IngredientsSchizandrol A is a bioactive lignan compound belonging to the dibenzocyclooctadiene class. Its systematic (IUPAC) name is 1,2,3,10,11,12-hexamethoxy-6,7-dimethyl-5,6,7,8-tetrahydrodibenzo[a,c]cyclooten-6-ol, with the molecular formula C24H32O7. The compound is identified by CAS Number 7432-28-2, with a molecular weight of 432.50 g/mol. It is also known in the literature as schizandrin, schisandrin, and gomisin C — a source of nomenclatural confusion that persists across different research and regulatory traditions. The compound is variously denoted as schisandrin, schizandrin, or schisandrol A in published sources.
Schizandrol A possesses a dibenzocyclooctadiene skeleton. Through its unique dibenzocyclooctadiene lignan structure, it demonstrates sophisticated biochemical mechanisms. The dihedral angles between the two aromatic rings are approximately 62.39–62.65°. Crystal packing is stabilized by a series of O—H⋯O and C—H⋯O hydrogen bonds, as well as C—H⋯π interactions.
Schizandrol A was isolated from Schisandra chinensis. Schisandra is a deciduous woody vine that can grow over 20 feet long, high into the tree canopy of wild forests of eastern Asia, with clusters of white flowers followed by medicinal red berries that are often wild-harvested. Native to northeastern China and eastern Russia, this climbing plant is widely distributed in the northeastern part of China, Korea, and Japan. Schizandrol A is an active component in schisandra, and also the representative component for the identification of schisandra.
Modern scientific research has shown that Schisandra chinensis contains lignans, essential oils, organic acids, vitamins, triterpenoids, sesquiterpenes, and polysaccharides, and that the lignans are the main active ingredient among them. About 40 of these lignan compounds, mainly of the dibenzocyclooctane type, have been isolated from S. chinensis. The most important bioactive lignans include schisandrin (also denoted as schizandrin or schisandrol A), schisandrin B, schisantherin A, schisantherin B, schisanhenol, deoxyschisandrin, and gomisin A. Schizandrol A is often paired with Schizandrol B and Schisandrin in full-spectrum extracts.
The medicinal use of Schisandra chinensis dates back to the Eastern Han Dynasty (25–220 AD), as recorded in the Shennong Bencao Jing (Divine Farmer's Materia Medica), where it was documented to have astringent, qi-tonifying, fluid-generating, kidney-nourishing, and heart-calming properties according to TCM theories. It was listed as a 'superior herb' in China's first herbal encyclopedia.
Schisandra is best known for its medicinal red berries that combine five different flavors — sweet, sour, salty, bitter, and pungent — giving rise to its Chinese name wu wei zi, meaning "five flavors fruit." Based on the "Five-Element" theory in TCM, the "five tastes" of the Schisandra berry refer to its influence on the five visceral organs of the body.
Schisandra has a long history of use in traditional Chinese medicine to treat liver conditions, stomach disorders, and as a tonic to improve vitality; it is also used in various formulas for fatigue and sleep. In both Chinese traditional medicine and Korean medicine, it has been used to treat diabetes, palpitation, insomnia, nocturnal enuresis, dysentery, cough, asthma, phlegm, and jaundice. The renowned Ming Dynasty pharmacologist Li Shizhen explicitly noted in the Bencao Gangmu (Compendium of Materia Medica) that Schisandra chinensis was used to treat liver deficiency syndromes.
In Korea, Schizandrae fructus has been used to make tea or liquor because of its five-kind flavors. Centuries ago in Russia, it was used by the Nanai people to promote stamina for hunters going on long voyages without much rest or nourishment.
Traditionally known as Wu Wei Zi, schisandra berries were consumed dried, decocted as teas, or incorporated into multi-herb formulations. Examples of various doses of schizandra preparations used in official medicine in Russia include Tinctura Fructum Schizandrae, prepared with air-dried fruits and 95% ethanol given as 20 to 30 drops twice daily.
The relationship between the chemical structure of S. chinensis compounds and their biological activity has been thoroughly investigated. Lignans such as schisandrin, gomisin, and schisandrins A to E are the main components of S. chinensis and exhibit a wide range of biological activities. They have antioxidant properties that help remove free radicals and protect cells from oxidative damage, and some lignans also have a hepatoprotective effect, supporting the protection and regeneration of liver cells.
Lignans derived from Schisandra chinensis have attracted significant attention for their diverse pharmacological activities and clinical potential; reviewed pharmacological properties include antioxidant, anti-inflammatory, neuroprotective, hepatoprotective, antibacterial/viral, antidiabetic, and anticancer effects.
Studies on the antioxidative and detoxification mechanisms of action of dibenzocyclooctadiene lignans have shown that they inhibit microsomal lipid peroxidation, reduce the concentration of superoxide radicals, inhibit microsomal NADPH oxidation in hepatocytes, and reduce the release of alanine aminotransferase (ALT) and lactate dehydrogenase, which increases membrane integrity and viability of hepatocytes. The mechanism of protective, antioxidant, and detoxifying action of lignans on hepatocytes is also based on increasing hepatic glutathione levels and the activity of glutathione reductase and glutathione S-transferase.
The active components of Schisandra sphenanthera aqueous extract — including schisandrin A, schizandrol A, and schizandrol B — regulated the phosphorylation levels of PI3K, AKT, IKK, and NF-κB and the expression of FOXO1 protein and upregulated the expression of Bcl-2 protein in the liver tissues of alcoholic liver disease rats.
The purposes of one published study were to explore the neuroprotective effects and potential molecular mechanism of Schizandrin A (Sch A); observations showed that Sch A could significantly down-regulate the increased production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 induced by lipopolysaccharide (LPS) both in BV-2 cells and primary microglia cells, and exerted obvious neuroprotective effects against inflammatory injury in neurons when exposed to microglia-conditioned medium. Investigation of the mechanism showed the anti-inflammatory effect of Sch A involved the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression levels, inhibition of the LPS-induced TRAF6-IKKβ-NF-κB pathway, and inhibition of Jak2-Stat3 pathway activation and Stat3 nuclear translocation.
Pretreatment with Schizandrol A (STA) inhibited MPP⁺-induced cytotoxicity in SH-SY5Y cells and MPTP-induced loss of TH-positive dopaminergic neurons in Parkinson's disease mice; the mechanism was suggested to increase cAMP-response element binding protein (CREB)-mediated Bcl-2 expression and activate PI3K/Akt signaling.
Pretreatment with schizandrin (100 μM) before glutamate treatment increased Bcl-XL and Bcl-2 expression and decreased Bax, Bak, AIF, Nodo G, and caspase-12; furthermore, glutamate-induced phosphorylation of JNK, p38, and ERK mitogen-activated protein kinases was attenuated by schizandrin treatment. The molecular mechanisms of schizandrin against glutamate-induced apoptosis may involve the regulation of Bcl-2 family proteins expression, and ER stress through blocking the activation of JNK, ERK, and p38 MAPK.
Research has found that schizandrol A did not affect the binding of dopamine to dopamine D1 or D2 receptors; these results indicate that the inhibition exerted by schizandrol A on the CNS may be related to the dopamine system, and the increase of dopamine turnover has nothing to do with dopamine receptors. The concentrations of the norepinephrine metabolite MHPG and the serotonin metabolite 5-HIAA showed changes in rat striatum and hypothalamus after schizandrol A treatment, but norepinephrine and serotonin levels were unaffected.
Schizandrol A promoted the activation of PI3K/Akt in acute myocardial ischemia mice and H9c2 cells treated with oxygen–glucose deprivation, downregulated the expression of NOX2, and significantly reduced myocardial infarction area while improving biochemical indicators and cardiac pathological changes, thus exerting cardiac protective effects.
In studies of myocardial ischemia/reperfusion injury, SA treatment significantly improved MI/R injury as reflected by reduced myocardium infarct size, attenuated histological features, and ameliorated biochemical indicators; SA profoundly ameliorated oxidative stress damage as evidenced by higher glutathione peroxidase (GSH-Px) and lower malondialdehyde (MDA) and reactive oxygen species (ROS); and SA alleviated myocardial apoptosis as evidenced by a reduction of cleaved caspase-3 expression and increase of the Bcl-2/Bax ratio. Further experiments demonstrated that SA had certain binding capability to the key functional protein 14-3-3θ, and mechanistically SA prevented myocardial apoptosis through upregulating 14-3-3θ expression.
A study showed that schizandrol A has an active antidepressant effect on lipopolysaccharide-induced depression in mice by regulating intestinal microbiota and inhibiting TLR4/NF-κB signal pathways in the hippocampus to reduce neuroinflammation.
A study in vitro and in vivo showed that schizandrol A inhibits pulmonary fibrosis by regulating the TGF-β signal pathway.
A 2021 study investigated Schizandrin A (Sch A), a major phytochemical from Schisandra chinensis (Schisandraceae), for its neuroprotective effect in Alzheimer's disease (AD). Sch A treatment in APP/PS1 mice repressed the proportions of iNOS⁺/Iba-1⁺ cells and IL-6 expression while enhancing the proportions of Arg-1⁺/Iba-1⁺ cells and IL-10 expression; in vitro, Sch A reduced CD16/32⁺ cell proportions, iNOS expression, and IL-6 levels, and enhanced CD206 cell proportions, Arg-1 expression, and IL-10 levels in BV2 cells. The research confirmed the neuroprotective effect of Sch A in AD, suggesting that Sch A may become a potential anti-AD agent.
A separate study reported that Schizandrol A protects against Aβ(1–42)-induced autophagy via activation of the PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons.
Evidence grade: All evidence is currently preclinical (animal models and cell culture). No human clinical trials on Schizandrol A for Alzheimer's disease have been reported in the identified literature.
One study systematically investigated the capacity of five dibenzocyclooctadiene lignans — schisandrin A, schisandrin B, schisandrin C, schizandrol A, and schisantherin A — to protect neuroblastoma SH-SY5Y cells from toxicity induced by 6-OHDA or MPP⁺; schisantherin A was found to be the most potent among these, though schizandrol A was among those tested. Pretreatment with Schizandrol A inhibited MPTP-induced loss of TH-positive dopaminergic neurons in Parkinson's disease mice, with a mechanism involving CREB-mediated Bcl-2 expression and PI3K/Akt signaling.
Evidence grade: Preclinical only (cell culture and rodent models). No human trials identified.
Research on the neuroprotective role of schizandrin (SA) in cerebral ischemia-reperfusion (I/R) highlighted that the compound significantly improved oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced PC12 cell injury via the AMPK/mTOR/autophagy pathway; SA decreased autophagy in OGD/R-injured PC12 cells, reflected by decreased Beclin-1 and LC3-II expression.
Evidence grade: Preclinical only.
In vitro studies suggest that schisandra has anti-inflammatory, anticancer, and cardioprotective effects; animal studies also suggest cardio- and liver-protective effects.
Findings demonstrated that Schisandra extracts significantly increased CYP3A and CYP2E1 activity in human liver cell lines, enhancing the liver's ability to detoxify harmful substances; Schisandra also promotes liver cell regeneration and repair, with the hepatoprotective effect including enhancing the proliferation of hepatocytes and reducing apoptosis.
The results of one in vivo study in mice showed that S. chinensis lignans (which include Schizandrol A and B as identified components) exhibited a dose-dependent effect on the regulation of hepatic antioxidant status, serum transaminases levels, hyperlipidemia, and hepatic fat deposition.
One line of research found that Schisantherin A (a related lignan) pretreatment reversed upregulated phosphorylation of JNK, p38, and ERK induced by hepatic ischemia/reperfusion injury, suggesting a role in protecting against I/R-induced liver injury by hindering activation of the MAPK pathway; this was described as a promising method for hepatic protection in I/R-induced pathological environments such as blood occlusion during liver resection and liver transplantation.
Modern pharmacological studies have revealed that Schisandra chinensis exhibits anti-inflammatory, immunomodulatory, antitussive, and antiasthmatic properties, making it clinically valuable for treating disorders of the central nervous system, cardiovascular system, digestive system, and endocrine system.
Evidence grade: The hepatoprotective evidence for Schizandrol A specifically is largely preclinical (animal and cell-based studies). Only a small number of studies have been conducted in humans and are too limited to draw any conclusions.
In a study of whether the cardioprotective effect of SA (Schizandrol A) is associated with regulating endogenous metabolites, comprehensive metabolomics profiling was performed in acute myocardial ischemia (AMI) mice following SA treatment (6 mg·kg⁻¹·d⁻¹, ip); SA treatment significantly decreased infarct size, preserved cardiac function, and improved biochemical indicators and cardiac pathological alterations. Additionally, SA (10, 100 μM) significantly decreased the apoptotic index in OGD-treated H9c2 cardiomyocytes in vitro.
Metabolomics analysis showed that schizandrol A could also regulate myocardial injury-related indicators such as glycine, serine and threonine metabolism, as well as lysine biosynthesis under acute myocardial ischemic pathological conditions; furthermore, Schizandrol A might also play a role in cardioprotective effects by improving oxidative stress damage.
Evidence grade: Preclinical (mouse and cell models). No human cardiac trials on isolated Schizandrol A have been identified.
Schizandrol A, with its multi-pharmacological activity, has been found to have a relatively large potential in the application of cancer treatment. Pharmacological actions documented for Schisandra lignans include a hepatoprotective effect, anti-oxidant, anti-tumor, anti-HIV, and antiviral activity, and antagonistic activity toward platelet-activating factor.
Some research suggests that schisandrol A may decrease P-glycoprotein (P-gp) activity to improve drug retention, which could have implications for cancer chemotherapy.
Evidence grade: Predominantly in vitro and early preclinical. No completed human oncology trials for isolated Schizandrol A have been identified in the searched literature.
A study showed that schizandrol A has an active antidepressant effect on lipopolysaccharide-induced depression in mice by regulating intestinal microbiota and inhibiting TLR4/NF-κB signal pathways in the hippocampus to reduce neuroinflammation.
Evidence grade: Animal model only. No human trials on the antidepressant effects of isolated Schizandrol A have been identified.
Schisandra has antioxidant activity and appears to protect the liver and nervous system; other animal studies suggest it may improve mental and physical functioning. However, clinical trials to support these uses are limited.
Schisandra chinensis has been widely used as a traditional herbal medicine to treat chronic coughs, fatigue, night sweats, and insomnia. Although schisandra is used to treat some lung symptoms in traditional Chinese medicine, clinical trials have not been conducted.
In rat pharmacokinetic studies, schizandrol A was rapidly absorbed after intragastric administration (Tmax = 2.07 h), with a longer duration (t1/2 = 9.48 h) and a large apparent volume of distribution (Vz/F = 111.81 L/kg). Schizandrol A can be detected in main organs, with the order of distribution being liver > kidney > heart > spleen > brain, with particularly high levels in the liver.
From a pharmacokinetic perspective, all lignans demonstrate high gastrointestinal absorption, supporting their oral administration potential; most compounds, including schisandrin A and schisandrin B, are capable of crossing the blood–brain barrier, highlighting their potential for neurological applications.
Five schizandrol A metabolites have been identified, including 2-demethyl-8(R)-hydroxyl-schizandrin, 3-demethyl-8(R)-hydroxyl-schizandrin, hydroxyl-schizandrin, demethoxy-schizandrin, and 2,3-demethyl-8(R)-hydroxyl-schizandrin, indicating that hydroxylation and demethylation may be the major metabolic pathways.
The major phase I metabolism pathways of schisandra lignans are demethylation and hydroxylation; specifically, the enzyme CYP3A4 catalyzes Schizandrin A to the schizandrol metabolite in the first step.
The oral bioavailability of schizandrin was approximately 15.56 ± 10.47% in rats; however, the oral bioavailability of herbal extract was higher than the single isolated compound. The bioavailability of schisandrin is largely affected by hepatic and intestinal first-pass metabolism, which limits clinical efficacy.
Traditionally, schisandra berries were consumed dried, decocted as teas, or incorporated into multi-herb formulations; modern products include capsules, tablets, tinctures, and powdered extracts that can be incorporated into beverages and functional foods, offering more standardized dosing compared to whole-fruit preparations.
Schisandra fruit is used as an adaptogen at dosages of 1.5 to 6 g/day of powdered product.
It is generally recommended to take them in a dose of 500 mg to 2 g per day, after a meal.
In a clinical study, schizandra tablets containing 91.1 mg of extract per tablet (extract standardized for schizandrin and gamma-schizandrin at a level of 3.1 mg/tablet) was used to improve athletic performance.
Current pharmacopoeial monographs indicate schisandrin determination as an assay; the reference technique used for standardization, as mentioned by the European Pharmacopoeia 8th edition (2013), Polish Pharmacopoeia X (2014), and WHO monograph (2007), is HPLC. The European Pharmacopoeia monograph recommends the use of TLC method to distinguish S. chinensis from S. sphenanthera, because the fruit of the second species has a different biosynthetic profile and is not considered a pharmacopoeial raw material.
No universally accepted standardized dose of S. chinensis extract has been established in the current literature, as studies use different preparations, lignan concentrations, and treatment goals. For this reason, product standardization and reporting of key lignans such as schisandrin or gomisin compounds are important when interpreting dose and activity.
While Schisandra chinensis is generally considered safe at moderate doses, data on its long-term safety, particularly with concentrated extracts or lignan-rich supplements, remains limited; short-term use appears to be well-tolerated, but prolonged consumption — particularly at high doses — raises concerns about potential adverse effects. The lack of comprehensive toxicological and pharmacokinetic studies hampers widespread adoption in clinical settings; further research is needed to establish safety profiles, optimal dosages, and potential interactions with other medications.
Schisandra chinensis has been reported to interact with multiple drug classes, posing clinical implications for co-administration with conventional therapies; a key challenge lies in its interaction with drug-metabolizing enzymes. When Schisandra lignans inhibit CYP450 enzymes and P-gp, drug metabolism is reduced, leading to higher drug concentrations in the bloodstream; this decreased metabolism and impaired efflux can result in increased drug bioavailability and toxicity.
Some lignans are substrates or inhibitors of key cytochrome P450 enzymes, including CYP2D6 and CYP2C9, potentially competing with other drugs for metabolism.
In one study, the in vivo metabolism of SC lignans and chlorzoxazone was significantly accelerated by 7-day pretreatment with SC alcoholic extract; both single and multiple dosing treatments of SC alcoholic extract remarkably decreased the in vivo metabolism of tacrolimus, as indicated by enhanced AUC (7–12 fold) and elevated Cmax (10 fold). These results revealed that SC extracts exhibited multifaceted effects on rat hepatic CYP450 enzymes; herb-drug interaction should be paid intense attention between SC components and drugs metabolized by different CYP450 enzymes.
In a rat model, co-administration of Wuzhi tablets — an ethanol extract of Schisandra sphenanthera — significantly altered cyclosporine A blood levels, suggesting sensitivity to CYP3A/P-gp modulation; additionally, Wuzhi tablets slightly increased tacrolimus blood concentration, while Schisandra fruit extract enhanced tacrolimus absorption by modulating first-pass metabolism in the gut and liver. These findings underscore the complexity of Schisandra-drug interactions, particularly for patients on long-term pharmacological treatments such as immunosuppressants and chemotherapeutics.
Schisandra has been reported to increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. It has similarly been reported to increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism.
Lignans with one or two methylenedioxyphenyl groups have been found to inhibit CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2E1 activities in a time- and concentration-dependent manner in human liver microsomes. This information may aid the prediction of possible drug interactions between Schisandra lignans and any co-administered drugs which are mainly metabolized by P450s.
Information regarding safety and efficacy in pregnancy and lactation is limited.
In one animal study in mice, hepatic lesions were observed in the high-dose SC group, indicating a potential side effect caused by long-term consumption of the high dose under chronic alcohol administration.
Existing clinical studies are often small and heterogeneous, limiting conclusions about standardized dosing, long-term safety, and real-world applicability. The vast majority of evidence on Schizandrol A's mechanisms and efficacy is derived from in vitro cell culture systems and animal models. The compound's effects in properly designed, adequately powered human clinical trials remain largely uninvestigated as of the current literature.
Health conditions that Schizandrol A may help support.
Schizandrol A is the principal bioactive lignan of Schisandra chinensis (five-flavor berry), a classical Chinese adaptogen used for fatigue, stress, and mental performance. It modulates the HPA axis and adrenal cortisol output. Clinical evidence from combination adaptogen trials (ADAPT-232: Rhodiola + Schisandra + Eleuthero) shows significant improvements in attention, speed, and fatigue in stressed adults. Schisandra lignans are documented to inhibit cortisol excess and support anti-fatigue effects via HPA axis signaling.
Schizandrol A is a lignan from Schisandra chinensis used in TCM for chronic cough, asthma, and lung Qi deficiency. Preclinical studies show it reduces lung oxidative stress and inflammatory cytokines relevant to respiratory conditions, and it is a constituent of TCM formulas clinically studied for COPD.
Schizandrol A is a dibenzocyclooctadiene lignan from Schisandra chinensis used in Traditional Chinese Medicine. It exerts CNS-modulating and adaptogenic effects, and limited studies suggest cognitive-enhancing and anti-fatigue properties.
Schizandrol A is a primary lignan of Schisandra chinensis, one of the adaptogens identified by HerbalGram/Herbal Reality (2021) as having multitarget effects on the neuroendocrine-immune system relevant to post-COVID recovery. Traditional TCM use for post-illness fatigue, respiratory recovery, and immune restoration has centuries of documentation.
A primary dibenzocyclooctadiene lignan from Schisandra chinensis, classified as one of the principal bioactive adaptogenic compounds. Shares the stress-modulating mechanistic and traditional evidence base of schisandrins and Schisandra as a whole, with HPA axis and adrenal cortex modulating activity.
Schizandrol A is a primary bioactive lignan from Schisandra chinensis used in TCM for liver protection and detoxification. As the principal hepatoprotective compound in Schisandra, it supports liver enzyme normalization and antioxidant defense, contributing to the whole-body cleansing role of Schisandra in TCM-based cleanse formulations.
Body systems that Schizandrol A may help support.
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