Schisandra

Scientific Name(s): Schisandra chinensis (Turcz.) Baillon, Schisandra arisanensis Hayata, Schisandra sphenanthera Rehd., Schisandra rubriflora Franch. Family: Schisandraceae. It is also called Kansura chinensis , Sphaerostemma japonica , Sphaerostemma japonicum , Maximoviczia chinensis , and Maximoviczia amurensis .

Common Name(s): Schisandra , schizandra , gomishi , hoku-gomishi , kita-gomishi (Japanese), wu-wei-zu (5 taste fruit), ji-chu or hoy tsi (Chinese), omiza (Korean), Maximowich's red grape , Limonnik (Russian)

Uses

Schisandra has been used as a tonic and restorative, as well as for liver protection, nervous system effects, respiratory treatment, and GI therapy. However, there are limited clinical trials to support these uses.

Dosing

Schisandra fruit is used as an adaptogen at dosages of 1.5 to 6 g/day. A standardized extract containing 3.4% schisandrin has been used in a clinical trial for improved athletic performance at 91 mg/day of extract. Examples of various doses used in Russia include the following: Tinctura Fructum : Schisandrae 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 : given as 0.5 to 1.5 g twice daily before lunch and dinner over 20 to 30 days; Schizandra seed extract : prepared with air-dried seed and 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 found to be cytotoxic against rat luteal cells and human decidual cells in vitro.

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). Findings from a study of healthy volunteers suggest patients receiving schisandra while concomitantly taking drugs that are P-glycoprotein (P-gp) substrates (eg, tacrolimus) may require a dosage adjustment.

Adverse Reactions

Research does not report any incidence of adverse effects.

Toxicology

The minimal toxic dose when given orally to mice is 3.6 g/kg. The acute toxicity was studied in mice, and following intraperitoneal administration, no effects on blood pressure, breath, or motility were noted; however, high doses caused convulsions (median effective dose [ED 50 ] = 175 mg/kg) and paresis (ED 50 = 370 mg/kg).

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. 1 S. chinensis is native to northeastern and north central China and is found in eastern Russia.

History

Schisandra is one of the many traditional Chinese herbs recommended for coughs and various nonspecific pulmonary diseases. 2 It has been studied extensively in Chinese and Japanese literature. Schisandra has been used for healing purposes for over 2,000 years. It is often used as an ethanolic tincture. The Chinese name for the plant, wu-wei-zu, means “5 taste fruit” and is associated with sweet, sour, bitter, astringent, and salty flavors. Salty and sour tastes were believed to have effects on the liver and testicles, while the bitter and astringent properties were beneficial to the heart and lungs. The sweet component had effects on the stomach. 3

Chemistry

Schisandra chemistry 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. 4 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. 5 More than 30 lignans have been identified in the seed, 2 including gomisins A, B, C, D, F, and G 6 ; tigloylgomisin P; and angeloylgomisin. 7 Other plant constituents include phytosterols, volatile oil, and vitamins C and E. 1 Analytical methods have been devised for processing and standardization purposes. 8 , 9 , 10 Metabolism of schisandra components has been reported. 11 , 12 , 13

Uses and Pharmacology

Besides serving as a tonic and restorative, schisandra has other reported uses, such as liver protection, nervous system effects, respiratory treatment, GI therapy, and adaptogenic properties.

Liver

The lignan components in 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 appear to be important in hepatoprotection. 2 , 14

Animal data

Animal studies on gomisin A offer convincing evidence of liver protection, including protective actions against halothane-induced hepatitis, 15 carbon tetrachloride, d-galactosamine and dl-ethionine toxicities, 16 , 17 hepatic failure induced by bacteria, 18 and preneoplastic hepatic lesions. 19 , 20 , 21 , 22 Gomisin A's mechanism for tumor inhibition may be a result of its ability to improve bile acid metabolism. 23 Gomisin A causes hepatic cell proliferation and improves liver regeneration, hepatic blood flow, and liver function recovery in rats. 24 These effects are caused by protection of the hepatocyte plasma membrane. 25 Ethanol extracts of schisandra have been found to increase liver weight in rats and mice. This action has been attributed to schizandrin B and schizandrol B. In another murine study, schisandrin B was found to reduce total cholesterol and triglyceride levels similarly to fenofibrate, as well as increase liver weights. 26

In a mouse study, extract added to a semipurified basal diet over a 14-day period increased the enzymatic metabolism of the mutagens benzo[a]pyrene (BaP) and aflatoxin B (AFB) and increased cytochrome P450 (CYP-450) activity. Despite this increased level of metabolism, schisandra extract increased the 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. 11 It is also recognized that the schizandrins and approximately 6 related compounds may temporarily inhibit or lower the activity of hepatic ALT. This has been observed in animals pretreated with hepatotoxins. 27 , 28 , 29

Clinical data

Research reveals no clinical data for the use of schisandra for its protective properties in the liver.

Nervous system

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. It is also used to treat irritability and memory loss. 1 Schisandra has been evaluated for its inhibitory effects on the CNS, as well. In Chinese medicine, it is used as a sedative for insomnia. 1 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 H 2 O 2 -induced cell death in SH-SY5Y cells. 30

Animal data

Schisandra in combination with other herbs has improved memory retention disorder and facilitated memory retention deficit in animal testing. This suggests a possible use in treating age-related memory deficits in humans. 31 Schisandra, in combination with Zizyphus spinosa and Angelica sinensis , has accelerated neurocyte growth and may prevent atrophy of neurocyte process branches. 32

The CNS inhibition mechanism has been evaluated and may be related to an effect on dopaminergic receptors. 33 Gomisin A has also inhibited spontaneous and methamphetamine-induced motor activity in animals. 34

In a murine model, schisandrin B was found to confer protection against brain infarction due to cerebral ischemia reperfusion. This protection occurred in a dose-dependent manner, with protection ranging from 10% to 33%. 35

Clinical data

In a phase 2a (randomized, double-blind, placebo-controlled) study, 40 healthy women who were under psychological stress were randomized to receive ADAPT-232 (containing S. chinensis , Eleutherococcus senticosus , and Rhodiola rosea ) or placebo before and after a series of attention, speed, and accuracy tests. In comparison with placebo, women receiving ADAPT-232 experienced improvements in attention, speed, and accuracy during stressful activities, as well as better quality of work. 36

Respiratory
Animal data

Schisandra has been used to treat respiratory ailments, such as shortness of breath, wheezing, and cough. 1 Gomisin A exerted antitussive effects when evaluated in guinea pigs. 35 In rat basophilic leukemia cells, schizandrins, schisandrols, gomisins, fargesin, eudesmin, and lirioresinol B dimethyl ether were found to inhibit leukotriene production by 5-lipoxygenase, with most potent inhibitory activity noted with schisandrol A and gomisins. These may be useful as antiallergic agents. 37

Clinical data

Research reveals no data for the utility of schisandra for the treatment of respiratory ailments.

GI
Animal data

In the rat intestine, schisandra extract reduces BaP metabolism, which is the opposite effect from that in the liver. Experiments 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-450 activity. 38 Schisandra has been used for treatment of diarrhea and dysentery. 1 One report found schisandra extract to have no effects on gastric secretory volume, gastric pH, or acid output, 39 while another study found schisandra to have inhibitory effects on gastric contraction and stress-induced gastric ulceration when administered intravenously and orally in rats. 34

Clinical data

Research reveals no data for the use of schisandra for GI problems.

Protection against doxorubicin-induced cardiotoxicity

Schisandra fructus has been suggested to exert antioxidant effects through inhibiting lipid peroxidation, the induction of the antioxidant system, as well as scavenging of reactive oxygen species. It has been investigated for its cytoprotective effects against doxorubicin-induced cardiotoxicity, caused by the production of free radicals. 40 In H9c2 cardiomyocytes, treatment with 150 mcg/mL and 300 mcg/mL of S. fructus extract was found to increase cell survival time by 15% and 25%, respectively, when compared with doxorubicin-controls ( P < 0.05). It was also found to inhibit lipid peroxidation caused by doxorubicin and inhibit the production of reactive oxygen species. 40

Animal data

Research reveals no animal data for the use of schisandra for protection against doxorubicin-induced cardiotoxicity.

Clinical data

Research reveals no clinical data for the use of schisandra for protection against doxorubicin-induced cardiotoxicity.

Other uses

The plant helps the body adapt to stress. It has been used to balance fluid levels, improve sexual stamina, treat rash, stimulate uterine contractions, and improve failing senses. 1 One report found antibacterial effects in alcohol and acetone extracts of the fruit. 4 In a study of pre- and post-menopausal women, treatment with a combination product containing S. chinensis among other components was found to increase urinary 2-OHE concentrations, suggesting a potential reduction in the risk of breast cancer. 41 Three lignans (gomisin N, gomisin J, and schisandran C) suppressed pro-inflammatory cytokine secretion in murine macrophages, suggesting a potential anti-inflammatory role. 42 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. 43 Schisandrol A and schisandrol B were found to enhance the corpora cavernosae relaxation induced by sildenafil by 2-fold in rabbits. Schisandrol A exerted the most relaxant effect. It may offer a synergistic role in patients who do not adequately respond to sildenafil monotherapy. 44 In mice, topical administration of an ethanolic extract of Schisandra nigra was found to promote hair growth. This occurred through down regulation of the transforming factor-beta-2 pathway and proliferation of dermal papilla. 45 In an in vitro study, several components isolated from Schisandra propinqua were found to exert antioxidant effects. 46 S. chinensis may be beneficial in improving glucose tolerance. 47

Dosage

Schisandra fruit is used as an adaptogen at dosages of 1.5 to 6 g/day. A standardized extract containing 3.4% of schisandrin has been used in a clinical trial to improve athletic performance at 91 mg/day of extract. 47 , 48 Examples of various doses used in Russia include 3 :

Tinctura Fructum Schisandrae 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 given as 0.5 to 1.5 g twice daily before lunch and dinner over 20 to 30 days.

Schizandra seed extract prepared with air-dried seed and 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 minimal. Various compounds from the stem of the S. propinqua were found to be cytotoxic in rat luteal cells and human decidual cells in vitro. 49

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 other concurrently administered drugs (eg, midazolam). 50 , 51 , 52 Additionally, in a study of healthy volunteers, a 14-day treatment course with S. chinensis 300 mg twice daily was found to significantly inhibit P-gp as measured by administration of talinolol and noted by the increased oral bioavailability of talinolol. Patients receiving schisandra while concomitantly taking drugs that are P-gp substrates (eg, tacrolimus) may require a dosage adjustment. 53 , 54 In rats, the administration of schisandrol B, an active component of schisandra, was found to increase the oral bioavailability of paclitaxel by approximately 3-fold. 55

Adverse Reactions

Research reveals little information regarding adverse reactions with the use of this product.

Toxicology

The minimum toxic dose given orally to mice was 3.6 g/kg. The acute toxicity was studied in mice, and following intraperitoneal administration, no effects on blood pressure, breath, or motility were noted; however, high doses caused convulsions (ED 50 = 175 mg/kg) and paresis (ED 50 = 370 mg/kg). 3

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