Schizandra Chinensis

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Schisandra Chinensis is a vine with flowers and fruits (berries) that grows in eastern Asia; namely Russia, China, Korea, and Japan. Although the bioactive components (the lignans of Schisandra) are found in all parts of the plant, they are most concentrated in the berries and thus Fructus Schisandra (fruits of Schisandra) have been used traditionally in these regions for their medicinal properties.

In Russia they were favored for their adaptogenic (stress reducing) and physical endurance enhancing properties, and in Traditional Chinese Medicine they were favored as a liver tonic and vitality/life enhancer. They have traditionally been used for a wide variety of purposes, such as the above outlined ones as well as sedative, hypnotic, circulation, respiratory, sexual enhancing, life extending, and inflammatory diseases.

Although there is preliminary evidence suggesting all the above may exist, currently the largest body of evidence (which is still somewhat limited relative to other supplements) looks at treatment of liver ailments and general protection (secondary to both stress reduction and increasing anti-oxidant defense of enzymes). A great deal of claims still need to be proven in Western controlled trials, however, and human studies are lacking despite the large usage of Schisandra Chinensis in traditional medicine.

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Clinical trials done in the West are lacking or confounded, and thus optimum doses cannot really be extrapolated from these. The best estimate at this moment in time may be falling back on traditional preparation methods, which are various:

• Dried fruit extract in a 1:6 w/v ratio against liquid (95% ethanol) and administered at 20-30 drops daily
• Dried fruit extract in a 1:20 w/v ratio against water, 150mL drank twice a day with meals
• Eating the powdered fruit or fruit extract (this is what is usually found in pills) at 1-3g daily, with meals

Schisandra Chinensis fruits can be brewed into wines or teas as well.

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Schizandra Chinensis has in your body, and how strong these effects are.

Level of Evidence	Effect	Change	Magnitude of Effect Size	Scientific Consensus	Comments
C	Nitric Oxide		Minor	100% See study	An increase in serum nitric oxide has been detected in one study in elite athletes
C	Cortisol		Minor	-- See study	Conditional influences on cortisol, with an apparent increase in cortisol of beginner atheltes at rest with decreases in exercise-induced cortisol in beginners and lower... show overall cortisol exposure in trained athletes

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Edit1. Sources and Composition

1.1. Sources

Schizandra Chinensis, sometimes referred to as Chinese Magnolia Vine, is a Traditional Chinese Medicine belonging to the family of Schisandraceae. It is a deciduous woody vine growing up to 8m long with yellowish-white to pinkish flowers and bears fruits 5-8mm in size and bearing a deep red color.^[2] These fruits are where the main bioactive components of Schizandra Chinensis exist, and they are sometimes referred to as Fructus Schizandra. The fruit has a slightly sour taste, and the seeds are more pungent and bitter.^[2]

Schizandra Chinensis grows in Russia (Primorsk and Khabarovsk regions, Kuril islands, southern Sakhalin) as well as North Eastern China, Korea, and Japan.^[2] It has traditionally been used for treatment of chronic cough and asthma, diabetes, urinary tract disorders and as a general tonic for treating Fatigue associated with illness; and some other reports suggest it may have been used as an astringent, antitussive, antidiarrhoeal, expectorant and sedative.^[2] Beyond traditional Chinese Medicine, it has been used in Russian medicine historically as well.^[3]

It is classified as a 'Qi-invigorating'^[4] under the 'Yang' family of herbs,^[5] 'Qi' is in reference to an abstract concept of vital energy which Schisandra appears to support, and Yang is viewed as a manifestation of body function supported by various organs.^[5]

Creeping Vine with red berries and pretty light-colored flowers that grows in the Eastern Asia region of the globe, and has a role in a few culture's traditional medicine

1.2. Traditional Preparation

Russian medicine has used air-dried fruits and 95% ethanol in a 1:6 w/v ratio to create tinctures, which are administered at 20-30 drops daily, and the seeds have also been used in a separate tincture with the same ratios.^[3] Water infusions at a 1:20 w/v ratio with the fruits have been used, and drank at 150mL twice daily, and the fruits themselves or a powdered fruit extract eaten at 1-3g a day separated into two doses of 0.5-1.5g usually before lunch and the evening meal.^[3] Consumption of Schizandria in this manner is done over a period of 20-30 days, with max efficacy peaking at 3-7 days into the period. Finally, the seed extract can be extracted with 95% ethanol at a 1:1 w/v ratio and administered in single (acute) doses of 0.05-0.2mL/kg.^[3]

In general, ethanolic extracts of the fruit are preferred due to higher extraction of lignans. The ethanolic extract per se is sometimes dubbed Wurenchun in traditional chinese medicine.^[6]

These methods outlined above are from a Russian review paper, and demonstrate a variety of methods of ingesting the fruit of Schisandra Chinensis as per your preference if getting the exact amount of bioactives is your goal

The berries of Schisandra Chinensis have also been used to make wines in China, and it is sometimes prepared as a bright red tea called omija cha in Korea.

These are tastier options with lesser bioactivity (?)

1.3. Composition

As a herbal compound, Shizandra Chinensis (technically Fructus Schizandra) contains:^[2]

• The lignan Schizandrin (actually a mixture of shisandrin, shisandrol A, and wuweizichun A; totalling 0.2-0.7% of total weight)^[7]
• The lignan Deoxyshizandrin (deoxyschisandrin, schisandrin A, wuweizisu A; totalling 0.1-9% of total weight)
• The lignan Gomisin A (schisandrol B, wuweizichun B, and wuweizi alcohol; totalling 0.1-3% of total weight)
• The lignan Gomisin N (pseudo-γ-schisandrin B; totalling 0.1-5%)
• The lignan γ-Shizandrin (schisandrin B, γ-schisandrin B, wuweizisu B; totalling 0.1–5%)
• A large amount of nortriterpenoids, such as Schindilactone C, Wuweizidilactone D, Micrandilactone B, Lancifodilactone C, and Hennidilactone D.^{[3][8][9][10]}
• Immunostimulatory polysaccharide SCP-IIa^[11]
• An unnamed α-iso-cubebenol^[12]
• Organic acids (citrus, tartaric, kinic, malic, fumaric, protocatechuic) at up to 18% of the fruit by weight^[13][14]
• Phytosterols such as stigmasterol^[13]
• Vitamin C and Vitamin E
• Trace elements (Nickel, Copper, Magnesium, Zinc); too low in quantity to be considered bioactive^[13]

Despite all lignans being bioactive and of concern, Schisandrin and y-Schisandrin tend to be seen as the 'main' lignans; the comprise 0.5% and 0.3% of the Schisandra fruit by weight, respectively and on average.^[3] The lignans tend to be named related to either the plant (lignans that sound like Shisandra) the Japanese tea Gomishi made from Schisandra berries (Gomisin lignans) or the Chinese name for the ethanolic extract of Schisandra, Wuweizi (some of the nortriterpenoids).

The lignans are also found in the shoot and leaves, just in a higher concentration in the fruits.^[13][15] Some of them possess an anti-oxidant capacity.^[16] It has been estimated that maximum value of total lignans reaches 6-11% at flowering in the stem and bark of Schisandra Chinensis, in which 3-8% was either Schisandrin, Schisandrol, or Gomisin A.^[3]

The main bioactives are the 'lignans', and all 30+ lignans seem to be categorized into 5 more precise categories; three bearing a name related to Shisandra and two bearing a name of Gomisin

1.4. Structure of Bioactives

The main bioactives in Fructus Schizandra are the lignans (30+ in total) that share a benzo{a,c}cyclooctadiene skeleton, some of which are depicted below:

Edit2. Pharmacology

2.1. Intestines and Bioavailability

When looking at select lignans (Schisandrin A, Schisandrol A, Schisandrin B) they are absorbed in the small intestines; all three sections but with preferential absorption in the duodenum, with Shisandrin A showing the best relative bioavailability^[17] and Schisandrin C appearing to be poorly absorbed in intestinal cells.^[18] In rats, deoxyschisandrin appears to be one of the most relatively absorbed lignans.^[19] Lignans appear to be fat-soluble, as assessed by Schisandrin (0.425+/-0.002mg/mL solubility in water at 25°C, 7.681+/-0.095mg/mL in oleic acid) and Schisandrin B (0.0346+/-0.004mg/mL water, 3.669+/-0.073mg/mL oleic acid) with slightly better solubility with Isopropyl myristate (IPM).^[6]

Studies looking to enhance bioavailability have noted that Schisandra may be rate-limited in the intestines by it's dissolution rate, as a self-emulsifying drug delivery system of oleic acid at 20%, Polysorbate 20 as surfactant at 65%, and Transcutol P as cosurfactant at 15% (Schisandra at 20% by weight) was shown to enhance bioavailability of Schisandrin and Schisandrin B by 292.2% and 205.8%, respectively.^[6]

Bioavailability of Schisandrin lignans is poor in water, and can be enhanced in the presence of fatty acids or a good solvent. Although most lignans appear to be absorbed, some have a relatively greater absorption than each other and they can increase each other's absorption (See: Nutrient-Nutrient Interactions section)

2.2. Serum

Delivered as Schisandra Chinensis extract^[19] noted the following serum parameters in rats after oral administration of a 7.5mL/kg (85% ethanolic extract) solution:

• Shisandrin (72.13 mg/kg) had a T_max of 8 hours, a C_max of 1,321ug/mL, an AUC to infinity of 13.59ug/mL/h, a half-life of 5.572 hours, and a clearance rate of 1.327L/h/kg.^[19]
• Shisantherin A (17.96 mg/kg) had a T_max of 6 hours, a C_max of 0.02395ug/mL, an AUC to infinity of 0.2872ug/mL/h, a half-life of 8.850 hours, and a clearance rate of 15.63L/h/kg.^[19]
• Deoxyshisandrin (14.56 mg/kg) had a T_max of 1 hour, a C_max of 0.1576ug/mL, an AUC to infinity of 1.549ug/mL/h, a half-life of 9.707 hours, and a clearance rate of 2.351L/h/kg.^[19] The T_max has been replicated elsewhere.^[20]
• γ-schisandrin (45.92 mg/kg) had a T_max of 8 hours, a C_max of 0.1295ug/mL, an AUC to infinity of 1.728ug/mL/h, a half-life of 12.06 hours, and a clearance rate of 6.643L/h/kg.^[19]
• Shisandrol B (22.54 mg/kg) had a T_max of 2 hours, a C_max of 0.8733ug/mL, an AUC to infinity of 6.346ug/mL/h, a half-life of 9.707 hours, and a clearance rate of 0.8824L/h/kg.^[19]
• Shisandrol C (3.99 mg/kg) had a T_max of 2 hours, a C_max of 0.08414ug/mL, an AUC to infinity of 0.7988ug/mL/h, a half-life of 6.839 hours, and a clearance rate of 1.249L/h/kg.^[19]

As the above study drug was a concentrated ethanolic extract (2g crude drug per mL of aliquot, 7.5mL aliquot per kg bodyweight), the above serum values correlate to an oral intake of 15g/kg Schisandra Chinensis dried fruit extract, which is a very large dose.^[19] thankfully, when looking directly at humans, 15mg of Schisandrin elevated plasma levels to a C_max of 96.1+/-14.1 ng/ml and remained in plasma for up to 8 hours after administration.^[21] Assuming no species differences (unproven assumption), this dose is appromixately 1/8^th what the rat study used assuming a 200lb man, and approximately 1.8^th the C_max; suggesting linearly constant absorption rates.

Other lignans, such as Gomisin A, appear to be well absorbed and reaches a peak serum concentration 15-30 minutes after oral absorption and with a half-life of 70min.^[22] Gomisin A is highly conjugated and metabolized in the blood, however, as 80% of it in serum is bound to proteins and a great deal metabolized.^[22][23]

All tested lignans appear to be absorbed by humans and rats, and their absorption is enhanced with co-consumption of the lignans with each other (as whole fruit extract; see nutrient interactions section) and when consumed with fatty acids or a proper solvent (see previous section on bioavailability) The T_max values spread from 1 hour to 8 hours, supporting a 'long-lasting' notion

2.3. Distribution

Distribution of Schisandrin (the lignan) appears to favor the liver, but has also been detected in the kidneys, lungs, heart, and spleen (quantitied in descending order).^[20]

Preliminary, but it appears to favor the organs that Traditional Chinese Medicine mentions it invigorates or replenishes

2.4. Enzymatic Notables

The entire fruit of Schisandra has been shown to activate the PXR receptor in rats, and increased Warfarin clearance rate.^[1] It (in reference to Schisandrol B in particular, but also the entire class of lignans in Schisandra^[24]) also acts as a P-glycoprotein inhibitor and can increase circulating Paclitaxel concentrations in rats^[25] and 300mg fruit extract has been shown to increase the C_max of talinolol by 51% and the 24-hour AUC by 47%, approximately double the potency of 120mg Ginkgo Biloba.^[26]

Schisandria Chinensis fruit extract is able to inhibit the CYP3A4 enzyme^[27] which metabolizes over 50% of pharmaceuticals; this inhibition may be due to the Lignan components, specifically Schisandrin A and B^[28] and more potently with Gomisin A.^[29] Despite a roughly equipotent inhibition of CYP3A4, the combination Kampo therapy including the fruit extract (Shoseiryuto) did not actually alter subsequent pharmacokinetics of nifedipine, a tracer drug.^[30]

Has potential to interact with a large range of pharmaceuticals, and should be used with caution in drug-drug combinations

Edit3. Direct Mechanisms

3.1. Anti-oxidation

Anti-oxidative capacity of Schisandra appears to be related to Hormesis; a phenomena similar to exercise where damage is induced only to subsequently protect and repair to a greater extent. The result of hormesis, described below, tends to be elevation of Heat Shock Proteins and increased expression of anti-oxidative enzymes in mitochondria such as Glutathione Reductase.

It was mechanistically demonstrated that mitochondria get an increase in glutathione status and the cell increases Heat Shock Protein expression secondary to ROS-stress from Schisandrin B interacting with P450; basically, Schisandrin B induces oxidation and the mitochondria responds with a empirically greater anti-oxidant response.^[31] This study was repeated with the same effects in liver cells^[32] and appears to be effective in neurons as well.^[33] It should be noted that the effects seen here extend to other lignans in Schisanda Chinensis (γ-Schisandrol, (+)Schisandrol B and (-)Schisandrol B, Schisandrol C), but the two Schisandrol B isomers appear to be more potent and thus the focus. Efficacy of a molecule is determined by the methylenedioxy group and on the Schisandrol B molecule it appears to be critical in these effects,^[34] dealkylation by CYP enzymes (P450) causes production of up to three metabolites^[35] which ultimately form a pro-oxidative quinone molecule;^[34] this pro-oxidative quinone appears to induce the hormetic and beneficial effects in mitochondria.^[36][37]

Gomisin lignans have also been implicating in interacting with Quinone Reductase in liver cancer cells, which was found to increase activity of the anti-oxidant response element (ARE) of the genome via enhanced Nrf2 translocation.^[38] This enhanced Nrf2 translocation can manifest itself as Heme-Oxygenase 1 induction and confer anti-inflammatory effects as well.^[39]

Schisandra lignans as hormetic anti-oxidants underlies most of the therapeutic, preventative, and (theoretically, not yet demonstrated) life enhancing properties of Schisandra Chinensis in most organ systems Schisandra has been demonstrated to reach (brain, liver, lungs, kidneys, spleen, and heart)

3.2. Circulation and Blood Flow

Circulation has been shown to be improved by approximately 9% after consumption of Schisandra at 130mg daily in persons who, although otherwise healthy, had slightly impaired blood flow.^[40]

The direct mechanism may be (in part) due to weak agonism of Estrogen receptors,^[41] which increases activity of the NO-cGMP pathway and induces endothelial relaxation. Increase Nitric Oxide circulating after ingestion of about 360mg Schisandra Chinensis extract has been noted in human athletes of both novice and elite caliber.^[42]

Another mechanism has been noted as well, Myosin-Light Chain dephosphorylation, which works in concert with the above estrogenic agonism in rat aortic cells.^[43][44]

Increased blood flow may underlie improvements in physical performance (not too thoroughly demonstrated), and may in part contribute to neural and hepatic benefits.

Direct action on smooth muscle cells and estrogen receptors may mediate improvements in blood flow

3.3. Cognition

In part, subjective improvements in cognition can be attributed to placebo or reductions in stress. Currently, the only human study on cognition related to Schisandra has been conducted under conditions of stress.^[45] Schisandra seems to possess adaptogenic properties, reducing the biochemical markers of perceived stress; this effect has been recorded as reductions in corticosterones, and reductions in stress-induced liver damage.

Another possible mechanisms of improved cognition is pertaining to acetylcholine, whereas consumption of Schisandra Chinensis fruits is associated with inhibiting Acetylcholinesterase (thereby increasing levels of acetylcholine) and simultaneously possessing the capacity to enhance Cholinergic signalling in the presence of a ligand.^[46]

Combination of anti-stress effects, sedation, increased acetylcholine transmission, and (theoretically) increased blood flow. One rabbit study from Russia in the 1930s claimed improved glucose utilization in neurons, but aside from not being indexed online this claim has not been reinvestigated

3.4. Enzyme/Transport Drug Interactions

Schisandra lignans are P-glycoprotein inhibitors, and can reduce the efflux of molecules into the lumen or out of a cell and indirectly increase bioactivity of molecules that are subject to P-Gp mediated efflux,^{[47][48][49][25]} including other lignans in Schisandra.^[18] Lignans have been implicated in reversing multi-drug resistance in cancer cells both in vitro and in vivo.^[50]

Edit4. Interactions with Cardiovascular Health

4.1. Cardiac Implications

Schisandrin B appears to be an active lignan in protecting the heart tissue from myocardial infarction damage via glutathione (primarily in the cardiac mitochondria^[51]), but only when preloaded suggesting a preventative effect rather than rehabilitative.^[36] An intragastric dose of 1.2mmol/kg Schisandrin B (0.48g/kg) was demonstrated protective in Myocardial reperfusion injury, and while Alpha-Lipoic Acid at the same dose was more protective against LDH leakage Schisandrin B was better able to aid in contractile recovery.^[52] Schisandrin B has been demonstrated to reduce Ca²⁺ permeability of mitochondria after oxidative insult via these protective mechanisms,^[53] and these protective effects may extend to Schisandrin C and γ-Schisandin, although not to Schisandrin A.^[54] Although Schisandrin B is seen as the most potent at this, the (-) isomer is more potent than the (+) isomer.^[55]

This increased glutathione content in cardiac mitochondria appears to be secondary to heat shock protein induction, particular Hsp25 and Hsp70, and an overall hormetic effect in heart cells (H9C2 cardiomyocytes) associated with P450.^[56] Incubation of Schisandrin B at 7.5 and 15uM is able to increase reactive oxygen species by 24% and 32%, respectively, which increased intracellular glutathione levels by 40 and 47%, respectively.^[31] Incubation with P450 inhibitors preventing ROS, and subsequently prevented both glutathione and Heat Shock Protein induction.^[31]

An alternate mechanism that may offer cardioprotection is inhibition of Smad2/3 complex translocation and MAPK activation via inhibiting TGFβ1 signalling in smooth muscle cells.^[57] TGFβ1 signalling was inhibited in a dose-dependent manner with full inhibition at 500ug/mL, and Smad2/3 phosphorylation was halved at 100ug/mL with no further reduction at 500ug/mL, and reduced nuclear translocation of Smad3; this inhibition was secondary to PPM1A activation, which reduces Smad phosphorylation.^[58] These effects were best seen with Schisandrin B, since Gomisin N induced cell death.^[57]

There is biological basis for claims of Schisandra Chinensis fruit extract (some of the lignans) to benefit the heart organ itself, and it appears to induce these benefits by a hormetic (induce a bit of harm, reap a greater amount of benefit) mechanism

4.2. Blood Flow

A lignan from Shisandra, Gomisin J, has been demonstrated to induce Nitric Oxide Synthase in the rat endothelium in the range of 1-30ug/mL.^[59] Induction of endothelial NOS has been demonstrated previously with Gomisin A^[60][44] Although the mechanism of action of endothelial relaxation is mostly due to Nitric Oxide, Myosin-Light Chain phosphatase may also be implicated.^[43] The pair of mechanisms confers a direct (MLC phosphatase) and indirect (eNOS) mechanism of relaxation, and may confer protection from heart diseases associated with blood vessels.

The relaxing effect of low doses seems to be inhibited by estrogen-receptor antagonists, suggesting that this mechanism (eNOS induction) is secondary to estrogen receptor activation.^[61] Schisandra has been demonstrated previously to activate estrogen receptors independent of estrogen.^[41]

Only one human study has been performed on this topic, with the hypothesis that improvements in liver function was secondary to increased blood circulation; it was found that 130mg Schisandra (confounded with 5mg Sesamin) daily was able to improve blood circulation by 9% in 1 week, and held roughly static during the second week of measurement at 9.7%.^[40]

Schisandra Chinensis extract appears to be able to increase blood flow and nitric oxide bioavailability, which can compliment the previously mentioned cardio-protective effects

Improvements in blood flow may also apply to the penis.^[62] Lignans were able to induce relaxation in pre-contracted (via phenylephedrine) cells by 8.0% at 0.1mg/mL and by 98.6% at 2mg/mL, suggesting an increasing dose-efficacy.^[62] The mechanisms appeared to be due to be inhibiting the influx of calcium ions, as there were no beneficial effects noted with Ca2+ preincubation.^[62]

4.3. Triglycerides and Cholesterol

One human study lasting 2 weeks and using 130mg Schisandra (with 5mg Sesamin) found no changes in triglycerides, HDL cholesterol, or LDL cholesterol.^[40]

Higher doses of Schisandra, especially isolated Schisandrin B, appear to elevate triglycerides; insofar that 0.5-0.8g/kg bodyweight Schisandrin B may be an experimental procedure to induce dose-dependent hypertriglyceridemia.^[63] However, Schisandrin B is able to reduce triglycerides in the liver and reduce pathology of Non-alcoholic fatty liver disease.^[64]

Edit5. Longevity and Life Extension

5.1. Hormesis and Mitochondria

In isolated heart cells, it was mechanistically demonstrated that mitochondria get an increase in glutathione status and the cell increases Heat Shock Protein expression secondary to ROS-stress from Schisandrin B interacting with P450; basically, Schisandrin B induces oxidation and the mitochondria responds with a empirically greater anti-oxidant response.^[31] This study was repeated with the same effects in liver cells^[32] and appears to be effective in neurons as well.^[33] It should be noted that the effects seen here extend to other lignans in Schisanda Chinensis (γ-Schisandrol, (+)Schisandrol B and (-)Schisandrol B, Schisandrol C), but the two Schisandrol B isomers appear to be more potent and thus the focus. Efficacy of a molecule is determined by the methylenedioxy group and on the Schisandrol B molecule it appears to be critical in these effects,^[34] dealkylation by CYP enzymes (P450) causes production of up to three metabolites^[35] which ultimately form a pro-oxidative quinone molecule;^[34] this pro-oxidative quinone appears to induce the hormetic and beneficial effects in mitochondria.^[36][37]

Due to these effects, Schisandrin B is being investigated as a hormetic anti-aging molecule.^[5][4] Studies in rats sugges that a low dose Schisandrin B content (0.012% w/w of the diet) can ameliorate the aging process and improve relative functional capacity of the organs that are usually deemed to be a target of Schisandra Chinensis; the brain, heart, kidney, and liver.^[65] There appear to be differing effects in young and old rats^[66] with more pronounced protective effects (induction of heat shock proteins) in younger rats.^[65]

In aged rats, Schisandrin B consumption was shown to increase neural ATP synthesis.^[65] One review^[5] noted that improved energy metabolism beneficially influences sirtuin expression;^[67] Sirtuins have been implicated in longevity theory every since Resveratrol was thought to be a direct inducer of them (since proven to be false).

Edit6. Interactions with Exercise

6.1. Animal Interventions

A review of Russian Literature^[3] cites three trials by the researcher Lupandin (in the years of 1965, 1981, 1986) that note increased work capacity in swimming mice, extending time to exhaustion from 71+/-4min to 120+/-11min, a 69% increase after a single dose of 0.05mL/kg 1:1 Schizandra:ethanol extract. Chronic administration over 2-4 weeks with 0.5mL/kg showed increased performance ranging from 39-67%, and this increased performance tended to appear 2-5 hours after administration; the original texts by Lupandin (and Lapadev, 1981) could not be located online.

One study on static physical loading noted that 1-10mg/kg total lignans of Schisandra (not the fruit extract per se) found that there was increased resistance to fatigue;^[3] like the above studies, the original text (Lupindin, 1989) could not be located.

Beyond the above Russian studies, two recent studies from China^[68][69] suggest that Fructus Chinensis prior to exercise can reduce changes in corticosterone and glucose that occur during exercise and offer a protective effect on adrenal glands, without influencing Testosterone or luteinizing hormone.

Inherent problems with copious amounts of Russian Research 50 years ago are that they tend to not be indexed online, and without full text access to said Review that collects them it is hard to prove they even exist

6.2. Human Interventions

When pre-loaded, Schizandra (2 capsules each of 94.1mg, giving 3.1mg Shizandrin and y-Shizandrin) is able to increase Cortisol levels in beginner trainers to levels that would normally be reached by exercise; this effect is not seen in experienced athletes (national level) and both populations experience a decline in post-exercise cortisol relative to placebo.^[42]

Nitric Oxide (NO) levels are increased prior to exercise in both beginner and trained athletes.^[42] In neither cortisol or NO were the effects seen with Shizandra amplified with exercise, instead spiking both biomarkers to exercise levels prior to exercise.^[42] The authors claimed this was due to a preparatory effect.

One study. It did show benefit and was nice in how it examined both elite athletes and beginners, but it was conducted in 1999 and no studies since then have attempted to replicate it

Edit7. Thermoregulation

7.1. Heat Stress

In mice subject to a thermal chamber (research method of overheating), Schisandra fruit extract at 0.2mL/kg (1:1 ethanolic extract) was able to enhance survival; rats in the control group died at an internal body temperature of 42.5◦C and Schisandra at 43.8◦C.^[3]

7.2. Cold Stress

In mice subject to a cold stress (10 minute swim in 12◦C water), subsequent administration of 0.2mL/kg Schisandra fruit extract was able to prolong exercise to exhaustion when swimming in normal water; higher doses in the 1-10mg/kg range of pure lignans had no effect and 100mg/kg exerted a negative influence (Lupandin 1981; Lebedev 1966).^[3]

In general, research from Russia past suggests Schisandra Fruit extract is able to exert an adaptogenic effect and reduce stress from abnormal temperatures

Edit8. Interactions with Glucose Metabolism

8.1. Diabetic Interactions

The ethanolic fragment of Fructus Schisandea has been demonstrated, in adipocytes, to improve insulin-stimulated glucose uptake via PPARγ agonism with a potency similar to rosiglitazone in vitro.^[70] via the PPAR-γ pathways in in vitro and in vivo studies|published=2011 May 17|authors=Kwon DY, Kim da S, Yang HJ, Park S|journal=J Ethnopharmacol] These effects were seen at 0.5-5ug/mL in vitro on fat cells, were not seen in the Min6 pancreatic cell line, and have been noted elsewhere to occur in liver cells.^[71]

In a model of type 1 diabetes, 5g/kg Fructus Schinensis was unable to significantly influence fasting Blood Glucose levels over 7 weeks supplementation.^[72]

The subsequent in vivo study in a rat model of type II diabetes (subject to 90% pancreatectomy) using a high fat (AIN-93) diet and 200mg lignan extract for 8 weeks found no alterations in body weight but decreased fasting glucose with improvements in insulin levels, although none of these parameters were significantly different relative to control.^[70] Significant effects have been noted in this same research model elsewhere but using Huang-Lian-Jie-Du-Tang, which contains the Cortex of Phellodendron Amurense, Gardenia Jasminoides, and Rhizoma Coptidis.^[73]

Preliminary evidence looking into traditional claims, but too early to come to any significant conclusions

Edit9. Interactions with Hormones

9.1. Estrogen

Schisandra Chinensis has been shown, in vitro, to act as a weak estrogen agonist and thus a phtyoestrogen, and can do so at low concentrations of 10ug/mL.^[41]

9.2. Testosterone

Shisandra was demonstrated, in vitro, to not influence the androgen receptor in transfected cell lines expressing the androgen receptor.^[41]

Edit10. Interactions with Neurology

10.1. Memory

A study in rats suggest that one of the lignans from Schisandra, Deoxyschizandrin, was able to increase memory and cognition in mice with excessive beta-amyloid pigmentation; this was hypothesized to be secondary to its anti-oxidative abilities, and suggests Schisandra may help Alzheimer's Disease symptoms.^[74] Schisandrin B also exerts a general protective effect on scopolamine-induced memory impairment.^[75] In this latter study, a preservation of glutathione levels was seen in rats subject to Schisandra.

In isolated brain homogenates, Schisandrin B at 25mg/kg bodyweight (oral administration, dissolved in Olive Oil, for 7 days) was as effective as Tetrahydroaminoacridine (THA) at 10mg/kg in inhibiting acetylcholinesterase, and was more effective in raising acetylcholine levels in these mice. The IC₅₀ of Scopalamine in inhibiting acetylcholinesterase was approximately 667uM.^[75] These memory preserving effects have also been observed with Schisandrin at 1 and 10mg/kg bodyweight in water extract, a feasible oral dose.^[46]

Schisandrin was also implicated in enhancing M1 receptor (cholinergic) neurotransmission as assessed by oxotermorine-induced tremors, able to enhance the tremoring effects of the drug while not confering any tremors on its own at this dose; oral doses of 1 and 10mg/kg bodyweight water extract were insignificantly different. ^[46] Injections of 175mg/kg Schisandrin do induce convulsions, however.

There is biological basis for Schisandra Chinensis in improving memory and focus related to acetylcholine, although studies are preliminary. The enhancement of cholinergic neurotransmission is particularly intriguing

10.2. Neuroinflammation

A lignan from Schisandra, Schisandrin B, has been shown in vitro to downregulate a wide-variety of pro-inflammatory cytokines released from microglia such as TNF-a, IL-1β, IL-6, PGE(2) and NO.^[76] These effects were theorized to be downstream from Toll-Like Receptor 4 interacting with its ligands, the proteins MyD88, IRAK-1 and TRAF-6. The demonstrated prevention of this signalling pathway in microglia prevented activation of nF-kB translocation, and may have prevented upregulation of the cytokines that were demonstrated to have been downregulated.^[76]

10.3. Stress and Anxiety

In accordance with traditional usage of Schisandra as a hypnotic and sedative (and to treat insomnia, historically^[77]), a study in mice found that oral administration of 100-200mg/kg bodyweight Schisandra extract was able to attenuate rises in catecholamines and cortisol associated with restraint stress and increase the amount of anxiolytic behaviours of mice (relative to control).^[77] Schisandra was more effective than Diazepam at normalizing adrenaline and serotonin changes in stress, but not dopamine.^[77] This reduction in activation of the HPA (Hypothalamus-Pituitary-Adrenal) axis seems to extend to exerise, where there is also noted attentuations in cortisol.^[69] In rats subject to the same restraint mentioned previously (a research model for Anxiety and Stress Relief), it was found that stress was able to increase tumor growth in rats already harboring tumors; 100-200mg/kg oral Schisandra fruit was able to normalize the immune system biomarkers and oxidation in test rats and reduced the amount of hepatic metastatic nodules.^[78] This anti-stress effect has been somewhat replicated in a human study using Schisandra which noted that cognition, accuracy and attention was increased during periods of study by stressed persons using the supplement relative to placebo, but this study was confounded by Siberian Ginseng and Rhodiola Rosea which also share an adaptogenic property.^[45]

Without a prior stress, administration of Schisandra at 25-100mg/kg demonstrated an anxiolytic effect and promoted sedation and sleepfulness in rats.^[79]

Appears to exert sedative and anxiety-reducing effects, in accordance with it's title as an adaptogen that reduces stress

Edit11. Interactions with other Organs

The four organs that Schisandra Chinensis fruit is said to target specifically are the Heart, Kidneys, Lungs, and mostly the liver. It has been demonstrated, in rats, to bioaccumulate in all these tissues.^[20]

11.1. Kidneys

High dose Schisandrin B has been demonstrated to decrease cyclosporin-induced cytotoxicity at an oral gavage dose of 20mg/kg bodyweight in vivo and in vitro in a HK-2 cell line at 2.5, 5, and 10uM concentrations.^[80] Serum parameters reflective of renal damage (MDA, creatinine, BUN) were reduced and histopathological changes attenuated.^[80] Gentamicin toxicity has also been ameliorated damage at oral doses of 1-10mg/kg bodyweight,^[81] and protection has also been demonstrated against mercucic chloride with 10mg/kg bodyweight Schisandrin B, but the mechanism appears to vary in vivo and in vitro.^[82]

Higher doses (5g/kg) have been demonstrated to decrease urinary albumin in type 1 diabetic animals.^[72] Secondary to reduced albumineria (which encourages podocyte damage^[83]) podocyte damage in these animals was reduced.^[72]

A pleiotropic protective effect of Schisandra on the kidneys appears to exist, via both anti-inflammatory mechanisms (inhibition of nF-kB) or encouraging mitochondrial integrity via Schisandrin B; that being said, the oral doses used in the above rat studies is very high and quite impractical for preventative medicine

11.2. Lungs

Schisandra chinensis, in vitro and in vivo, was able to dose-dependently attenuate lung inflammation in mice insulted with lipopolysaccharide when consumed at 10, 50, or 100mg/kg daily.^[84]

11.3. Liver

Schisandra Chinensis has traditionally been known as a liver 'tonic' in Traditional Chinese medicine, and is present in higher concentrations in the liver relative to the serum and other organs.^[20] In Western Herbal Medicine, it holds a spot in hepatoprotection treatment, used in acute or chronic liver disease and poor liver function and its usage in this regard dates back to the 1970s.^[85][86] Interestingly, two pharmaceutical liver therapies have been synthesized using Schisandrin C as a model; Diphenyl Dimethyl Bicarboxylate (DDB)^[87] and Bicyclol.^[88]

A study delineating how Schisandra affects the liver practically found that both the anti-oxidative protection (mediated via glutathione induction) and anxiolytic effects of reducing corticosterone were crucial (as psychological stress may adversely affect liver function^[89]).^[85] Furthermore, Schisandra offers a protective effect on hepatic (liver) tumor cells that are responsive to stress.^[78] On the anti-oxidant side of things, induction of glutathione (S-transferase and reductase) and buffering anti-oxidant status prior to chemical insult has been demonstrated to protect against aflatoxin,^[90] cadmium,^[90] Hepatitis C,^[91] and carbon tetrachloride.^[92] It is said to confer a protective effect that is not specific for a toxin, but instead general.^[90]

In regards to liver enzymes; Schisandra lignans can reduce a stress-induced increase of ALT from 96.7±6.3IU/L to 29.70-34.76IU/L, with 100mg/kg being more effective than 200mg/kg; the control group in this study had ALT levels at 17.5 ± 4.7IU/L.^[85] These benefits have been noted in humans with 260mg Schisandra extract plus 10mg Sesamin daily, and alongside the reductions in liver enzymes (ALT, AST) the increase in anti-oxidant enzymes (glutathione, reductase) as well as a reduction in fatty liver and inflammatory markers was seen; no significant influences were noted on bilirubin.^[93] A study on blood flow in humans using half the dose of the previous study found increased blood circulation with no influence on liver enzymes; these humans were healthy, so either the dose or prior disease state may account for the discrepancy.^[40]

Appears to offer both a preventative and rehabilitative liver protection effect, which may be due to a combination of factors (anxiety and stress reduction lessens the adverse effects of stress on the liver, direct protection via anti-oxidant enzymes, increased general blood circulation). Human studies are limited, so conclusions are preliminary despite promising

Edit12. Interactions with Aesthetics

12.1. Hair

A separate species of Schizandra (Schizandra Nigra) has been found to promote hair growth in mice.^[94] This study applied a 50% ethanolic extract to the back of mice (20mcg/mL, 0.2mL application for 15 days) as well as in vitro and noted a prolongation of the Anagen phase of hair (an observation similar to that of Miloxidil), though to be secondary to a reduction of TGF-β2 which induces catagen and suppresses Anagen.^[94] Whether these effects extend to Schizandra Chinensis are unknown.

Edit13. Nutrient-Nutrient Interactions

13.1. Adapt-232

Adapt-232 is a patented blend of Rhodiola Rosea, Siberian ginseng (Eleutherococcus Senticoccus), and Schizandria Chinensis. This blend has been used in clinical trials before, on cognitive function under stress^[45] ultraweak biophoton emission,^[95] and as an adjunct therapy during pneumonia.^[96] All three herbs are considered adaptogens.^[97]

In research animals, Adapt-232 has been implicated in increasing physical endurance and time to exhaustion in mice^[98] and in increasing secretion of neuropeptide Y and Hsp72 in isolated cell cultures.^[99]

Rhodiola Rosea is a 2.8:1 concentration with 70% ethanolic extraction, Siberian Ginseng at 10.5:1 concentration and 70% ethanolic extraction, and Shizandria at 1.2:1 concentration with 95% ethanolic extraction.^[45] This gives a by weight standardization of 0.5% rosavin, 0.32% rhodioloside, and 0.05% tyrosol from Rhodiola; 0.37% schizandrin and 0.24% γ-schizandrin from Schizandria, and 0.15% eleutherosides B and E per 450mg capsule, which delivers 270mg of total bioactive compounds (the latter value is where the percentages are in reference to).^[45]

A combination of adaptogens that, although have not been shown to be synergistic, have been used alongside each other with good results

13.2. Itself

The lignans may be synergistic with each other in regards to absorption, as isolated deoxyschisandrin (at 14.56mg/kg bodyweight) confers a C_max of 0.08023ug/mL yet the same dose in a solution of lignans from Schisandra confers a C_max of 0.1576ug/mL (+96%); AUC to infinity is increased in the blend by 457%, and half-life extended by 42% with no influence on T_max at 1 hour.^[19] This study on deoxyshisandrin has been replicated^[100] and a study was conducted investigating the lignan Shisandrin and found similar results, in where the bioavailability and half-life of Schisandrin was increased almost two-fold at the same dose when consumed via Schisandra Chinensis fruit extract.^[101]

A possible mechanisms is due to less intestinal efflux, as many lignans inhibit P-glycoprotein^[24] (a protein in cells and the intestines that send molecules back out into the intestinal lumen or out of a cell) yet some lignans are actually subject to this protein.^[18] Consumption of the P-glycoprotein substrate with the inhibitors (both lignans) may decrease efflux and inadvertently increase bioavailability.

Combinations of lignans may be better absorbed than isolated lignans, thus a supplement using the whole fruit powder is likely to be more effective than taking a supplement with an isolated lignan

13.3. Sheng-Mai-San

Sheng-Mai-San is a herbal combination in Traditional Chinese medicine consisting of Schisandra Chinensis Fruit, Radix Panax ginseng, and Radix Ophiopogon japonicus in a ratio of 3:2:6 by weight; aqueous extract. The combination is touted to treat heart diseases.^[102]

And it has been demonstrated that the combination of herbs results in better bioavailability of Schisandrin (a lignan used as biomarker) than does a basic aqueous extract of Schisandra fruit delivering the same about of Schisandrin.^[101] Whereas isolated Shisandrin at 5mg/kg delivered an AUC of 31766.4+/-7551.1ug/mL, the AUC from Schisandra was 70209.1+/-29155.0ug/mL and from the Sheng-Mai-San concoction 116697.4+/-35816.4ug/mL.^[101] This is a 121% enhancement of average AUC using the whole plant, and a 267% enhancement of average AUC using the three herbs.^[101]

Similar to the Dang-Gui Buxue Tang concotion of Angelicae Sinensis and Astragalus Membranaceous, it appears that the historical combination of herbs has biological basis

13.4. Ninjin-Yoei-To

Ninjin-Yoei-To, with the slightly easier to remember name of TJ-108 and equally complex name of Ren-Shen-Yang-Rong-Tang, is a herbal concoction from Kampo (Japanese medicine) that contains Schisandra Chinensis as the primary active ingredient (in regards to liver protection^[91]). Compounds in this concoction include Polygala Root, Citrus Unshiu Peel (which, alongside Schisandra, are unique to Ninjin-Yoei-To) as well as ginseng, Cinnamon bark, Japanese angelica root, Astragalus Membranaceous root, peony root, rehmannia root, atractylodes rhizome, poria sclerotium, and glycyrrhiza.^[103] The combination of all herbs as powdered extracts is taken at 15g daily for humans.

This particular blend appears to be protective of the liver. In rats, it has been demonstrated to protect from hepatitis C^[91] and various forms of toxicity to the liver,^[104][105] and other organs like the lung^[106] and brain.^[107][108]

The more interesting studies attributed to Ninjin-Yoei-To are recovery of lost scent in rats after 28 days supplementation.^[109]

The combination of herbs in Ninjin-Yoei-To exists, and should be noted; that being said, it is incredibly confounded and hard to delineate which bioactives do what and to what degree

There is a related mixture of herbs simply called Ninjin-To by some studies, which retains Ginseng radix, Glycyrrhizae radix, Atractylodis rhizome and adds in Zingiberis siccatum rhizoma; this concoction does not include Schisandra Chinensis.

13.5. Sesamin

Sesamin is a lignan from sesame seeds, which appears to exert hepatoprotective properties in rats.^[110] The combination has been used in two human studies, one on liver function^[93] and another on blood viscosity and circulation.^[40] Synergy between these two supplements has not yet been demonstrated.

Edit14. Safety and Toxicology

The first reported oral toxicity of Schisandra Chinensis seed powder has been reported to be 3.6g/kg in mice, whereas the ethanolic extract of the fruit was was non-toxic in dogs.^[3] Schizandrin (isolated lignan) was able to induce convulsions when injected at 175mg/kg bodyweight in mice and paresis at double that dose; however, no deaths occurred.

References

1. Mu Y, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther. (2006)
2. WHO Monograph: Fructus Schisandra
3. Panossian A, Wikman G. Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol. (2008)
4. Leong PK, Chen N, Ko KM. Mitochondrial decay in ageing: 'Qi-invigorating' schisandrin B as a hormetic agent for mitigating age-related diseases. Clin Exp Pharmacol Physiol. (2012)
5. Lam PY, Ko KM. Schisandrin B as a hormetic agent for preventing age-related neurodegenerative diseases. Oxid Med Cell Longev. (2012)
6. Shao B, et al. Enhanced oral bioavailability of Wurenchun (Fructus Schisandrae Chinensis extracts) by self-emulsifying drug delivery systems. Drug Dev Ind Pharm. (2010)
7. Guo YX, et al. Aqueous two-phase system coupled with ultrasound for the extraction of lignans from seeds of Schisandra chinensis (turcz.) Baill. Ultrason Sonochem. (2012)
8. Huang SX, et al. Structural characterization of schintrilactone, a new class of nortriterpenoids from Schisandra chinensis. Org Lett. (2007)
9. Huang SX, et al. Wuweizidilactones A-F: novel highly oxygenated nortriterpenoids with unusual skeletons isolated from Schisandra chinensis. Chemistry. (2007)
10. Huang SX, et al. Isolation and characterization of biogenetically related highly oxygenated nortriterpenoids from Schisandra chinensis. Org Lett. (2007)
11. Chen Y, et al. An immunostimulatory polysaccharide (SCP-IIa) from the fruit of Schisandra chinensis (Turcz.) Baill. Int J Biol Macromol. (2012)
12. Kim JE, et al. The α-iso-cubebenol compound isolated from Schisandra chinensis induces p53-independent pathway-mediated apoptosis in hepatocellular carcinoma cells. Oncol Rep. (2012)
13. Szopa A, Ekiert H. In vitro cultures of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine)--a potential biotechnological rich source of therapeutically important phenolic acids. Appl Biochem Biotechnol. (2012)
14. Li L, et al. Determination of three organic acids in Schisandrae Chinensis Fructus by HPLC. Zhongguo Zhong Yao Za Zhi. (2011)
15. Schisandra chinensis (Turcz.) Baill
16. Pi Z, et al. Correlation of lignans content and antioxidant activities of Schisandra chinensis fruits by using stoichiometry method. Zhongguo Zhong Yao Za Zhi. (2012)
17. Chen XM, et al. Intestinal absorption of the effective components of Schisandra chinensis Baill by rats single-pass perfusion in situ. Yao Xue Xue Bao. (2010)
18. Madgula VL, et al. Transport of Schisandra chinensis extract and its biologically-active constituents across Caco-2 cell monolayers - an in-vitro model of intestinal transport. J Pharm Pharmacol. (2008)
19. Mao S, et al. Rapid determination and pharmacokinetics study of lignans in rat plasma after oral administration of Schisandra chinensis extract and pure deoxyschisandrin. Biomed Chromatogr. (2011)
20. Guan J, et al. Pharmacokinetics and tissue distribution of Schisandra chinensis extract in mice. Zhong Yao Cai. (2011)
21. Ono H, et al. Determination of schizandrin in human plasma by gas chromatography-mass spectrometry. J Chromatogr B Biomed Appl. (1995)
22. Matsuzaki Y, et al. Studies on the metabolic fate of gomisin A (TJN-101). I. Absorption in rats. Yakugaku Zasshi. (1991)
23. Matsuzaki Y, et al. Determination of gomisin A (TJN-101) and its metabolite in rat serum by gas chromatography-mass spectrometry. Yakugaku Zasshi. (1991)
24. Pan Q, et al. Dibenzocyclooctadiene lingnans: a class of novel inhibitors of P-glycoprotein. Cancer Chemother Pharmacol. (2006)
25. Jin J, et al. Enhancement of oral bioavailability of paclitaxel after oral administration of Schisandrol B in rats. Biopharm Drug Dispos. (2010)
26. Fan L, et al. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. (2009)
27. Iwata H, et al. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos. (2004)
28. Li WL, et al. Inhibitory effects of schisandrin A and schisandrin B on CYP3A activity. Methods Find Exp Clin Pharmacol. (2010)
29. Wan CK, et al. Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis. Phytomedicine. (2010)
30. Makino T, Mizuno F, Mizukami H. Does a kampo medicine containing schisandra fruit affect pharmacokinetics of nifedipine like grapefruit juice. Biol Pharm Bull. (2006)
31. Chen N, et al. Cytochrome P-450-catalyzed reactive oxygen species production mediates the (-)schisandrin B-induced glutathione and heat shock responses in H9c2 cardiomyocytes. Indian J Pharmacol. (2012)
32. Leong PK, et al. Cytochrome P450-catalysed reactive oxygen species production mediates the (-)schisandrin B-induced glutathione and heat shock responses in AML12 hepatocytes. Cell Biol Int. (2012)
33. Chen N, Chiu PY, Ko KM. Schisandrin B enhances cerebral mitochondrial antioxidant status and structural integrity, and protects against cerebral ischemia/reperfusion injury in rats. Biol Pharm Bull. (2008)
34. Ip SP, et al. Methylenedioxy group as determinant of schisandrin in enhancing hepatic mitochondrial glutathione in carbon tetrachloride-intoxicated mice. Biochem Pharmacol. (1997)
35. Cui YY, Wang MZ. Aspects of schizandrin metabolism in vitro and in vivo. Eur J Drug Metab Pharmacokinet. (1993)
36. Yim TK, Ko KM. Schisandrin B protects against myocardial ischemia-reperfusion injury by enhancing myocardial glutathione antioxidant status. Mol Cell Biochem. (1999)
37. Yim TK, Ko KM. Methylenedioxy group and cyclooctadiene ring as structural determinants of schisandrin in protecting against myocardial ischemia-reperfusion injury in rats. Biochem Pharmacol. (1999)
38. Lee SB, et al. Induction of the phase II detoxification enzyme NQO1 in hepatocarcinoma cells by lignans from the fruit of Schisandra chinensis through nuclear accumulation of Nrf2. Planta Med. (2009)
39. Ryu EY, et al. Anti-inflammatory effect of heme oxygenase-1 toward Porphyromonas gingivalis lipopolysaccharide in macrophages exposed to gomisins A, G, and J. J Med Food. (2011)
40. Tsi D, Tan A. Evaluation on the combined effect of Sesamin and Schisandra extract on blood fluidity. Bioinformation. (2008)
41. Lee YJ, et al. Extracts from Schizandra chinensis fruit activate estrogen receptors: a possible clue to its effects on nitric oxide-mediated vasorelaxation. Biol Pharm Bull. (2004)
42. Panossian AG, et al. Effects of heavy physical exercise and adaptogens on nitric oxide content in human saliva. Phytomedicine. (1999)
43. Park JY, et al. The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta. J Ethnopharmacol. (2009)
44. Park JY, et al. Gomisin A from Schisandra chinensis induces endothelium-dependent and direct relaxation in rat thoracic aorta. Planta Med. (2007)
45. Aslanyan G, et al. Double-blind, placebo-controlled, randomised study of single dose effects of ADAPT-232 on cognitive functions. Phytomedicine. (2010)
46. Egashira N, et al. Schizandrin reverses memory impairment in rats. Phytother Res. (2008)
47. Wan CK, et al. Gomisin A alters substrate interaction and reverses P-glycoprotein-mediated multidrug resistance in HepG2-DR cells. Biochem Pharmacol. (2006)
48. Fong WF, et al. Schisandrol A from Schisandra chinensis reverses P-glycoprotein-mediated multidrug resistance by affecting Pgp-substrate complexes. Planta Med. (2007)
49. Yoo HH, et al. Effects of Schisandra lignans on P-glycoprotein-mediated drug efflux in human intestinal Caco-2. Planta Med. (2007)
50. Huang M, 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. (2008)
51. Chiu PY, Ko KM. Time-dependent enhancement in mitochondrial glutathione status and ATP generation capacity by schisandrin B treatment decreases the susceptibility of rat hearts to ischemia-reperfusion injury. Biofactors. (2003)
52. Ko KM, Yiu HY. Schisandrin B modulates the ischemia-reperfusion induced changes in non-enzymatic antioxidant levels in isolated-perfused rat hearts. Mol Cell Biochem. (2001)
53. Chiu PY, et al. Schisandrin B stereoisomers protect against hypoxia/reoxygenation-induced apoptosis and inhibit associated changes in Ca2+-induced mitochondrial permeability transition and mitochondrial membrane potential in H9c2 cardiomyocytes. Life Sci. (2008)
54. Chen N, Ko M. Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts. Biol Pharm Bull. (2010)
55. Chiu PY, 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. Mol Cell Biochem. (2006)
56. Chiu PY, Ko KM. Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats. Mol Cell Biochem. (2004)
57. Park EJ, et al. Schisandrin B suppresses TGFβ1 signaling by inhibiting Smad2/3 and MAPK pathways. Biochem Pharmacol. (2012)
58. Lin X, et al. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. (2006)
59. Park JY, et al. Gomisin J from Schisandra chinensis induces vascular relaxation via activation of endothelial nitric oxide synthase. Vascul Pharmacol. (2012)
60. Park JY, et al. Gomisin A induces Ca2+-dependent activation of eNOS in human coronary artery endothelial cells. J Ethnopharmacol. (2009)
61. Rhyu MR, et al. Aqueous extract of Schizandra chinensis fruit causes endothelium-dependent and -independent relaxation of isolated rat thoracic aorta. Phytomedicine. (2006)
62. Han DH, et al. Effects of Schisandra chinensis extract on the contractility of corpus cavernosal smooth muscle (CSM) and Ca2+ homeostasis in CSM cells. BJU Int. (2012)
63. Pan SY, et al. A novel experimental model of acute hypertriglyceridemia induced by schisandrin B. Eur J Pharmacol. (2006)
64. Pan SY, et al. Schisandrin B from Schisandra chinensis reduces hepatic lipid contents in hypercholesterolaemic mice. J Pharm Pharmacol. (2008)
65. Ko KM, et al. Long-term schisandrin B treatment mitigates age-related impairments in mitochondrial antioxidant status and functional ability in various tissues, and improves the survival of aging C57BL/6J mice. Biofactors. (2008)
66. Chiu PY, et al. Chronic schisandrin B treatment improves mitochondrial antioxidant status and tissue heat shock protein production in various tissues of young adult and middle-aged rats. Biogerontology. (2006)
67. Hipkiss AR. Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms. Biogerontology. (2008)
68. Sun LJ, et al. Effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in rats undergoing experimental chronic psychological stress, navigation and strenuous exercise. Zhonghua Nan Ke Xue. (2009)
69. Xia P, Sun LJ, Wang J. Effects of fructus schisandrae on the function of the pituitary-testis axis and carbohydrate metabolism in rats undergoing experimental navigation and high-intensity exercise. Zhonghua Nan Ke Xue. (2011)
70. The lignan-rich fractions of Fructus Schisandrae improve [insulin sensitivity
71. Zhang J, Shi LL, Zheng YN. Dibenzocyclooctadiene lignans from Fructus Schisandrae Chinensis improve glucose uptake in vitro. Nat Prod Commun. (2010)
72. Zhang M, et al. Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy. J Ethnopharmacol. (2012)
73. Park S, et al. Huang-Lian-Jie-Du-Tang supplemented with Schisandra chinensis Baill. and Polygonatum odoratum Druce improved glucose tolerance by potentiating insulinotropic actions in islets in 90% pancreatectomized diabetic rats. Biosci Biotechnol Biochem. (2009)
74. Hu D, et al. Deoxyschizandrin Isolated from the Fruits of Schisandra chinensis Ameliorates Aβ1-42-induced Memory Impairment in Mice. Planta Med. (2012)
75. Giridharan VV, et al. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice. Free Radic Res. (2011)
76. Zeng KW, et al. Schisandrin B exerts anti-neuroinflammatory activity by inhibiting the Toll-like receptor 4-dependent MyD88/IKK/NF-κB signaling pathway in lipopolysaccharide-induced microglia. Eur J Pharmacol. (2012)
77. Chen WW, et al. Pharmacological studies on the anxiolytic effect of standardized Schisandra lignans extract on restraint-stressed mice. Phytomedicine. (2011)
78. Tang SH, et al. The protective effect of schisandra lignans on stress-evoked hepatic metastases of P815 tumor cells in restraint mice. J Ethnopharmacol. (2011)
79. Huang F, et al. Sedative and hypnotic activities of the ethanol fraction from Fructus Schisandrae in mice and rats. J Ethnopharmacol. (2007)
80. Zhu S, et al. Protective Effect of Schisandrin B Against Cyclosporine A-Induced Nephrotoxicity In Vitro and In Vivo. Am J Chin Med. (2012)
81. Chiu PY, Leung HY, Ko KM. Schisandrin B Enhances Renal Mitochondrial Antioxidant Status, Functional and Structural Integrity, and Protects against Gentamicin-Induced Nephrotoxicity in Rats. Biol Pharm Bull. (2008)
82. Stacchiotti A, et al. Different role of Schisandrin B on mercury-induced renal damage in vivo and in vitro. Toxicology. (2011)
83. Karalliedde J, Viberti G. Proteinuria in diabetes: bystander or pathway to cardiorenal disease. J Am Soc Nephrol. (2010)
84. Bae H, et al. Effects of Schisandra chinensis Baillon (Schizandraceae) on lipopolysaccharide induced lung inflammation in mice. J Ethnopharmacol. (2012)
85. Pu HJ, et al. Correlation between Antistress and Hepatoprotective Effects of Schisandra Lignans Was Related with Its Antioxidative Actions in Liver Cells. Evid Based Complement Alternat Med. (2012)
86. Pao TT, et al. Studies on Fructus schizandrae. I. Its effect on increased SGPT levels in animals caused by hepatotoxic chemical agents. Zhonghua Yi Xue Za Zhi. (1974)
87. Diphenyl Dimethyl Bicarboxylate in the Treatment of Viral Hepatitis, Adjuvant or Curative?
88. A Novel Antihepatitis Drug, Bicyclol, Prevents Liver Carcinogenesis in Diethylnitrosamine-Initiated and Phenobarbital-Promoted Mice Tumor Model
89. Bao L, et al. Bilberry extract protect restraint stress-induced liver damage through attenuating mitochondrial dysfunction. Fitoterapia. (2010)
90. Ip SP, et al. Effect of a lignan-enriched extract of Schisandra chinensis on aflatoxin B1 and cadmium chloride-induced hepatotoxicity in rats. Pharmacol Toxicol. (1996)
91. Cyong JC, et al. Clinical and pharmacological studies on liver diseases treated with Kampo herbal medicine. Am J Chin Med. (2000)
92. Ip SP, et al. Schisandrin B protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione redox status in mouse liver. Free Radic Biol Med. (1996)
93. Chiu HF, et al. Improvement of Liver Function in Humans Using a Mixture of Schisandra Fruit Extract and Sesamin. Phytother Res. (2012)
94. Kang JI, et al. Promotion effect of Schisandra nigra on the growth of hair. Eur J Dermatol. (2009)
95. Schutgens FW, et al. The influence of adaptogens on ultraweak biophoton emission: a pilot-experiment. Phytother Res. (2009)
96. Narimanian M, et al. Impact of Chisan (ADAPT-232) on the quality-of-life and its efficacy as an adjuvant in the treatment of acute non-specific pneumonia. Phytomedicine. (2005)
97. Chan SW. Panax ginseng, Rhodiola rosea and Schisandra chinensis. Int J Food Sci Nutr. (2012)
98. Panossian A, et al. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine. (2009)
99. Panossian A, et al. Adaptogens stimulate neuropeptide y and hsp72 expression and release in neuroglia cells. Front Neurosci. (2012)
100. Deng X, et al. Determination of deoxyschizandrin in rat plasma by LC-MS. J Pharm Biomed Anal. (2008)
101. Xu M, et al. Pharmacokinetic comparisons of schizandrin after oral administration of schizandrin monomer, Fructus Schisandrae aqueous extract and Sheng-Mai-San to rats. J Ethnopharmacol. (2008)
102. Yao HT, et al. Shengmai San reduces hepatic lipids and lipid peroxidation in rats fed on a high-cholesterol diet. J Ethnopharmacol. (2008)
103. Kamei T, et al. The effect of a traditional Chinese prescription for a case of lung carcinoma. J Altern Complement Med. (2000)
104. Takano F, et al. Oral Administration of Ren-Shen-Yang-Rong-Tang 'Ninjin'yoeito' Protects Against Hematotoxicity and Induces Immature Erythroid Progenitor Cells in 5-Fluorouracil-induced Anemia. Evid Based Complement Alternat Med. (2009)
105. Ochi T, Kawakita T, Nomoto K. Effects of Hochu-ekki-to and Ninjin-youei-to, traditional Japanese medicines, on porcine serum-induced liver fibrosis in rats. Immunopharmacol Immunotoxicol. (2004)
106. Tanaka K, Sawamura S. Therapeutic effect of a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito) on nitric oxide-mediated lung injury in a mouse infected with murine cytomegalovirus. Int Immunopharmacol. (2006)
107. Egashira N, et al. Ninjin-yoei-to (Ren-Shen-Yang-Rong-Tang) and Polygalae radix improves scopolamine-induced impairment of passive avoidance response in mice. Phytomedicine. (2003)
108. Kobayashi J, et al. Effect of a traditional Chinese herbal medicine, Ren-Shen-Yang-Rong-Tang (Japanese name: Ninjin-Youei-To), on oligodendrocyte precursor cells from aged-rat brain. Int Immunopharmacol. (2003)
109. Yamasaki A, et al. Effect of Ninjin-yoei-to (Rensheng-Yangrong-Tang) on olfactory behavior after olfactory nerve transection. Phytomedicine. (2008)
110. Akimoto K, et al. Protective effects of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents. Ann Nutr Metab. (1993)

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