibit the growth of several human colorectal cancer cells (HCT-15 at 6.1 μM; HCT-116 at 5.5 μM; HT-29 at 10.3 μM; SW-480 at 13.1 μM; SW-620 at 11.1 μM) through inhibition of mTOR and induction of ER stress.
Previous studies indicated that Timo AIII presented cytotoxicity effects in various kinds of cancer cells, including breast cancer, hepatocellular cancer, cervical cancer, colon cancer, nasopharyngeal cancer, pancreatic cancer, lung cancer, renal cancer, chronic myelogenous leukemia, ovarian carcinoma, osteosarcoma, leukemia, and melanoma. All of this evidence, however, derives exclusively from cell culture (in vitro) and animal model studies; no clinical human oncology trials have been published.
Six steroidal saponins isolated from the rhizome of A. asphodeloides inhibited platelet aggregation in human blood and activated partial thromboplastin times. Timosaponin A-III exhibited the strongest effect on hemolysis. Timosaponin B-II inhibited blood coagulation and formation of a thrombus in rabbits. Timosaponin B-II may also enhance fibrinolytic activity and accelerate thrombolysis at higher doses.
Anemarrhenae Rhizoma (AR, "zhimu" in Chinese) is frequently used as a traditional Chinese medicine to treat Alzheimer's disease (AD) and other memory deficits associated with aging. AR and its components have demonstrated immunomodulatory, anti-inflammatory, anti-diabetes, anti-tumor, anti-depression, and anticoagulation activities.
TBII and timosaponin E1 notably enhanced learning and memory capacities, presumably related to promoting the scavenging of free radicals. Sarsasapogenin-aglycone B (SAaB) at three different doses (50, 100, and 200 mg/kg) could remarkably enhance the learning and memory capacities in rats with Aβ25–35-induced dementia, presumably through promoting the scavenging of free radicals.
Evidence strength: Anemarrhena asphodeloides possesses therapeutic potential in the treatment of diabetes, Alzheimer's disease, Parkinson's disease, and other diseases, but there is a pressing need to investigate the current therapeutic agent information and the evidence of clinical studies on toxicity and adverse effect of Anemarrhena asphodeloides. All neuroprotective evidence to date is derived from preclinical (animal model and in vitro) studies. Robust, controlled human clinical trials in neurodegenerative diseases have not been conducted.
Anemarrhena asphodeloides Bunge possesses a variety of pharmacological activities including blood sugar regulation, immune enhancement, and antioxidant properties. Due to these health benefits, A. asphodeloides is widely utilized as a functional food.
In one preclinical study using streptozotocin-induced diabetic rats, after oral administration of Anemarrhena asphodeloides polysaccharides (AAP) at 100 and 200 mg·kg⁻¹ for 28 days, there was a significant decrease in blood glucose, hepatic transaminases (SGPT, SGOT), alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), LDL, and blood urea nitrogen (BUN), along with a significant increase in body weight, fasting serum insulin, pancreatic insulin, and HDL.
Total saponins from Anemarrhena asphodeloides were reported to ameliorate diabetes-associated cognitive decline in rats and mediate Aβ decreases in the brain.
Evidence strength: Evidence for antidiabetic effects is preclinical only (animal models and cell studies). Clinical studies on the main therapeutic aspects — including diabetes and Alzheimer's disease — as well as toxicity and adverse effect studies, will undoubtedly be the focus of future investigation. No controlled human clinical trials on Anemarrhena for glycemic management have been published in the peer-reviewed literature identified in this review.
The medicine presents anti-inflammatory, antipyretic, sedative, and diuretic effects in its traditional use context. In laboratory studies using LPS to activate mouse N9 microglia, among twenty-six isolated compounds, four compounds significantly inhibited LPS-induced nitric oxide (NO) production by more than 50% at 25 μM. The non-cytotoxic compound Timosaponin BIII (TBIII) and trans-Hinokiresinol (t-HL) at 50 μM showed significant anti-inflammatory activity.
Evidence strength: Anti-inflammatory evidence is primarily from in vitro macrophage and microglia models, with supporting animal model studies. No controlled human clinical trials have been identified specific to inflammatory conditions.
TAIII-induced autophagy plays a protective role in TAIII-induced death signaling, and failure to mount an autophagic response is associated with heightened sensitivity to TAIII-induced apoptosis. The multiple death-promoting and apparently tumor-selective responses to TAIII, its ability to inhibit mTORC1, and the possibility of further enhancing its cytotoxicity by pharmacological inhibition of autophagy make TAIII an attractive candidate for development as a cancer therapeutic agent.
Timosaponin AIII as an effective constituent isolated from Anemarrhena asphodeloides has been proven to possess the ability to induce cell death in various cancer cells. It is a major steroidal saponin widely used as an anti-pyretic, anti-diabetic, anti-inflammatory, anti-platelet aggregator, and anti-depressant agent in traditional Chinese medicine. Recent pharmacological study showed that timosaponin AIII had potent cytotoxicity and the potential to be developed as an anticancer agent; however, the molecular mechanism underlying the anticancer activity has not been fully elucidated.
Evidence strength: All anticancer evidence is preclinical (in vitro cell lines and animal models). No human clinical oncology trials have been reported.
In ovariectomy-induced mouse models, Anemarrhena asphodeloides (AA) significantly improved bone mineral density values and bone microarchitecture. Postmenopausal osteoporosis is characterized by elevated bone resorption activity mediated by osteoclasts. Both AA and its pairing herb showed synergistic effects on inhibiting NFATc1, the master regulator of osteoclastogenesis.
Mangiferin from AA, and berberine and magnoflorine from its paired herb Phellodendron chinense, suppress osteoclast differentiation. Anemarrhena asphodeloides contains multiple active ingredients that may exert therapeutic effects on osteoporosis by regulating targets such as AKR1C1, AKR1C2, ABCC1, SMO, and AKT1, and key signaling pathways like PI3K-Akt and VEGF.
Evidence strength: Evidence is based on animal models (ovariectomized mice) and network pharmacology/molecular docking analyses. Human clinical data are absent.
Timosaponin A-III (TA-III) is known to exist in Anemarrhena asphodeloides as one of the major chemical components. Its photoprotective properties on UVB-exposed HaCaT cells were evaluated in terms of antiwrinkle effects and skin safety in a clinical trial. MMP-1, tissue inhibitor of metalloproteinases (TIMPs), and pro-inflammatory cytokines were measured in HaCaT cells following UVB irradiation. To evaluate clinical safety of an agent containing 0.25% of TA-III for use on human skin, female subjects (n = 21) between the ages of 43 and 55 were selected. UVB irradiation increased MMP-1 expression and pro-inflammatory cytokines, and these increases were attenuated by TA-III pretreatment of UVB-exposed HaCaT cells.
Evidence strength: This represents the most direct human-subject safety data for a topical TAIII-containing product, though the trial was small (n = 21) and focused on skin safety and tolerability rather than therapeutic efficacy in a disease context. Conclusions are preliminary.
The aim of one study was to evaluate the protective action of xanthones from A. asphodeloides rhizomes on the PC12 cell line exposed to the neurotoxic agent 3-nitropropionic acid (3-NP). The xanthone-enriched fraction of the ethanolic extract, rich in polyphenolic xanthone glycosides, at concentrations from 5 to 100 μg/mL, was examined. The results showed a significant increase in the number of cells surviving after treatment with the xanthone fraction with exposure to neurotoxic 3-NP, and decreased morphological changes in PC12 cells in a dose- and time-dependent manner. The most effective protective action was observed when PC12 cells were pre-incubated with the fraction. This effect may contribute to the traditional indications of this herb for neurological and cognitive complaints.
Evidence strength: In vitro (cell line) only. Results cannot be directly extrapolated to human outcomes.
The Baihe Zhimu decoction — which contains Anemarrhena rhizome — has been used in clinical treatment of depression after more than two thousand years of clinical practice. TAIII is isolated from the medicinal herb Anemarrhena asphodeloides, which is used as an antipyretic, anti-inflammatory, antidiabetic, and antidepressive agent in traditional Chinese medicine. Modern research is ongoing; the available clinical evidence for the formula (not Anemarrhena alone) is limited and based primarily on traditional usage and preclinical mechanistic studies rather than registered, adequately powered randomized controlled trials.
Studies have shown that the extracts and compounds from Anemarrhena asphodeloides have extensive pharmacological activities, such as nervous system activity, antitumor, anti-inflammatory, antidiabetic, anti-osteoporotic, antiallergic, antiplatelet aggregation, antimicrobial, antiviral, anti-aging, hair growth-promoting, and cell-damage-preventing properties.
The root, or rhizome, is used medicinally and is often dried for use in decoctions. In TCM practice the rhizome may also be incorporated into wine, tea, or functional food preparations, and is found as an ingredient in composite herbal formulae. The following dosage ranges have been reported in cited studies:
No standardized human oral dosing regimen for Anemarrhena rhizome extract has been established through controlled clinical trials in the reviewed literature.
Although Anemarrhena asphodeloides and its extractions have been widely used medically for thousands of years, there have been no reports of hepatotoxicity from the whole herb. However, isolated constituents present a different picture.
Timosaponin A3 (TA3), one of the major steroidal saponin components isolated from Anemarrhena asphodeloides, displays promising pharmacological activity in improving learning, memory, and antineoplastic activity. One research group found that TA3 had a very high concentration in rat liver after a single oral administration, and in an acute toxicity study, rat liver showed extensive ballooning degeneration and vacuolization. This acute toxicity may prevent efforts to develop TA3 into a drug candidate if the mechanism of toxicity remains unclear.
The hepatotoxicity of Timo AIII was the most-documented safety concern identified, and the pharmacokinetics and toxicity of Timo AIII need further studies in diverse animal models. Interestingly, mangiferin, which is an active component in A. asphodeloides Bunge and possesses anti-oxidant ability, attenuated Timo AIII-induced hepatotoxicity, suggesting a potential in-plant modulatory relationship.
A significant cytotoxicity was observed at higher xanthone fraction concentrations (over 10 µg/mL) and longer incubation time (48 h) in PC12 cell studies, which requires caution in future research and thorough investigation into potential adverse effects.
The efficacy and pharmacokinetics of the biologically active components in Anemarrhenae Rhizoma (AR) would be affected by the interaction of P-glycoprotein (P-gp) and effective components in AR. The efflux ratio of mangiferin (MGF), TAIII, TBII, and baohuoside I (BHI) was greater than 2 and significantly decreased with the co-administration of verapamil, indicating MGF, TAIII, TBII, and BHI as substrates of P-gp. This finding implies potential pharmacokinetic interactions with other P-gp substrates or inhibitors, though the clinical significance of this has not been established in humans.
Six steroidal saponins isolated from the rhizome inhibited platelet aggregation in human blood and activated partial thromboplastin times. Timosaponin A-III exhibited the strongest effect on hemolysis. Timosaponin B-II inhibited blood coagulation and formation of a thrombus in rabbits. These data suggest the possibility of additive effects with anticoagulant or antiplatelet pharmaceutical agents, though this interaction has not been formally studied in humans.
Avoidance is indicated in patients with known allergy or hypersensitivity reactions to A. asphodeloides or its constituents.
Evaluating the quality and toxicity of Anemarrhena asphodeloides is essential to confirm its safe use in humans. The plant is widely used in traditional medicine and has diverse chemical constituents with obvious biological activities. Nevertheless, more studies should be carried out in animals and humans to evaluate the cellular and molecular mechanisms involved in its biological activity and confirm its safe use.
In light of long traditional use and modern phytochemical and pharmacological studies, Anemarrhena asphodeloides has demonstrated a strong potential for therapeutic and health-maintaining purposes. Both the extracts and chemical components isolated from the plant showed a wide range of biological activities. More pharmacological mechanisms on main active compounds (TBII, TAIII, mangiferin and other ingredients) are necessary to be explored. The current body of research is characterized by rich in vitro and animal-model data alongside a very limited number of human studies. Current studies on the chemical constituents and pharmacological mechanisms of Anemarrhena asphodeloides lack depth, and more studies on phytochemistry and the mechanisms of the main active ingredients (TBII, TAIII, and mangiferin) in displaying certain biological activities should be encouraged to fully understand the compounds responsible for the pharmacological effects.
Health conditions that Anamarrhena may help support.
Body systems that Anamarrhena may help support.
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