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Schisandra

Scientific Name(s): Schisandra arisanensis Hayata, Schisandra chinensis (Turcz.) Baillon, Schisandra fructus, Schisandra rubriflora Franch., Schisandra sphenanthera Rehd.
Common Name(s): Gomishi, Hoku-gomishi, Hoy tsi, Ji-chu, Kita-gomishi, Limonnik, Maximowich's red grape, Omiza, Schisandra, Schizandra, Wu-wei-zu

Clinical Overview

Use

Schisandra has been used as a tonic and restorative, and as a treatment for respiratory and GI disorders. Schisandra has also demonstrated liver protectant, nervous system stimulant, and adaptogenic effects. However, clinical trials to support these uses are limited.

Dosing

Schisandra fruit is used as an adaptogen at dosages of 1.5 to 6 g/day of powdered product. In a clinical study, schizandra tablets containing 91.1 mg of extract per tablet (extract standardized for schizandrin and gamma-schizandrin at a level of 3.1 mg/tablet) was used to improve athletic performance. Examples of various doses of schizandra preparations used in official medicine in Russia include the following: Tinctura Fructum Schizandrae prepared with air-dried fruits and 95% ethanol given as 20 to 30 drops twice daily. Tinctura Seminum Schizandrae prepared with dried seeds and 95% ethanol, given as 20 to 30 drops twice daily. Infusion Fructum Schizandrae prepared with air-dried fruits and water (1:20 w/v), given as 150 mL twice daily. Fructum Schizandrae contains air-dried fruits, given at a dose of 0.5 to 1.5 g twice daily. Schizandra seed powder 0.5 to 1.5 g administered twice daily before lunch and the evening meal for 20 to 30 days. Schizandra seed extract prepared by extracting air-dried seeds with 95% ethanol, given as a single dose of 0.05 or 0.2 mL/kg.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Various compounds from the stem of Schisandra propinqua were cytotoxic against rat luteal cells and human decidual cells in vitro.

Interactions

Because of its documented effects on hepatic and gastric enzyme activity, particularly cytochrome P450 (CYP-450) 3A, it is possible that schisandra may interfere with the metabolism of coadministered drugs (eg, midazolam). Findings from a study of healthy volunteers suggest that dosage adjustment may be needed in individuals concomitantly taking P-glycoprotein (P-gp) substrates (eg, tacrolimus).

Adverse Reactions

Research reveals little information regarding adverse reactions with use of schisandra.

Toxicology

No data.

Botany

Schisandra spp. are climbing, aromatic, woody vines with white, pink, yellow, or reddish male or female flowers. The fruits are globular and red with several kidney-shaped seeds. The fruit is harvested in autumn when fully ripened.Chevalier 1996 S. chinensis is native to northeastern and north central China and is found in eastern Russia. Synonyms are Kansura chinensis, Sphaerostemma japonica, Sphaerostemma japonicum, Maximoviczia chinensis, and Maximoviczia amurensis.

History

Schisandra is one of many traditional Chinese herbs recommended for treating cough and various nonspecific pulmonary diseases.Hikino 1984 It has been studied extensively in Chinese and Japanese literature. Schisandra has been used for healing purposes in traditional medicine for more than 2,000 years, often as an ethanolic tincture. The Chinese name for the plant, "wu-wei-zu," means "5 taste fruit" because schisandra is associated with sweet, sour, bitter, and salty flavors and an astringent effect. Salty and sour tastes were believed to have effects on the liver and testicles, while the bitter and astringent properties were thought to be beneficial to the heart and lungs. The sweet component was believed to have effects on the stomach.Panossian 2008 The plant has also been traditionally used to manage stress, balance fluid levels, improve sexual stamina, treat rash, stimulate uterine contractions, and improve failing senses. Schisandra has also been used for treatment of diarrhea and dysentery.Chevalier 1996

Chemistry

The chemistry of schisandra has been studied extensively. The fruit contains reducing sugars and up to 10% organic acids (carboxylic, malic, citric, tartaric). The seeds contain reducing sugars, alkaloids, and fatty esters; however, no flavones, glycosides, or tannins are found in the seeds or fruit.Ma 1968 Approximately 2% of the fruit (by weight) is composed of lignans with a dibenzocyclooctane skeleton (eg, schizandrin, deoxyschizandrin, and related compounds such as schizandrol and schizanderer). In some specimens, the lignan content can approach 19% in the seeds and 10% in the stems.Song 1983 More than 30 lignans have been identified in the seed,Hikino 1984 including gomisins A, B, C, D, F, and GIkeya 1979; tigloylgomisin P; and angeloylgomisin.Ikeya 1980 Other plant constituents include phytosterols, volatile oil, and vitamins C and E.Chevalier 1996 Analytical methods have been devised for processing and standardization purposes.Rao 1986, Suprunov 1975, Zhu 1988 Metabolism of schisandra components has been reported.Cui 1992, Cui 1993, Hendrich 1986

Uses and Pharmacology

Schisandra has been used as a tonic and restorative, and as a treatment for respiratory and GI disorders. Schisandra has also demonstrated liver protectant, nervous system stimulant, and adaptogenic effects. However, clinical trials to support these uses are limited.

Antibacterial effects

In vitro data

In one report, alcohol and acetone extracts of S. chinensis fruit demonstrated antibacterial activity.Ma 1968

Anti-inflammatory effects

In vitro data

In one study, 3 lignans (gomisin N, gomisin J, and schisandran C) suppressed proinflammatory cytokine secretion in murine macrophages, suggesting potential anti-inflammatory activity.Oh 2010

Antioxidant effects

In vitro data

In an in vitro study, several components isolated from Schisandra propinqua were found to exert antioxidant effects.Huang 2009

Doxorubicin-induced cardiotoxicity

It has been suggested that Schisandra fructus exerts antioxidant effects through inhibition of lipid peroxidation, induction of the antioxidant system, and scavenging of reactive oxygen species. S. fructus has been investigated for its cytoprotective effects against doxorubicin-induced cardiotoxicity caused by the production of free radicals.Choi 2008

In vitro data

In a study of H9c2 cardiomyocytes, treatment with 150 mcg/mL and 300 mcg/mL of an S. fructus extract increased cell survival time by 15% and 25%, respectively, compared with doxorubicin controls (P<0.05). The extract also inhibited lipid peroxidation caused by doxorubicin and inhibited the production of reactive oxygen species.Choi 2008

Erectile dysfunction

Animal data

In a study evaluating the effects of an ethanol extract and active components of the fruit of S. chinensis in rabbits, the lignans schisandrol A and schisandrol B enhanced the corpora cavernosae relaxation induced by sildenafil by 2-fold. Schisandrol A exerted the greatest relaxant effect and may have a synergistic role for patients with erectile dysfunction who do not adequately respond to sildenafil monotherapy.Kim 2011

GI effects

Animal data

Schisandra extract reduces benzo[a]pyrene (BaP) metabolism in the rat intestine but has an opposite effect in the liver. Experimental studies show that it increases the activity of glutathione S-transferase. In the intestine, schisandra shifts BaP metabolism in favor of diols and 3-hydroxybenzo[a]pyrene and away from BaP-4,5-epoxide and the mutagenic BaP quinones. Schisandra does not increase intestinal CYP activity.Salbe 1985 In one report, schisandra extract had no effects on gastric secretory volume, gastric pH, or acid output,Hernandez 1988 while another study showed schisandra had inhibitory effects on gastric contraction and stress-induced gastric ulceration when administered intravenously and orally in rats.Maeda 1981

Glucose effects

Animal data

In a study in mice, schisandra extract resulted in a decrease in glycogen content in the liver and muscles and an increase in glucose level in the liver and blood, suggesting the adaptogen stimulates glycogenolysis.Panossian 2008

Hair growth

Animal data

In mice, topical administration of an ethanolic extract of Schisandra nigra was found to promote hair growth through down-regulation of the transforming growth factor–beta-2 pathway and proliferation of dermal papilla.Kang 2009

HIV

Clinical data

In a safety and efficacy study, treatment with a combination product containing schisandra was not found to improve quality-of-life parameters, viral load, or CD4 counts in asymptomatic HIV patients.Maek-a-nantawat 2009

Liver protectant effects

The lignan components of schisandra possess pronounced liver protectant effects. The active principles appear to be the lignans wu-wei-zu C, shisantherin D, deoxygomisin A, gomisin N, and gomisin C. The presence of 1 or 2 methylenedioxy groups appears to be important in hepatoprotection.Hikino 1984, Maeda 1982

Animal data

Animal studies of gomisin A offer evidence of liver protection, including protective actions against halothane-induced hepatitisJiaxiang 1993; carbon tetrachloride, d-galactosamine, and dl-ethionine toxicitiesKo 1995, Takeda 1986; hepatic failure induced by bacteriaMizoguchi 1991; and preneoplastic hepatic lesions.Miyamoto 1995, Nomura 1994, Nomura 1994, Ohtaki 1994 Gomisin A's mechanism for tumor inhibition may be a result of its ability to improve bile acid metabolism.Ohtaki 1996 Gomisin A increased hepatic blood flow and accelerated hepatic cell proliferation and liver function recovery following partial hepatectomy in rats.Takeda 1986 These effects were caused by protection of the hepatocyte plasma membrane.Nagai 1989 Ethanol extracts of schisandra have been found to increase liver weight in rats and mice, an action attributed to schizandrin B and schizandrol B. In another murine study, schisandrin B reduced total cholesterol and triglyceride levels in a manner similar to fenofibrate, and also increased liver weights.Pan 2008

In a mouse study, a schisandra ethanol extract added to a semipurified basal diet over a 14-day period increased the enzymatic metabolism of the mutagens BaP and aflatoxin B (AFB), and increased CYP-450 activity. Despite this increased level of metabolism, schisandra extract increased in vitro mutagenicity of AFB. However, chemicals inducing similar patterns of enzymes have been found to reduce the in vivo binding of AFB to DNA.Hendrich 1986 Schizandrins and approximately 6 related compounds may temporarily inhibit or lower the activity of hepatic ALT, as observed in animals pretreated with hepatotoxins.Bao 1980, Maeda 1985, Pao 1974

Clinical data

In a randomized, placebo-controlled trial, a commercially available mixture of schisandra with sesamin (2,064 mg/day) was administered for 5 months to 40 patients with borderline liver dysfunction. Compared with placebo, the mixture reduced ALT and AST in a time-dependent manner and improved fatty liver disease. Overall antioxidant capacity was increased, and measurements of oxidative stress, including total free radicals, superoxide anion radicals, and thiobarbituric acid reactive substances, were decreased.Chiu 2013

Menopause

Clinical data

In a study of pre- and postmenopausal women, treatment with a combination product containing S. chinensis was found to increase urinary 2-OHE concentrations, suggesting a potential role in reducing the risk of breast cancer.Laidlaw 2010

In a double-blind, randomized, placebo-controlled trial in 36 postmenopausal women, schisandra extract (392 mg twice daily for 12 weeks) demonstrated a positive effect on the severity of menopausal symptoms. No significant difference was observed between groups for mean total Kupperman Index scores at 6 or 12 weeks. However, when evaluated with respect to group and time, schisandra extract led to lower total symptom scores over time, with significantly greater improvement specifically for hot flushes (P=0.018), sweating (P=0.009), and heart palpitations (P=0.015).Park 2016

Nervous system effects

Schisandra is a nervous system stimulant that reportedly increases reflex responses and improves mental alertness. In China, the berries are used to treat mental illnesses such as depression. Schisandra is also used to treat irritability and memory loss. Schisandra has also been evaluated for its inhibitory effects on the CNS. Although a stimulant, it is used as a sedative for insomnia in Chinese medicine.Chevalier 1996 A phenolic-rich component from S. chinensis may be beneficial in the prevention and treatment of neurodegenerative conditions such as Alzheimer disease, Parkinson disease, and Huntington disease, as noted by a dose-dependent reduction in H2O2-induced cell death in SH-SY5Y cells.Jung 2007

Animal and experimental data

In a study of mice, schisandra in combination with other herbs improved memory retention disorder and facilitated memory retention deficit, suggesting a possible role in treating age-related memory deficits in humans.Nishiyama 1996 Schisandra in combination with Zizyphus spinosa and Angelica sinensis has accelerated neurocyte growth and may prevent atrophy of neurocyte process branches.Hu 1994

Schisandra's mechanism of CNS inhibition has been evaluated and may be related to an effect on dopaminergic receptors.Zhang 1991 Gomisin A has also inhibited spontaneous and methamphetamine-induced motor activity in animals.Maeda 1981

In a murine model, schisandrin B conferred dose-dependent protection against brain infarction caused by cerebral ischemia/reperfusion, with protection ranging from 10% to 33%.Chen 2008

Clinical data

In a phase 2a, randomized, double-blind, placebo-controlled study, 40 healthy women performing stressful cognitive tasks were randomized to receive ADAPT-232 (a standardized fixed combination containing S. chinensis, Eleutherococcus senticosus, and Rhodiola rosea) or placebo before and after a series of attention, speed, and accuracy tests. Compared to the placebo group, women receiving ADAPT-232 experienced improvements in attention, speed, and accuracy, as well as in quality of work under stressful conditions.Aslanyan 2010

Respiratory

Schisandra has traditionally been used to treat respiratory ailments such as shortness of breath, wheezing, and cough.Chevalier 1996

In vitro data

In rat basophilic leukemia cells, schizandrins, schisandrols, gomisins, fargesin, eudesmin, and lirioresinol B dimethyl ether inhibited leukotriene production by 5-lipoxygenase, with the most potent inhibitory activity noted with schisandrol A and gomisins. Therefore, these compounds have the potential to be developed as antiallergic agents.Lim 2009

Stress

Clinical data

In humans, nonspecific resistance to stress involves the nervous, endocrine, and immune systems. A systematic review of adaptogens (plant extracts shown to enhance these responses) was conducted to determine efficacy in stress-induced fatigue and mental performance, using 2 grading scales (European Medicines Agency Assessment Scale and Natural Standards Evidence-Based Validated Grading Rationale). Use of schisandra for mental fatigue was assigned a grade B recommendation (according to both scales), based on nonrandomized clinical trials that showed an improvement in endurance and mental performance with a single dose (7 trials [N=1,712]) and with repeated administration (1 trial [n=665]). Schisandra use for symptoms of asthenia (fatigue and weakness) received a grade B/C recommendation (5 trials [N=406]). Evidence levels ranged from IIa to III, reflecting the availability of well-conducted studies but also a lack of randomized trials.Panossian 2009

Tacrolimus-sparing effects

Clinical data

In China, schisandra and tacrolimus are often coadministered when drug-induced hepatitis occurs in transplant recipients. A tacrolimus-sparing effect was reported in a study of 64 renal transplant patients treated with a prednisone, mycophenolate, and tacrolimus regimen with or without schisandra. After 6 months, a 34% reduction in tacrolimus dosage was observed in the group receiving schisandra compared with the schisandra-free group (14.3%), resulting in an estimated savings per day per patient day of $6.15.Xin 2011

Dosing

Schisandra fruit is used as an adaptogen at dosages of 1.5 to 6 g/day of powdered product. In a clinical study, schizandra tablets containing 91.1 mg of extract per tablet (extract standardized for schizandrin and gamma-schizandrin at a level of 3.1 mg/tablet) was used to improve athletic performance.Panossian 1999, Panossian 2008, Schisandra 1999 Examples of various doses of schizandra preparations used in official medicine in Russia include the followingPanossian 2008:

  1. Tinctura Fructum Schizandrae prepared with air-dried fruits and 95% ethanol given as 20 to 30 drops twice daily.

  2. Tinctura Seminum Schizandrae prepared with dried seeds and 95% ethanol, given as 20 to 30 drops twice daily.

  3. Infusion Fructum Schizandrae prepared with air-dried fruits and water (1:20 w/v), given as 150 mL twice daily.

  4. Fructum Schizandrae contains air-dried fruits, given at a dose of 0.5 to 1.5 g twice daily.

  5. Schizandra seed powder 0.5 to 1.5 g administered twice daily before lunch and the evening meal for 20 to 30 days.

  6. Schizandra seed extract prepared by extracting air-dried seeds with 95% ethanol, given as a single dose of 0.05 or 0.2 mL/kg.

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is limited. Various compounds from the stem of S. propinqua were found to be cytotoxic in rat luteal cells and human decidual cells in vitro.Chen 2001 Schisandra use was ruled out as a probable cause in a case of congenital syngnathism (maxilla and mandible fusion) that led to the early death of an infant born to consanguineous parents.Villanueva-García 2009

Interactions

Because of its documented effects on hepatic and gastric enzyme activity, particularly CYP3A, it is possible that schisandra may interfere with the metabolism of coadministered drugs (eg, midazolam).Gurley 2012, Jiang 2010, Lai 2009, Xin 2009 Additionally, in a study of healthy volunteers, a 14-day treatment course with S. chinensis 300 mg twice daily was found to inhibit P-gp, based on increased oral bioavailability of the P-gp substrate talinolol; dosage adjustment may be needed in individuals concomitantly taking P-gp substrates (eg, tacrolimus).Fan 2009, Xin 2007 In clinical trials, schisandra administration resulted in a 1.5-, 2.1-, and 2-fold increase in area under the curve (AUC) of talinolol, tacrolimus, and midazolam, respectively.Gurley 2012 In rats, the administration of schisandrol extracts increased the oral bioavailability of paclitaxel by approximately 3-fold and more than doubled the AUCs of midazolam, nifedipine, paclitaxel, and tacrolimus.Gurley 2012, Jin 2010 Schisandra may induce the metabolism of warfarin.Koncic 2013

Adverse Reactions

Research reveals little information regarding adverse reactions with use of schisandra.

Toxicology

The minimum toxic dose of schisandra when given orally to mice was 3.6 g/kg. In a study of acute toxicity in mice, no effects on blood pressure, breath, or motility were noted following intraperitoneal administration; however, high doses caused convulsions (median effective dose [ED50]=175 mg/kg) and paresis (ED50=370 mg/kg).Panossian 2008 Symptoms of overdose (restlessness, insomnia, or dyspnea) have been reported.Koncic 2013

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