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

Introduction/Overview

Myristic acid (CAS No.: 544-63-8) is a saturated tetradeca-carbon fatty acid widely found in various animal and plant fats, especially abundant in milk fat, coconut oil, palm oil, and nutmeg oil. As a natural fatty acid, myristic acid is not only an important component of cell membrane lipids but also attracts widespread attention in pharmacology and natural product research due to its unique bioactivity. In recent years, with in-depth research into the biological functions of fatty acids, myristic acid has gradually become a potential therapeutic molecule due to its significant antibacterial, anti-inflammatory, and analgesic effects. This paper systematically reviews the chemical structure and physicochemical properties, sources and extraction, pharmacological activity and mechanism of action of myristic acid, druggability evaluation, and its clinical application prospects, aiming to provide theoretical basis and research directions for pharmacological research and clinical development of this natural product.

Chemical structure and physicochemical properties

The chemical name of myristic acid is Tetradecanoic acid, with the molecular formula C14H28O2 and a molecular weight of 228.3760. Its structure consists of a saturated fatty acid chain composed of 14 carbon atoms, ending with a carboxyl group (–COOH). The structural characteristics of myristic acid give it strong hydrophobicity and high lipid solubility.

In terms of physicochemical properties, myristic acid has a LogP value of 6.3923, indicating high lipophilicity, poorly soluble in water (about 0.0116 mg/mL), but easily soluble in organic solvents such as ethanol, ether, and chloroform. Its topological polar surface area (TPSA) is 37.3 Ų, indicating low polarity. Myristic acid has excellent blood-brain barrier penetration ability, which opens its potential for applications in central nervous system-related diseases. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity, while the Ames test was 0.0, indicating no significant mutagenicity.

Plant Origins and Extraction Methods

Myristic acid is widely found in various vegetable oils and fats, with higher levels in nutmeg oil, coconut oil, palm oil, and milk fat. The myristic acid content in nutmeg oil can reach about 16-21%, coconut oil about 16%, and palm oil slightly lower. Due to its wide distribution, myristic acid is relatively easy to extract.

Traditional extraction methods mainly rely on saponification and esterification of fatty acids, followed by solvent extraction and distillation for separation and purification. Modern extraction technologies include supercritical fluid extraction (SFE), microwave-assisted extraction (MAE), and enzymatic hydrolysis, which can improve extraction efficiency, reduce the use of organic solvents, and be more environmentally friendly. During extraction, vegetable oils are typically saponified to produce sodium fatty acid salts, then released by acidification to release free fatty acids, followed by purification by column chromatography or high-performance liquid chromatography (HPLC) to obtain high-purity myristic acid.

Pharmacological activity research

Antibacterial activity

Myristic acid exhibits broad-spectrum antibacterial activity, inhibiting the growth of various Gram-positive and Gram-negative bacteria. Studies have shown that myristic acid has a significant inhibitory effect on Staphylococcus aureus, Streptococcus pneumoniae, E. coli, and Pseudomonas aeruginosa. Its antibacterial mechanism mainly involves disrupting the integrity of bacterial cell membranes, interfering with membrane protein function, thereby causing leakage of cell contents and bacterial death. In addition, myristic acid also shows certain inhibitory effects on fungi such as Candida albicans.

Anti-inflammatory activity

Myristic acid exerts anti-inflammatory effects by modulating the NF-κB signaling pathway. NF-κB is a key transcription factor regulating inflammatory responses. Myristic acid can inhibit NF-κB activation and reduce the expression of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6, thereby alleviating inflammation. Both in vivo and in vitro experiments confirmed that myristic acid significantly reduces inflammatory markers in inflammatory models, suggesting its potential therapeutic value in inflammatory diseases.

Analgesic effect

Myristic acid also exhibits certain analgesic effects, possibly related to its anti-inflammatory properties. By inhibiting the release of inflammatory mediators, myristic acid can reduce pain caused by inflammation. Additionally, some studies suggest it may participate in analgesia by regulating neurotransmitter release and ion channel activity, but the specific mechanism still needs further clarification.

Mechanism of action and molecular targets

The pharmacological effects of myristic acid involve multiple molecular targets and signaling pathways, with particular performance in antibacterial and anti-inflammatory properties.

Antimicrobial-related targets

Myristic acid targets various microbial targets, including:

• GYRA (DNA gyrase subunit A): Myristic acid may hinder DNA replication and transcription by interfering with the function of bacterial DNA gyrase.
• GYPB (glycoprotein B): affects bacterial cell wall synthesis.
• FTSZ (Cell Division Protein): Inhibits bacterial cell division.
• FABI (fatty acid synthase): interferes with fatty acid biosynthesis and damages cell membrane structure.
• DHFR (dihydrofolate reductase): blocks bacterial folate metabolism and inhibits nucleic acid synthesis.
• MECA (cell membrane protein), PENA (penicillin-binding protein): affect cell wall synthesis and maintenance.
• ERG11 (fungal cytochrome P450 14α-demethylase) and CYP51A1: inhibits fungal sterol synthesis.
• CDR1 (fungal ABC transporter): regulates drug efflux; myristic acid may enhance antifungal effects by inhibiting this protein.

Anti-inflammatory mechanism

Myristic acid inhibits the NF-κB signaling pathway, blocking the transcriptional expression of inflammatory mediators and reducing the infiltration and activation of inflammatory cells. Additionally, myristic acid may regulate the MAPK pathway and inhibit oxidative stress responses, further reducing inflammatory damage.

Analgesia mechanism

Analgesic effects may involve inhibiting inflammatory mediators at peripheral nerve endings and regulating pain transmission pathways in the central nervous system. The high blood-brain barrier penetration of myristic acid supports its potential in central analgesia.

Druggability evaluation and pharmacokinetics

The druggability evaluation of myristic acid indicates that it has certain development potential. A high LogP value (6.3923) suggests strong lipophilus, making it easy to penetrate cell membranes and the blood-brain barrier, but may also affect its water solubility and bioavailability. Low water solubility (0.0116 mg/mL) is a major challenge in formulation development and requires improvement through drug carrier systems or structural modifications.

Its high penetration of the blood-brain barrier provides advantages for its application in the treatment of neurological diseases. A negative hERG channel inhibition test indicates a low risk of cardiotoxicity, while the Ames test shows no mutagenicity and good safety.

Pharmacokinetics, myristic acid is mainly absorbed orally through the intestines, with metabolic pathways primarily β-oxidation and esterification, and finally excreted through urine and bile. Its half-life and bioavailability are greatly affected by lipid solubility and metabolic enzyme activity, and further systematic research is needed.

Prospects and outlooks for clinical applications

Due to its multiple biological activities, myristic acid has broad clinical application prospects. Its antibacterial activity provides a natural molecular basis for developing novel anti-infective drugs, with potential advantages especially in resistant strains. Its anti-inflammatory and analgesic properties make it a candidate for treating chronic inflammatory diseases, arthritis, and neuropathic pain.

Future research should focus on:

1. Drug formulation optimization: Overcoming limitations of poor water solubility and low bioavailability, developing novel delivery systems such as nanocarriers and liposomes.
2. In-depth analysis of the mechanism of action: Using molecular biology and structural biology techniques, the interaction patterns between myristic acid and its target have been clarified.
3. Pharmacokinetic and toxicological studies: Systematic evaluation of its metabolism, distribution, and long-term safety in vivo.
4. Preclinical and clinical trials: Verify efficacy and safety, and promote translation to clinical applications.

Additionally, as a member of the fatty acid family, the synergistic effects and metabolic regulatory mechanisms of myristic acid with other fatty acids are also worth in-depth exploration.

Conclusion

As a natural saturated fatty acid, myristic acid has become a hot topic in pharmacological research for natural products due to its remarkable antibacterial, anti-inflammatory, and analgesic properties. It exerts biological effects through multiple targets and pathways, demonstrating promising drug potential. Despite poor water solubility and bioavailability limitations, with advances in formulation technology and pharmacological mechanism research, myristic acid is expected to become an important candidate for next-generation natural product drugs. Future systematic research and clinical validation will lay a solid foundation for its clinical application, promoting its widespread use in anti-infective, anti-inflammatory, and pain management fields.