Product name: Ligustrazine Hydrochloride
Synonym name: Chuanxiongzine Hydrochloride, Tetramethylpyrazine hydrochloride
Catalogue No.: BP0864
Cas No.: 76494-51-4
Formula: C₈H₁₃ClN₂
Mol Weight: 172.656
Botanical Source: Ligusticum chuanxiong Hort.
Physical Description:
Type of Compound: Miscellaneous

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.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

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

Introduction/Overview

Ligustrazine hydrochloride (CAS No.: 76494-51-4) is a natural product derived from the traditional Chinese medicine Ligusticum chuanxiong Hort., attracting attention for its significant cardiovascular protective effects. As an important herb in traditional Chinese medicine for promoting blood circulation and removing blood stasis, Chuanxiong's main active ingredient, Chuanxiongzidine, has demonstrated multi-target and multi-mechanism therapeutic potential in modern pharmacological research. Tetramethylpyrazine hydrochloride, with its excellent water solubility, high bioavailability, and low side effects, has become an important candidate for developing novel therapeutic drugs for cardiovascular diseases. This paper will systematically review the chemical structure and physicochemical properties of tetramethylpyrazine hydrochloride, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, pharmacokinetic characteristics, as well as its clinical application prospects and future research directions, aiming to provide theoretical basis and reference for further research and clinical translation of this natural product.

Chemical structure and physicochemical properties

The chemical name of tetramethylpyrazine hydrochloride is 2,3,5,6-tetramethylpiperazine hydrochloride, with the molecular formula C8H14N2· HCl, molecular weight 136.1980. Its structural core is a piperazine ring, which carries four methyl substituents. Its hydrochloride form imparts good water solubility (5.9652 mg/mL), which is beneficial for drug formulation development and absorption in the body. The LogP value was 1.8234, indicating moderate lipid solubility that facilitates penetration of cell membranes and the blood-brain barrier (BBB), and its TPSA (topological pole surface area) is 25.78 Ų, further supporting its good membrane permeability. It is worth noting that tetramethylpyrazine hydrochloride does not show hERG channel inhibitory activity, indicating a low risk of cardiotoxicity. The Ames test result was 0.0, indicating no significant mutagenicity and relatively high safety.

Plant Origins and Extraction Methods

The parent compound of tetramethylpyrazine hydrochloride is mainly found in the rhizomes of Chuanxiong. Ligusticum chuanxiong is the dried rhizome of the umbellifery plant Ligusticum chuanxiong Hort., widely distributed in Sichuan, Yunnan, and other regions of China. Traditional extraction methods mostly use water or alcohol extraction combined with acid-base adjustment to obtain crude extracts of tetramethylpyrazine. In modern processes, ultrasound-assisted extraction, microwave-assisted extraction, and column chromatography purification techniques are widely used to improve extraction efficiency and purity.

The typical process typically includes: after drying and crushing ligusticum, extraction using ethanol or methanol, combined with acidic conditions to promote the formation of tetramethylpyrazine hydrochloride, followed by steps such as activated carbon decolorization and silica gel column chromatography, ultimately obtaining tetramethylpyrazine hydrochloride crystals. In recent years, advances in green solvents and continuous flow extraction technologies have further optimized extraction processes, improving yield and environmental friendliness.

Pharmacological activity research

The pharmacological activity of tetramethylpyrazine hydrochloride in the cardiovascular system has been validated by numerous in vivo and in vitro experiments, mainly manifesting as multiple effects such as resistance to ischemia-reperfusion injury, vasodilation, anti-platelet aggregation, anti-inflammation, and antioxidant effects.

1. Prevents myocardial ischemia-reperfusion injury
   Tetramethylpyrazine hydrochloride can significantly reduce myocardial cell apoptosis and inflammatory responses caused by myocardial ischemia-reperfusion, improve microcirculation in myocardial tissue, and reduce the area of myocardial infarction. Animal models demonstrate that it exerts myocardial protective effects by regulating oxidative stress levels and suppressing the release of inflammatory mediators.

2. Dilates blood vessels and improves microcirculation
   Tetramethylpyrazine hydrochloride can promote nitric oxide (NO) production, activate vascular endothelial cells, dilate coronary arteries and peripheral vessels, and improve hemodynamics. Its vasodilatory effect helps lower blood pressure and improve tissue perfusion.

3. Anti-platelet aggregation and antithrombosis
   This compound can inhibit platelet activation and aggregation, reducing the risk of thrombosis, and is suitable for the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases.

4. Anti-inflammatory and antioxidant effects
   Tetramethylpyrazine hydrochloride reduces vascular endothelial cell inflammation by inhibiting the expression of inflammatory factors such as ICAM-1 and VCAM-1; At the same time, it eliminates free radicals, reduces oxidative stress damage, and protects the cardiovascular system.

Mechanism of action and molecular targets

The multi-target mechanism of tetramethylpyrazine hydrochloride forms the basis for its cardiovascular protective effects. Through molecular biology techniques and network pharmacological analysis, several key targets have been identified:

• SELP (P-selectin): Tetramethylpyrazine hydrochloride inhibits SELP expression, reduces platelet adhesion to endothelial cells, and lowers the risk of thrombosis.
• PPARG (Peroxisome Proliferator-Activated Receptor γ): Activates the PPARG signaling pathway, regulates lipid metabolism and inflammatory responses, and improves atherosclerosis.
• ACE (angiotensin-converting enzyme): inhibits ACE activity, lowers angiotensin II levels, exerts antihypertensive and anti-myocardial remodeling effects.
• AKT1 (protein kinase B): activates the AKT1 pathway, promoting myocardial cell survival and angiogenesis.
• ADRB2 (β2 adrenergic receptor): regulates myocardial contractility and vasodilation.
• KCNH2 (hERG potassium channel): Tetramethylpyrazine hydrochloride does not inhibit this channel, reducing the risk of arrhythmias.
• NOS3 (endothelial nitric oxide synthase): enhances NOS3 expression, promotes NO synthesis, and improves vascular function.
• ICAM1 and VCAM1 (intercellular adhesion molecules): downregulate their expression, reducing inflammation and vascular endothelial damage.
• SLC8A1 (sodium-calcium exchange protein): regulates cardiac cell calcium homeostasis and protects myocardial function.

The synergistic regulation of these targets enables tetramethylpyrazine hydrochloride to exert multidimensional protective effects in the pathological processes of cardiovascular diseases.

Druggability evaluation and pharmacokinetics

Tetramethylpyrizine hydrochloride has excellent druggability parameters. Moderate molecular weight (136.2 Da) and LogP (1.82) met the Lipinski rule, indicating good oral bioavailability. The low TPSA value facilitates cell membrane penetration and blood-brain barrier permeability, supporting its potential application in central nervous system-related cardiovascular diseases.

Toxicological evaluation showed that tetramethylpyrazine hydrochloride had no significant hERG channel inhibitory effect, reducing the risk of arrhythmias. Ames test was negative, indicating no mutagenicity and relatively high safety.

Pharmacokinetic studies show that tetramethylpyrazine hydrochloride is rapidly absorbed orally, has a moderate plasma half-life, is widely distributed, and can especially effectively cross the blood-brain barrier. Its main metabolic pathway is hepatic enzymatic metabolism, with metabolite toxicity. Excretion is mainly done through the kidneys, so the risk of accumulation in the body is low.

Prospects and outlooks for clinical applications

As a natural product derivative with multiple targets and mechanisms, tetramethylpyrazine hydrochloride shows broad application prospects in the prevention and treatment of cardiovascular diseases. Clinical studies have preliminarily confirmed its efficacy in coronary heart disease, cerebrovascular ischemia, myocardial ischemia-reperfusion injury, and other diseases, with mild side effects and good tolerability.

In the future, with the development of precision medicine, tetramethylpyrizine hydrochloride can be combined with genomics and metabolomics methods to further clarify its personalized indications and medication regimens. Meanwhile, research based on nanotechnology and novel drug delivery systems is expected to improve bioavailability and targeting, enhancing therapeutic outcomes.

In addition, the potential applications of tetramethylpyrazine hydrochloride in neuroprotection, anti-inflammation, and antioxidant fields are also worth further exploration, especially in neurological function recovery after stroke and the comprehensive management of chronic cardiovascular and cerebrovascular diseases, where it may play an important role.

Conclusion

Chuanxiong hydrochloride, as a natural derivative derived from traditional Chinese medicine Chuanxiong, demonstrates significant cardiovascular protective effects due to its unique chemical structure and excellent physicochemical properties. Its multi-target and multi-mechanism pharmacological activity provides new ideas and strategies for the prevention and treatment of cardiovascular diseases. Its excellent druggability and high safety make it a strong candidate for cardiovascular drug development. In the future, through in-depth molecular mechanism research, optimized drug formulations, and large-scale clinical trials, tetramethylpyrazine hydrochloride is expected to achieve broader clinical applications and benefit a wide range of patients.