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Synonym name:
Catalogue No.: BP0728
Cas No.: 11041-94-4
Formula: C16H18ClNO3
Mol Weight: 307.774
Botanical Source:
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
72.7200
1.5134
.4231
1.3347
1.7828
9.7360
Low
59.6150
2.9198
No
Yes
No
No
Yes
No
0.6
Yes
No
No
No
Higenamine hydrochloride (CAS No.: 11041-94-4) is an important natural alkaloid, first isolated from the traditional Chinese medicine Aconitum spp. As a bioactive molecule, demehuline hydrochloride has gradually attracted attention in recent pharmacological research, demonstrating broad application potential due to its multi-target and multifunctional pharmacological properties. Its main activities include selective inhibition of LSD1 (lysine-specific demethylase 1), anti-inflammatory, antibacterial, and neuroprotective functions. Additionally, nomethaurine hydrochloride regulates signaling pathways such as PI3K/Akt and SMAD2/3, showing significant effects in inhibiting apoptosis and promoting bone formation, involving cardiovascular protection, osteoporosis, cancer, and inflammatory diseases.
This paper aims to systematically review the chemical structure, origin, and extraction method of demehuline hydrochloride, elaborate on its pharmacological activity and mechanism of action, and, combining druggability parameters and pharmacokinetic characteristics, explore its clinical application prospects and development directions, providing scientific support for subsequent basic and clinical research.
The chemical name of demeh-methalmine alkaloid hydrochloride is (S)-1-(4-hydroxyphenyl)-2-methylaminoethanol hydrochloride, with the molecular formula C16H17NO3· HCl, molecular weight 271.3160. Its structural core is the phenylethanolamine framework, which includes a para-hydroxybenzene ring and a chiral center, possessing strong hydrophilicity and some lipid solubility. The LogP value was 1.5134, indicating moderate lipid solubility, which facilitates cell membrane penetration but still has good water solubility (solubility 1.3347 mg/mL). The topological pole surface area (TPSA) was 72.72 Ų, indicating moderate polarity, which may affect oral absorption and blood-brain barrier permeability.
The hydrochloride form of demehuline hydrochloride improves its water solubility and stability, facilitating formulation development. Its blood-brain barrier penetration ability is relatively low, suggesting limited direct action in the central nervous system, but it exerts neuroprotective effects through peripheral mechanisms. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenic test result was 0.6, indicating a low genotoxicity risk and meeting drug safety requirements.
Demehydracaline hydrochloride is mainly found in plants of the genus Aconitum carmichaelii, especially in the rhizomes of Aconitum carmichaelii and related species. Aconite plants hold an important place in traditional Chinese medicine and are commonly used for pain relief, anti-inflammation, and the treatment of cardiovascular diseases. As one of its active ingredients, desmethalmine may not have as high content as major alkaloids such as aconitine, but it has attracted much attention due to its unique pharmacological effects.
Traditional extraction methods typically use alcohol solvents (such as ethanol or methanol) for reflux extraction of dried plant rhizomes, followed by acid-base adjustment and liquid-liquid distribution, combined with column chromatography techniques (such as silica gel columns and C18 reversed-phase columns) for purification. In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity. High-performance liquid chromatography (HPLC) and mass spectrometry techniques are widely used for qualitative and quantitative analysis of desmethamine to ensure the quality and stability of extracts.
Demehylalkaloid hydrochloride, as a selective LSD1 inhibitor, has an IC50 of about 1.47 μM and can effectively suppress LSD1 demethylation activity. LSD1, as a histone demethylase, plays a key role in regulating gene expression and tumor development. Normethamine demonstrates potential antitumor activity by inhibiting LSD1 and regulating the epigenetic status of tumor cells.
Demethamine hydrochloride has significant anti-inflammatory effects. Both in vitro and in vivo experiments have shown that it can inhibit the release of inflammatory mediators and reduce inflammatory responses. Its anti-inflammatory mechanism involves downregulating the activity of pro-inflammatory cytokines such as IL-1β, TNF-α, and NF-κB signaling pathways. Additionally, desmehuline has inhibitory effects on various bacteria, especially Gram-positive bacteria, suggesting its potential in infectious diseases.
Normehuline hydrochloride can weaken IL-1β-induced neuronal apoptosis through the ROS-mediated PI3K/Akt signaling pathway, protecting brain cells from hypoxic-ischemic injury. This mechanism activates cell survival signals, inhibits the expression of apoptosis-related proteins, and alleviates oxidative stress and inflammatory responses, demonstrating its potential therapeutic value in stroke and neurodegenerative diseases.
Recent studies have shown that desmethamine promotes osteoblast differentiation and bone formation through the SMAD2/3 signaling pathway, improving osteoporosis. This mechanism provides new targets and ideas for drug development for bone metabolic diseases.
Normethaurine hydrochloride exhibits multiple protective effects in the cardiovascular system. Its targets include SELP, PPARG, ACE, AKT1, ADRB2, KCNH2, NOS3, ICAM1, VCAM1, and SLC8A1, covering vasodilatory, anti-inflammatory, antioxidant, myocardial protection, and electrophysiological stability. Normethaline improves hemodynamics and reduces myocardial ischemic injury by activating β2 adrenergic receptors (ADRB2) and regulating NO synthase (NOS3) activity, offering potential adjuvant therapeutic value for heart failure and myocardial infarction.
The mechanisms of action of demehuline hydrochloride are complex and diverse, mainly realized through the following signaling pathways and molecular targets:
LSD1 inhibition: By competitively inhibiting LSD1 enzyme activity, it regulates histone methylation status, influences gene transcription, and suppresses tumor cell proliferation and migration.
PI3K/Akt signaling pathway: desmethamine activates the PI3K/Akt pathway, promotes cell survival, inhibits inflammatory mediator production, reduces oxidative stress and apoptosis, and protects nerve and cardiomyocytes.
SMAD2/3 signaling pathway: By activating TGF-β-related SMAD2/3 signaling, it promotes osteoblast differentiation, enhances bone formation, and improves osteoporosis.
β2 adrenergic receptor (ADRB2) agonist: Nomethaline acts as an ADRB2 agonist, regulating heart rate and vasodilation, improving cardiovascular function.
Anti-inflammatory targets: Downregulate selectin (SELP), intercellular adhesion molecules (ICAM1, VCAM1), and PPARG and other inflammation-related molecules, inhibiting leukocyte adhesion and inflammatory responses.
Electrophysiological regulation: By affecting potassium channel KCNH2 and calcium exchange protein SLC8A1, it stabilizes the membrane potential of myocardial cells and prevents arrhythmias.
In summary, demethaurine hydrochloride exerts its broad pharmacological effects through multi-target and multi-pathway synergistic effects.
The druggability evaluation of desmethaurine hydrochloride indicates that it has promising potential for drug development. Molecular weight is 271.3160, conforming to the Lipinski rule, LogP is 1.5134, and moderate lipid solubility is beneficial for oral absorption. TPSA was 72.72 Ų, indicating moderate polarity, which is beneficial for cell membrane passage but has low blood-brain barrier penetration.
Good water solubility (1.3347 mg/mL), facilitating formulation development and in vivo delivery. The hERG channel inhibition test was negative, reducing the risk of cardiotoxicity. Ames test results showed no significant mutagenicity and relatively high safety.
Pharmacokinetics, nomehuline hydrochloride has moderate bioavailability after oral administration, is widely distributed in the body, but has low concentrations in brain tissue. Metabolism mainly occurs through the hepatic CYP450 enzyme system, and the metabolites are safe. The main excretory route is the kidneys. Moderate half-life, suitable for daily administration.
Currently, systematic clinical pharmacokinetic studies are lacking, and further clarification of their in vivo metabolic kinetics and drug interactions is needed in the future.
Nomehuline hydrochloride shows broad clinical application potential in multiple disease fields due to its multiple pharmacological activities.
Tumor Treatment: As an LSD1 inhibitor, desmethaline can regulate the epigenetic status of tumor cells, inhibit tumor growth and metastasis, and is expected to be developed as a new anti-tumor drug in the future, especially in combination with chemotherapy or immunotherapy.
Cardiovascular diseases: Its combined effects on myocardial protection, vasodilation, and anti-inflammation make it suitable as an adjunct treatment for myocardial ischemia, heart failure, arrhythmias, and other conditions, improving patient prognosis.
Neuroprotection: By inhibiting inflammation and oxidative stress and reducing nerve cell apoptosis, desmethamine is expected to be used in the prevention and treatment of stroke and neurodegenerative diseases.
Osteoporosis: Promotes bone formation This provides new approaches for osteoporosis treatment and may be developed as a bone metabolism regulator in the future.
Inflammation and infection: Its anti-inflammatory and antibacterial activities make it a potential therapeutic agent for inflammatory and infectious diseases.
Although demeauline hydrochloride demonstrates multifaceted therapeutic potential, its clinical application still faces many challenges, such as systematic clinical safety and efficacy verification, formulation optimization, and pharmacokinetic improvement. Future research should focus on in-depth mechanism analysis, clinical trial design, and combination drug strategies, promoting clinical translation.
As a versatile natural product, demehate hydrochloride has shown unique advantages in pharmacological research. Its selective LSD1 inhibitory effect and multi-target regulatory capability give it broad application prospects in tumors, cardiovascular systems, neuroprotection, and bone metabolism. Combined with favorable druggability parameters and safety evaluation, demeh-methaline hydrochloride has the potential to become a candidate molecule for novel drugs.
Future research needs to strengthen systematic elucidation of its mechanism of action, improve pharmacokinetic and toxicological data, conduct multicenter clinical trials, and promote its translational application in clinical practice. The in-depth development of demehulutine alkaloid hydrochloride not only enriches the research content of natural product pharmacology but also provides new drug resources and strategies for the treatment of related diseases.
Shenshuai
Wenjing
Hedandan
