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Schisandra

Scientific Name

Schisandra chinensis

Common Name

Wu wei zi, schizandra, five flavor berry, fructus schisandra, gomishi, omicha, ngu mie gee

Clinical Summary

Derived from the fruit of the plant. Schisandra is used in traditional Chinese medicine for cough, wheezing, diarrhea, spontaneous sweating ⁽¹⁾ and as an adaptogen. Various lignans are believed responsible for the activity of schisandra. In animal models, schisandra protects the liver against various toxins ⁽⁷⁾ ⁽¹²⁾, prolongs pentobarbital sleep time ⁽⁸⁾, and increases cardiac contractility without affecting blood pressure ⁽¹⁰⁾. In vitro studies have shown that schisandra has anti-inflammatory ⁽¹³⁾ ⁽¹⁴⁾, anticancer ⁽¹⁵⁾ properties, and protects against adriamycin-induced cardiotoxicity ⁽¹¹⁾. No human trials have been performed with this supplement.
No adverse events have been reported ⁽¹⁰⁾. Additional research is necessary to understand the efficacy and to uncover possible interactions associated with this supplement.

Purported Uses

Asthma
Cough
Diarrhea
Indigestion
Influenza
Liver disease
Premenstrual syndrome
Strength and stamina
Sweating

Constituents

Lignans: Schizandrin, gamma-schizandrin, schizandrol, deoxyschizandrin ⁽¹⁾
Volatile oils ⁽²⁾
Vitamins: A, C, E ⁽²⁾
Others: Hydrocarbon derivatives (e.g. sesquicarene, beta-2-bisabolene, beta-chamigrene, alpha-ylangene) ⁽¹⁾, triterpenoid (nigranoic acid) ⁽³⁾

Mechanism of Action

The mechanism of action is unknown. Schisandra has antioxidant activity. Animal studies suggest that water- and alcohol-based extracts promote myocardial contractility without effects on blood pressure, stimulate the respiratory center, induce uterine smooth muscle contractions, and increase hepatic glutathione levels and the activities of glucose-6-phosphate and glutathione reductase ⁽⁴⁾. Protection from hepatotoxicity and improvements in phase I metabolism are documented in rats administered 1 ml/kg carbon tetrachloride 24 hours after exposure to schisandra extract ⁽⁵⁾ ⁽⁹⁾. Schisandra extract appears to increase DT-diaphorase activity within rat hepatocytes resulting in protection from menadione-induced toxicity ⁽⁷⁾. In rats, repeated administration of schisandra extract at 10 mg and 25 mg doses reduces the extent of cycloheximide-induced amnesia ⁽⁶⁾. Nigranoic acid, a triterpenoid extract from schisandra plants stems, shows limited activity against HIV-1 reverse transcriptase in vitro at an IC50 of 200 mcg/ml ⁽³⁾. Schisandrin B and schisandrol B have variable effects on pentobarbital-induced sleep in mice: 12.5 mg/kg prolongs sleep while 100 mg/kg shortens the sleep interval. Schisandrin C increases pentobarbital sleep period at all doses ⁽⁸⁾.

Pharmacokinetics

No formal pharmacokinetic studies have been performed. Animal data suggests that schisandra increases metabolism via induction of cytochrome P450 and/or glutathione reductase pathway ⁽¹⁾.

Adverse Reactions

CNS depression ⁽²⁾
Heartburn ⁽¹⁰⁾

Herb-Drug Interactions

Cytochrome P450 3A4 substrates: Schisandra inhibits CYP3A and can affect the intracellular concentration of drugs metabolized by this enzyme ⁽¹⁷⁾.
P-Glycoprotein substrates: Schisandra was shown to inhibit P-Gp activity and can interfere with the metabolism of certain drugs ⁽¹⁶⁾.
Tacrolimus: Schisandra sphenanthera, a different species, was shown to increase the blood level of tacrolimus, an immunosuppressant, in liver transplant patients. However, there was no increase in the side effects ⁽¹⁸⁾.

Herb Lab Interactions

Lower AST, ALT, Alkaline phosphate

References

Huang KC. The Pharmacology of Chinese Herbs, 2^nd ed. New York: CRC Press; 1999.

Fetrow CW, et al. Professional’s Handbook of Complementary and Alternative Medicines. Philadelphia: Springhouse; 1999.

Sun HD, et al. Nigranoic acid, a triterpenoid from Schisandra sphaerandra that inhibits HIV-1 reverse transcriptase. J Nat Prod 1996;59:525-7.

Ko KM, et al. Effect of a lignan-enriched fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity. Planta Med 1995;61:134-7.

Zhu M, et al. Evaluation of the protective effects of schisandra chinensis on phase I drug metabolism using a CCl4 intoxication model. J Ethnopharmacol 1999;67:61-8.

Hsieh MT, et al. The ameliorating effect of the water layer of fructus schisandrae on cycloheximide-induced amnesia in rats: interaction with drugs acting at neurotransmitter receptors. Pharmacol Res 2001;43:17-22.

Ip SP, Yiu HY, Ko KM. Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity. Mol Cell Biochem 2000;208:151-5.

Brinker F. Herb Contraindications and Drug Interactions, 3^rd ed. Sandy (OR): Eclectic Medical Publications; 2001.

Zhu M, et al. Improvement of phase I drug metabolism with schisandra chinensis against CCl₄ hepatotoxicity in a rat model. Planta Med 2000;66:521-5.

Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medica. Revised Ed. Seattle: Eastland Press; 1993.

You JS, Pan TL, Hou YC. Schisandra chinensis protects against adriamycin-induced cardiotoxicity in rats. Chang Gung Med J 2006; 29(1): 63-70.

Stacchiotti A, Li Volti G, Lavazza A, Rezzani R, Rodella LF. Schisandrin B stimulates a cytoprotective response in rat liver exposed to mercuric chloride. Food Chem Toxicol. 2009 Nov;47(11):2834-40.

Ci X, Ren R, Xu K, et al. Schisantherin A Exhibits Anti-inflammatory Properties by Down-Regulating NF-kappaB and MAPK Signaling Pathways in Lipopolysaccharide-Treated RAW 264.7 Cells. Inflammation. 2009 Nov 14. [Epub ahead of print]

Lee YJ, Park SY, Kim SG, et al. Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS-stimulated macrophages from Schisandra chinensis. Biochem Biophys Res Commun. 2010 Jan 22;391(4):1687-1692.

Park C, Choi YW, Hyun SK, et al. Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells. Int J Mol Med. 2009 Oct;24(4):495-502.

Fan L, Mao XQ, Tao GY, et al. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. 2009 Mar;39(3):249-54.

Lai L, Hao H, Wang Q, et al. Effects of short-term and long-term pretreatment of Schisandra lignans on regulating hepatic and intestinal CYP3A in rats. Drug Metab Dispos. 2009 Dec;37(12):2399-407.

Jiang W, Wang X, Xu X, Kong L. Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients. Int J Clin Pharmacol Ther. 2010 Mar;48(3):224-9.

How It Works

Bottom Line: Schisandra has not been shown to treat cancer.

Schisandra is a fruit extract used in traditional Chinese medicine. Scientists do not know how Schisandra works, but laboratory experiments have begun to identify some of its biological activities.

Schisandra has antioxidant activity, which means that it neutralizes free radicals that can cause cellular and genetic damage. When tested in animals, schisandra had the following effects: 1) an increase in contractility of the heart 2) an increase in contractions of the uterus 3) faster breathing rate 4) and an increase in the level and activity of an important detoxifying compound, glutathione, in the liver. Schisandra also appears to affect the central nervous system of rats, but the exact effects have not been elucidated yet. One extract of schisandra was able to inhibit the activity of HIV in the test tube, but this effect has not been tested in animals or humans.

Purported Uses

To treat asthma
This claim is not backed by research.
To treat coughs
No scientific evidence supports this use.
To treat diarrhea
There are no studies to support this claim.
To relieve indigestion
No scientific evidence supports this use.
To treat the flu
This claim is not based on research.
To treat liver disease
Animal studies show that schisandra can protect rats’ livers from chemically-induced damage, but there is no proof from clinical trials that it can treat liver disease in humans.
To prevent and treat premenstrual syndrome (PMS)
This claim is not backed by scientific evidence.
To increase strength and stamina
There are no studies that validate this claim.
To reduce sweating
No scientific evidence supports this use.

Research Evidence

No clinical trials have tested whether schisandra has biological effects in humans, or whether it is safe to take for long periods of time.

Patient Warnings

Although no drug interactions have been reported, schisandra may induce the activity of metabolic enzymes in the liver that are responsible for breaking down many other medications. If this is the case, it might lower the blood levels of other medications, reducing their effectiveness. Patients should talk with their doctors about the possibility of such drug interactions.
This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.

Do Not Take If

If you are taking drugs that are substrates of Cytochrome P450 3A4 (Schisandra may increase the risk of side effects of these drugs).
If you are taking drugs that are substrates of P-Glycoprotein (Schisandra may increase the risk of side effects of these drugs).

Side Effects

Heartburn
Sedation

Dosage (Inside MSKCC Only)

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Aliases

Wu Wei Zi

E-mail your questions and comments to aboutherbs@mskcc.org.

Last updated: August 9, 2011