Product name: Tigloylgomisin H
Synonym name:
Catalogue No.: SBP04216
Cas No.: 66069-55-4
Formula: C₂₈H₃₆O₈
Mol Weight: 500.588
Botanical Source:
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
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

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

HPLC of Tigloylgomisin H

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

Introduction/Overview

In the field of natural product chemistry and pharmacology research, lignin compounds have attracted much attention due to their extensive biological activities. Tigloylgomisin H (CAS number: 66069-55-4) is derived from the traditional Chinese medicine Schisandra chinensis（Schisandra chinensis）A biphenyl cyclooctene lignin isolated from the fruit. Schisandra chinensis is known for its calming, nourishing qi, and promoting diuresis effects. Modern pharmacological research has revealed that its active ingredients have significant potential in liver protection, antioxidant, anti-inflammatory, and anti-tumor effects. As one of the members, the unique biological activity spectrum of Tigecyl Gomisine H, especially its ability to selectively activate phase II detoxifying enzymes as a single functional inducer, has shown important research value in the field of chemoprevention, especially in the prevention of liver cancer. This article aims to provide a systematic review of the chemical structure, plant origin, pharmacological activity, mechanism of action, pharmacological evaluation, and clinical application prospects of Tizoxystrobin H, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

Ti'goylgomixin H belongs to the biphenyl cyclooctene class of lignans, with a molecular formula of C28H34O8 and a molecular weight of 500.5880. Its basic skeleton consists of two phenylpropane units connected by side chain β - carbon atoms to form a biphenyl structure and form a cyclooctadiene ring. The structural feature of Tigoloyloxy H is that it has a Tigoloyloxy substituent attached to its C-6 or C-7 position (depending on stereochemistry), which is one of its important active groups. The introduction of 2-methyl-2-butenoic acid significantly affects the lipophilicity and interaction ability with target proteins of the compound.

From the analysis of physical and chemical properties, the compound has high lipid solubility, with a calculated LogP value of 4.4122, indicating that it is easy to penetrate cell membranes, but has poor water solubility (about 0.0070 mg/mL), which poses certain challenges for its formulation development. Its topological polar surface area (TPSA) is 92.68 Å ², belonging to a moderately polar molecule. Preliminary pharmacological risk assessment shows that Tizoxystrobin H has a high blood-brain barrier permeability potential, suggesting its potential role in central nervous system related diseases. However, attention should also be paid to its potential effects in the central nervous system. Importantly, the compound did not show hERG potassium channel inhibitory activity in the preliminary screening (hERG inhibition: No), and the Ames test result was 0.0, indicating a low risk of mutagenicity and a relatively good safety starting point.

Plant sources and extraction methods

The main source of Tijiaogaomixin H is Schisandra chinensis, a plant of the Schisandra genus in the Schisandraceae family（Schisandra chinensis Dry and ripe fruit of (Turcz.) Baill. Schisandra chinensis is mainly distributed in Northeast China, South Korea, Japan, and the Far East region of Russia. Its fruit is rich in various lignans, such as schisandrin, schisandrin esters, and gossypol series. Among them, the content of kaempferol is relatively low but the activity is significant.

Its extraction and separation usually follow the conventional process of natural product chemistry. Firstly, the dried Schisandra fruit is crushed and subjected to reflux extraction or ultrasound assisted extraction using organic solvents such as methanol, ethanol, or acetone. The crude extract obtained was concentrated under reduced pressure and subjected to gradient extraction with solvents such as petroleum ether, ethyl acetate, and n-butanol in sequence. The main enrichment site of thienoxystrobin H was in the ethyl acetate extraction site. Further purification often relies on a combination of various chromatographic techniques, including silica gel column chromatography (using chloroform methanol or petroleum ether ethyl acetate system gradient elution), reverse phase silica gel column chromatography (such as ODS, using methanol water system elution), and high-performance liquid chromatography (HPLC) preparation. Through nuclear magnetic resonance (NMR, including 1H-NMR, 13C-NMR, 2D-NMR), mass spectrometry (MS), and comparison with literature data, its chemical structure can be ultimately identified. Modern green extraction techniques such as supercritical CO2 fluid extraction are also being explored for efficient extraction of such high-value lignin due to their high selectivity and absence of solvent residues.

Pharmacological activity research

Although the pharmacological activity research of Tigeramide H is currently in the preclinical stage, its outstanding potential in cancer chemoprevention and anti-inflammatory has been revealed.

1. Cancer chemopreventive activity The most significant feature of this compound is its ability to act as a single functional inducer, specifically inducing phase II detoxifying enzymes. Research has shown that Ticinol can effectively induce the activity of quinone reductase (QR, i.e. NAD (P) H: quinone oxidoreductase 1, NQO1) in mouse liver cancer cell Hepa1c1c7. NQO1 is a key antioxidant and detoxifying enzyme in cells, which can reduce carcinogenic quinones to hydroquinone, promote their subsequent binding and excretion, and protect cells from oxidative damage and carcinogenic attacks. The induction effect of Tigecyl Gomisine H is highly selective and does not induce phase I metabolic enzymes (such as cytochrome P450), avoiding the risk of activating pre carcinogens into terminal carcinogens. This makes it an ideal candidate for chemoprevention, especially for the prevention of liver cancer.

2. anti-inflammatory activity In addition to its detoxifying enzyme inducing effect, tigenoxicam H has also shown clear anti-inflammatory effects in various inflammatory models. Its anti-inflammatory effect involves the regulation of multiple key inflammatory mediators and signaling pathways. Research has shown that this compound can inhibit the expression of inflammatory factors such as tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and inducible nitric oxide synthase (NOS2) induced by stimuli such as lipopolysaccharide (LPS). In addition, it can inhibit the activity of cyclooxygenase-1 (PTGS1/COX-1) and reduce the production of prostaglandin inflammatory mediators. In pain related neurogenic inflammation, the potential regulatory effects of tigecycline H on transient receptor potential vanillic acid subtype 1 (TRPV1) and anchored protein subtype 1 (TRPA1) channels are also worth noting. These broad anti-inflammatory targets suggest promising applications in the treatment of chronic inflammatory diseases such as arthritis, colitis, and neuroinflammation.

Mechanism of action and molecular targets

The core mechanism by which Tigeramide H exerts its pharmacological effects lies in its precise regulation of the cellular defense system, and its molecular target network mainly revolves around antioxidant stress response elements (ARE) and inflammatory signaling pathways.

1. The core role of Nrf2 ARE pathway As a single functional inducer, the core mechanism by which Tijiaogaomixin H induces NQO1 and other phase II detoxifying enzymes is achieved through the activation of the nuclear factor E2 related factor 2 (Nrf2) signaling pathway. In the resting state, Nrf2 binds to its inhibitory protein Keap1 in the cytoplasm and is degraded by ubiquitination. Tigecyl Golimicin H may promote the dissociation and stabilization of Nrf2 from Keap1 by modifying key cysteine residues on Keap1 or affecting the interaction between Nrf2 and Keap1. Subsequently, Nrf2 translocates to the nucleus and binds to antioxidant response elements (ARE), initiating the transcription of a series of downstream cell protective genes, including NQO1, glutathione S-transferase (GST), heme oxygenase-1 (HO-1), etc. This pathway is the core defense mechanism for cells to resist oxidative stress and electrophilic toxins, and it is also the molecular basis for the chemopreventive effect of Tizoxystrobin H.

2. Multiple targets for anti-inflammatory effects Its anti-inflammatory effect involves intervention in multiple classic inflammatory signaling pathways

   • NF - κ B pathway This compound can inhibit the activity of nuclear factor kappa B inhibitory protein kinase beta (IKBKB/IKK β), thereby preventing the phosphorylation and degradation of nuclear factor kappa B inhibitory protein (I κ B), ultimately inhibiting the nuclear translocation of transcription factor RELA (p65), and downregulating the expression of inflammatory genes such as TNF - α, IL-6, and NOS2.
   • STAT3 pathway It may inhibit cytokine signaling such as IL-6 through upstream action, thereby reducing the phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3), blocking its mediated pro-inflammatory and pro survival signals.
   • Inflammasome pathway The inhibition of cysteine protease-1 (CASP1) activity suggests that tigecycline H may interfere with the assembly and activation of inflammasomes such as NLRP3, thereby reducing the release of mature inflammatory factors such as interleukin-1 β (IL-1 β).
   • Enzymes and ion channels Directly or indirectly inhibiting PTGS1 (COX-1) and regulating pain sensing channels such as TRPV1 and TRPA1 is another aspect of its anti-inflammatory and analgesic effects.

These mechanisms do not exist in isolation, and the activation of the Nrf2 pathway itself has a strong anti-inflammatory effect, as products such as HO-1 can inhibit the production of pro-inflammatory mediators. Therefore, Tigeramide H constructs a multi-target, networked pharmacological mode of action by synergistically activating protective pathways (Nrf2) and inhibiting destructive pathways (NF - κ B, STAT3, etc.).

Evaluation of drug properties and pharmacokinetics

Based on its physical and chemical parameters and preliminary biological data, a preliminary evaluation was conducted on the pharmacological properties of Tizoxystrobin H.

1. Drug like properties and absorption distribution The molecular weight (500.6) is slightly higher than the conventional upper limit (500) of the "Five Rules for Generic Drugs", but still within an acceptable range. A higher lipophilicity (LogP>4) suggests that its oral bioavailability may face challenges, as excessive lipophilicity may result in poor solubility in gastrointestinal contents or undergo strong first pass metabolism in the intestinal wall and liver. Its high blood-brain barrier permeability (predicted) suggests its ability to enter the central nervous system, which may be advantageous for the treatment of central related diseases, but potential central side effects also need to be evaluated. At present, there is a lack of detailed experimental data on its absorption, distribution, metabolism, and excretion (ADME) in the body.

2. Metabolism and Safety As an exogenous substance, Tigeramide H is likely to be mainly metabolized by the liver cytochrome P450 enzyme system in vivo. Its Tigeramide group and methoxy and hydroxyl groups on the lignin skeleton may become metabolic sites, generating glucuronic acid or sulfate complexes. Its non inhibition of hERG channels is an important safety benefit, reducing the risk of causing QT interval prolongation and apical torsion ventricular tachycardia in the heart. The Ames test negative preliminarily ruled out its direct genotoxicity, but a complete genotoxicity combination test and long-term toxicology research are still needed.

3. Gap in pharmacokinetic research At present, there is almost no available literature on the pharmacokinetic studies of the Ticinol Golimicin H system, including its absolute bioavailability, plasma protein binding rate, tissue distribution characteristics, identification of major metabolites, elimination half-life, and other key parameters. This is the core information gap that must be filled to advance towards drug development. The establishment of highly sensitive in vivo analysis methods using liquid chromatography tandem mass spectrometry (LC-MS/MS) technology is a prerequisite for conducting these studies.

Clinical application prospects and prospects

The unique pharmacological properties exhibited by Tigecyl Gomimicin H indicate potential directions for its clinical application, but at the same time, it also faces typical challenges from lead compounds to candidate drugs.

1. Potential application areas：

   • Chemotherapy prevention of liver cancer As a highly selective NQO1 inducer, tigoylgomicin H is very suitable to be developed as a chemopreventive drug or functional food supplement for high-risk groups of liver cancer (such as chronic hepatitis B/hepatitis C infection, cirrhosis patients). Its "single function" characteristic (not inducing I-phase enzymes) has a safety advantage compared to certain bifunctional inducers (such as benzo [a] pyrene).
   • Anti inflammatory treatment Its multi-target anti-inflammatory mechanism makes it promising in the treatment of chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, asthma, etc. Compared with existing nonsteroidal anti-inflammatory drugs (NSAIDs), its ability to enhance cellular antioxidant defense through the Nrf2 pathway may bring additional tissue protective benefits.
   • Neuroprotection and analgesia Combining its anti-inflammatory activity and potential BBB permeability, it may have value in neuroinflammation associated with neurodegenerative diseases such as Alzheimer's disease, as well as TRP channel mediated chronic pain management.

2. Challenges faced and future research directions：

   • Optimize bioavailability Its poor water solubility and potential low oral bioavailability are the primary obstacles. Future research needs to be improved through pharmaceutical methods, such as preparing nanocrystals, liposomes, solid dispersions, or cyclodextrin inclusion complexes, or synthesizing more water-soluble derivatives or prodrugs through structural modification.
   • In depth mechanism research Further clarification is needed on the exact site and mode of its interaction with Keap1 protein, and to elucidate the direct or indirect mechanisms by which it inhibits targets such as IKK β and STAT3. Verify the necessity of Nrf2 in its function using gene knockout or knockdown techniques.
   • System preclinical evaluation Comprehensive preclinical pharmacodynamics (validated in more disease animal models), pharmacokinetics, and toxicology studies (including acute toxicity, long-term toxicity, reproductive toxicity, etc.) must be conducted to evaluate its effective dose window and safety.
   • Explore combination therapy Considering its combination with existing drugs such as chemotherapy drugs and targeted drugs, utilizing its ability to induce detoxifying enzymes and anti-inflammatory properties, to alleviate the toxic side effects of traditional drugs or overcome drug resistance, may be a valuable strategy.

Conclusion

As a biphenylcyclooctene lignan derived from traditional Chinese medicine Schisandra chinensis, Tigecylgomisin H has established significant research value in the field of cancer chemoprevention and anti-inflammatory treatment due to its unique ability to specifically induce phase II detoxifying enzyme NQO1 through the Nrf2 ARE pathway, as well as its inhibitory effects on multiple inflammatory pathways such as NF - κ B and STAT3. Its characteristic as a "single function inducer" enhances cellular defense while avoiding potential risks, reflecting the wisdom of natural products in regulating complex biological networks. Although there are obvious shortcomings in drug formulation, especially in solubility and systemic pharmacokinetics, these challenges are precisely the areas that modern medicinal chemistry and pharmacy can focus on addressing. In the future, through interdisciplinary collaboration, we will delve into the details of its molecular action, optimize its physicochemical properties, and complete systematic preclinical development. Tigeramide H is expected to develop from a potential natural lead compound into an innovative drug or health product for the prevention and treatment of liver diseases and inflammation related diseases, contributing modern power from traditional medicine to human health.