Schisandrin B

Schisandrin B
Chemical structure of schisandrin B
Other names gamma-Schisandrin Gamma-schizandrin gomisin N
style="background: #F8EABA; text-align: center;" colspan="2" | Identifiers
CAS number	61281-37-6, 64121-95-5 66211-45-8
PubChem	108130
SMILES
style="background: #F8EABA; text-align: center;" colspan="2" | Properties
Molecular formula	C23H28O6
Molar mass	400.46 g/mol
Exact mass	400.188589 u
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Schisandrin B is a chemical compound.

Over the past few decades, the pharmacological activities of Schisandrin B, an active ingredient isolated from Fructus Schisandrae, have been extensively studied. Early evidence indicated that Schisandrin B could produce beneficial effects on liver function, particularly in enhancing the detoxification of xenobiotics and the regeneration of liver. Recent studies have further demonstrated the protective effect of Schisandrin B on free radical-induced damage in various vital organs, including the heart, liver, kidney, brain and skin.

Investigations on the biochemical mechanism(s) involved in the generalized tissue protection afforded by Schisandrin B have revealed its capability of enhancing antioxidant capacity and counteracting mitochondrial decay; both are crucial determinants in cell survival. In addition, the ability of Schisandrin B to induce the expression of heat shock proteins, which are endogenous protein molecules for cellular protection against various stressful stimuli, represents a fundamental mechanism involved in tissue protection. Recently, a stereoisomer of Schisandrin B, (−)Schisandrin B, has been shown to be the most potent in producing antioxidant protection. Given the novel anti-stress potential, Schisandrin B/(−)Schisandrin B may be used as a universal “cell protectant” for the prevention and treatment of tissue damage caused by environmental pollutants, physical exercise and aging. The beneficial effects of Schisandrin B/(−)Schisandrin B on cardiac and liver function, as well as mitochondrial functional ability and antioxidant capacity, would make it a superb ingredient for functional foods, herbal dietary supplements, and skincare products used for safeguarding against free radicals.

Usages

Fructus Schisandrae, the fruit of Schisandra chinensis (Turcz), Baillon, or Wu-Wei-Zi, transliterally meaning “the fruit of five tastes” in Chinese, is a commonly used tonic herb in traditional Chinese medicine, particularly for the treatment of liver ailments.

Schisandrin B, the most abundant active ingredient of Fructus Schisandrae, could produce a generalized tissue protective effect, which can likely be attributed to its ability to enhance mitochondrial functional ability and antioxidant capacity. Recent findings have also shown that chronic treatment with a low dose of Schisandrin B increased mitochondrial functional ability and antioxidant capacity in various tissues, including the brain, heart, liver, and skeletal muscle, in both young and old rats. Given the role of mitochondrial decay in aging, the maintenance of mitochondrial structural and functional integrity may have important implications in preventing age-related diseases and retarding the aging process.

Heart

While coronary heart disease remains a major health problem in industrialized countries, the exploration of possible preventive measures aimed at ameliorating the negative consequences (including debilitation and death) arising from a heart attack or cardiac arrest has been an area of intensive research. Schisandrin B is an active ingredient from Schisandra berry, which is traditionally used as a cardiotonic. Some findings demonstrated that Schisandrin B could enhance mitochondrial energy generation capacity and antioxidant defense, as well as heat shock protein production. It also suggests Schisandrin B can target mitochondria and render them more resistant to permeability transition – a process that eventually leads to necrotic and apoptotic cell death. That strengthens the belief that Schisandrin B can serve as a heart protecting agent of natural origin.

Liver

The liver is an important organ responsible for a host of biochemical reactions, particularly those for detoxifying harmful substances. The chronic exposure of the body to toxic substances, such as alcohol, dietary contaminants, and environmental pollutants, can damage the liver tissues, eventually leading to liver diseases such as cirrhosis and liver cancer. Researchers have long been attempting to find a safe and effective liver protecting agent. Some findings have demonstrated the liver protective effect of Schisandrin B against various toxicant challenges. The increased resistance of mitochondria to calcium ion-induced disruption caused by Schisandrin B prevents the programmed cell death of liver cells under stressful conditions; Schisandrin B could also protect against chemical toxin-induced liver damage by enhancing the mitochondrial defense against free radicals, which represents a unique mechanism of action among other antioxidants; Schisandrin B protects against apoptotic cell death caused by immune molecules through enhancing the production of heat shock protein 70 production in the liver. The finding, which is corroborated by the long history of Schisandra as a liver tonic, supports the use of Schisandrin B as an agent for safeguarding liver health.

Brain

The brain is highly vulnerable to oxidative damage caused by free radicals because of its high lipid and iron contents. The maintenance of a high antioxidant capacity in brain tissues is instrumental to prevent brain disorders such as post-stroke syndrome, Parkinson’s disease and Alzheimer’s disease. It is indicated that Schisandrin B decreases the death rate following an oxidative challenge to brain tissues. The protective effect is mediated by the increase in antioxidant capacity of brain tissues. This finding, together with previous reports on the liver and heart, supports the notion that Schisandrin B is able to produce generalized tissue protection against oxidative damage caused by free radicals.

Muscle

Unfamiliar or strenuous physical exercise can cause injury not only to skeletal muscle, but also to the liver. Free radicals are involved in the development of exercise-mediated tissue injury. Antioxidant supplementation is commonly used as a means for alleviating the exercise-induced muscle damage. It is also believed that the liver can supply glutathione (a natural antioxidant found in all cell types) to skeletal muscle in order to remove free radicals generated from the exercising muscle. The enhancement of liver glutathione status therefore represents an effective approach to counteracting the free radicals arising from exercise. It is indicated that the Schisandrin B-enriched extract, but not -tocopherol (vitamin E), can protect against exercise-induced muscle damage through the enhancement of liver glutathione status.

Kidney

Gentamicin, which is a commonly used antibiotic for the treatment of severe bacterial infections, can cause kidney toxicity. A recent finding indicates that long-term Schisandrin B treatment can enhance the resistance of kidney mitochondria to free radicals arising from gentamicin metabolism, thereby protecting against gentamicin-induced kidney toxicity.

Skin

Scientific studies have attributed skin aging to “Depleted Cellular Constituents (such as Collagen, Elastin, Hyaluronic Acid)”, “Oxidative Damages”, and “Inflammation” as the major causes. While this is true, scientists are now discovering a fundamental factor – mitochondrial decay – in skin aging. Skin aging can be ameliorated by various sophisticated skincare treatments, most of which are intended to “resurface” the epidermis by renewing skin cells. However, recent scientific studies have demonstrated that the enhancement of mitochondrial antioxidant capacity and functional ability by Schisandrin B is instrumental in revitalizing aging skin. Experimental results also showed that it can suppress the solar light-induced collagen-digesting enzyme production in human skin cells.

Types

Long-term treatment with Schisandrin B has been found to mitigate the age-related decline in mitochondrial antioxidant and functional ability, which is associated with an improved survival in both male and female mice. Stereoisomer of Schisandrin B have been recently identified - (+/-)gamma-Schisandrin and (-)Schisandrin B. (-)Schisandrin B possesses a more favorable pharmacological profile than the others.

References

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2. Chiu and Ko. SCHISANDRIN B-INDUCED INCREASE IN CELLULAR GLUTATHIONE LEVEL AND PROTECTION AGAINST OXIDANT INJURY ARE MEDIATED BY THE ENHANCEMENT OF GLUTATHIONE SYNTHESIS AND REGENERATION IN AML12 AND H9C2 CELLS. BioFactors 2006; 26: 221-230

3. Yim and Ko. SCHISANDRIN B PROTECTS AGAINST MYOCARDIAL ISCHEMIA-REPERFUSION INJURY BY ENHANCING MYOCARDIAL GLUTATHIONE ANTIOXIDANT STATUS. Molecular and Cellular Biochemistry 1999; 196: 151-156

4. Yim and Ko. METHYLENEDIOXY GROUP AND CYCLOOCTADIENE RING AS STRUCTURAL DETERMINANTS OF SCHISANDRIN IN PROTECTING AGAINST MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN RATS. Biochemical Pharmacology 1998; 57: 77-81

5. Chiu and Ko. SCHISANDRIN B PROTECTS MYOCARDIAL ISCHEMIA-REPERFUSION INJURY PARTLY BY INDUCING HSP25 AND HSP70 EXPRESSION IN RATS. Molecular and Cellular Biochemistry 2004; 266: 139-144

6. Ko and Chiu. STRUCTURAL DETERMINANTS OF SCHISANDRIN B WHICH ENHANCE MITOCHONDRIAL FUNCTIONAL ABILITY AND GLUTATHIONE STATUS AS WELL AS HEAT SHOCK PROTEIN EXPRESSION IN RAT HEARTS AND H9C2 CELLS. Molecular and Cellular Biochemistry 2005; 276: 227-234

7. Chiu et al. ()SCHISANDRIN B IS MORE POTENT THAN ITS ENANTIOMER IN ENHANCING CELLULAR GLUTATHIONE AND HEAT SHOCK PROTEIN PRODUCTION AS WELL AS PROTECTING AGAINST OXIDANT INJURY IN H9C2 CARDIOMYOCYTES. Molecular and Cellular Biochemistry 2006; 289: 185-191

8. Ip et al.SCHISANDRIN B PROTECTS AGAINST CARBON TETRACHLORIDE TOXICITY BY ENHANCING THE MITOCHONDRIAL GLUTATHIONE REDOX STATUS IN MOUSE LIVER. Free Radical Biology & Medicine 1996; 21: 709-712

9. Ip and Ko. THE CRUCIAL ANTIOXIDANT ACTION OF SCHISANDRIN B IN PROTECTING AGAINST CARBON TETRACHLORIDE HEPATOTOXICITY IN MICE: A COMPARATIVE STUDY WITH BUTYLATED HYDROXYTOLUENE. Biochemical Pharmacology 1996; 52: 1687-1693

10. Ip et al.METHYLENEDIOXY GROUP AS DETERMINANT OF SCHISANDRIN IN ENHANCING HEPATIC MITOCHONDRIAL GLUTATHIONE IN CARBON TETRACHLORIDE-INTOXICATED MICE. Biochemical Pharmacology 1997; 54: 317-319

11. Ip et al.EFFECTS OF SCHISANDRIN B PRETREATMENT ON TUMOR NECROSIS FACTOR- INDUCED APOPTOSIS AND HSP70 EXPRESSION IN MOUSE LIVER. Cell Stress & Chaperones 2001; 6: 44-48

12. Chiu et al. HEPATOPROTECTIVE MECHANISM OF SCHISANDRIN B: ROLE OF MITOCHONDRIAL GLUTATHIONE ANTIOXIDANT STATUS AND HEAT SHOCK PROTEINS. Free Radical Biology & Medicine 2003; 35: 368-380

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14. Chiu et al. SCHISANDRIN B DECREASES THE SENSITIVITY OF MITOCHONDRIA TO CALCIUM ION-INDUCED PERMEABILITY TRANSITION AND PROTECTS AGAINST CARBON TETRACHLORIDE TOXICITY IN MOUSE LIVERS. Biol Pharm Bull 2007; 30: 1108-1112

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