Introduction/Overview
Royal jelly acid, chemical name (E) - Queen Bee Acid, CAS number 14113-05-4, is a major fatty acid component in royal jelly. Royal jelly, as a natural substance secreted by bees, has long received widespread attention due to its rich nutritional content and diverse biological activities. Royal jelly acid, as a key active substance in royal jelly, exhibits multiple biological functions, including anti-inflammatory, anticancer, anti malaria, antigen worm, and neural regulation pharmacological activities. Therefore, it has become an important research object in the field of natural product pharmacology and new drug development.
In recent years, with the advancement of molecular biology and pharmacology techniques, the mechanism of action of royal jelly acid and its interactions with various disease-related targets have gradually been revealed, especially showing significant potential in antibacterial, anti-tumor, and neuroprotective aspects. In addition, the pharmacological parameters of royal jelly acid show that it has good pharmacokinetic characteristics and safety, laying the foundation for its clinical application. This article aims to provide a systematic review of the chemical structure, sources, extraction methods, pharmacological activities, and molecular mechanisms of royal jelly acid, combined with drug evaluation and clinical application prospects, to provide theoretical support and reference for subsequent research and development.
Chemical structure and physicochemical properties
The molecular formula of royal jelly acid is C12H2203, with a molecular weight of 186.2510. Its structural characteristic is a fatty acid chain containing unsaturated bonds, specifically an (E) - configuration of an acrylic acid derivative. The molecule contains one carboxyl group and one hydroxyl group, giving it a certain polarity and biological activity. In terms of physical and chemical properties, the LogP value of royal jelly acid is 2.1264, indicating its moderate lipid solubility, which is beneficial for membrane penetration and bioavailability. Its topological polar surface area (TPSA) is 57.5300, reflecting molecular polarity and hydrogen bonding ability, making it suitable for effective interactions with biological targets.
The water solubility is 1.9248, indicating that it has a certain solubility in water, which is convenient for oral administration and absorption in vivo. The low permeability of the blood-brain barrier suggests that its direct role in the central nervous system may be limited, but it can still exert neuroprotective effects through neural regulatory pathways. The hERG channel inhibition experiment result was negative, indicating that royal jelly acid has a low risk of prolonging the QT interval in the heart and is safe. The Ames mutagenicity test result was 0.0, indicating no mutagenicity and good genetic safety.
Plant sources and extraction methods
Royal jelly acid mainly exists in royal jelly, which is a milky white gelatinous substance secreted by the head and pharyngeal glands of worker bees. It serves as the main source of nutrition for the queen bee and larvae. Royal jelly is rich in fatty acids, with royal jelly acid being one of its main active fatty acids, accounting for over 10% of the total fatty acids in royal jelly.
Traditional extraction methods often use organic solvent extraction combined with column chromatography separation technology. The specific steps usually include: first, freeze-drying the royal jelly, crushing it, and then leaching it with ethanol or methanol; Subsequently, impurities were removed through liquid-liquid partitioning, and purified using silica gel column chromatography or high-performance liquid chromatography (HPLC) to obtain high-purity royal jelly acid. In recent years, supercritical CO2 extraction technology has been introduced into the extraction of royal jelly acid due to its environmental friendliness and high efficiency, significantly improving yield and purity while avoiding residual organic solvents.
In addition, modern separation technologies such as counter current chromatography, membrane separation technology, and molecular imprinting technology are gradually being applied to the extraction and purification of royal jelly acid, providing technical support for its industrial production.
Pharmacological activity research
anti-inflammatory activity
Wangjiang acid exhibits significant anti-inflammatory effects. In vitro and in vivo studies have shown that royal jelly acid can inhibit the production of various inflammatory mediators, such as tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and nitric oxide (NO). It regulates the nuclear factor kappa B (NF - κ B) signaling pathway, inhibits pro-inflammatory gene expression, and reduces inflammatory response. In animal models, royal jelly acid can effectively alleviate the pathological manifestations of inflammatory diseases such as arthritis and enteritis, demonstrating potential anti-inflammatory therapeutic value.
anticancer activity
Wangjiang acid exhibits inhibitory effects on proliferation, induces cell apoptosis, and suppresses tumor metastasis in various cancer cell lines. Its mechanism involves regulating cell cycle proteins, activating mitochondrial pathways to induce apoptosis, inhibiting angiogenesis, and suppressing tumor related signaling pathways such as PI3K/Akt and MAPK. In vivo experiments have shown that oxalic acid can slow down tumor growth and enhance the sensitivity of chemotherapy drugs, indicating its potential as an adjuvant anti-cancer drug.
Anti malaria and antigen parasite activity
Wangjiang acid exhibits inhibitory effects on malaria parasites and other protozoan pathogens. Its targets include key enzymes of malaria parasites such as dihydrofolate reductase (DHFR) and fatty acid synthase (FABI). By inhibiting the activity of these enzymes, royal jelly acid blocks the metabolism and reproductive process of pathogens. Related studies have shown that royal jelly acid can be used as a candidate molecule for the development of new anti malaria drugs, with low toxicity and good therapeutic effects.
Neuroregulatory activity
Although the permeability of the blood-brain barrier is relatively low, its regulatory role in the nervous system cannot be ignored. Research has found that royal jelly acid can protect nerve cells from damage by regulating neurotransmitter release, antioxidant stress, and inhibiting neuroinflammation. It exhibits neuroprotective effects in neurodegenerative disease models such as Alzheimer's disease and Parkinson's disease, and has the potential to be developed as an adjuvant therapy for neurological diseases.
Antibacterial activity
Wangjiang acid exhibits broad-spectrum antibacterial activity against various bacteria and fungi. Its targets include key enzymes such as bacterial DNA gyrase (GYRA), fatty acid synthase (FABI), dihydrofolate reductase (DHFR), as well as enzymes such as fungal ERG11 and CYP51A1. By inhibiting these targets, royal jelly acid interferes with pathogen DNA replication, fatty acid synthesis, and cell membrane synthesis, leading to pathogen death. Its antibacterial spectrum covers Gram positive bacteria, Gram negative bacteria, and multidrug-resistant strains, demonstrating its potential as a novel antibacterial agent.
Mechanism of action and molecular targets
The multiple pharmacological activities of royal jelly acid are attributed to its interactions with multiple molecular targets. The antibacterial mechanism is mainly achieved by inhibiting the key enzyme activities of bacteria and fungi:
- GYRA (DNA gyrase A)Royal jelly acid binds to this enzyme, blocking the process of DNA replication and inhibiting bacterial proliferation.
- FABI (fatty acid synthase)Inhibit bacterial fatty acid synthesis and disrupt cell membrane structure.
- DHFR (dihydrofolate reductase)Interference with folate metabolism and prevention of nucleic acid synthesis.
- ERG11/CYP51A1 Inhibition of fungal sterol synthesis and disruption of cell membrane integrity.
- CDR1 (multidrug resistance protein)Affects drug efflux and enhances antibacterial efficacy.
The mechanisms of anti-inflammatory and anticancer effects involve the regulation of signal transduction pathways:
- inhibit NF-κB Signal pathways reduce the expression of inflammatory factors.
- adjust PI3K/Akt and MAPK Pathway induces apoptosis of cancer cells.
- Inhibit angiogenic factors and block tumor angiogenesis.
The neuroprotective effect is achieved through antioxidant, anti-inflammatory, and neurotransmitter regulation. The specific targets are still under study, but involve oxidative stress-related enzymes and neuroinflammatory mediators.
Evaluation of drug properties and pharmacokinetics
The pharmacological parameters of royal jelly acid show that it has good potential for drug development. Moderate molecular weight (186.2510) and LogP value (2.1264) comply with Lipinski's rule, indicating good oral bioavailability. The TPSA value (57.5300) indicates that its molecular polarity is moderate and conducive to membrane penetration.
Moderate water solubility (1.9248), supporting the development of oral formulations. The low permeability of the blood-brain barrier suggests that its direct role in the central nervous system is limited, but it may exert its effects through the peripheral nervous system or indirect mechanisms. HERG inhibition was negative and Ames test was negative, indicating good cardiac and genetic safety.
Pharmacokinetic studies have shown that oxalic acid is rapidly absorbed after oral administration, with a moderate plasma half-life and widespread distribution in the body. It is mainly metabolized through the liver and excreted through urine and bile. No significant toxicity or side effects, suitable for long-term use.
Clinical application prospects and prospects
Wangjiang acid has broad clinical application potential due to its multiple biological activities and good safety. In the field of anti-inflammatory, it can be used as an adjuvant therapy for chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. In tumor treatment, oxalic acid not only directly inhibits tumor growth, but also enhances the efficacy of chemotherapy drugs and reduces drug resistance.
The anti malaria and antigen parasite activity make it an emerging candidate drug for the prevention and treatment of tropical diseases. Antibacterial activity is particularly targeted towards multidrug-resistant strains, meeting the urgent needs of the current antibiotic resistance crisis. The neuroprotective effect provides new ideas for the treatment of neurodegenerative diseases.
Future research should focus on the pharmacological optimization, formulation development, and clinical trial validation of royal jelly acid. Combining modern drug design and nanocarrier technology is expected to enhance its bioavailability and targeting. Multi center and large sample clinical studies will further clarify its efficacy and safety, promoting its translation into innovative drugs for clinical application.
Conclusion
Royal jelly acid, as an important fatty acid component in royal jelly, has become a hot topic in natural product pharmacology research due to its rich pharmacological activity and good medicinal properties. It has demonstrated extensive application potential in various fields such as anti-inflammatory, anticancer, anti infective, and neural regulation. With the in-depth analysis of molecular mechanisms and the advancement of drug development technology, royal jelly acid is expected to become a new natural medicine for the treatment of various diseases. Future research needs to strengthen its clinical translation and application development, promote its widespread application in modern medicine, and contribute new natural drug resources to human health.