What is Ferulic acid?
Ferulic acid is a natural phenolic compound belonging to the hydroxycinnamic acid family and is found in a variety of plants (maximum in flaxseed), including cereals (especially rice, oats and wheat), fruits (especially oranges, dates and pineapple), vegetables (maximum in tomatoes, artichokes and carrots). It is known for its antioxidant and anti-inflammatory properties and has attracted growing interest in the field of pharmacology for its therapeutic potential in various pathologies, especially inflammatory ones. The chemical structure of ferulic acid allows the neutralization of free radicals, offering protection against oxidative damage and inflammation.
Pharmacological properties of Ferulic acid
Ferulic acid has numerous properties that make it an interesting compound for research and medicine. Its ability to neutralize free radicals is due to the presence of a methoxy group and a hydroxyl group in its chemical structure. This makes ferulic acid highly effective in preventing cellular damage caused by reactive oxygen species (ROS), which are often associated with chronic inflammation. Several studies indicate that ferulic acid can inhibit the release of pro-inflammatory cytokines (e.g. TNF-α and IL-6), key mediators of chronic inflammation. By acting on specific signaling pathways, such as MAP-kinase and NF-κB, ferulic acid reduces the activation of these inflammatory pathways, playing an important role in mitigating the symptoms of inflammation. Through these effects, some research suggests that ferulic acid may protect against neuronal damage, thus preventing neurodegenerative diseases such as Alzheimer’s disease. It may act as a modulator of neuroinflammation, reducing oxidative stress and inhibiting neuronal apoptosis.
Molecular targets of ferulic acid
Ferulic acid exerts its pharmacological effects by acting on several molecular targets:
NF-κB: inhibition of the transcription factor NF-κB is one of the main mechanisms through which ferulic acid reduces inflammation. NF-κB is a key regulator of inflammatory and immune responses; by inhibiting its activation, ferulic acid prevents the production of pro-inflammatory cytokines.
MAPK (Mitogen-Activated Protein Kinases): ferulic acid interferes with this signaling pathway, which is responsible for regulating several cellular responses, including inflammation. The effects of ferulic acid on the reduction of MAPK activity contribute to its anti-inflammatory action.
COX-2 (Cyclooxygenase-2): COX-2 is a key enzyme in inflammation and in the production of inflammatory prostaglandins. Ferulic acid has shown an inhibitory effect on COX-2, thus reducing the synthesis of prostaglandins and other related inflammatory mediators.
ROS (Reactive Oxygen Species): Ferulic acid counteracts the effects of oxidative free radicals and inhibits cell oxidation, protecting against damage associated with oxidative stress.
Effects of ferulic acid in inflammatory diseases
Ferulic acid has shown therapeutic potential for several inflammatory conditions, such as rheumatoid arthritis, ulcerative colitis and neurodegenerative diseases. Studies suggest that it could be used as an adjuvant in existing pharmacological treatments, contributing to the reduction of inflammatory symptoms and improving the quality of life of patients.
Rheumatoid Arthritis
Ferulic acid has shown promising effects in the treatment of rheumatoid arthritis (REA) due to its antioxidant and anti-inflammatory properties. REA is a chronic inflammatory and autoimmune disease characterized by inflammation of the joints, which leads to damage to the joint structures and, in the long term, to deformity and disability. Ferulic acid acts by modulating the inflammatory and oxidative pathways involved in the pathogenesis of REA. The cellular NF-κB pathway is one of the main signaling pathways implicated in chronic inflammation and the pathogenesis of REA. A study by Lee et al. (2017) demonstrated that ferulic acid treatment in animal models of arthritis significantly reduced the production of TNF-α and IL-6, improving the symptoms of joint inflammation.
Ferulic acid has been shown to inhibit the activation of NF-κB, thereby reducing the expression of pro-inflammatory genes and the intensity of joint inflammation (Kim et al., 2018). Oxidative stress plays a crucial role in the progression of REA, exacerbating tissue damage and inflammation. Ferulic acid, due to its potent antioxidant activity, neutralizes free radicals and reduces oxidative damage in joint cells. Zhang et al. (2019) showed that ferulic acid was able to increase the activity of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, while reducing ROS (reactive oxygen species) levels in inflamed joint cells.
Inflammatory Bowel Disease
Ferulic acid has been the subject of extensive research for its therapeutic potential in inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease. Ferulic acid reduces the production of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), which play a key role in the pathogenesis of IBD. This is achieved through the inhibition of IKK-alpha and IKK-beta kinases upstream of NF-kB. A study by Li et al. (2016) demonstrated that ferulic acid treatment in animal models of colitis led to a significant reduction in pro-inflammatory cytokines, reducing the clinical symptoms of the disease. Zhang et al. (2018) showed that ferulic acid reduced NF-κB levels in inflamed intestinal tissues, helping to limit tissue damage. The integrity of the intestinal barrier is compromised in IBD (leaky gut), allowing the passage of bacteria and toxins that exacerbate inflammation.
Ferulic acid helps maintain the function of the intestinal barrier, reducing intestinal permeability and preventing the passage of harmful agents. Ferulic acid has been shown to improve the integrity of the intestinal barrier by increasing the production of junctional proteins such as occludin and claudin, which are essential for maintaining barrier function. A recent study by Wang et al. (2020) showed that ferulic acid, administered in animal models of colitis, preserves the integrity of the intestinal barrier and reduces permeability, thus protecting the intestinal mucosa. Ferulic acid can positively influence the composition of the intestinal microbiota, which plays a crucial role in regulating intestinal inflammation. In animal model studies, ferulic acid promotes the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium, while reducing pathogenic bacteria, indicating that the therapeutic effects of ferulic acid in humans are multifaceted and have multiple mechanisms of action.
What is caffeic acid?
Like ferulic acid, caffeic acid is a phenolic acid belonging to the cinnamic acid family, present in numerous plants, especially in coffee, tea, fruit (very high in blueberries) and vegetables (very high in carrots, chard root, radicchio, eggplants, cauliflower, Brussels sprouts, Chinese cabbage) and spices (sage, parsley, turmeric, basil, thyme and oregano). Given the name, it is clear that the largest source of all are coffee beans. It is known for its antioxidant, anti-inflammatory, antimicrobial and anti-carcinogenic properties. These characteristics make it a natural compound of great pharmacological interest, especially for the treatment and prevention of inflammatory and degenerative diseases.
Molecular targets of caffeic acid
Caffeic acid acts on several molecular targets, which explain its pharmacological properties. They are essentially superimposable to those of ferulic acid, namely the activation of the NF-kB factor, stress family MAP-kinases (p38 and JNK) and the cyclooxygenase COX-2. Caffeic acid therefore acts in a similar way to many nonsteroidal anti-inflammatory drugs (NSAIDs), but with a natural and less aggressive profile that anyway needs more amounts for effectiveness.
Pharmacological properties of caffeic acid
Caffeic acid has numerous beneficial biological effects that make it a potential and promising therapeutic agent:
- Antioxidants: caffeic acid is a powerful antioxidant. Its ability to neutralize free radicals and prevent oxidative damage is linked to the presence of phenolic groups in its structure. This protective effect is useful for reducing oxidative stress associated with many chronic and degenerative diseases.
- Anti-inflammatory: Studies have shown that caffeic acid can modulate inflammatory pathways by reducing the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. The inhibitory effect of caffeic acid on several inflammatory signaling pathways, such as NF-κB and MAPK, contributes to reducing chronic inflammation.
- Immunomodulatory: Caffeic acid appears to have a positive effect on the immune response. This effect, combined with the reduction of inflammation, may be useful for treating chronic inflammatory or autoimmune diseases.
The effects of caffeic acid in inflammatory diseases
Caffeic acid shows therapeutic potential in several chronic inflammatory conditions, such as arthritis, inflammatory bowel disease, and neurodegenerative diseases.
Autoimmune Diseases
Caffeic acid has been shown to modulate the immune response, reducing the hyperactivation of the immune system that underlies autoimmune diseases. A study by Wang et al. (2018) showed that caffeic acid can reduce the proliferation of T cells and the activation of macrophages, which are central elements in the immune response. This effect leads to a decrease in the production of pro-inflammatory cytokines, improving the regulation of the immune system. The anti-inflammatory properties of caffeic acid can reduce symptoms associated with rheumatoid arthritis, such as swelling and joint pain. By inhibiting cytokines and inflammatory mediators, caffeic acid can reduce chronic joint damage.
The NF-κB and JAK/STAT pathways are frequently hyperactivated in autoimmune diseases. Caffeic acid has been shown to inhibit the activation of the NF-κB pathway, reducing the expression of inflammatory mediators. A study by Zhang et al. (2019) showed that caffeic acid can reduce the activity of the JAK/STAT pathway, attenuating inflammation in experimental models of lupus erythematosus. Caffeic acid exerts a moderate immunosuppressive effect, which may be useful for controlling hyperactive immune responses without completely suppressing the immune system. This effect was observed by Yamada et al. (2021), who studied caffeic acid treatment in animal models of autoimmune thyroiditis (Hashimoto’s type), showing a reduction in lymphocytic infiltration into the thyroid gland.
The anti-inflammatory and neuroprotective properties of caffeic acid may play a significant role in counteracting the pathological processes of multiple sclerosis. Demyelination is a hallmark of MS. Caffeic acid has shown the ability to protect myelin sheaths and promote remyelination. A study by Chen et al. (2021) reported that caffeic acid contributes to oligodendrocyte survival and myelin synthesis, promoting the regeneration of damaged tissues in the central nervous system. In addition, it may modulate the immune response in the disease: according to a study by Park et al. (2022), caffeic acid reduces the proliferation of autoreactive T lymphocytes and the production of inflammatory cytokines, contributing to an improvement in the clinical course of MS.
Summary
As can be seen from this information, natural polyphenols are valuable allies in the prevention and potential management of autoimmune conditions. Their multiple biological actions allow them to act at multiple levels, a property that is often not possessed by other immunosuppressive or immunomodulatory drugs currently used in the treatment of autoimmune syndromes. To this end, knowing the major sources of these phenolic acids can be managed through a personalized dietary approach.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
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