Health Care Professional Information

Scientific Name
Schisandra chinensis, Schisandra sphenanthera
Common Name

Wu wei zi, schizandra, five flavor berry, fructus schisandra, gomishi, omicha, omija, ngu mie gee, Chinese magnolia vine fruit, Wurenchun

Clinical Summary

Schisandra is derived from the fruit of the plant and is used in traditional Chinese medicine for coughs and wheezing (1), various liver diseases (2), stomach disorders (3), spontaneous sweating (4), and as an adaptogen (5). In vitro studies have shown that schisandra has anti-inflammatory (1) (6) and anticancer (7) (8) properties, and protects against adriamycin-induced cardiotoxicity (9). In animal models, schisandra protects the liver against various toxins (10) (11), has beneficial effects after myocardial infarction (12), enhances endurance and metabolism (13), improves cognitive functioning (14), and exhibits antimicrobial (15), antioxidant, neuroprotective (16), and anti-hyperglycemic activity (17) (18) (19). Active lignans isolated from schisandra, particularly schisandrin A, were found to reverse P-glycoprotein (Pgp)-mediated multidrug resistance of various cancer cell lines to doxorubicin, vincristine, and paclitaxel (20).

Very few human trials have been performed with this supplement. Two small clinical trials suggest improvements in subjects with fatty liver disease using a mixture of schisandra fruit extract and sesamin, a lignan marketed as a fat-reduction supplement (21), and possible benefit for those with chronic hepatitis C virus when used in combination with other oral antioxidants (22). Another small trial of a proprietary herbal combination that included schisandra suggests improved performance of cognitive tasks (23). Schisandra was also found to reduce tacrolimus-associated side-effects of diarrhea and agitation and to improve liver function in liver transplant patients (24). Additional research is necessary to determine actual efficacy attributable to schisandra and to uncover possible interactions or side effects associated with this supplement.

Purported Uses
  • Asthma
  • Cough
  • Diarrhea
  • Indigestion
  • Liver disease
  • Strength and stamina
  • Sweating
Constituents
  • Lignans: Schisandrins, gamma-schizandrin, deoxyschizandrin, gomisin A, schisantherin A and B
  • Polysaccharides
  • Anthocyanins: cyanidin-3-O-xylosylrutinoside
  • Sesquiterpenes: α-iso-cubebenol
  • Other hydrocarbon derivatives: sesquicarene, β-2-bisabolene, β-chamigrene, α-ylangene
  • Triterpenoids: nigranoic acid
  • Volatile oils
  • Vitamins: A, C, E
    (1) (3) (6) (8) (12) (18) (20) (25) (26)
Mechanism of Action

Lignans in schisandra have been linked to various effects including hepatoprotective (10), antiproliferative, and estrogenic activities (27). In vitro, schisantherins downregulated pro-inflammatory cytokines and mediators by blocking NF-κB and MAPK signaling (1). In animal toxicity models, pretreatment with schisandra lignans increased DT-diaphorase activity associated with enhanced menadione elimination (10), and provided hepatoprotection and improved Phase I metabolism 24 h after carbon tetrachloride exposure (28) (29). Other animal studies suggest that schisandra increases hepatic glutathione levels and glucose-6-phosphate and glutathione reductase activities (17). It also inhibits α-glucosidase activity, thereby lowering postprandial blood glucose levels (19), and can improve cardiac function after ischemic injury by downregulating inflammatory cytokines, activating the eNOS pathway, inhibiting apoptosis, and enhancing cell proliferation (12). In amyloid-beta-induced memory impairment, schisandra increased superoxide dismutase and glutathione peroxidase activities and glutathione levels in the cerebral cortex and hippocampus of mice while decreasing malondialdehyde and oxidized glutathione (14). It also enhanced endurance and metabolism in the skeletal muscle of exercised rats by upregulating PGC-1α expression (13).

α-iso-cubebenol in schisandra inhibited iNOS and COX-2 expression in lipopolysaccharide-stimulated macrophages (6) and reversed septic shock by triggering protective downstream signaling pathways in a mouse sepsis model (15).The anthocyanin cyanidin-3-O-xylosylrutinoside (Cya-3-O-xylrut) has been identified as responsible for its antioxidant activity (18).

In human renal cell carcinoma cells, a schisandra polysaccharide identified as SCP induced apoptosis via caspase-3 and -9 activation, increased PARP cleavage, and inactivation of the ERK pathway (8). Another polysaccharide known as SCPP11 exhibited antitumor effects in hepatic cancer models via increased thymus index as well as serum IL-2 and TNF-alpha levels, and enhanced phagocytosis and NO production (26). Pgp-mediated chemotherapy drug-resistance in various cancer cell lines was reversed by schisandrins through the inhibition of Pgp and total protein kinase C function/expression (20).

Schisandra coadministration increases oral bioavailability of tacrolimus via inhibition of Pgp-mediated efflux and cytochrome P450 3A-mediated metabolism, and reduction of intestinal first-pass effect (30).

Pharmacokinetics

In animal models, PK parameters of schisandra lignans varied significantly by gender and indicated higher bioavailability in female rats with both single- and multi-dose administration (31). T1/2 of all tested lignans was 2–9 times longer for female than male rats. Cmax and AUC0−t of schisandrin, schisandrol B, deoxyschisandrin, and γ-schisandrin were 5–50 times higher for female than male rats. PK profiles for multiple doses in both genders were similar to corresponding single-dose profiles with the exception of γ-schisandrin, which was eliminated more slowly in females after multiple administration.

In general, schisandra lignans ingested orally have poor water-solubility and bioavailability (32).

Adverse Reactions

No serious side effects have been reported, although schisandra is not well studied in humans. A few minor adverse events, such as sleepiness and cold extremities, were observed in both treatment and placebo groups in one small trial (23).

Herb-Drug Interactions
  • Cytochrome P450 3A4 and 1A2 substrates: Schisandra inhibits CYP3A4 and CYP1A2 and can affect the intracellular concentration of drugs metabolized by these enzymes. Long-term use can also induce CYP3A4 activity (33) (34).
  • P-glycoprotein substrates: Schisandra can inhibit Pgp activity and interfere with the metabolism of certain drugs (35) (36).
  • Tacrolimus: Schisandra can increase blood levels of tacrolimus, an immunosuppressant, in liver transplant patients (24).
Herb Lab Interactions

Schisandra can reduce levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but did not change total or direct bilirubin levels (21).

Dosage (Inside MSKCC Only)
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References
  1. 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. Apr 2010;33(2):126-136.
  2. Park HJ, Lee SJ, Song Y, et al. Schisandra chinensis prevents alcohol-induced fatty liver disease in rats. J Med Food. Jan 2014;17(1):103-110.
  3. Sun HD, Qiu SX, Lin LZ, et al. Nigranoic acid, a triterpenoid from Schisandra sphaerandra that inhibits HIV-1 reverse transcriptase. J Nat Prod. May 1996;59(5):525-527.
  4. Lin RD, Mao YW, Leu SJ, et al. The immuno-regulatory effects of Schisandra chinensis and its constituents on human monocytic leukemia cells. Molecules. 2011;16(6):4836-4849.
  5. Panossian A, Wikman G. Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol. Jul 23 2008;118(2):183-212.
  6. 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. Jan 22 2010;391(4):1687-1692.
  7. 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. Oct 2009;24(4):495-502.
  8. Liu SJ, Qu HM, Ren YP. SCP, a polysaccharide from Schisandra chinensis, induces apoptosis in human renal cell carcinoma Caki-1 cells through mitochondrial-dependent pathway via inhibition of ERK activation. Tumour Biol. Feb 7 2014.
  9. You JS, Pan TL, Hou YC. Schisandra chinensis protects against adriamycin-induced cardiotoxicity in rats. Chang Gung Med J. Jan-Feb 2006;29(1):63-70.
  10. Ip SP, Yiu HY, Ko KM. Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity. Mol Cell Biochem. May 2000;208(1-2):151-155.
  11. Stacchiotti A, Li Volti G, Lavazza A, et al. Schisandrin B stimulates a cytoprotective response in rat liver exposed to mercuric chloride. Food Chem Toxicol. Nov 2009;47(11):2834-2840.
  12. Chen P, Pang S, Yang N, et al. Beneficial effects of schisandrin B on the cardiac function in mice model of myocardial infarction. PLoS One. 2013;8(11):e79418.
  13. Kim YJ, Yoo SR, Chae CK, et al. Omija fruit extract improves endurance and energy metabolism by upregulating PGC-1alpha expression in the skeletal muscle of exercised rats. J Med Food. Jan 2014;17(1):28-35.
  14. Hu D, Cao Y, He R, et al. Schizandrin, an antioxidant lignan from Schisandra chinensis, ameliorates Abeta1-42-induced memory impairment in mice. Oxid Med Cell Longev. 2012;2012:721721.
  15. Lee SK, Kim SD, Kook M, et al. Therapeutic effects of alpha-iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, against sepsis. Biochem Biophys Res Commun. Oct 26 2012;427(3):547-552.
  16. Xu X, Zhou X, Zhou XW, et al. Schizandrin prevents dexamethasone-induced cognitive deficits. Neurosci Bull. Oct 2012;28(5):532-540.
  17. Ko KM, Ip SP, Poon MK, et al. Effect of a lignan-enriched fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity. Planta Med. Apr 1995;61(2):134-137.
  18. Kim SH, Joo MH, Yoo SH. Structural identification and antioxidant properties of major anthocyanin extracted from Omija (Schizandra chinensis) fruit. J Food Sci. Mar 2009;74(2):C134-140.
  19. Jo SH, Ha KS, Moon KS, et al. In Vitro and in Vivo Anti-Hyperglycemic Effects of Omija (Schizandra chinensis) Fruit. Int J Mol Sci. 2011;12(2):1359-1370.
  20. Huang M, Jin J, Sun H, et al. Reversal of P-glycoprotein-mediated multidrug resistance of cancer cells by five schizandrins isolated from the Chinese herb Fructus Schizandrae. Cancer Chemother Pharmacol. Nov 2008;62(6):1015-1026.
  21. Chiu HF, Chen TY, Tzeng YT, et al. Improvement of liver function in humans using a mixture of schisandra fruit extract and sesamin. Phytother Res. Mar 2013;27(3):368-373.
  22. Melhem A, Stern M, Shibolet O, et al. Treatment of chronic hepatitis C virus infection via antioxidants: results of a phase I clinical trial. J Clin Gastroenterol. Sep 2005;39(8):737-742.
  23. Aslanyan G, Amroyan E, Gabrielyan E, et al. Double-blind, placebo-controlled, randomised study of single dose effects of ADAPT-232 on cognitive functions. Phytomedicine. Jun 2010;17(7):494-499.
  24. Jiang W, Wang X, Xu X, et al. Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients. Int J Clin Pharmacol Ther. Mar 2010;48(3):224-229.
  25. Chu C, Zhang S, Tong S, et al. An efficient strategy for the extraction and purification of lignans from Schisandra chinensis by a combination of supercritical fluid extraction and high-speed counter-current chromatography. J Sep Sci. Dec 2013;36(24):3958-3964.
  26. Zhao T, Mao G, Mao R, et al. Antitumor and immunomodulatory activity of a water-soluble low molecular weight polysaccharide from Schisandra chinensis (Turcz.) Baill. Food Chem Toxicol. May 2013;55:609-616.
  27. Liu HW, Yu XZ, Padula D, et al. Lignans from Schisandra sphenathera Rehd. et Wils. and semisynthetic schisantherin A analogues: absolute configuration, and their estrogenic and anti-proliferative activity. Eur J Med Chem. Jan 2013;59:265-273.
  28. Zhu M, Lin KF, Yeung RY, et al. Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model. J Ethnopharmacol. Oct 1999;67(1):61-68.
  29. Zhu M, Yeung RY, Lin KF, et al. Improvement of phase I drug metabolism with Schisandra chinensis against CCl4 hepatotoxicity in a rat model. Planta Med. Aug 2000;66(6):521-525.
  30. Qin XL, Bi HC, Wang XD, et al. Mechanistic understanding of the different effects of Wuzhi Tablet (Schisandra sphenanthera extract) on the absorption and first-pass intestinal and hepatic metabolism of Tacrolimus (FK506). Int J Pharm. Apr 15 2010;389(1-2):114-121.
  31. Xu H, Gan J, Liu X, et al. Gender-dependent pharmacokinetics of lignans in rats after single and multiple oral administration of Schisandra chinensis extract. J Ethnopharmacol. May 2 2013;147(1):224-231.
  32. Shao B, Tang J, Ji H, et al. Enhanced oral bioavailability of Wurenchun (Fructus Schisandrae Chinensis extracts) by self-emulsifying drug delivery systems. Drug Dev Ind Pharm. Nov 2010;36(11):1356-1363.
  33. 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. Dec 2009;37(12):2399-2407.
  34. Su T, Mao C, Yin F, et al. Effects of unprocessed versus vinegar-processed Schisandra chinensis on the activity and mRNA expression of CYP1A2, CYP2E1 and CYP3A4 enzymes in rats. J Ethnopharmacol. Apr 19 2013;146(3):734-743.
  35. 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. Mar 2009;39(3):249-254.
  36. Liang Y, Zhou Y, Zhang J, et al. In vitro to in vivo evidence of the inhibitor characteristics of Schisandra lignans toward P-glycoprotein. Phytomedicine. Aug 15 2013;20(11):1030-1038.
  37. Huang KC. The Pharmacology of Chinese Herbs. Boca Raton, FL: CRC Press; 1999.

Consumer Information

How It Works


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) protection of the liver and nervous system, 2) improved mental and physical functioning, 3) antidiabetic effects, and 4) reversal of resistance to chemotherapy drugs by tumor cells. The small number of studies in humans is too limited to draw any conclusions.

Purported Uses
  • To treat lung problems
    Although schisandra is used to treat some pulmonary symptoms in traditional Chinese medicine, there are no clinical trials to support this use.
  • To treat coughs
    Schisandra is used in traditional medicine to treat coughs. No scientific studies to support this use have been conducted.
  • To treat gastrointestinal problems
    The traditional use of schisandra to treat diarrhea and indigestion is not yet supported in clinical trials. A small study in liver transplant patients suggests schisandra may help with the side effect of diarrhea associated with immune suppressant medication.
  • To treat liver disease
    Animal studies do show that schisandra can protect the liver from chemically-induced damage. In humans, one small study in liver transplant patients suggests schisandra can improve liver function. Another small study indicates it may be helpful in combination with other treatments for chronic hepatitis. However, these are uncontrolled trials that are inconclusive. Larger, more rigorous studies are needed to confirm these results.
  • To increase strength and stamina
    There are no human studies that validate this claim.
  • To reduce sweating
    The traditional use of schisandra to treat excessive sweating is not supported in clinical trials.
Research Evidence

Only a few small trials of schisandra used along with other substances or preparations have been published. Human studies that examine the effect of schisandra alone are needed to determine whether it has beneficial effects and whether there are any side effects.

Patient Warnings

Schisandra may reduce the effectiveness of some drugs or increase their adverse effects. Patients should talk with their doctors about the possibility of such drug interactions.

Do Not Take If
  • You are taking drugs that are substrates of cytochrome P450 3A4 or 1A2: Schisandra may increase the risk of toxicity or reduce the effects of these drugs.
  • You are taking drugs that are substrates of P-glycoprotein: Schisandra may increase the risk of side effects of these drugs.
Side Effects

No serious side effects have been reported. At the same time, schisandra is not well studied in humans.

Special Point

Schisandra can reduce the levels of certain liver enzymes on lab tests.

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