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Zhi Mu

Scientific Name(s): Anemarrhena asphodeloides Bunge.
Common Name(s): Anemarrhena rhizome, Zhi mu

Clinical Overview

Use

Numerous in vitro and animal studies on the anti-inflammatory, antimicrobial, antiplatelet, antidiabetic, and anticancer activity of A. asphodeloides and its application for improved learning and memory have been published.

Dosing

Zhi mu is available from commercial manufacturers. The most common dosage forms are the whole herb, capsules, and teas for treating "cold and bitter" conditions. Manufacturers suggest using three to six 500 mg capsules two to three times daily as a tea. However, some capsule formulations are a proprietary blend of herbs and are available in several strengths.

Contraindications

Avoid use in patients with known allergy or hypersensitivity reactions to A. asphodeloides or its constituents.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Information regarding adverse reactions with A. asphodeloides is limited.

Toxicology

Limited clinical studies are available on the toxicology of A. asphodeloides. There were no effects on mortality, body weight, or organ systems in rats receiving a 5 g/kg dose of WIN-34B (2 kg of dried Lonicera japonica flowers and 1 kg of A. asphodeloides root). Long-term toxicity studies in rats receiving WIN-34B at 1,000 or 2,000 mg/kg for 13 weeks resulted in no notable abnormalities.

Botany

A. asphodeloides belongs to the family Liliaceae and is an evergreen perennial native to China, Korea, and Japan. The plant grows to a height of 0.5 m and a width of 1 m, and the thin leaves grow up to 70 cm long. The clusters of small, white to light-purple flowers are hermaphroditic (having both male and female organs) and blossom from August to September.Chevallier 1996, Park 2003, He and 2011

History

A. asphodeloides is listed in the Pharmacopoeia of the People's Republic of China and used medicinally to remove heat, quench fire, support the production of body fluid, and alleviate dryness syndrome.Zhou 2007 In Korea, mainland China, and Japan, the rhizomes have been traditionally used for their anodyne, antidiabetic, anti-inflammatory, antipyretic, diuretic, antidepressant, antiplatelet aggregator, and sedative properties.Youn 2009, Kim 2009, Kang 2010 The most commonly prescribed triple-drug Chinese herbal formula in Taiwan for insomnia in 2002 contained A. asphodeloides.Chen 2010 In traditional Chinese medicine, the rhizomes are also used for the treatment of lung disease.Bao 2007

Chemistry

The rhizome's medicinal activity is primarily associated with mangiferin and steroidal saponins, such as sarasapogenin and timosaponin AII and BII.Jung 2009 The foaming properties of the saponins have commercial applications and are added to shampoos, liquid detergents, toothpastes, and beverages.Chen 2010 Additional studies review the known chemical components of the rhizome.Youn 2009, Kang 2010, Zhang 1999 A pharmacokinetics study in rats on the intravenous (IV) and oral administration of the pharmacologically active constituent timosaponin B-II document oral bioavailability of only 1.1%.Cai 2008

Uses and Pharmacology

Numerous in vitro and animal studies on the anti-inflammatory, antimicrobial, antiplatelet, antidiabetic, and anticancer activity of A. asphodeloides and its application for improved learning and memory have been published.

Anti-inflammatory

In vitro and animal data

Anemasaponin B, a steroidal saponin isolated from the rhizomes of A. asphodeloides, exhibited anti-inflammatory activity in a macrophage cell line stimulated by LPS.Kim 2009 Anemasaponin B also attenuated production of pro-inflammatory mediators and inhibited inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alfa, and interleukin-6 expression by downregulating their transcript. WIN-34B, an herbal formulation containing A. asphodeloides, inhibited carrageenan-induced paw edema and croton oil-induced ear edema in mice at 400 mg/kg, similar to the anti-inflammatory effects of celecoxib 100 mg/kg.Kang 2010 WIN-34B also exhibited more effective antinociceptive and anti-inflammatory activity than that of celecoxib in osteoarthritic animal models. No adverse GI or cardiac effects were documented.Kang 2010, Huh 2011

Antimicrobial

In vitro data

A methanol extract of A. asphodeloides rhizome containing nysal exhibited strong antifungal activity against the plant pathogenic fungi Magnaphothe grisea and Rhizoctonia solani, and the plant pathogenic oomycete Phytophthora capsici. Nyasol also inhibited the mycelial growth of Colletotrichum orbiculare, P. capsici, Pythium ultimum, R. solani, and Cladosporium cucumerinum.Park 2003 An isolated compound similar to nyasol from an ethyl acetate A. asphodeloides rhizome extract inhibited the growth of 38 strains of fungi and 5 strains of bacteria.Iida 1999 An herbal preparation containing A. asphodeloides may improve immune system functioning through the production of various cytokines.Jeong 2004

Antioxidant

The effect of 3 sapogenins was examined on induced superoxide production in human neutrophils.Ma 2001 The effect of the antioxidant activity was in the order of sarsasapogenin > tigogenin > hecogenin. A rhizome water extract of A. asphodeloides exhibited free-radical scavenging activity.Yingming 2004, Oh 2007

Antiplatelet

In vitro data

Six steroidal saponins isolated from the rhizome of A. asphodeloides inhibited platelet aggregation in human blood and activated partial thromboplastin times.Zhang 1999 Timosaponin A-III exhibited the strongest effect on hemolysis, anemarrhenasaponin IA had a slight effect, and the other saponins had no effect.

In vivo data

Timosaponin B-II inhibited blood coagulation and formation of a thrombus in rabbits, but had no thrombolytic effect in a rabbit arteriovenous shunt model.Lu 2011 Timosaponin B-II may enhance fibrinolytic activity and accelerate thrombolysis at higher doses.

Diabetes

In vitro data

A. asphodeloides inhibited alpha-glucosidase (reducing the impact of carbohydrates on blood glucose) and angiotensin-converting enzyme.He 2011

In vivo data

A rhizome hot water extract of A. asphodeloides reduced blood glucose levels in alloxan-induced diabetic mice. The hypoglycemic mechanism may involve inhibition of hepatic gluconeogenesis or glucogenolysis.Nakashima 1993 Oral administration of a rhizome water extract (90 mg/kg) of A. asphodeloides reduced blood glucose levels and serum insulin levels in KK-Ay mice.Miura 2001 The active components of the extract were mangiferin and its glucoside, which may exert antidiabetic activity by increasing insulin sensitivity.Miura 2001 Mangiferin prevented progression of diabetic nephropathy in streptozotocin-induced diabetic rats by decreasing urinary albumin excretion and improving creatinine clearance.Li 2010 The mechanism involved inhibition of several key pathological pathways, thus reducing progression of diabetic nephropathy.

Cancer

In vitro data

Timosaponin A-III, a saponin isolated from the rhizome of A. asphodeloides, is an autophagy- and apoptosis-inducing agent to cancer cells. Timosaponin A-III exhibited cytotoxicity to several carcinoma cell lines, including hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human nasopharyngeal carcinoma cells (SUNE-1), and human cervical epithelioid carcinoma cells (HeLa).Sy 2008 Its mechanism of action may include inducing apoptosis through caspase-4 activation, induction of transcriptional changes in breast cancer cells, and inhibition of mammalian target of rapamycin C1 in cancer cells, which has negative consequences for protein translation and cell growth, often leading to activation of autophagy.King 2009 The rhizomes of A. asphodeloides directly inhibited the growth of 2 gastric cancer cell lines, MKN45 and KATO-III cells, in a dose-dependent manner.Takeda 2001 A. asphodeloides induced apoptosis by activating caspase 3 or a caspase 3-like protease. A traditional Chinese medicine prescription, which contains A. asphodeloides 14.3 g, inhibited the growth of MCF-7 and MDA-MB-231 human breast cancer cells by inducing apoptosis, blocking cell cycle progression by regulating cell cycle-related factor, activating the mitochondrial pathway, and modulating the Bcl-2 family of proteins in mice.Hsu 2006 Sarsasapogenin inhibits growth of human 1547 osteosarcoma cells and HepG2 human hepatoma cells by inducing cell apoptosis through cell cycle arrest in G2/M phase.Bao 2007 Sarsasapogenin-induced apoptosis may involve activation of key signaling molecules regulating mitochondrial dysfunction.Ni 2008

Cardiovascular system

Saponins from the rhizome of A. asphodeloides saponin may modulate the function of vein endothelial cells.Chavan 2006 Timosaponin A-III induced relaxation of phenylephrine-induced vascular contraction by enhancing release of nitric oxide from endothelial cells.Wang 2002, Lim 2009

Chronic fatigue syndrome

A review article on traditional Chinese medicine documents the use of the rhizome of A. asphodeloides to treat chronic fatigue syndrome.Chen 2010

Corneal opacity

One clinical study documents the therapeutic use of traditional Chinese herbs (including A. asphodeloides) combined with subconjunctival injection of sodium iodide to effectively treat corneal opacity.Zhang 2007 A pharmacokinetic study found that mangiferin passes the blood-retina barrier after a single IV administration; therefore, its antioxidant activity may be beneficial in treating eye diseases.Hou 2010

Depression

At a dose of 50 mg/kg, sarsasapogenin inhibited monoamine oxidase (MAO)-A activity (17%) and MAO-B activity (15%) in mouse brains and increased noradrenaline and serotonin levels.Ren 2006

Estrogenic activity

Ethanol extracts of A. asphodeloides have documented estrogen modulatory activity.Kim 2008 Additional studies also document estrogen-like activity.Jeong 2003, Paruthiyil 2009

Hyperlipidemia

Saponins may reduce total cholesterol, triglycerides, and low-density lipoproteins and may improve microcirculation.Young 2009, Li 2006, Li 2006

Learning and memory

In vivo data

Mangiferin reversed scopolamine-induced learning deficits in mice by acetylcholine esterase inhibition, cholinergic receptor stimulation, and anti-inflammatory activity.Jung 2009 Scopolamine reduced acetylcholine levels, and mice treated with oral mangiferin 20 mg/kg recovered the reduced acetylcholine levels by 75%. Timosaponins may also protect against learning and memory impairment caused by amyloid beta-peptide in rats by promoting scavenging of free radicals.Ouyang 2005 Timosaponin A-III improved scopolamine-induced learning and memory deficits in mice by inhibiting activation of proinflammatory cytokines and acetylcholinesterase.Lee 2009 Several compounds isolated from A. asphodeloides also improved learning and memory impairment by upregulating neurotrophic factors that promote neural cell survival, neuronal differentiation, and prevention of neuronal apoptosis in the central and peripheral nervous systems.Tsukamoto 2005, Zhong 2006, Shin 2008

Osteoporosis

Saponins stimulated osteoblast reproduction and alkaline phosphatase activity. Mangiferin and neomangiferin inhibited tartrate-resistant acid phosphatase, a biochemical marker of osteoclast function and bone resorption.Qin 2008

Prostatitis

No difference was found in patients being treated with minocycline versus a Chinese herbal combination, which included the rhizome of A. asphodeloides, for prostatitis. The Chinese herbal combination enhanced the vitality of sperm more effectively than minocycline.Chen 2006

Schizophrenia

No significant benefit was observed with the adjunctive use of sarsasapogenin with risperidone in patients with schizophrenia dominated by negative symptoms in an 8-week double-blind, randomized, placebo-controlled trial (n=80). Total scores of disease severity and general psychopathology, memory functioning, as well as verbal and performance IQ did not differ significantly between groups receiving risperidone only or risperidone plus sarsasapogenin (200 mg/day). The addition of sarsasapogenin did not result in adverse events, which were comparable between groups.Xiao 2011

Testosterone

A rhizome diethyl ether extract of A. asphodeloides exhibited testosterone 5 alpha-reductase inhibitory activity.Matsuda 2001

Dosing

Zhi mu is available from commercial manufacturers. The most common dosage forms are the whole herb, capsules, and teas for treating "cold and bitter" conditions. Manufacturers often suggest using 3 to six 500 mg capsules 2 to 3 times daily as a tea. However, some capsule formulations are a proprietary blend of herbs and are available in several strengths.

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Caution is advisable in patients taking A. asphodeloides-containing products and anticancer, anti-inflammatory, antidepressant, antipsychotic, antibacterial, or hormone replacement therapy because limited information is available on potential drug-herb interactions with these medications.

Adverse Reactions

Information regarding adverse reactions with the use of A. asphodeloides is limited.

Toxicology

Limited clinical studies are available on the toxicology of A. asphodeloides. There were no effects on mortality, body weight, or organ systems in rats receiving a 5 g/kg dose of WIN-34B (2 kg of dried L. japonica flowers and 1 kg of A. asphodeloides root). Long-term toxicity studies in rats receiving WIN-34B at 1,000 or 2,000 mg/kg for 13 weeks resulted in no notable abnormalities.

References

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Cai F, Sun L, Gao S, Yang Y, Yang Q, Chen W. A rapid and sensitive liquid chromatography-tandem mass spectrometric method for the determination of timosaponin B-II in blood plasma and a study of the pharmacokinetics of saponin in the rat. J Pharm Biomed Anal. 2008;48(5):1411-1416.19027255
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Chen R, Moriya J, Yamakawa J, Takahashi T, Kanda T. Traditional Chinese medicine for chronic fatigue syndrome. Evid Based Complement Alternat Med. 2010;7(1):3-10.18955323
Chen YF, Yang CH, Chang MS, Ciou YP, Huang YC. Foam properties and detergent abilities of the saponins from Camellia oleifera. Int J Mol Sci. 2010;11(11):4417-4425.21151446
Chen ZX, Luo YJ. Prescription of common Anemarrhena rhizome and amur corktree bark in the treatment of prostatitis in M. urealyticum accompanied by asthenospermia. Chin J Clin Rehabil. 2006;10(43):76-78.
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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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