Chinese Herbal List

Fructus Schisandrae


Latin Name: Fructus Schisandrae
Common Name: Schisandra Schisandra
Scientific Name: Schisandra chinensis (Turcz.) Baill. / Schisandra sphenanthera Rehd. et Wils.
 Chinese Name: 五味子
Pinyin Name: wu wei zi
 The dried mature fruit of Schisandra chinensis (Turcz.) Baill. and S. sphenanthera Rehd. et Wils., a perennial deciduous vine plant of the Magnoliaceae family.1
Schisandra chinensis (Turcz.) Baill. is mainly produced in Jilin, Liaoning, Heilongjiang and Hebei provinces of China, and is known as northern schisandra.

Schisandra sphenanthera Rehd. et Wils. is mainly produced in Hubei, Henan, Shaanxi, Shanxi, Gansu and Sichuang provinces of China, and is known as southern schisandra. 

The herb is used in dried form, or processed with vinegar or honey.   
Schisandra is sour and sweet in flavor, warm in nature, and mainly manifests its therapeutic actions in the lung, heart and kidney meridians. 1

As the Chinese name of the herb suggests, schisandrae is a fruit with five flavors, which are sour, bitter, sweet, pungent and salty. The Bencao Congxin (New Compilation of Materia Piedica) (Wu Yilo, 1757) stated, "Schisandra is warm in nature. It contains all five flavors." The fruit skin is sweet, the fleshy tissue is sour and the seed core is bitter and pungent. All these parts have salty flavor. The predominant flavors of this herb, however, are sour and salty.
Northern schisandra contains 3% volatile oils, including sesquicarene, β2-bisabolene, β-chamigrene and α-ylangene. It also contains approximately 5% lignans, and contains 9.11% organic acids, which include citric acid, malic acid, tartaric acid, succinic acid and vitamin C. The seeds contain 33% fatty oil.
 
The lignans include schisandrin, and its derivatives α-, β-, γ-, δ-, ε-schisandrin, pseudo-γ-schisandrin, deoxyschisandrin, neoschisandrin, schisandrol and others. In addition to the above isolated lignan ingredients, the following lignan ingredients are also isolated, including gomisins A, B, C, D, E, F, G, H, J, N, O, (-)-gomisin K1, (+)-gomisin K2, (+)-gomisin K3, (-)-gomisin L1, (-)-gomisin L2, (±)-gomisin M1, (+)-gomisin M2, epigomisin O, angeloylgomisin Q, angeloylgomisin P and tigloylgomisin P. The last two compounds are optical isomers.
 
Other compounds include citral, chlorophyll, sterols, vitamins C, E, resins, tannin and little amount of sugars.
 
Southern schisandra contains active ingredients Schisandrin A, Schisantherin A, B, C, D, E and others.  
 
Schisandra consolidates lung, nourishes kidney, promotes body fluids production, arrests sweat and seminal discharges, controls diarrhea, soothes heart and calm down spirit. 1

Schisandra is often used for deficient lung and kidney disharmonies, chronic cough or breathing difficulty, seminal emission, frequent urination, diarrhea, profuse sweating, and mouth dryness.1
 
Respiratory problems due to lung and kidney deficiencies 
In case of breathing difficulty or chronic cough, schisandra is often selected with cornus fruit, processed rhemannia rhizome and Chinese yam; for those who also accompanied cold fluid retention and lead to excess throat discharges, pungent and warming herbs are ofte n selected to work with schisandra, such as ephedra, Manchurian wildginger and dried ginger.    
 
Fluid damages due to yin deficiency or fluid depletion
 
Sweating problems
Spontaneous sweating and night sweats may be associated with lung qi deficiency; schisandra can be selected to work with root of ephedra herb and oyster shell (calcined) to arrest the situations. 
 
Seminal emission
This is usually associated with insecurity of kidney qi; schisandra can be selected to work with herbs like mantis egg-case, cherokee rose fruit and fossil bone and arrests the situation.  
 
Persistent diarrhea 
When this is associated with cold and deficiency in spleen and kidney; schisandra can be selected to work with herbs like psoralea, medicinal evodia fruit and nutmeg; a representative formula is the Four Gods Pill.
 
Palpitations, insomnia and dream-disturbed sleep
The symptoms usually indicate depletion of yin and blood, that fails to nourish the heart and makes spirit uneasy. Schisandra benefits both heart and kidneys, and also soothe the heart and calm down spirit. The herb is often selected with rehmannia root, red sage root and sour jujube seed. Generally, schisandra is a common ingredient in the sleeping remedies.
 

Modern TCM also uses schisandra to treat nervous breakdown, chronic hepatitis, liver cirrhosis, chronic bronchis, emphysema, fatigue and general weakness after major illness. Schisandra powder for oral administration can also be used for transaminase (ALT and AST) elevations. 

1. Liver Protective Effects 

Animal studies 
Protective effects on CCl4-induced liver damage: Rats were treated with 0.1% (v/v) tetrachloromethane (CCl4) in peanut oil 10ml/kg i.p. (intra-peritoneal injection) to induce liver damage. Six hours after administration, various crude extracts of Fructus Schisandrae, which are equivalent to 10g/kg raw herb, were administered to the rats by gavage once daily for four days. Liver damage was then increased by further injection of CCl4 six hours after the last dose of Fructus Schisandrae. Results showed that the ethanol extract of Fructus Schisandrae seed core had significant effects in lowering ALT (alanine aminotransferase). It also reduced histopathological damage of the liver. However, a Fructus Schisandrae ethanol extract from fleshy tissue and a water extract from the seed core showed no effects. Liver protective effects were thought to be related to active ingredients contained in the seed core, which were fat-soluble.4,5
 
Protective effects in immunological liver damage: Liver damage induced by chemicals like CCl4 and thioacetamide is known as toxic hepatitis. This liver damage model can also be accomplished by immunological methods. Propionobacteria acnes (a gram-positive, non-sporing, anaerobic bacilli) was injected i.v. to mice tails to sensitize macrophages and Kupffer cells aggregated in the liver. After several days, lipopolysaccaride (bacteria toxin material) was injected i.v. into mice tails to activate the macrophages in the liver. As a result, a large amount of cytotoxic substances were released by the white blood cells causing liver damage.
 
This study showed that pretreatment with gomisin A (one of the active ingredients in Fructus Schisandrae) at a dose of 100mg/kg once daily for ten days had protective effects in the above immunological liver damage model. ALT (alanine aminotransferase) levels and mouse death rates were reduced as compared to controls.8
 
In vitro studies 
Protection for damaged liver cells: In vitro studies were done by extracting hepatocytes (liver cells) through collagenase perfusion. After liver damage induction on the liver cells by CCl4, both transaminase and lipid peroxidation product malondialdehyde (MDA) levels increased. Coagulation and liver cell membrane surface microvilli damage was observed. Pretreatment with 1mmol/L schizandrin B was shown to reduce various CCl4 induced damaging changes.6
 
Inhibitory effects of CCl4 induced lipid peroxidation on liver microsomes and inhibitory effects on covalent binding between 14CCl4 and liver microsomal lipids and proteins: CCl4 induced liver cell damage is caused by CCl3, a free radical produced after liver cytochrome P450 activation. CCl3 is highly reactive and can induce covalent bonding with macromolecules such as lipids and proteins on biological membranes. As a result, the structure and functions of biological membranes such as the endoplasmic reticulum will be affected.
 
 
(i) In this in vitro study, rat liver microsomes (containing P450) were mixed with 0.1mg NADPH and 1mml of various ingredients of Fructus Schisandrae. The mixture was then warmed in a water bath at 37°C for 15 minutes. Afterwards, 10µl of diluted CCl4 (20-fold ethanol dilution) was added and warmed in a water bath for 30 minutes. The amount of malondialdehyde (MDA) produced was measured. Results showed that active ingredients of Fructus Schisandrae, which have protective effects in CCl4-induced liver damage, generally could inhibit the production of MDA as well.
 
(ii) Same procedures and methods were repeated with 14CCl4. 14CCl4 that covalently bonded with liver microsomal lipids and proteins was extracted and its radioactivity was measured. Results were similar to the inhibitory effects in lipid peroxidation as reported in (i). Those active ingredients of Fructus Schisandrae, which had inhibitory effects in CCl4 induced liver lipid peroxidation, could also inhibit covalent bonding of 14CCl4 to liver microsomal lipids and proteins.7 
 
Clinical observation
In a clinical observation, capsule formulation of Fructus Schisandrae seed core oil extract was used to treat chronic active hepatitis. Each capsule contains 0.4g seed core oil, and the capsules were taken orally three capsules three times daily. One treatment period lasted for two months. thirty six cases were observed. The effectiveness in lowering ALT was reported to be 82.3%. 

2. Liver Detoxification Effects 

Animal studies 
Effects on liver enzyme systems: Studies10-13 showed that when rats and mice were given oral administration of schisandrin A, schisandrin B, schisandrin C, schisandrol B and schisanhenol at a dose of 200mg/kg once daily for three days, there were increases in liver microsome cytochrome P-450, NADPH-P450-reductase, aminopyrine demethylatase, benzo(a,c)pyrene hydroxylase and hepatic microsomal proteins, which suggests enzyme activity for drug metabolism increases with administration of these active ingredients. Additionally, schisandrin B selectively induced P-450 activity in the in the smooth endoplasmic reticulum (ER) of liver cells. 14
 
Cell culture studies
Effects on liver enzyme systems: Rat liver microsomes treated with schisandrin B or schisandrol B were shown to increase the rate of metabolism of the carcinogen 3H-benzo (a, c) pyrene and the non-carcinogen 3H-estradiol. They accelerate transformation of carcinogen 3H-benzo(a,c)pyrene towards metabolic products with low carcinogenicity. They also antagonize the mutagenecity of carcinogen such as 3H-benzo(a,c)pyrene suggesting that certain ingredients contained in Fructus Schisandrae can enhance liver detoxification.15 

3. Protect Against Damage by Oxygen Free Radicals 

Oxygen free radicals refer to superoxide anions (O2-) and hydroxide free radicals (-OH). Too many oxygen free radicals produced in the cells will damage macromolecules such as nucleic acids, proteins, enzymes and biological membrane, leading to many adverse outcomes. Causes of certain diseases are associated with damage by oxygen free radicals. Examples include alcoholic hepatitis, inflammation, arthritis, reperfusion injuries following heart, brain or kidney ischemia, radiation injuries, aging and certain tumors.
 
Among the many tissue damage reactions caused by oxygen free radicals, lipid peroxidation of polyunsaturated fatty acids in biological membranes is the one of the most fundamental damage reactions. In light of the antagonistic effects shown by certain lignan ingredients in Fructus Schisandrae against CCl4-induced membrane lipid peroxidation of liver microsomes, these compounds may have similar antagonistic effects in membrane lipid peroxidation caused by oxygen free radicals.9 
    
Animal studies 
Protective effect against peroxidation: An acute ethanol intoxication mouse model was employed to study the lipid peroxidation inhibitory effects of the ingredients of Fructus Schisandrae. Alcohol is known to cause liver damage. One of the reasons is that it may lead to liver lipid peroxidation. In the study, mice were given by mouth Fructus Schisandrae once daily for three days. At the last dose, mice were fasted for eight hours. Fifty percent alcohol was then administered by mouth at a dose of 15ml/kg, 12 hours later, MDA content in the liver tissue was measured. Results showed that after taking alcohol, MDA content in mice liver increased approximately two-fold. But when mice groups were pretreated with 0.5-1g alcohol crude extract, schisanhenol or 200mg/kg schisandrin B, the liver tissue MDA content measured was lower than the above control. Other active ingredients, Schisandrol A and B did not show significant lipid peroxidation inhibitory effects in vitro and also had no significant effects on the liver MDA elevation caused by acute alcohol intoxification. Therefore, the in-vivo and in-vitro study results were consistent. 16
 
Direct free radical scavenging effect: Using Electron Spinning Resonance (ESR), it was found that some active ingredients of Fructus Schisandrae, such as schisanhenol and schisandrin B and C, were able to scavenge O2- and -OH directly. 17-18
 
Promote the activity of anti-oxidative enzymes: In the cells, oxygen radicals generated are normally cleared by an oxygen radical scavenging enzymatic system. For instance, enzymes like superoxide dismutase (SOD), catalase and glutathione peroxidase (GSHPX) can scavenge O2-, -OH, H2O2 and LOO.
 

SOD   
O2- + O2-  →  O2 + H2O2  
2H+ 


catalase   
H2O2  →  O2 + 2H2O 


SOD   
2H2O2 + RH  →  2H2O + R 


GSH-PX 
ROOH + 2 GSH → ROH + GSSG + H2O

After rats were orally fed with 200mg/kg schisandrin B once a day for three consecutive days, cytosol SOD and catalase levels were significantly elevated. With more SOD and catalase activity, the body can clear up O2-,-OH and H2O2- more efficiently and thus alleviate damage caused by oxygen radicals.
 
Summarizing all of the above studies on oxidation, several ingredients of Fructus Schiandrae possess (1) O2-.and-OH scavenging effect (2) anti-H2O2 induced oxidative effects and (3) SOD and catalase activity promoting effects.15 
   
4. Effects on the Central Nervous System 
    
Animal studies 
Sedative effects: Animal experiments showed that schisandrols and its constituents, such as schisandrol A and schisandrol B, had tranquilizing-like effects on the central nervous system. In one study, rats were given i.p. injection of 60 or 120mg/kg schisandrol A. Fifiteen minutes later, either 50mg/kg of phenobarbital sodium or 180mg/kg of barbital sodium was injected. It was found that Schisandrol A had inhibitory effects on mice voluntary activities. As the dose increased, frequency of voluntary activities decreased.
 
Schisandrol A given by i.p. injection or by gavage feeding caused stupor in rats. The ED50 (effective dose) for i.p. injection was 107 (87-131.6) mg/kg, and the ED50 for oral dosing was 314 (340-420)mg/kg. Intra-ventricular injection of dopamine (5-45µg/kg) could antagonize the stupor caused by schisandrol A, but, injections of noradrenaline, 5-hydroxytryptamine (5-HT), acetylcholine (Ach), glycine or dopamine plus 5-HT could not antagonize the stupor caused by schisandrol A. This showed that the stupor causing effects of schisandrol A might be related to the dopaminergic system. 19 
   
5. Effects on the Respiratory System 
    
Animal studies 
Excitatory effects: When normal, anaesthetized rabbits and anaesthetized dogs were given i.v. injection of Fructus Schisandrae decoction at dose groups of 0.1-0.5ml/kg and 0.5-1.0ml/kg, there were excitatory effects on the respiratory system. Both respiratory depth and rate increased. It also antagonized respiratory inhibition caused by morphine. When the acidity of the decoction was neutralized, the effects were slightly weakened. Tincture dosage forms also had similar actions. While there was excitation on respiration, blood pressure was depressed. Even after removing the vagus nerve and carotid sinus, respiratory excitation still existed. Therefore it was believed that the respiratory excitation was caused by direct stimulation of the respiratory center.
 
When rabbits were pretreated with Phenobarbital to induce respiratory inhibition, the i.v. injection of Fructus Schisandrae decoction at a dose of 0.5ml/kg could increase the respiratory frequency and amplitude and maintain regular respiratory rhythm. 20
 
Schisandrin at a dose of 5~10mg/kg had excitatory effects on respiration. 21 On the other hand, when rats were given i.v. injection of gomisin at a dose of 5mg/kg, there was nearly no effects on respiration. 
 
When mice were administered by gavage with 5g/kg Fructus Schizandrae extract, seed suspension or fruit seed coat suspension for two days, no cases of death were reported, suggesting that Fructus Schizandrae is of low toxicity. 22
 
Mice fed with 0.6 or 1.2g/kg Fructus Schizandrae ethanol extract once a day for ten days showed mild intoxification syndromes such as reduction in activities and erect hair. No change in hemogram and morphology of major organs was observed.
 
By Rec-assay, a hot water extract (90oC) of Fructus Schizandrae was able to induce mutation, while a warm water extract (45oC) was not. 23
 
Fifteen to sixty minutes after mice were fed by gavage with 10-15g/kg of lipid oil Fructus Schizandrae, symptoms such as breathing difficulty and activity reduction started to appear. After one to two days, cases of death were reported. Mice treated by gavage with 0.28g/kg volatile oil extract of Fructus Schizandrae experienced breathing difficulty and ataxia. All animals were found dead 1 to 3 hours later.6
 
Schisandrin B was noted to be of lower toxicity. When ten mice were fed with a single dose of 2g/kg schisandrin B, no animal was found dead. When another 10 mice were gavage fed with 200mg/kg/day schisandrin B for 30 days, abnormalities in growth, major organs and hemoglobin levels were not observed. When schisandrin B was given to dogs, by gavage, once a day for four weeks, there were no detected changes in body weight, appetite, hemogram, liver tissues, and liver and kidney functions. 
For decoction, the usual dose of schisandra is 3～6g. Schisandra is also ground to make pills or powder form for oral administration. 1 
Schisandra is contraindicated in individuals with unresolved cold and flu, fever, onset of cough or measles.3
  1. Lui Dai Quan, ed. Chinese Medicine. Shanghai Scientific and Technical Publishers, 2000-6. 
  2. Li Jia Shi, ed. Chinese Medicine Identification. Shanghai Scientific and Technical Publishers, 2000-6. 
  3. Wu Yiluo. New Compilation of Materia Medica. 1757AD. 
  4. Bao Tiantong, Liu Geng-tao, Song-Zhen-Yu et. al. Studies on Fructus Schisandrae Chinensis I: Its effect on increased SGPT levels in animals caused by hepatotoxic chemical agents. Chin. Med. J. 1974; 54: 275.  
  5. Bao TT, Liu GT, Song ZY et. al. Studies on Fructus Schisandrae III: Some pharmacological actions of schizandrin B. Chin. Med. J. 1975; 55:498.  
  6. Zhang TM, Wang BE and Liu GT. Action of Schizandrin B, an antioxidant, on lipid peroxidation in primary cultured hepatocytes. Acta Pharmacol Sin. 1989; 10(4):353.  
  7. Liu Keng-Tao and Lesca P. Pharmacological properties of dibenzocyclooctene derivative isolated from Fructus Schizandrae, III Inhibitory effects on carbon tetrachloride induced lipid peroxidation, metabolism and covalent binding of carbon tetrachloride to lipids. Chem.-Biol. Inter. 1982, 41:39.  
  8. Mizoguchi Yasuhiro, Shin Tohkan and Morisawa Seiji. Effects of Gomisin A in an immunological induced acute hepatic failure model. Planta Med. 1991; 57:11.  
  9. Qu zhishan, et al. Efficacy analysis of 30 cases of chronic hepatitis treatment with Fructus Schisandrae seed core oil, Journal of Bai Qiuen Medical University 1988; 29(9): 47. 
  10. Liu KT, Cresteil T and Le Provost E et. al., Specific evidence that schizandrins induce a phenobarbital-like cytochrome P-450 from separated rat liver. Biochem Biophys Res Commun. 1981; 103: 1131.  
  11. Liu KT and Lesca P., Pharmacological properties of dibenzocycloctene derivatives isolated form Fructus Schisandrae chinensis II: Introduction of phenobarbital-like hepatic monooxygenases. Chem-Biol. Inter. 1982; 39:315.   
  12. Liu GT an Wei HL., Induction of hepatic microsomal monooxygenases by schisanhenol. Acta Pharmacol Sin. 1985; 6:41.   
  13. Liu GT., Effects of some compounds isolated form Chinese Medicinal herbs on hepatic Microsomal cytochrome P-450 and their potential biological consequences. Drug Met. Rev. 1991; 23: 439.    
  14. Li Y and Liu GT., Effects of schizandrins and biphenyl dimethyl dicarboxylate on enzymes of liver smooth and rough endoplasmic reticula in rat. Acta Pharmacol. Sin. 1987; 8:560. 
  15. Lu H and Liu GT,. Effects of schisandrins and biphenyl dimethyl dicarboxylate on enzymes and estradiol metabolism. Acta Pharmacol Sin. 1990; 11(3):331.   
  16. Lu H and Liu GT., Effect of dibenzo (a, c) cycloctene lignans isolated from Fructus Schisandrae on lipid peroxidation and anti-oxidative enzyme activity. Chem-Biol. Inter. 1991; 78:77.    
  17. Zhao BL, Liu GT and Xin WJ et al., Scavenging effect of schizandrins on active oxygen radicals. Cell Biol Inter Reports. 1990; 14(2):99. 
  18. Li XJ, Liu GT and Xin WJ et al. Scavenging effects on active oxygen radicals by schizandrins with different structures and configuration. Free Radic. Biol. And Med. 1990; 9:99.   
  19. Song W. Quality of Schisandra incarnata Stapf. Zhongguo Zhong Yao Za Zhi 1991 Apr; 16(4): 204-6, 253. 
  20. Liu Zongxiang, et al. Pharmacological experiment of Fructus Schisandrae, Chinese Medicine of Tianjin 1986; 3(3):28. 
  21. Wang benxiang, et al. Pharmacology of North Fructus Schisandrae, Journal of Medicine of Tianjin 1965; 7(4):338.   
  22. Song ziqi, Song peiyin. 50 cases in severe asthma treatment with 3 herbs, Journal of Traditional Chinese Medicine 1988; 29(9): 47.   
  23. Liu KT. Studies on Fructus Schisandra chinensis. Final Report on "Seminar on the Use of Medicinal Plants in Health Care". Tokyo, Japan, Sept. 13-17. 1977. World Health Organization Regional Office for the Western Pacific. PP. 101-112. Manila. Philippines.    
  24. Quoted in "Wang BX ed. Modern Pharmacological studies on Chinese Medicine. Tianjin Scientific Technology Publishing, 1999: 1248-1250".

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