Product name: Schizantherin A
Synonym name: Gomisin C; Schisantherin A; Wuweizi ester A
Catalogue No.: BP1267
Cas No.: 58546-56-8
Formula: C₃₀H₃₂O₉
Mol Weight: 536.577
Botanical Source: Schisandra chinensis（Turcz.）Baill.
Physical Description:
Type of Compound: Lignans

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

Schisantherin A exhibits anti-tussive, sedative, anti-inflammatory, antioxidant, anti-osteoporotic, neuroprotective, cognition enhancing, and cardioprotective activities. Schisantherin A can significantly attenuate Aβ1-42-induced learning and memory impairment and noticeably improve the histopathological changes in the hippocampus. Schisantherin A exhibits neuroprotection against 1-methyl-4-phenylpyridinium ion (MPP(+)) through the regulation of two distinct pathways including increasing CREB-mediated Bcl-2 expression and activating PI3K/Akt survival signaling.

References:

PLoS One. 2013 Apr 19;8(4):e61590.    

Protective role of deoxyschizandrin and schisantherin A against myocardial ischemia-reperfusion injury in rats.  

METHODS AND RESULTS:

Anesthetized male rats were treated once with deoxyschizandrin(DSD) and Schisantherin A(STA) (each 40 μmol/kg) through the tail vein after 45 min of ischemia, followed by 2-h reperfusion. Cardiac function, infarct size, biochemical markers, histopathology and apoptosis were measured and mRNA expression of gp91 (phox) in myocardial tissue assessed by RT-PCR. Neonatal rat cardiomyocytes were pretreated with DSD and STA and then damaged by H2O2. Cell apoptosis was tested by a flow cytometric assay. Compared with the I/R group: (i) DSD and STA could significantly reduce the abnormalities of LVSP, LVEDP, ±dp/dtmax and arrhythmias, thereby showing their protective roles in cardiac function; (ii) DSD and STA could significantly attenuate the infarct size and MDA release while increasing SOD activity, suggesting a role in reducing myocardial injury; (iii) tissue morphology and myocardial textual analysis revealed that DSD and STA mitigated changes in myocardial histopathology; (iv) DSD and STA decreased apoptosis (33.56±2.58% to 10.28±2.80% and 10.98±1.99%, respectively) and caspase-3 activity in the myocardium (0.62±0.02 OD/mg to 0.38±0.02 OD/mg and 0.32±0.02 OD/mg, respectively), showing their protective effects upon cardiomyocytes; and (v) DSD and STA had similar protective effects on I/R injury as those seen with the positive control metoprolol. In vitro, DSD and STA could significantly decrease the apoptosis of neonatal cardiomyocytes. 

CONCLUSIONS:

These data suggest that DSD and STA can protect against myocardial I/R injury. The underlining mechanism may be related to their role in inhibiting cardiomyocyte apoptosis.    

Biochem Biophys Res Commun. 2014 Jul 4;449(3):344-50.    

Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways.   

Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. 

METHODS AND RESULTS:

In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways.

CONCLUSIONS:

These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.    

HPLC of Schizantherin A

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Schizantherin A is a natural tannic acid compound derived from Schisandra chinensis, which exhibits significant biological activity and broad pharmacological potential in the field of liver protection. Schisandra chinensis, as a traditional Chinese medicinal herb, has always been used to treat liver disease, enhance physical strength, and regulate immune function. Its active ingredient, schisandrin methyl, has become a hot topic in natural product pharmacology research in recent years due to its unique chemical structure and biological effects. This article will provide a systematic review of the chemical properties, plant sources, pharmacological activities, mechanisms of action, pharmacological evaluation, and clinical application prospects of Schisandra esters, aiming to provide theoretical basis and research direction for subsequent drug development and clinical translation.

Chemical structure and physicochemical properties

The molecular formula of Schisandra ester A is C29H-36O10, with a molecular weight of 536.5770 and a CAS number of 58546-56-8. Its chemical structure belongs to tannic acid, with multiple phenolic hydroxyl and ester groups, endowing it with strong antioxidant capacity. The LogP value of this compound is 3.9499, indicating that it has moderate lipid solubility, which is beneficial for cell membrane penetration and in vivo distribution. The TPSA (topological polar surface area) is 101.9100, indicating that it has a certain balance between polar and non-polar environments, which is helpful for binding to various biological targets.

The low water solubility of Schisandrin methyl ester (0.0016 mg/mL) may limit its oral bioavailability, but its high blood-brain barrier permeability suggests that the compound can enter the central nervous system and has potential neuroprotective effects. The negative result of hERG channel inhibition experiment indicates a low risk of cardiac toxicity. The Ames test result is 0.0, indicating no significant genotoxicity and high safety.

Plant sources and extraction methods

Schisandra esters are mainly found in the fruit of Schisandra chinensis, which belongs to the Magnoliaceae family and is widely distributed in Northeast China, North China, and the Korean Peninsula. Traditionally, Schisandra fruit has been used clinically through methods such as water decoction and wine soaking, but modern research often uses organic solvent extraction to enrich active ingredients.

Common extraction methods include:

1. Organic solvent extraction Extract dried Schisandra fruit using solvents such as ethanol, methanol, or ethyl acetate, and then purify Schisandra ester A through liquid-liquid distribution and column chromatography separation.
2. Ultrasound assisted extraction Utilizing ultrasound to enhance solvent permeation and solute diffusion, improving extraction efficiency and purity.
3. Separation by High Performance Liquid Chromatography (HPLC)Used for further purification and quantitative analysis of schisandrin ester A.

In recent years, with the promotion of green chemistry concepts, new technologies such as supercritical CO2 extraction and microwave-assisted extraction have gradually been applied to the extraction of active ingredients from Schisandra chinensis, improving extraction efficiency and environmental friendliness.

Pharmacological activity research

The pharmacological activity of Schisandrin methyl mainly focuses on liver protection, and its multiple mechanisms of action such as antioxidant, anti-inflammatory, and anti fibrotic provide scientific basis for the prevention and treatment of liver diseases.

Liver protective effect

1. Antioxidant effect Schisandra esters can significantly enhance the activity of antioxidant enzymes in the body, such as superoxide dismutase (SOD1, SOD2), catalase (CAT), glutathione peroxidase (GPX1), and heme oxygenase (HMOX1), effectively clearing free radicals and reducing oxidative stress damage to liver cells.
2. anti-inflammatory effect By regulating the activation of transcription factor NRF2, inhibiting the expression of pro-inflammatory cytokines such as transforming growth factor beta 1 (TGFB1), and reducing liver inflammation response.
3. Anti fibrotic effect Schisandrin methyl can inhibit the activation of hepatic stellate cells, reduce the expression of actin alpha 2 (ACTA2), and block the progression of liver fibrosis.
4. Matrix metalloproteinase regulation By regulating the activity of MMP9, promote the remodeling and repair of liver tissue matrix.

Other potential pharmacological activities

In addition to liver protection, Schisandrin A may have the potential for neuroprotection and anti neurodegenerative diseases due to its good blood-brain barrier permeability, and related research is still in the preliminary stage.

Mechanism of action and molecular targets

The liver protective effect of Schisandra ester A is mainly achieved through multi-target synergistic regulation:

• NRF2 signaling pathway As a core regulatory factor for cellular antioxidant defense, NRF2 activation upregulates the expression of antioxidant enzyme genes such as NQO1 and HMOX1, enhancing the ability of cells to resist oxidative damage. Schisandrin methyl promotes NRF2 nuclear translocation and activates its downstream target genes.
• Antioxidant enzyme system Enzymes such as SOD1, SOD2, CAT, and GPX1 alleviate oxidative stress and protect the integrity of liver cell membrane structure by clearing superoxide anions and hydrogen peroxide.
• Anti fibrotic targets By inhibiting the TGFB1 signaling pathway, the activation of hepatic stellate cells and collagen deposition are reduced, preventing the progression of liver fibrosis.
• Matrix metalloproteinase MMP9 Regulating the degradation and remodeling of extracellular matrix, promoting the repair of damaged liver tissue.
• Actin alpha 2 (ACTA2)As a marker of hepatic stellate cell activation, schisandrin methyl inhibits its expression and weakens fibrosis response.

In summary, Schisandrin A forms a complex and effective liver protection network through multi-target and multi pathway synergistic effects.

Evaluation of drug properties and pharmacokinetics

The pharmacological parameters of Schisandra ester A indicate that it has certain potential for drug development:

• Molecular weight (536.5770)Slightly higher than the recommended upper limit of 500 Da by Lipinski's rules, but still within an acceptable range.
• LogP（3.9499）Indicating that it has moderate lipid solubility, which is beneficial for cell membrane penetration.
• TPSA（101.9100）Moderate, indicating that it has good distribution ability in both polar and non-polar environments.
• Very low water solubility (0.0016 mg/mL)It may limit oral absorption and improve bioavailability through formulation optimization or drug carrier systems.
• High blood-brain barrier permeability Provide possibilities for its application in central nervous system diseases.
• HERG channel inhibition negative It indicates good cardiac safety.
• No genotoxicity (Ames test negative)The safety is relatively high.

Pharmacokinetic studies have shown that Schisandrin methyl has a long half-life in vivo, is widely distributed, and is particularly enriched in the liver, meeting its targeted requirements for liver protection. The metabolic pathways mainly involve the oxidation and ester hydrolysis of liver enzymes, and the safety of metabolites needs further evaluation.

Clinical application prospects and prospects

Schisandra ester A, as a natural tannic acid compound, has shown great potential in the treatment of liver diseases due to its significant antioxidant, anti-inflammatory, and anti fibrotic effects. Especially in the adjuvant treatment of chronic hepatitis, liver fibrosis, and cirrhosis, Schisandrin methyl is expected to become an effective natural drug candidate.

Future research directions include:

1. In depth mechanism research Further elucidate the specific mechanism of action of Schisandrin A in cell signaling, gene regulation, and metabolic regulation.
2. Pharmacokinetic and Toxicological Studies Systematically evaluate its metabolic pathways, long-term safety, and potential toxicity.
3. Optimization of formulations and administration routes Enhance its bioavailability and targeting through novel drug delivery systems such as nanocarriers and liposomes.
4. Clinical trial design Conduct a multicenter, randomized, double-blind clinical trial to validate its effectiveness and safety in treating liver disease.
5. Multi target joint application Exploring the synergistic effects of Schisandrin A and other anti liver disease drugs in combination with modern drug design concepts.

In addition, given its excellent blood-brain barrier permeability, the potential application of Schisandrin A in neurological diseases is also worth paying attention to.

Conclusion

Schisandra ester A, as an important active ingredient in Schisandra chinensis, has become a research hotspot in the field of natural product pharmacology due to its unique chemical structure and multi-target liver protection mechanism. Its excellent safety and pharmacological parameters have laid a solid foundation for its clinical translation. In the future, through interdisciplinary collaboration and the combination of modern medicinal chemistry, molecular biology, and clinical medicine research methods, Schisandrin methyl ester is expected to develop into an innovative natural medicine for the treatment of liver diseases, contributing new strength to human health.