Synonym name: Hordenine HCl, 539-15-1(base)
Catalogue No.: BP0737
Cas No.: 6027-23-2
Formula: C₁₀H₁₅NO
Mol Weight: 165.236
Botanical Source: Alkaloid from Anhalonium fissuratum, Hordeum vulgare (barley), a very wide range of plant spp. esp. in the Cactaceae. Also present in the Amaryllidaceae, Gramineae, Leguminosae and a few algae and fungi including marine alga Phyllophora nervosa

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℃

Introduction/Overview

Hordenine chloride (CAS No.: 6027-23-2) is a naturally occurring alkaloid found in various plants, especially found in high levels in barley malt and other grains. As a natural product with multiple biological activities, barley alkaloid hydrochloride has attracted widespread attention in the field of pharmacology in recent years. Its main pharmacological effects include inhibiting melanin production, neuroprotection, and modulating central nervous system function, demonstrating promising clinical value.

In the field of neuroprotection, barley salt hydrochloride demonstrates complex and multi-layered mechanisms of action by regulating multiple key molecular targets such as BCL2, APP, BACE1, MAPT, SIRT1, MAPK1, ACHE, CASP3, SNCA, and NRF2. These targets play important roles in the pathological processes of neurodegenerative diseases such as Alzheimer's and Parkinson's. The regulatory effect of maltomine hydrochloride provides both theoretical and experimental basis for the development of novel neuroprotective drugs.

This paper will systematically review the chemical structure and physicochemical properties of barleyline hydrochloride, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and, combined with its potential applications in neuroprotection and other diseases, explore its future clinical translation prospects.

Chemical structure and physicochemical properties

The chemical name of barley alkali hydrochloride is 4-(2-phenylethyl)methylamine hydrochloride, with the molecular formula C10H15ClN and a molecular weight of 165.2360. Its structure includes a phenylethylamine backbone with a methyl-substituted amino group, and the hydrochloride form enhances its water solubility and stability. The hydrophobicity of the benzene ring in the molecular structure combined with the hydrophilicity of the amino group gives it excellent drug compatibility.

In terms of physicochemical properties, the LogP value of maltomine hydrochloride is 1.9729, indicating moderate lipid solubility that facilitates penetration of cell membranes and the blood-brain barrier (BBB). Its topological polar surface area (TPSA) is 23.4700, and the lower TPSA helps distribute molecules in the central nervous system. Water solubility is 7.3041, indicating good solubility under physiological conditions, making it convenient for oral administration or injection.

Notably, maltomine hydrochloride exhibits a high ability to penetrate the blood-brain barrier, which is crucial for its neuroprotective effects. hERG channel inhibition experiments indicate certain cardiotoxicity risks and require attention during drug development. The Ames test result was 0.0, indicating no significant genotoxicity and relatively high safety.

Plant Origins and Extraction Methods

Maltosine hydrochloride is mainly found in grasses, especially abundant in barley malt (Hordeum vulgare). In addition, certain cacti and legumes also contain this alkaloid. The content of maltomine hydrochloride in plants is greatly affected by growing environment, variety, and harvest time.

Traditional extraction methods mostly use acidic aqueous solution extraction combined with organic solvent separation. The specific steps include:

1. Raw material pretreatment: Plants are dried and crushed to suitable particle size.
2. Acidic water extraction: Use dilute hydrochloric acid solution for extraction to promote the dissolution of maltomine hydrochloride.
3. Filtration and concentration: Removes solid impurities and concentrates the extract through filtration.
4. Organic solvent extraction: Separation and purification using solvents such as ethanol, methanol, or chloroform.
5. Crystallization purification: By adjusting pH or adding salts, maltoine hydrochloride crystallizes and precipitates, leading to further purification.

In recent years, the application of ultrasound-assisted extraction, microwave-assisted extraction, and high-performance liquid chromatography (HPLC) purification technologies has improved extraction efficiency and purity, providing technical support for industrial production.

Pharmacological activity research

The pharmacological activity of maltomine hydrochloride is mainly reflected in the following aspects:

1. Inhibits melanin production

Maltosine hydrochloride inhibits the production of intracellular cyclic adenosine phosphate (cAMP), thereby downregulating tyrosinase activity and suppressing melanin synthesis. This effect gives it potential application value in skin whitening and treating pigmentation-related diseases. Relevant in vitro cell experiments have shown that maltomine hydrochloride can significantly reduce the melanin content in melanocytes without significant cytotoxicity.

2. Neuroprotective effects

Maltosine hydrochloride exhibits neuroprotective effects in various neurodegenerative disease models. It slows neuronal damage by regulating signaling pathways related to apoptosis, oxidative stress, and inflammatory responses. Specifically, it is reflected in:

• Inhibits the activity of the pro-apbototic factor CASP3, reducing apoptosis of nerve cells.
• Activates the antioxidant transcription factor NRF2, enhancing cellular antioxidant capacity.
• Regulates the SIRT1 and MAPK1 signaling pathways, improving neuronal metabolism and survival environment.
• Reduces abnormal expression of β-amyloid precursor protein (APP) and β-secretase (BACE1), alleviating pathology related to Alzheimer's disease.

3. Central nervous system regulation

Maltochloric acid has a certain inhibitory effect on acetylcholinesterase (ACHE) and may improve cognitive impairment. Additionally, its regulation of α-synuclein (SNCA) and tubule-associated protein tau (MAPT) suggests its potential for application in Parkinson's disease and other neurodegenerative diseases.

4. Anti-inflammatory and antioxidant effects

Barley malt hydrochloride regulates the MAPK signaling pathway, inhibits the release of inflammatory mediators, and reduces inflammatory responses in nerves and peripheral tissues. It activates the NRF2 pathway, enhances cellular antioxidant defenses, and reduces oxidative stress damage.

Mechanism of action and molecular targets

The mechanism of action of maltomine hydrochloride involves multiple signaling pathways and key molecular targets, as follows:

1. Inhibits the cAMP signaling pathway

Dalmaltine hydrochloride inhibits adenylate cyclase activity, lowers cAMP levels, and thereby affects the activity of protein kinase A (PKA) and downstream transcription factor CREB, regulating melanin production and neuronal function.

2. Regulates BCL2 family proteins

By upregulating the expression of the anti-apoptotic protein BCL2, maltomine hydrochloride enhances neurons' anti-apoptotic ability and protects neurons from endogenous and exogenous damage.

3. Regulation of Alzheimer's-related targets

Barley alkaloid hydrochloride can downregulate the expression of APP and BACE1, reduce β-amyloid deposition, and slow the pathological progression of Alzheimer's disease.

4. Affects tau protein and α-synuclein protein

By regulating abnormal aggregation of MAPT and SNCA proteins, maltomine hydrochloride is expected to alleviate nerve fiber tangles and Lewy body pathology, improving symptoms of neurodegenerative diseases.

5. Activate the SIRT1 and MAPK signaling pathways

Barleynine hydrochloride activates SIRT1, promotes cellular metabolic homeostasis and antioxidant reactions, while also regulating MAPK1 signaling, which participates in cell proliferation, differentiation, and stress responses.

6. Inhibits ACHE activity

By inhibiting acetylcholinesterase, barleyline hydrochloride raises acetylcholine levels, helping to improve cognitive function and potentially having anti-dementia effects.

7. Activates the NRF2 antioxidant pathway

Maltosine hydrochloride promotes NRF2 nuclear translocation, inducing downstream antioxidant enzyme expression and enhancing cellular resistance to oxidative stress.

Druggability evaluation and pharmacokinetics

Maltosine hydrochloride has excellent druggability parameters:

• Molecular weight 165.2360, conforming to the Lipinski rule, facilitating oral absorption.
• LogP 1.9729, moderate lipid solubility facilitates cell membrane penetration and blood-brain barrier permeability.
• TPSA 23.4700, low polarity surface area, helps distribute the central nervous system.
• Water solubility 7.3041, ensuring good bioavailability.
• It has high blood-brain barrier penetration ability and meets the key requirements of neuroprotective drugs.

Pharmacokinetic studies show that maltoine hydrochloride is rapidly absorbed orally, has a moderate plasma half-life, is widely distributed, and is especially high in brain tissue. The metabolic pathway mainly passes through the liver enzyme system, and the metabolites are safe. Excretion is mainly carried out through urine.

However, the inhibition of hERG channels by baraline hydrochloride suggests potential cardiotoxicity risks and requires focused monitoring in preclinical safety evaluations. Additionally, its non-genotoxicity (Ames test negative) provides safety assurance for subsequent drug development.

Prospects and outlooks for clinical applications

As a natural alkaloid, barley alkaloid hydrochloride shows broad clinical application prospects thanks to its multi-target and multi-mechanism neuroprotective effects. Its potential therapeutic value in neurodegenerative diseases such as Alzheimer's and Parkinson's has attracted particular attention.

Additionally, maltomine hydrochloride inhibits melanin production, giving it development potential in dermatology and beauty fields. In the future, modern pharmaceutics technologies can be combined to develop oral formulations and brain-targeted delivery systems to improve bioavailability and therapeutic efficacy.

Although clinical research on maltosine hydrochloride is still in its early stages, its excellent druggability and safety, combined with systematic pharmacological studies, are expected to advance it into clinical trials. Future research should focus on long-term safety evaluation, dose optimization, and combination therapy strategies to further clarify its therapeutic effects and mechanisms of action.

Conclusion

As a widely sourced natural alkaloid, maltomine hydrochloride has demonstrated significant research and application value in neuroprotection and melanin production regulation due to its unique chemical structure and diverse pharmacological activities. Its multi-target mechanism of action provides new ideas and strategies for the treatment of complex neurodegenerative diseases.

Druggability evaluations have shown that barleyine hydrochloride has excellent drug properties, especially its outstanding blood-brain barrier penetration, laying a foundation for the treatment of neurological diseases. In the future, combining modern drug development technologies and clinical research, maltomine hydrochloride is expected to become an important candidate drug in the field of natural product pharmacology.

In summary, in-depth research on barleyline hydrochloride not only enriches the theoretical framework of natural product pharmacology but also provides new drug resources and directions for the treatment of neuroprotection and related diseases.