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

Introduction/Overview

Cinnamyl Alcohol (CAS No.: 104-54-1) is a naturally occurring aromatic alcohol compound widely distributed in various plants, especially abundant in chestnut flowers. As a reduced product of cinnamaldehyde, cinnamyl not only imparts the distinctive aromatic aroma to plants but has also attracted widespread attention in pharmacology and natural product chemistry due to its diverse biological activities. In recent years, with the growing prominence of public health issues such as obesity, inflammatory diseases, and fungal infections, cinnamol has become a research hotspot due to its multiple pharmacological effects—anti-obesity, antioxidant, anti-inflammatory, and antifungal. This paper will systematically review the chemical structure, physicochemical properties, plant origin, extraction methods, pharmacological activity, and mechanism of action of cinnamyl alcohol, combined with druggability evaluation and pharmacokinetics, to explore its clinical application prospects, and provide theoretical basis and practical guidance for pharmacological research of natural products.

Chemical structure and physicochemical properties

The chemical name of cinnamol is 3-phenyl-2-propenol, with the molecular formula C9H10O and a molecular weight of 134.18. Its structural feature is that a benzene ring connects to a side chain containing an unsaturated carbon-carbon double bond, with a hydroxyl group (-OH) at the end, making it an aromatic alcohol. This structure imparts certain lipophilicity and hydrophilicity to cinnamyl, exhibiting moderate physicochemical properties.

In terms of physicochemical parameters, cinnamol has a LogP value of 1.96, indicating good lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 20.23 Ų, and the number of hydrogen bond acceptors is 1, indicating moderate molecular polarity that facilitates binding to biological targets. It has relatively high water solubility, about 1900 mg/L, indicating good solubility in body fluids and facilitating oral absorption. Toxicological evaluation showed that cinnamol LD50 is about 2000 mg/kg, with low toxicity, no significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition. Ames' mutagenicity test results were negative, indicating high safety. Additionally, cinnamol has strong blood-brain barrier penetration ability, suggesting its potential application value in central nervous system diseases.

Plant Origins and Extraction Methods

Cinnamol is mainly found in various aromatic plants, with chestnut flowers (Castanea mollissima Blume) as its primary source. As a traditional Chinese medicinal herb, chestnut flowers contain abundant cinnamol in their volatile oils. In addition, cinnamol can also be isolated from plants such as cinnamon trees (Cinnamomum spp.) and clove (Syzygium aromaticum).

There are various extraction methods, commonly including steam distillation, solvent leaching, and supercritical CO2 extraction. Steam distillation is suitable for extracting volatile oils and can effectively obtain essential oil blends containing cinnamon. Solvent extraction often uses ethanol, methanol, or ethyl acetate as solvents, optimizing extraction efficiency by adjusting solvent polarity. In recent years, supercritical CO2 extraction has become the preferred technology for extracting cinnamol due to its environmental friendliness, efficiency, and good protection for heat-sensitive components. After extraction, qualitative and quantitative analyses of cinnamon alcohol were performed using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) techniques to ensure the purity and active ingredient content of the extract.

Pharmacological activity research

Anti-obesity effects

Cinnamol demonstrates significant anti-obesity effects by regulating the expression of lipid metabolism-related genes, especially by inhibiting overexpressed peroxisome proliferator-activated receptor γ (PPARγ). As a key transcription factor for adipocyte differentiation and lipid storage, PPARγ's abnormal activation is closely related to obesity and metabolic syndrome. Cinnamol can downregulate PPARγ expression, inhibit adipocyte formation and lipid accumulation, and improve obesity-related metabolic disorders.

Antioxidant effects

Cinnamol has excellent free radical scavenging ability, effectively reducing oxidative stress levels. In vitro experiments show that cinnamol can scavenge free radicals such as DPPH and ABTS, and enhance the activity of intracellular antioxidant enzymes (such as superoxide dismutase SOD, glutathione peroxidase GPx), thereby reducing oxidative damage. This role is of great significance for the prevention and treatment of chronic inflammation, cardiovascular diseases, and neurodegenerative diseases.

Anti-inflammatory effects

Cinnamol exerts anti-inflammatory effects by regulating inflammatory signaling pathways and inhibiting the release of pro-inflammatory factors. Studies have found that cinnamol can inhibit activation of the NF-κB signaling pathway, reduce the expression of inflammatory mediators such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), thereby alleviating inflammatory responses. This action gives cinnamol potential therapeutic value in inflammatory diseases such as arthritis and enteritis.

Antifungal effects

Cinnamol exhibits inhibitory activity against various fungal pathogens, with related targets including ERG11, CYP51A1, CDR1, FKS1, MLS1, CYP51, MDR1, CHS3, ALS3, and CDR2. ERG11 and CYP51A1 encode key enzymes in fungal cell membrane synthesis; cinnamol inhibits fungal growth by disrupting these targets, disrupting the integrity of fungal cell membranes. Inhibition of multidrug resistance-related proteins such as CDR1 and MDR1 helps overcome fungal resistance and enhances the effectiveness of antifungal treatment. Preclinical studies have shown that cinnamol combined with traditional antifungal drugs can enhance efficacy and reduce the risk of resistance.

Mechanism of action and molecular targets

The multiple pharmacological effects of cinnamol are attributed to its interactions with various molecular targets. Its anti-obesity effect mainly regulates PPARγ expression by negatively regulating PPARγ expression and blocking the adipocyte differentiation signaling pathway. The antioxidant and anti-inflammatory effects involve inhibiting inflammatory signaling pathways such as NF-κB and MAPK, reducing the generation of inflammatory factors, enhancing intracellular antioxidant enzyme activity, and alleviating oxidative stress.

In its antifungal mechanism, cinnamol targets key enzymes ERG11 (encoding 14α-demethylase) and CYP51 family proteins in fungal cell membranes, inhibiting ergosterol biosynthesis and leading to membrane dysfunction. At the same time, cinnamol inhibits fungal multidrug resistance-related transporters CDR1 and MDR1, blocking drug efflux and enhancing intracellular accumulation of antifungal drugs. Actions on FKS1 (β-1,3-glucan synthase) and CHS3 (chitin synthase) disrupt cell wall structures, further weakening fungal viability.

Molecular docking and cell experiments validated the binding affinity and functional regulation of cinnamol to the above targets, revealing the molecular basis of its multi-target synergistic effects.

Druggability evaluation and pharmacokinetics

Cinnamol performs excellently in terms of druggability. Its molecular weight of 134.18 complies with the Lipinski rule, with a moderate LogP value of 1.96, good water solubility, and is beneficial for oral absorption and internal distribution. The extremely low polar surface area and number of hydrogen bond receptors facilitate cell membrane penetration and blood-brain barrier penetration, suggesting its potential application in central nervous system diseases.

Toxicological studies show that cinnamol has low acute toxicity (LD50 about 2000 mg/kg), no hepatotoxicity, cardiotoxicity, or hERG channel inhibition, and the Ames test is negative, indicating high safety. The strong permeability of the blood-brain barrier suggests its potential in treating neuroinflammation and other brain diseases.

Pharmacokinetic studies show that cinnamol is rapidly absorbed orally, has high bioavailability, is widely distributed in the body, and is mainly metabolized through hepatic enzymes, with safe and non-toxic metabolites. The main excretion routes are urine and bile. Its excellent pharmacokinetic characteristics lay the foundation for clinical application.

Prospects and outlooks for clinical applications

Based on cinnaminol's multi-target and multi-pathway pharmacological activity, it shows broad clinical application prospects in anti-obesity, anti-inflammatory, antioxidant, and antifungal fields. Especially in adjunctive therapy for obesity and metabolic syndrome, cinnamol is expected to become a safe and effective natural drug candidate by regulating PPARγ and related signaling pathways. Additionally, cinnamyl's anti-inflammatory and antioxidant properties offer new approaches for treating chronic inflammatory diseases and neurodegenerative diseases.

In the antifungal field, cinnamol targets multiple fungal targets, especially resistance-related proteins, showing potential to overcome resistance. In the future, it can be used in combination with existing antifungal drugs to improve efficacy and reduce the risk of resistance. The good safety profile and blood-brain barrier permeability of cinnamol also give it potential advantages in treating central nervous system infections such as fungal meningitis.

However, clinical research on cinnamol is still in its early stages, urgently requiring systematic preclinical and clinical trials to verify its efficacy and safety. Future research should focus on optimizing formulation processes, clarifying dose-effect relationships, exploring combination drug strategies, and deeply analyzing molecular mechanisms. In addition, the pharmacokinetic characteristics and metabolic pathways of cinnamol need further clarification to guide rational clinical medication.

Conclusion

As a natural product with a wide origin, simple structure, and rich bioactivity, cinnamyl alcohol demonstrates promising drug potential and clinical application prospects due to its multiple pharmacological effects including anti-obesity, antioxidant, anti-inflammatory, and antifungal effects. Its multi-target mechanism of action and excellent safety provide a solid foundation for the development of novel natural drugs. In the future, by deepening pharmacological mechanism research, optimizing extraction and preparation technologies, and conducting systematic clinical evaluations, cinnamon alcohol is expected to become an important natural medicine in the prevention and treatment of various diseases, contributing new strength to human health.