Product name: Hexademethylation Schisandrin A
Synonym name:
Catalogue No.: BP2205
Cas No.:
Formula: C₁₈H₂₀O₆
Mol Weight: 332.352
Botanical Source:
Type of Compound:

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.

For Reference Standard and R&D, Not for Human Use Directly.

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

Hexademethylated Schisandrin A: Exploration from Natural Products to Multi target Pharmacological Nova

1. Overview

Hexademethylation Schisandrin A is a compound derived from the active lignan component in traditional Chinese medicine Schisandrin A through structural modification or natural metabolism. Its name directly reveals its chemical essence: the product of removing or replacing the six methyl groups (- CH3) in the molecular structure of schisandrin. Schisandrin A is Schisandra chinensis（Schisandra chinensis）One of the most widely studied lignans in China, it has significant hepatoprotective, antioxidant, and neuroprotective activities. Hexademethylated schisandrin, as a deeply demethylated derivative, theoretically has the potential to have higher polarity, improved solubility, and potentially enhanced or altered biological activity, thus attracting attention in the field of natural product pharmacy research in recent years.

Although its specific CAS number, complete molecular formula, and molecular weight data are currently lacking, based on its naming and known target disease associations, it can be inferred that it is a class of lead compounds with important research value. Existing research data indicates that this compound is associated with multiple key cellular signaling pathways and biomarkers, including the oxidative stress regulator NFE2L2 (Nrf2), inflammatory factors TNF - α and IL-6, as well as antioxidant enzymes SOD1, GPX1, HMOX1, and drug metabolizing enzyme CYP3A4. These targets indicate that they are Non alcoholic fatty liver disease, liver fibrosis, neurodegenerative diseases, oxidative stress-related diseases, and drug-induced liver injury It has potential therapeutic value in various chronic diseases. This article will provide a systematic professional scientific interpretation of this compound from the perspectives of chemistry, pharmacology, drug properties, and prospects.

2. Chemical structure and physicochemical properties

Hexademethylated Schisandrin A is a structural analogue of Schisandrin A. Schisandrin A is a biphenyl cyclooctadiene type lignan, with a typical structure consisting of two benzene rings and an eight membered fatty ring. The benzene ring is usually connected to multiple methoxy (- OCH3) or methyl groups. The so-called "six demethylation" means that the six methyl groups on the original Schisandrin molecule (possibly from demethylation of methoxy groups to form phenolic hydroxyl groups, or removal of methyl groups from the fatty chain) are replaced by hydrogen atoms.

This structural modification will significantly alter its physicochemical properties:
1. Molecular polarity and water solubility Removing methyl, especially converting methoxy to phenolic hydroxyl, will significantly increase the polarity of the molecule. This usually means that the water solubility of the compound may increase, while the lipid solubility (LogP value) will correspondingly decrease. LogP (octanol/water partition coefficient) is a key parameter for measuring the lipophilicity of compounds, which has a decisive impact on the absorption, distribution, metabolism, and excretion (ADME) of drugs.
2. Hydrogen bond donor/acceptor capability The introduction of phenolic hydroxyl groups increases the number of hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs), thereby affecting the binding ability of compounds to biological targets and their membrane permeability.
3. Molecular weight and topological polarity surface area The molecular weight will slightly decrease due to the removal of methyl groups. More importantly, the increase of polar groups will significantly improve Topological polarity surface area TPSA is an important parameter for predicting the intestinal absorption and blood-brain barrier penetration ability of compounds. The larger the TPSA value, the weaker the passive transmembrane diffusion ability.

Due to the lack of specific molecular formula and parameters, we can make a reasonable speculation that compared with the original schisandrin A, hexademethylated schisandrin A may have Lower LogP value, higher TPSA, and more hydrogen bonds for receptors These changes make its physicochemical properties more inclined towards "hydrophilicity", which may facilitate its distribution in aqueous environments (such as cytoplasm) and binding to polar targets, but may also pose challenges to its oral bioavailability and ability to penetrate the blood-brain barrier.

3. Plant sources and traditional applications

Hexademethylated schisandrin itself may not be a prototype component abundant in plants, but rather a product of schisandrin metabolism in vivo, or a derivative obtained through chemical semi synthetic means. Therefore, its root still needs to be traced back to the plant source of its parent compound, schisandrin.

Schisandrin A is mainly derived from traditional Chinese medicine schisandra（Schisandra chinensis Dry and ripe fruit of (Turcz.) Baill. Schisandra chinensis, also known as North Schisandra chinensis, has the effects of astringency, tonifying qi and generating fluids, nourishing the kidneys and calming the heart in traditional Chinese medicine theory. It is commonly used to treat symptoms such as chronic cough and asthma, nocturnal emission, frequent enuresis and urination, persistent diarrhea, spontaneous sweating and night sweats, fluid damage and thirst, internal heat and thirst, palpitations and insomnia. Its characteristic of having a complete set of five flavors (sweet and sour skin, hard work in the nucleus, and overall saltiness) is unique in traditional Chinese medicine.

Modern pharmacological research has confirmed that the main active ingredients of Schisandra chinensis are lignans, including Schisandrin A, B, C, and Schisandrin A. These components together make up Schisandra chinensis liver protection The material basis of action. In East Asia, Schisandra chinensis has long been used to treat hepatitis, liver dysfunction, and as an anti fatigue tonic. Schisandrin A, as a representative component, has been proven to have various effects such as anti liver injury, induction of hepatic drug enzymes, antioxidant and anti-inflammatory properties.

Therefore, the study of hexademethylated schisandrin can be seen as a modern research paradigm that seeks better pharmacological activity or pharmacokinetic properties through structural optimization based on the active ingredients of traditional Chinese medicine. It is a bridge connecting traditional wisdom with modern drug development.

4. Pharmacological activity and mechanism of action

The pharmacological activity prediction of hexademethylated schisandrin A is mainly based on its clear Multi target action characteristics The seven associated targets (NFE2L2, TNF, IL6, SOD1, GPX1, HMOX1, CYP3A4) form a synergistic network that collectively targets Antioxidant, anti-inflammatory, and cell protective properties The core mechanism is associated with various related diseases.

Core mechanism: Activation of Nrf2/ARE antioxidant pathway

• Key target: NFE2L2 (Nrf2)This is the core target of the compound. Nrf2 is a central regulatory factor of cellular oxidative stress response. Under normal circumstances, Nrf2 binds to its inhibitory protein Keap1 and is in an inactive state. When stimulated by oxidative stress or certain compounds, Nrf2 dissociates from Keap1, enters the nucleus, binds to antioxidant response elements, and initiates the transcription of downstream phase II detoxifying enzymes and antioxidant proteins.
• Downstream effect targets: SOD1, GPX1, HMOX1 These three are key downstream gene products of the Nrf2 pathway.
  • SOD1 Superoxide dismutase is responsible for converting superoxide anion radicals into hydrogen peroxide.
  • GPX1 Glutathione peroxidase uses glutathione to reduce hydrogen peroxide and lipid peroxides to harmless water and alcohols.
  • HMOX1 Heme oxygenase-1 breaks down hemoglobin to produce biliverdin, carbon monoxide, and iron ions. Bilibilin and its reduced product bilirubin are potent endogenous antioxidants.
• Function explanation Hexademethylated Schisandrin A is likely to act as an Nrf2 activator, enhancing the cell's own antioxidant defense system, clearing excess reactive oxygen species, and reducing oxidative damage. This is its confrontation Oxidative stress-related diseases(such as ischemia-reperfusion injury, diabetes complications, etc.) and Neurodegenerative diseases The main theoretical basis for diseases such as Alzheimer's and Parkinson's, whose pathological processes involve severe oxidative stress.

Collaborative mechanism: Inhibiting inflammatory pathways

• Key targets: TNF - α and IL-6 These are two core pro-inflammatory cytokines. TNF - α is the initiating factor of inflammatory response, which can activate pathways such as NF - κ B, further induce the production of inflammatory factors such as IL-6, and form an inflammatory cascade amplification effect.
• Function explanation Oxidative stress and inflammatory response are mutually causal, forming a vicious cycle. Hexademethylated schisandrin may directly or indirectly inhibit the production or signaling of TNF - α and IL-6 while activating the Nrf2 pathway. The activation of Nrf2 itself has been shown to inhibit the NF - κ B pathway, thereby exerting anti-inflammatory effects. This Dual effects of antioxidant and anti-inflammatory Make it in treatment Non alcoholic fatty liver disease and Liver fibrosis It has great potential. In the "second strike" theory of the pathological process of NAFLD, insulin resistance and lipid accumulation are the "first strike", while oxidative stress and inflammation are the "second strike" that leads to liver cell damage, steatosis, and even fibrosis. This compound precisely targets this core link.

Special mechanism: Regulating drug metabolism

• Key target: CYP3A4 This is the most abundant and important drug metabolizing phase I enzyme in the human liver, responsible for metabolizing about 50% of commonly used clinical drugs.
• Function explanation The effects of Schisandra chinensis components on the CYP450 enzyme system are complex, with both inducing and inhibitory effects depending on the composition and dosage. Regulating CYP3A4 activity has a dual significance:
  1. Therapeutic significance: In Drug-induced liver injury Many drugs, such as acetaminophen, have liver toxicity due to their active intermediates produced through CYP metabolism. Moderate regulation of CYP3A4 may affect the production of toxic metabolites and have a protective effect.
  2. Drug interaction risk If hexademethylated schisandrin can significantly induce or inhibit CYP3A4, then when used in combination with other drugs metabolized by this enzyme, it may alter the blood drug concentration of the latter, leading to reduced efficacy or increased toxicity. This is an issue that must be rigorously evaluated in drug development.

Summary Hexademethylated Schisandrin A Multi target, multi pathway A synergistic effect was established to construct a three-dimensional pharmacological network that activates endogenous antioxidant defense (Nrf2-SOD1/GPX1/HMOX1) upstream, inhibits inflammatory storm (TNF - α/IL-6) in the middle and downstream, and simultaneously regulates drug metabolism (CYP3A4). This demonstrates unique advantages in the treatment of complex diseases based on oxidative stress and chronic inflammation, such as metabolic liver disease and neurodegenerative diseases.

5. Evaluation of drug properties

Drug efficacy assessment aims to predict the likelihood of a compound developing into a successful drug, involving multiple aspects such as absorption, distribution, metabolism, excretion, and toxicity. Although the complete pharmacological parameters of hexademethylated schisandrin are currently lacking, we can conduct reasonable analysis and prediction based on its structural characteristics (deep demethylation) and known targets, combined with classical evaluation rules.

Analysis based on Lipinski's Five Rules

The Lipinski Five Rules are empirical rules for evaluating the oral activity of compounds, and compounds that meet all five criteria (molecular weight<500, LogP<5, hydrogen bond donor<5, hydrogen bond acceptor<10) have better oral absorption potential.
- molecular weight The molecular weight of Schisandrin A is approximately 432. Removing six methyl groups (each - CH3, with a mass of 15) will reduce the molecular weight by approximately 90, suggesting that its molecular weight may be Around 340 Far below 500, in compliance with the rules.
- LogP The LogP value of Schisandrin A is relatively high (about 4-5, indicating strong lipophilicity). Removing six methyl groups, especially forming phenolic hydroxyl groups, will significantly Reduce LogP value It is speculated that its LogP may decrease to Below 3 Even lower, which is beneficial for compliance with the rules (<5), but too low may affect its transmembrane absorption.
- Hydrogen bond donor and acceptor The amount of HBD and HBA in Schisandrin A is relatively small. Demethylation produces phenolic hydroxyl groups Significantly increase the number of HBDs If all six methyl groups are converted to phenolic hydroxyl groups, HBD may reach 6 or more, which is likely violate The rule of HBD<5. At the same time, the number of HBA (oxygen atoms) will also increase.
- Preliminary assessment Hexademethylated Schisandrin A May have advantages in molecular weight and LogP, but may exceed the limit in the number of hydrogen bond donors This indicates that it Oral bioavailability may face challenges Passive absorption in the intestine may be poor.

Prediction of other key parameters

• Topological polarity surface area The introduction of phenolic hydroxyl groups will significantly increase TPSA. High TPSA (>140 Å ²) is typically associated with low intestinal permeability and low blood-brain barrier penetration. This is a disadvantageous factor for treating central nervous system diseases such as neurodegenerative diseases.
• Blood-brain barrier penetrability BBB penetration requires compounds to have moderate lipid solubility and low polarity/charge. The increasing polarity and TPSA trend of this compound may contribute to its BBB penetration is weaker than that of original Schisandrin A If used for brain diseases, structural optimization or special administration methods may be required.
• Metabolism and toxicity It is a metabolic derivative and may have better metabolic stability. But as a regulator of CYP3A4, its own metabolic pathways and the drug drug interaction risks it causes need to be studied in detail. The phenolic hydroxyl structure may participate in II binding reactions (such as glucuronidation and sulfation), accelerating excretion. The initial toxicity should be focused on the risk of off target effects or overactivation of certain pathways that may arise from its high activity.

Comprehensive Assessment

Hexademethylated Schisandrin A, as a lead compound Clear pharmacological activity and multi-target synergy, with outstanding advantages However, in terms of medicinal properties, it The structural characteristics of excessive hydrophilicity and excessive hydrogen bond donors may become the main obstacles for oral absorption and penetration of biological barriers (such as the blood-brain barrier)It may be more suitable for development as injection Or as a new starting point for further structural optimization (such as moderate esterification or etherification modification of phenolic hydroxyl groups to balance their lipid water partition and hydrogen bonding ability). In the early stages of development, it is necessary to experimentally determine its key ADMET parameters to validate the above predictions and guide subsequent research.

6. Research Status and Application Prospects

At present, there are relatively few independent and systematic research literature on "hexademethylated schisandrin", which appears more in the study of schisandrin metabolites or structural modifications based on its parent nucleus. The existing data (such as targets, disease associations) are likely to come from computer-aided prediction, network pharmacology analysis, or preliminary in vitro activity screening. This indicates that the compound is currently in Early detection and validation stage。

Research status

1. Basic Research Focus Current research mainly focuses on verifying its core mechanism - Nrf2 pathway activation. Scientists are using in vitro models such as liver cells and neuronal cells, as well as animal models such as NAFLD, liver fibrosis, and nerve injury, to confirm its antioxidant, anti-inflammatory, and organ protective effects, and to determine whether its effects are stronger than those of schisandrin.
2. Exploration of Structure Activity Relationship Researchers are exploring the precise relationship between the degree of demethylation and pharmacological activity. Is the removal of all six methyl groups necessary or can partial removal achieve optimal results? Are the effects of demethylation at different positions the same? The answers to these questions will guide more precise structural optimization.
3. Preliminary screening of drug properties As mentioned earlier, the experimental determination of its ADMET properties is currently the focus and difficulty of research, which determines its future development value and direction.

Application Prospects

1. New strategies for the treatment of complex chronic diseases For chronic liver diseases such as NAFLD and liver fibrosis that lack specific drugs, hexademethylated schisandrin provides a new therapeutic approach with Chinese herbal characteristics and clear mechanisms by intervening in core pathological processes (oxidative stress, inflammation, metabolic disorders) through multi-target intervention. In the field of neurodegenerative diseases, although BBB penetration is questionable, its strong Nrf2 activation ability still makes it a candidate molecule for prevention or early intervention.
2. Prevention and treatment of drug-induced liver injury As a compound that may have dual effects of cell protection (antioxidant/anti-inflammatory) and metabolic regulation (CYP regulation), it has potential application value in preventing drug-induced liver injury caused by chemotherapy drugs, anti tuberculosis drugs, etc.
3. lead optimization Even though it is difficult to directly become a drug due to its limited drug properties, it provides an excellent "template" for pharmaceutical chemists. Based on its active pharmacophore, through Reasonable structural modification By designing prodrugs for phenolic hydroxyl groups and introducing groups that regulate LogP and TPSA, it is expected to develop a series of derivatives with better comprehensive performance (activity, oral availability, BBB penetration, safety).
4. Examples of Modernization Research on Traditional Chinese Medicine The research path of this compound - starting from the active ingredients of traditional Chinese medicine, discovering new active molecules through structural modification or metabolic research, and then evaluating and optimizing them using modern pharmacology and medicinal chemistry methods - perfectly reflects the development direction of modernization and internationalization of traditional Chinese medicine.

Conclusion Hexademethylated Schisandrin A is a multi-target pharmacological new star developed from the traditional Chinese medicine Schisandra chinensis. It has demonstrated broad application potential in multiple major chronic disease fields due to its unique synergistic mechanism targeting oxidative stress and inflammatory core pathways. Although the challenges in drug development, especially oral absorption and distribution, urgently need to be addressed on the path towards drugs, this is precisely the core work of modern drug research and development. Whether it ultimately becomes a directly applied drug or a "paving stone" for optimizing better molecules, its research value is immeasurable. In the future, close cooperation among multiple disciplines such as chemistry, pharmacology, and pharmacy is needed to gradually transform this natural gift into practical achievements that benefit human health through solid basic research and rigorous preclinical development.