Synonym name: 12-Hydroxyoleic acid; Ricinusoleic acid; Ricinic acid; Ricinolic acid
Catalogue No.: BP1217
Cas No.: 141-22-0
Formula: C18H34O3
Mol Weight: 298.467
Botanical Source: Occurs in castor oil and other oils e.g. grape, Lesquerella densipila and ergot (Claviceps purpurea)
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℃
57.5300
5.2913
2.9561
.0135
1.8404
2.3725
High
94.5566
2.6995
No
Yes
No
No
No
No
0.0
No
No
Yes
No
Ricinoleic acid, also known as 12-hydroxy-9-octadecenoic acid, is a unique monohydroxy unsaturated fatty acid with a CAS number of 141-22-0. As the main active ingredient in Castor oil, with a content of up to 85-90%, ricinoleic acid has long played an important role in traditional medicine, especially known for its significant laxative and oxytocin inducing effects. Modern pharmacological research reveals that its biological activity goes far beyond this, demonstrating multiple pharmacological potentials including anti-inflammatory, anti anxiety, and anti-tumor effects, transforming it from a traditional plant component to a hot topic in modern natural product pharmacology research.
In recent years, with a deeper understanding of the fatty acid signaling pathway and its role in disease regulation, ricinoleic acid, as an endogenous agonist of prostaglandin EP3 receptors, has attracted widespread attention for its complex biological effects. Especially in the field of tumor research, preliminary evidence shows that ricin may affect the proliferation, apoptosis and metastasis of malignant tumor cells such as breast cancer by regulating multiple key signal nodes such as AMPK, STAT3, and BCL-2. At the same time, as a chemical derived from renewable resources, its application background in the pharmaceutical, cosmetics, and materials industries also provides a unique starting point for the development of its medicinal properties. This article aims to systematically review the chemical properties, pharmacological activities, molecular mechanisms of action, and pharmacological potential of ricinoleic acid, in order to provide a comprehensive academic perspective for the modern research and development of this ancient natural product.
Ricinolic acid is a C18 long-chain fatty acid with a molecular formula of C ₁₈ H ∝₄ O ∝ and a molecular weight of 298.4670. The core of its structure lies in three key modification sites on the carbon chain: a cis double bond at position 9 (- CH=CH -), a hydroxyl group at position 12 (- OH), and a carboxyl group at the end (- COOH). This structure, which introduces hydroxyl groups in the middle of the fatty acid chain, is relatively rare in nature, endowing ricinoleic acid with unique physicochemical properties and biological activity.
The presence of hydroxyl groups significantly changes the polarity of the molecule. Its topological polar surface area (TPSA) is 57.53 Å ², which is higher than that of ordinary non hydroxylated fatty acids, indicating its potential for hydrophilicity. However, its long carbon chain and double bond structure contribute significantly to its hydrophobic properties, and the calculated lipid water partition coefficient (LogP) is 5.2913, indicating its high lipophilicity. This contradictory characteristic is reflected in its solubility: ricinoleic acid has an extremely low solubility in water, only 0.0135 mg/mL, and is easily soluble in most organic solvents such as ethanol, ether, and chloroform. This amphiphilic structure enables it to interact with biological membranes and may affect its binding mode with target proteins.
The carboxyl group of ricinoleic acid typically exists in a deprotonated anionic form (ricinoleic acid radical) at physiological pH, while the hydroxyl group can act as a hydrogen bond donor or acceptor, participating in molecular recognition. Its high LogP value also indicates a high blood-brain barrier permeability, which is consistent with its reported central nervous system activity, such as anti anxiety. In addition, ricinoleic acid contains a chiral center (C-12), and its naturally occurring form is mainly in the R configuration. Its stereochemistry is crucial for its biological activity.
Ricinolic acid is almost exclusively enriched in the seeds of the Euphorbiaceae plant Ricinus communis L. Castor oil is the main product obtained by pressing or solvent extraction from castor seeds, in which ricinoleic acid exists in the form of triglycerides, accounting for more than 85% of the total fatty acid content. This high concentration is extremely special in vegetable oil, making castor oil the only important source for commercial production of ricinoleic acid.
The industrial production of ricinoleic acid usually adopts a two-step method. Firstly, crude castor oil is obtained from castor seeds by cold pressing, hot pressing, or organic solvent extraction (such as n-hexane). Crude oil needs to undergo refining steps such as degumming, deacidification, decolorization, and deodorization to remove phospholipids, free fatty acids, pigments, and odor substances, resulting in refined castor oil. The second step is to release free ricinoleic acid from refined castor oil. This is mainly achieved through Alkali catalyzed saponification reaction or Enzymatic hydrolysis Complete. The saponification method uses sodium hydroxide or potassium hydroxide to hydrolyze castor oil triglycerides into ricinoleic acid salt (soap), which is then acidified with a strong acid (such as sulfuric acid or hydrochloric acid) to precipitate free ricinoleic acid. The product is then washed with water, dried, and purified (such as distillation or crystallization) to obtain the desired product. Enzymatic methods (such as using lipase) have milder conditions, higher selectivity, and can better maintain the natural configuration of fatty acids, but the cost is higher. For high-purity ricinoleic acid used in research (such as ≥ 85% or higher), it is often necessary to combine column chromatography, urea inclusion (using the characteristic of ricinoleic acid hydroxyl groups forming inclusion complexes to separate saturated fatty acids), or preparative high-performance liquid chromatography for further purification.
The pharmacological activity spectrum of ricinoleic acid is extensive and complex, with some effects even appearing contradictory, which is closely related to its multi-target properties.
1. Gastrointestinal and uterine smooth muscle effects:
This is the most classic and relatively clear pharmacological effect of ricinoleic acid. After oral administration, ricinoleic acid is hydrolyzed and released in the small intestine, activating prostaglandin EP3 receptors on intestinal epithelial cells, triggering strong secretion and peristaltic effects, leading to watery diarrhea, which is the basis of its use as a potent laxative (castor oil). Similarly, its excitatory effect on the EP3 receptor of uterine smooth muscle can induce uterine contractions, which has been historically used for induced labor.
2. Anti inflammatory and immune regulatory activity:
Ricinolic acid exhibits context dependent immunomodulatory effects. In various acute and chronic inflammation models, such as carrageenan induced paw edema in rats and acetic acid induced increased intra-abdominal capillary permeability in mice, ricinoleic acid exhibits significant anti-inflammatory effects. Its mechanism may be related to the inhibition of pro-inflammatory mediators (such as TNF - α, IL-6) production and regulation of immune cell function. However, there are also studies reporting that under certain conditions (such as specific cell types or concentrations), it may exhibit pro-inflammatory properties, suggesting that its immune regulatory effects have fine concentration and microenvironment dependencies.
3. Central nervous system activity:
Animal experiments have shown that ricinoleic acid has anti anxiety like effects. In classic anxiety models such as elevated cross maze and dark box, administering ricinoleic acid can increase animal exploratory behavior. Its high blood-brain barrier permeability supports its direct central role, and the potential mechanism may involve regulation of the neurotransmitter system (such as the GABAergic system) or specific membrane receptors.
4. Antitumor activity:
In recent years, the pharmacological activity of ricinoleic acid in the field of tumors has become a new research hotspot. In breast cancer research, ricinic acid has been proved to inhibit the proliferation, invasion and migration of many breast cancer cell lines (such as MCF-7, MDA-MB-231), and induce cell apoptosis and cell cycle arrest. It also showed the potential of sensitizing chemotherapy drugs to drug resistant breast cancer cells. These effects suggest that ricinoleic acid may be a candidate anti-tumor molecule with multi pathway inhibitory ability.
5. Other activities:
Research has also shown that ricinoleic acid has certain antibacterial, antifungal, analgesic, and skin penetration promoting effects, the latter of which makes it valuable for application in transdermal drug delivery systems.
The multiple pharmacological activities of ricinic acid stem from its regulation of multiple molecular targets and signal pathways, especially in breast cancer. The research on the mechanism of action has revealed a complex network.
1. Prostaglandin EP3 receptor activation:
This is the core mechanism by which it mediates smooth muscle contraction (diarrhea, uterine contractions). Ricinolic acid acts as a ligand for the EP3 receptor (EC50 is approximately 0.5 μ M in MEG-01 cells), and upon activation, it inhibits adenylate cyclase through Gi protein, reducing intracellular cAMP levels and leading to smooth muscle contraction.
2. Multi target mechanism in breast cancer:
Current studies suggest that ricinic acid may play an anti breast cancer effect through the following key targets and pathways:
* AMPK (PRKAA1) activation: AMPK is a core regulatory factor in cellular energy metabolism. Ricinolic acid may inhibit protein synthesis and cell proliferation by activating AMPK, suppressing its downstream mammalian target protein (mTOR) pathway, and inducing autophagy.
* Regulation of apoptosis pathway: Ricinolic acid can downregulate the expression of anti apoptotic protein BCL-2, and may also affect mitochondrial membrane potential, promote cytochrome C release, activate caspase cascade reaction, and ultimately induce cancer cell apoptosis.
* STAT3 signal suppression: STAT3 is an important oncogenic transcription factor that is continuously activated and associated with tumor growth, survival, and immune evasion. Ricinolic acid may reduce the phosphorylation (activation) of STAT3 by inhibiting the activity of JAK or upstream receptor tyrosine kinases, thereby downregulating the expression of its target genes (such as Cyclin D1, BCL-2, MMP-2).
* Estrogen receptor beta (ESR2) interaction: The structure of ricinic acid may interact with ESR2, which may interfere with estrogen signaling pathway in estrogen receptor positive breast cancer.
* Drug efflux pump inhibition: Research has shown that ricinoleic acid may inhibit the function of ABC transporter superfamily members such as ABCB1 (P-gp) and ABCG2 (BCRP). These two proteins are the main cause of multidrug resistance (MDR) in cancer cells, and inhibiting them can reverse resistance, enhance the accumulation and efficacy of chemotherapy drugs in cells.
* Target points related to invasion and metastasis: Ricinolic acid can downregulate the expression and activity of matrix metalloproteinase MMP-2, thereby inhibiting the degradation and invasion ability of cancer cells towards the basement membrane. In addition, its potential impact on MAPT (microtubule associated protein tau) and LCK (lymphocyte specific protein tyrosine kinase) may also involve the regulation of cytoskeleton rearrangement and signal transduction.
* Regulation of protein kinase C (PRKCA): PKC α plays a dual role in cell proliferation and apoptosis, and the regulation of its activity by ricinoleic acid may be part of its effector network.
It should be pointed out that most of the above mechanism networks are based on in vitro cell experiments, and the cross dialogue between various pathways and their specific contributions in the in vivo tumor microenvironment still need further systematic research to clarify.
Based on the provided parameters and existing knowledge, the preliminary evaluation of the pharmacological properties of ricinoleic acid is as follows:
Pharmacokinetic (ADME) characteristics:
* Absorption and distribution: The high lipophilicity (LogP>5) of ricinoleic acid facilitates its passive diffusion and transmembrane absorption. After oral administration, its triglyceride form is hydrolyzed by intestinal pancreatic lipase, and free ricinoleic acid is absorbed. Its high blood-brain barrier permeability prediction supports its central effects. In the body, it may bind to serum albumin like other fatty acids for transport and distribute to organs such as adipose tissue and liver.
* Metabolism: As a fatty acid, ricinoleic acid is mainly metabolized through β - oxidation, and its hydroxyl and double bonds may affect the oxidation rate and produce unique metabolic intermediates. It may also form esters through ω - oxidation or binding with glycerol, cholesterol, etc. Its hydroxyl group provides sites for II binding reactions such as glucuronidation and sulfation, which facilitates its excretion.
* Excretion: Metabolites are mainly excreted through the kidneys and urine, while the unmetabolized portion may be excreted through bile.
Analysis of pharmacological parameters:
* Advantage: The molecular weight is moderate (298.5), meeting the small molecule standards for drug like properties. High blood-brain barrier permeability is an advantage for central nervous system drugs. critical The safety warning indicators show optimism: Its HERG inhibition risk is' no 'This means that the risk of inducing QT interval prolongation and tip twisting ventricular tachycardia in the heart is relatively low;The Ames test result is 0.0 Under the conditions of this experiment, no mutagenicity was observed, which is an important positive signal for early safety assessment of the drug.
* Challenge: The main challenge lies in its extremely low Water solubility（0.0135 mg/mL）， This will pose difficulties for formulation development and may require the use of solubilization techniques such as salt formation, cyclodextrin inclusion, preparation of nano formulations or liposomes. High LogP values may also pose potential risks of tissue accumulation and require attention in long-term toxicity experiments.
* Pharmacokinetic research gap: At present, there is still a lack of systematic and quantitative pharmacokinetic studies on ricinoleic acid (such as absolute bioavailability, half-life, clearance rate, tissue distribution quantitative data) in public literature, which is a key information gap that must be filled in order to move towards drug development.
Ricinolic acid, a traditional medicinal plant oil component, is demonstrating diverse potential for modern clinical applications.
1. Tumor therapy adjuvants or novel anti-cancer lead compounds:
In view of its multi pathway inhibitory effect on breast cancer cells, especially on the activation of AMPK, the inhibition of STAT3 and the potential inhibitory ability on ABCB1/ABCG2 efflux pump, one of the most promising directions of ricinic acid is as follows:Adjuvant therapy strategy for breast cancer It can be explored: ① in combination with existing chemotherapy drugs (such as doxorubicin, paclitaxel) to reverse multidrug resistance, reduce chemotherapy dose and toxicity; ② As a supplement to hormone therapy or targeted therapy; ③ Based on its mechanism of action, develop its derivatives or analogues to optimize activity and drug properties, and create novel anti-tumor drug lead compounds.
2. Neurological disorders:
Its anti anxiety activity and good blood-brain barrier penetration ability make it of research value in the treatment of anxiety disorders and stress-related disorders. Further clarification is needed on the central target and the safety of long-term medication.
3. Gastrointestinal drugs:
The mechanism of its potent laxative effect is clear, and the development of safer and dose controllable ricinoleic acid derivatives or new formulations for the treatment of refractory constipation or preoperative bowel preparation remains a feasible direction.
4. External preparations:
With its anti-inflammatory, analgesic and penetration promoting properties, it can be used in topical creams, gel or patches for the treatment of skin inflammation and arthritis. Its application as a functional ingredient (moisturizing, soothing) in cosmetics also exists.
Challenges and future research directions:
* Mechanism depth and specificity: It is necessary to use chemical biology methods (such as probe molecules) to accurately identify its direct target and clarify whether its "multi-target" effect originates from the regulation of a single upstream control node or truly interacts directly with multiple target proteins.
* Balance between activity and toxicity: Its potent laxative effect is both therapeutic and dose limiting toxicity. Future research needs to be conducted through Structural modification By modifying its carboxyl, hydroxyl, or double bonds, the aim is to "differentiate" its different pharmacological activities and obtain derivatives with more specific activity and wider therapeutic window.
* Advanced delivery system: To address the issue of poor water solubility, new delivery systems such as nanoemulsions, lipid nanoparticles, and polymer micelles have been developed to improve their bioavailability and achieve tumor targeted delivery or controlled release.
* Pre clinical and clinical evaluation of the system: Standardized preclinical pharmacodynamic (more in vivo tumor models), pharmacokinetic, and toxicological studies must be completed to provide solid data support for its clinical trial application.
Ricinolic acid, a hydroxy fatty acid derived from the ancient castor plant, is undergoing a magnificent transformation from its traditional use to a star molecule in modern pharmacology. Its unique chemical structure lays the foundation for its extensive biological activity, from the classic EP3 receptor-mediated smooth muscle effect to the emerging anti-tumor effects involving multiple targets such as AMPK, STAT3, BCL-2, all of which demonstrate its enormous potential as a bioactive molecule. Although it faces challenges such as low water solubility and lack of systematic pharmacokinetic data in terms of drug properties, its good safety signals in hERG inhibition and mutagenicity screening are encouraging. In the future, through in-depth molecular mechanism analysis, rational drug chemical modification, and innovative formulation technology, ricinoleic acid and its derivatives are expected to open up new drug development paths in fields such as tumor adjuvant therapy, neurological diseases, and topical formulations, fully demonstrating the translational medical value from traditional natural products to modern innovative drugs.
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