Schisandra

Purported Benefits, Side Effects & More
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Schisandra

Purported Benefits, Side Effects & More
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Schisandra

Common Names

  • Wu wei zi
  • Schizandra
  • Five flavor berry
  • Gomishi
  • Omicha
  • Omija
  • Ngu mie gee

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Schisandra is a fruit extract used in traditional Chinese medicine, but few studies have been conducted in humans.

Schisandra has a long history of use in traditional Chinese medicine to treat liver conditions, stomach disorders, and as a tonic to improve vitality. It is also used in various formulas for fatigue and sleep. Its Chinese name, wu wei zi, means five-flavored fruit, to reflect the five flavors recognized in TCM: sour, bitter, sweet, salty, and pungent.

Scientists do not know how Schisandra works, but lab experiments have begun to identify some possible effects. Schisandra has antioxidant activity and appears to protect the liver and nervous system. Other animal studies suggest it may improve mental and physical functioning. Only a small number of studies have been conducted in humans and are too limited to draw any conclusions.

What are the potential uses and benefits?
  • To treat lung problems and coughs
    Although schisandra is used to treat some lung symptoms in traditional Chinese medicine, clinical trials have not 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
    A 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 uncontrolled trials are inconclusive and larger, more rigorous studies are needed.
  • To increase strength and stamina
    A small study in older adults doing regular low-intensity exercise suggests that a schisandra extract may enhance skeletal muscle strength, but it did not affect muscle mass. Additional studies are needed.
  • To reduce sweating
    A small trial in women suggests that schisandra may help menopausal symptoms including hot flushes and sweating.
What are the side effects?

No serious side effects have been reported, but schisandra is not well studied in humans.

What else do I need to know?

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 CYP1A2, 3A4, or 3A5: In vitro and animal studies suggest schisandra can affect how these drugs are metabolized. Clinical relevance has yet to be determined.
  • You are taking drugs that are substrates of P-glycoprotein: Schisandra may increase the risk of side effects of these drugs.

Special Point:

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

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For Healthcare Professionals

Scientific Name
Schisandra chinensis, Schisandra sphenanthera
Clinical Summary

Schisandra has a long history of use in traditional Chinese medicine to treat coughs (1), liver conditions (2), stomach disorders (3), sweating (4), as an adaptogen (5), and as a tonic to improve vitality. It is also used in various formulas for fatigue and sleep. Its Chinese name, wu wei zi, means five-flavored fruit, to reflect the five flavors recognized in TCM: sour, bitter, sweet, pungent, and salty.

In vitro studies suggest that schisandra has anti-inflammatory (1) (6), anticancer (7) (8), and cardioprotective effects (9). Animal studies also suggest cardio- and liver-protective effects (10) (11) (12). Schisandra appeared to enhance endurance and metabolism (13), improve cognitive functioning (14), and exhibit antimicrobial (15), antioxidant, neuroprotective (16), and anti-hyperglycemic activities (17) (18) (19) in other preclinical models. Active lignans isolated from schisandra, particularly schisandrin A, appeared to reverse P-glycoprotein-mediated multidrug resistance of various cancer cell lines to doxorubicin, vincristine, and paclitaxel (20).

Studies in humans are limited. Some suggest improvements in patients with fatty liver disease or hepatitis C when schisandra is used in combination with other substances (21) (22). In liver transplant patients, schisandra appeared to reduce tacrolimus-associated side-effects of diarrhea and agitation and improve liver function (24). In a small study of renal transplant patients who were CYP3A5 expressers, a schisandra preparation reduced tacrolimus dosing requirements, improved initial dose accuracy, and resulted in fewer dose changes (38). In small studies of women, schisandra did not induce significant changes in obesity-related measures (39), but was helpful for menopausal symptoms (40). A study of a proprietary formulation that included schisandra suggests improved performance of cognitive tasks (23). In older adults doing regular low-intensity exercise, preliminary data suggest supplementation with a schisandra extract may enhance skeletal muscle strength, but it did not affect muscle mass (42).

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 and Benefits
  • Cough
  • Diarrhea
  • Indigestion
  • Liver disease
  • Strength, stamina
  • Sweating
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). The anthocyanin Cya-3-O-xylrut has been identified as responsible for its antioxidant activity (18).

In animal toxicity models, pretreatment with schisandra lignans provided liver-protective effects via increased DT-diaphorase activity (10), and improved Phase I drug metabolism (28) (29). Schisandra also increased hepatic glutathione levels and glucose-6-phosphate and glutathione reductase activities (17). It lowered blood glucose levels via inhibition of α-glucosidase activity (19), and improved post-ischemic cardiac function 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 rat skeletal muscle by upregulating PGC-1α expression (13).

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 increased oral bioavailability of tacrolimus via inhibition of Pgp-mediated efflux and CYP3A-mediated metabolism, and reduction of intestinal first-pass effect (30).

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
  • CYP1A2, 3A4, and 3A5 substrates: In vitro studies suggest that lignans isolated from schisandra can inhibit CYP3A4 and CYP3A5 enzymes (41). Animal studies suggest 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). Clinical relevance has yet to be determined.
  • P-glycoprotein substrates: Lab and human studies suggest schisandra can inhibit P-gp activity and may interfere with the metabolism of certain drugs (35) (36).
  • Tacrolimus: In liver transplant patients, schisandra increased blood levels of tacrolimus, an immunosuppressant (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 (OneMSK Only)
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. 2014 Jun;35(6):5369-74.
  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.
  38. Li J, Chen S, Qin X, et al. Wuzhi Tablet (Schisandra sphenanthera Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: a Two-Phase Prospective Study. Drug Metab Dispos. Nov 2017;45(11):1114-1119.
  39. Song MY, Wang JH, Eom T, et al. Schisandra chinensis fruit modulates the gut microbiota composition in association with metabolic markers in obese women: a randomized, double-blind placebo-controlled study. Nutr Res. Aug 2015;35(8):655-663.
  40. Park JY, Kim KH. A randomized, double-blind, placebo-controlled trial of Schisandra chinensis for menopausal symptoms. Climacteric. Dec 2016;19(6):574-580.
  41. Zhao J, Sun T, Wu JJ, et al. Inhibition of human CYP3A4 and CYP3A5 enzymes by gomisin C and gomisin G, two lignan analogs derived from Schisandra chinensis. Fitoterapia. Jun 2017;119:26-31.
  42. Cho YH, Lee SY, Lee CH, et al. Effect of Schisandra chinensis Baillon extracts and regular low-intensity exercise on muscle strength and mass in older adults: A randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. Jun 1 2021;113(6):1440-1446.
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