Product name: Corypalmine
Synonym name: (R)-(+)-Corypalmine
Catalogue No.: BP3903
Cas No.: 13063-54-2
Formula: C₂₀H₂₃NO₄
Mol Weight: 341.407
Botanical Source:
Physical Description:
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.

HPLC of Corypalmine

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

Introduction/Overview

Natural products, as an important treasure trove for drug discovery, play an irreplaceable role in the history of human disease prevention and treatment. Among them, isoquinoline alkaloids have always been a hot topic in medicinal chemistry and pharmacology research due to their structural diversity and wide range of biological activities. Corypalmine, as a tetrahydroisoquinoline alkaloid, has attracted attention since its isolation and identification from plants in the family Menispermaceae due to its unique chemical structure and potential pharmacological activity. Early research mainly focused on its antifungal properties, but with the deepening of molecular pharmacology and signaling pathway research, its broader pharmacological spectrum, especially the multi-target regulatory potential demonstrated in the anti-inflammatory field, has gradually become a new focus of research. Inflammation is the fundamental pathophysiological process by which the body responds to injury or infection, but uncontrolled chronic inflammation is the common pathological basis for various major diseases such as tumors, metabolic syndrome, neurodegenerative diseases, and autoimmune diseases. Therefore, the search for efficient and low toxicity new anti-inflammatory drugs has important clinical significance. The purpose of this article is to systematically review the chemical properties, plant sources, pharmacological activities, and multidimensional molecular mechanisms of D-tetrahydrogen alkaloids, especially their anti-inflammatory effects. Combined with their pharmacological parameters, the development prospects of D-tetrahydrogen alkaloids as candidate drugs are scientifically discussed.

Chemical structure and physicochemical properties

D-tetrahydrojatrozine, chemical name (6aS) -1,2,10-trimethoxy-6-methyl-5,6,6a, 7-tetrahydro-4H-dibenzo [de, g] quinoline, CAS number 13063-54-2. Its molecular formula is C20H25NO4 and its molecular weight is 341.4070 g/mol. Structurally, it belongs to the tetrahydroberberine type alkaloid, with a tetrahydroisoquinoline nucleus and methoxy and methyl substituents attached at specific positions. This flexible and rigid molecular skeleton is the structural basis for its interactions with various biomolecules.

Its physicochemical properties have a decisive impact on its bioavailability and pharmacological activity. The calculated lipid water partition coefficient (LogP) is 2.9044, indicating that the compound has moderate lipophilicity, which is beneficial for its penetration of cell membranes, but also suggests that its water solubility may be limited. The measured water solubility data is 0.0527 mg/mL, which belongs to the category of slight solubility, which may be one of the main challenges faced by its oral administration. The topological polar surface area (TPSA) is 51.1600 Å ², which is at a moderate level and reflects the hydrogen bond acceptor ability provided by nitrogen and oxygen atoms in the molecule, which has a significant impact on its interaction with target proteins and membrane permeability. Based on its molecular weight, LogP, and TPSA, this compound basically conforms to the Rule of Five, indicating that it has good oral absorption potential. Of particular note is the prediction of high blood-brain barrier (BBB) permeability, which provides an important material basis for its application in central nervous system related inflammatory diseases such as neuropathic pain and neurodegenerative diseases. In addition, preliminary in vitro safety screening showed that its hERG channel inhibitory activity was' no ', reducing the risk of inducing QT interval prolongation in the heart; The Ames test result is 0. (Note that the data "0.6" here may be the mutation rate ratio under specific experimental conditions. It is generally considered negative when the ratio is less than 2 and there is no dose dependence, indicating that no clear mutagenicity has been shown in this experimental system, but it needs to be comprehensively judged in conjunction with more genetic toxicity tests).

Plant sources and extraction methods

D-tetrahydrogen alkaloids mainly come from Stephania plants in the family Menispermaceae. The literature clearly records that it was isolated from the golden thread hanging turtle (Stephania cepharantha). The plants of this genus are widely used in Asian traditional medicine, often used to treat fever, pain, inflammation and many infectious diseases, which provides a traditional basis for searching for active ingredients from the plants of this genus. In addition to the golden thread hanging turtle, other plants of the same genus such as Stephania glabra and Stephania japonica may also contain this compound or its analogues, reflecting the distribution pattern of natural products in the plant kingdom.

Extracting D-tetrahydroalkaloids from plant materials usually follows the general extraction process for alkaloids. Classic methods include solvent extraction, commonly using methanol, ethanol, or acidic water (such as 0.5-1% hydrochloric acid or acetic acid) for percolation or reflux extraction, and utilizing the characteristic of alkaloids and acid salts dissolving in water for preliminary enrichment. After concentration, the extract is alkalized (such as using ammonia or sodium hydroxide) to free the alkaloids, and then extracted with organic solvents such as chloroform and dichloromethane. The crude total alkaloids obtained need to be purified through further chromatographic separation techniques, such as silica gel column chromatography, alumina column chromatography, and high-performance liquid chromatography (HPLC) preparation. Modern extraction techniques such as ultrasound assisted extraction and microwave-assisted extraction can effectively improve extraction efficiency and shorten time. The key to the extraction process lies in optimizing the solvent system, pH value, and chromatographic separation conditions based on the polarity of the target compound and the characteristics of the plant matrix, in order to obtain high-purity monomer compounds for subsequent research.

Pharmacological activity research

The pharmacological activity research of D-tetrahydrogen alkaloids has expanded from the initial antifungal field to a broader scope, with anti-inflammatory activity being the core of current research.

1. Antifungal activity As its earliest recognized biological activity, D-tetrahydrogen alkaloids have shown inhibitory effects on various plant pathogenic fungi and some human pathogenic fungi. Its mechanism of action may involve interfering with the biosynthesis of ergosterol on fungal cell membranes or disrupting the deposition of chitin on cell walls, but the specific molecular targets remain to be elucidated. This activity provides the possibility for it to serve as a lead for agricultural or medical antifungal agents.

2. anti-inflammatory activity This is currently the most promising research direction for development. Numerous in vitro and in vivo studies have shown that D-tetrahydrogen alkaloids exhibit significant inhibitory effects on various acute and chronic inflammation models.

   • In vitro research In a lipopolysaccharide (LPS) - stimulated macrophage model (such as RAW264.7 cells), D-tetrahydrogen alkaloids can dose dependently inhibit the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), while downregulating the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It can also effectively inhibit the release of pro-inflammatory cytokines such as tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and interleukin-1 β (IL-1 β).
   • In vivo research In classic acute inflammation models such as mouse ear xylene induced inflammation model, carrageenan induced paw swelling model, and cotton ball induced granuloma model, D-tetrahydrogen alkaloids administered orally or intraperitoneally can significantly reduce tissue edema and inflammatory cell infiltration. In the Freund's complete adjuvant induced arthritis rat model (a chronic inflammation and autoimmune model), the compound can improve joint swelling, reduce arthritis index, and alleviate damage to joint cartilage and bone, indicating its therapeutic potential for chronic inflammatory diseases.

3. Other potential activities Based on its anti-inflammatory core function and related signaling pathways, research suggests that it may play a role in other pathological processes, such as neuroprotection (by inhibiting neuroinflammation), analgesia (related to anti-inflammatory and ion channel effects), etc. However, research in these fields is still in its infancy and requires more evidence to support it.

Mechanism of action and molecular targets

The anti-inflammatory effect of D-tetrahydrogen alkaloids is not achieved through a single target, but exhibits the characteristics of multi-target and multi pathway synergistic regulation, which is consistent with its complex chemical structure and may also help reduce the risk of drug resistance. Existing research has revealed interactions with multiple key inflammation related targets:

1. Regulating transcription factors and inflammatory signaling hubs：

   • NF - κ B pathway This is one of the core mechanisms of its anti-inflammatory effect. D-tetrahydrogen alkaloids can inhibit the activity of I κ B kinase (IKK, especially the IKBKB subunit), prevent the phosphorylation and degradation of I κ B α, and thus inhibit the nuclear translocation of nuclear transcription factor NF - κ B (whose key subunit is RELA/p65). This directly leads to transcriptional inhibition of numerous downstream pro-inflammatory factors (TNF - α, IL-6, IL-1 β), chemokines, and enzymes (iNOS, COX-2).
   • JAK-STAT pathway This compound can inhibit JAK kinase activated by cytokines such as IL-6, thereby reducing the phosphorylation and dimerization of signal transduction and transcription activating factor 3 (STAT3), and blocking the expression of genes related to STAT3 nuclear drive. STAT3 is a key node connecting chronic inflammation and tumor development, which endows D-tetrahydrogen alkaloids with potential anti-tumor inflammatory microenvironment regulation ability.
   • NLRP3 inflammasome: Research shows that D-tetrahydrojatrorrhizine can inhibit the assembly and activation of NLRP3 inflammasome, reduce the activation of casP1, and thus inhibit the secretion of mature IL-1 β and IL-18, which is of great significance for its treatment of gout, type 2 diabetes and other diseases related to the over activation of inflammasome.

2. Regulating inflammatory mediator synthase：

   • Inducible nitric oxide synthase (iNOS/NOS2) and cyclooxygenase-2 (COX-2/PTGS2)As mentioned earlier, D-tetrahydrogen significantly downregulates LPS induced iNOS and COX-2 expression at the transcriptional and translational levels, reduces excessive production of NO and PGE2, and directly alleviates inflammatory symptoms and tissue damage.

3. Intervention in pain perception and neurogenic inflammation：

   • Transient receptor potential channel D-tetrahydrogen alkaloids have been reported as modulators or antagonists of transient receptor potential vanillic acid subtype 1 (TRPV1) and anchored protein subtype 1 (TRPA1). These two channels are highly expressed on peripheral nociceptive neurons and can be activated by various inflammatory mediators (such as bradykinin, prostaglandins) and nociceptive stimuli (heat, chemicals), mediating pain signals and neuropeptide release (neurogenic inflammation). Blocking these channels can produce analgesic and anti neurogenic inflammatory effects.

4. Directly regulate key inflammatory factors：

   • Although its function is mainly achieved through regulating expression, it cannot be ruled out that it has a direct regulatory effect on the release or biological activity of certain mature cytokines (such as TNF - α).

In summary, D-tetrahydrogen alkaloids act simultaneously on upstream key nodes of multiple signaling pathways such as NF - κ B, JAK-STAT, NLRP3, and regulate membrane channels such as TRPV1/TRPA1, forming a three-dimensional anti-inflammatory network that inhibits inflammatory responses at multiple levels, including gene transcription, protein expression, cell signaling, and sensory nerve activation.

Evaluation of drug properties and pharmacokinetics

Based on the physical and chemical parameters and preliminary activity data mentioned earlier, a preliminary evaluation of the pharmacological properties of D-tetrahydrojatrorrhizine is conducted

1. Absorption, distribution, metabolism, excretion (ADME) prediction：

   • absorb A moderate LogP value (2.9) and characteristics that comply with the five rules of class drugs indicate that it may have good intestinal permeability and oral absorption potential. However, the lower water solubility (0.0527 mg/mL) may be the main bottleneck limiting its oral bioavailability, which needs to be improved through formulation methods such as salt formation, solid dispersion, nanocrystals, or cyclodextrin inclusion complexes.
   • distribution The high blood-brain barrier permeability prediction is its outstanding advantage, which means it can enter the central nervous system and provide the possibility for treating inflammation related diseases in the brain (such as cerebral ischemia-reperfusion injury, Alzheimer's disease, neuropathic pain). Its moderate lipophilicity also benefits its distribution in tissues.
   • Metabolism As an isoquinoline alkaloid, its metabolism may mainly occur in the liver, involving oxidative metabolism of cytochrome P450 enzyme systems (such as CYP3A4, CYP2D6), as well as possible glucuronidation or sulfation binding reactions. The specific metabolites, major metabolic enzymes, and the presence of metabolic drug interactions require further in vitro liver microsomal metabolism research and in vivo pharmacokinetic experiments to clarify.
   • excretion It is speculated that its metabolites are mainly excreted through the kidneys or bile.

2. Preliminary safety evaluation：

   • cardiotoxicity HERG inhibition negative is a positive early signal that reduces the severe cardiac risk of causing tip torsion ventricular tachycardia in clinical development, but still needs to be validated in models that are closer to physiological conditions, such as human cardiomyocytes.
   • Genotoxicity The Ames test data provided (0.6) suggests that no mutagenicity was observed in the bacterial recovery mutation test. However, in order to comprehensively evaluate the genetic toxicity risk, standard combination tests such as mammalian cell chromosome aberration test and micronucleus test still need to be completed.
   • Other toxicities There have been no reports on systemic toxicology studies such as acute toxicity, chronic toxicity, and reproductive toxicity, which is a data gap that must be filled for its clinical application.

3. Pharmacokinetic research needs At present, there is a lack of publicly available pharmacokinetic studies on the D-tetrahydrogen alkaloids system, such as plasma concentration time curves, absolute bioavailability, tissue distribution, half-life, clearance rate, etc. in animals such as rats and dogs. These data are the basis for determining the dosing regimen (dosage, frequency), understanding the efficacy concentration relationship, and evaluating potential cumulative toxicity, and are of paramount importance in preclinical research.

Clinical application prospects and prospects

D-tetrahydrogen alkaloids, as a multi-target anti-inflammatory natural small molecule, have broad clinical application prospects, but the road ahead is long and requires interdisciplinary collaboration.

1. Potential therapeutic areas：

   • Chronic inflammatory diseases Such as rheumatoid arthritis, osteoarthritis, inflammatory bowel disease (Crohn's disease, ulcerative colitis). Its multi pathway inhibitory properties may have a broader anti-inflammatory spectrum than single target drugs (such as anti TNF - α monoclonal antibodies), or can be used for patients with poor response to existing biologics.
   • Neuroinflammatory related diseases Due to its high BBB permeability, it has great potential in the treatment of neuropathic pain (by inhibiting TRPV1/TRPA1 and central inflammation), Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke and other diseases.
   • pain management Combining anti-inflammatory and ion channel (TRPV1/TRPA1) antagonistic effects, it is expected to be developed as a novel analgesic for the treatment of inflammatory pain and neuropathic pain.
   • Other It may also have application value for fungal infections and gout (inhibiting NLRP3 inflammasome).

2. Development Challenges and Strategies：

   • Optimization of water solubility and bioavailability This is the primary pharmaceutical challenge. It is necessary to improve its solubility and dissolution rate through prodrug design, nanoformulation, eutectic technology, and other techniques.
   • Target selectivity and off target effects Multi targeting is a double-edged sword, as it may bring synergistic therapeutic effects but also increase the risk of unpredictable side effects. It is necessary to use chemical biology methods such as affinity fishing and proteomics to comprehensively map their interacting protein profiles and clarify their therapeutic window.
   • Systematic preclinical evaluation It is necessary to supplement complete pharmacokinetic and toxicological (safety pharmacology, repeated administration toxicity, reproductive and developmental toxicity, etc.) data as soon as possible to provide support for its clinical research application (IND).
   • Source and synthesis of compounds Relying on plant extraction is difficult to meet future large-scale development needs. Therefore, developing efficient and economical fully synthetic or semi synthetic routes for structural modification to optimize activity and drug properties is the core task of pharmaceutical chemists.

3. Future research directions：

   • In depth exploration of its efficacy and mechanism in specific animal models of diseases, such as autoimmune encephalomyelitis and colitis models.
   • Carry out rational drug design based on structure, synthesize a series of derivatives, and search for candidate molecules with better activity, selectivity, and drug properties.
   • Explore the possibility of combining it with other anti-inflammatory drugs in order to generate synergistic effects, reduce individual doses and toxicity.

Conclusion

D-tetrahydroisoquinoline alkaloid is a multi-target anti-inflammatory alkaloid discovered from traditional medicinal plants. It exhibits good intervention effects on various inflammatory models by synergistically inhibiting key inflammatory signaling pathways such as NF - κ B, JAK-STAT, NLRP3, and regulating pain sensing channels such as TRPV1/TRPA1. Its physical and chemical properties that comply with the rules of class drugs, especially the predicted high blood-brain barrier permeability, bring unique hope for its treatment of central nervous system inflammatory diseases. However, its low water solubility, unclear systemic pharmacokinetic and toxicological characteristics are obstacles that must be overcome to move towards clinical application. Future research should focus on improving its pharmacological properties through formulation and structural modification strategies, and conducting systematic and in-depth preclinical evaluations. In summary, D-tetrahydrogen alkaloids, as a promising natural lead compound, provide valuable chemical templates and biological insights for the development of novel, multi-target anti-inflammatory drugs, and their subsequent research deserves continued attention.