Implications for Cancer Therapy

Nature has generously offered a wide range of herbs (e.g., thyme, oregano, rosemary, sage, mint, basil) rich in many polyphenols and other phenolic compounds with strong antioxidant and biochemical properties. This paper focuses on several natural occurring phenolic acids (caffeic, carnosic, ferulic, gallic, p-coumaric, rosmarinic, vanillic) and first gives an overview of their most common natural plant sources. A summary of the recently reported antioxidant activities of the phenolic acids in o/w emulsions is also provided as an in vitro lipid-based model system. Exploring the interfacial activity of phenolic acids could help to further elucidate their potential health properties against oxidative stress conditions of biological membranes (such as lipoproteins). Finally, this review reports on the latest literature evidence concerning specific biochemical properties of the examined phenolic acids.

Phenolic Acids of Plant Origin—A Review on Their Antioxidant Activity In Vitro (O/W Emulsion Systems) Along with Their in Vivo Health Biochemical Properties

Caffeic acid is a plant-derived compound that is classified as hydroxycinnamic acid which contains both phenolic and acrylic functional groups. Caffeic acid has been greatly employed as an alternative strategy to combat microbial pathogenesis and chronic infection induced by microbes such as bacteria, fungi, and viruses. Similarly, several derivatives of caffeic acid such as sugar esters, organic esters, glycosides, and amides have been chemically synthesized or naturally isolated as potential antimicrobial agents. To overcome the issue of water insolubility and poor stability, caffeic acid and its derivative have been utilized either in conjugation with other bioactive molecules or in nanoformulation. Besides, caffeic acid and its derivatives have also been applied in combination with antibiotics or photoirradiation to achieve a synergistic mode of action. The present review describes the antimicrobial roles of caffeic acid and its derivatives exploited either in free form or in combination or in nanoformulation to kill a diverse range of microbial pathogens along with their mode of action. The chemistry employed for the synthesis of the caffeic acid derivatives has been discussed in detail as well.

Caffeic Acid and Its Derivatives: Antimicrobial Drugs toward Microbial Pathogens.

Coffee is one of the most widely consumed beverages worldwide. It is usually identified as a stimulant because of a high content of caffeine. However, caffeine is not the only coffee bioactive component. The coffee beverage is in fact a mixture of a number of bioactive compounds such as polyphenols, especially chlorogenic acids (in green beans) and caffeic acid (in roasted coffee beans), alkaloids (caffeine and trigonelline), and the diterpenes (cafestol and kahweol). Extensive research shows that coffee consumption appears to have beneficial effects on human health. Regular coffee intake may protect from many chronic disorders, including cardiovascular disease, type 2 diabetes, obesity, and some types of cancer. Importantly, coffee consumption seems to be also correlated with a decreased risk of developing some neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and dementia. Regular coffee intake may also reduce the risk of stroke. The mechanism underlying these effects is, however, still poorly understood. This review summarizes the current knowledge on the neuroprotective potential of the main bioactive coffee components, i.e., caffeine, chlorogenic acid, caffeic acid, trigonelline, kahweol, and cafestol. Data from both in vitro and in vivo preclinical experiments, including their potential therapeutic applications, are reviewed and discussed. Epidemiological studies and clinical reports on this matter are also described. Moreover, potential molecular mechanism(s) by which coffee bioactive components may provide neuroprotection are reviewed.

Neuroprotective Effects of Coffee Bioactive Compounds: A Review.

Hydroxycinnamic acids (HCAs) are important natural phenolic compounds present in high concentrations in fruits, vegetables, cereals, coffee, tea and wine. Many health beneficial effects have been acknowledged in food products rich in HCAs; however, food processing, dietary intake, bioaccessibility and pharmacokinetics have a high impact on HCAs to reach the target tissue in order to exert their biological activities. In particular, metabolism is of high importance since HCAs' metabolites could either lose the activity or be even more potent compared to the parent compounds. In this review, natural sources and pharmacokinetic properties of HCAs and their esters are presented and discussed. The main focus is on their metabolism along with biological activities and health benefits. Special emphasis is given on specific effects of HCAs' metabolites in comparison with their parent compounds.

Natural Sources, Pharmacokinetics, Biological Activities and Health Benefits of Hydroxycinnamic Acids and Their Metabolites.

Caffeic acid (CA) is a phenolic compound synthesized by all plant species and is present in foods such as coffee, wine, tea, and popular medicines such as propolis. This phenolic acid and its derivatives have antioxidant, anti-inflammatory and anticarcinogenic activity. In vitro and in vivo studies have demonstrated the anticarcinogenic activity of this compound against an important type of cancer, hepatocarcinoma (HCC), considered to be of high incidence, highly aggressive and causing considerable mortality across the world. The anticancer properties of CA are associated with its antioxidant and pro-oxidant capacity, attributed to its chemical structure that has free phenolic hydroxyls, the number and position of OH in the catechol group and the double bond in the carbonic chain. Pharmacokinetic studies indicate that this compound is hydrolyzed by the microflora of colonies and metabolized mainly in the intestinal mucosa through phase II enzymes, submitted to conjugation and methylation processes, forming sulphated, glucuronic and/or methylated conjugates by the action of sulfotransferases, UDP-glucotransferases, and o-methyltransferases, respectively. The transmembrane flux of CA in intestinal cells occurs through active transport mediated by monocarboxylic acid carriers. CA can act by preventing the production of ROS (reactive oxygen species), inducing DNA oxidation of cancer cells, as well as reducing tumor cell angiogenesis, blocking STATS (transcription factor and signal translation 3) and suppression of MMP2 and MMP-9 (collagen IV metalloproteases). Thus, this review provides an overview of the chemical and pharmacological parameters of CA and its derivatives, demonstrating its mechanism of action and pharmacokinetic aspects, as well as a critical analysis of its action in the fight against hepatocarcinoma.

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Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma.

Pancreatic cancer is an aggressive, devastating disease due to its invasiveness, rapid progression, and resistance to surgical, pharmacological, chemotherapy, and radiotherapy treatments. The disease develops from PanINs lesions that progress through different stages. KRAS mutations are frequently observed in these lesions, accompanied by inactivation of PTEN, hyperactivation of the PI3K/AKT pathway, and chronic inflammation with overexpression of COX-2. Nimesulide is a selective COX-2 inhibitor that has shown anticancer effects in neoplastic pancreatic cells. This drug works by increasing the levels of PTEN expression and inhibiting proliferation and apoptosis. However, there is a need to improve nimesulide through its encapsulation by solid lipid nanoparticles to overcome problems related to the hepatotoxicity and bioavailability of the drug.

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Luis Eduardo Mosquera Narvaez

Papers

Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma.

Can Nimesulide Nanoparticles Be a Therapeutic Strategy for the Inhibition of the KRAS/PTEN Signaling Pathway in Pancreatic Cancer?