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Open accessJournal ArticleDOI: 10.3390/MOLECULES26051335

The Pluripotent Activities of Caffeic Acid Phenethyl Ester.

02 Mar 2021-Molecules (Multidisciplinary Digital Publishing Institute)-Vol. 26, Iss: 5, pp 1335
Abstract: Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honey bee-hive propolis. The mentioned compound, a well-known NF-κB inhibitor, has been used in traditional medicine as a potent anti-inflammatory agent. CAPE has a broad spectrum of biological properties including anti-viral, anti-bacterial, anti-cancer, immunomodulatory, and wound-healing activities. This review characterizes published data about CAPE biological properties and potential therapeutic applications, that can be used in various diseases.

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Topics: Caffeic acid phenethyl ester (77%), Propolis (58%)
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5 results found


Open accessJournal ArticleDOI: 10.3390/MOLECULES26102930
Jelena Šuran1, Ivica Cepanec, Tomislav Mašek1, Božo Radić  +3 moreInstitutions (1)
14 May 2021-Molecules
Abstract: Propolis is a honeybee product known for its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. It is rich in bioactive molecules whose content varies depending on the botanical and geographical origin of propolis. These bioactive molecules have been studied individually and as a part of propolis extracts, as they can be used as representative markers for propolis standardization. Here, we compare the pharmacological effects of representative polyphenols and whole propolis extracts. Based on the literature data, polyphenols and extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-κB to the pro-proliferative MAPK/ERK pathway. In addition, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway, and they all have antimicrobial activity. These similarities do not imply that we should attribute the action of propolis solely to the most representative compounds. Moreover, its pharmacological effects will depend on the efficacy of these compounds' extraction. Thus, we also give an overview of different propolis extraction technologies, from traditional to modern ones, which are environmentally friendlier. These technologies belong to an open research area that needs further effective solutions in terms of well-standardized liquid and solid extracts, which would be reliable in their pharmacological effects, environmentally friendly, and sustainable for production.

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Topics: Propolis (60%)

4 Citations


Open accessJournal ArticleDOI: 10.3389/FCIMB.2021.700305
Abstract: Candida albicans is the main fungal species associated with the development of oral candidiasis. Currently, therapeutic options for these infections are limited by the adverse effects of antifungal drugs and by the emergence of drug resistant strains. Thus, the development of new antifungal agents is needed for the prevention and treatment of oral Candida infections. Caffeic acid phenethyl ester (CAPE) is a natural compound from propolis polyphenolic groups that exhibits many pharmacological properties. In this study, we investigated whether CAPE can have antifungal and immunomodulatory effects on oral candidiasis. Preliminary tests to assess the antifungal activity of CAPE were performed using the Minimum Inhibitory Concentration (MIC) assay that demonstrated inhibition in a range from 16 to 32 μg/mL, confirming its antifungal activity on several C. albicans strains isolated from the oral cavity. Subsequently, we analyzed Candida spp biofilms formed in vitro, in which CAPE treatment at 5 x MIC caused a reduction of 68.5% in the total biomass and ~2.60 Log in the viable cell count (CFU/mL) in relation to the untreated biofilm (p<0.0001). Next, RNA was extracted from untreated and CAPE-treated biofilms and analyzed by real-time qPCR. A series of genes analyzed (ALS1, ECE1, EPA1, HWP1, YWP1, BCR1, BGR1, CPH1, EFG1, NDT80, ROB1, TEC1, UME6, SAP2, SAP5, PBL2, and LIP9) were downregulated by CAPE compared to the untreated control group (p<0.0001). In in vivo studies using Galleria mellonella, the treatment with CAPE prolonged survival of larvae infected by C. albicans by 44.5% (p < 0.05) and accompanied by a 2.07-fold increase in the number of hemocytes. Flow cytometry revealed the most prominent increases were in types P2 and P3 hemocytes, granular cells, which phagocytize pathogens. In addition, CAPE treatment decreased the fungal load in the hemolymph and stimulated the expression of antifungal peptide genes such as galiomicin and gallerimycin. The antifungal and immunomodulatory activities observed in G. mellonella were extended to a murine model of oral candidiasis, in which CAPE decreased the levels of C. albicans colonization (~2 log CFU/mL) in relation to the untreated control group. In addition, CAPE treatment significantly reduced pseudomembranous lesions, invasion of hyphae on epithelium surfaces, tissue damage and inflammatory infiltrate (p < 0.05). CAPE was also able to increase the expression of β-defensin 3 compared to the infected and untreated group by 3.91-fold (p < 0.0001). Taken together, these results show that CAPE has both antifungal and immunomodulatory effects, making it a promising natural antifungal agent for the treatment and prevention of candidiasis and shows impact to oral candidiasis.

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2 Citations


Book ChapterDOI: 10.1007/978-981-16-4935-6_8
Faizan Uddin, Mehboob Hoque1Institutions (1)
01 Jan 2021-
Abstract: Despite the concerted efforts in pursuit of developing effective therapy, the human race has merely succeeded in its fight against cancer. The limited success in this battle against cancer may be attributed to the development of resistance to the available therapeutic regimens, frequent recurrence, metastasis, tumor heterogeneity, and immune evasion. The sub-populated cancer stem cells (CSCs) are often held responsible for cancer relapse, therapy resistance, and metastasis. The stemness and tumorigenicity of CSCs are regulated by various pathways such as Wnt/β-catenin, hedgehog, PI3K-AKT, JAK-STAT, TGF-β, and notch signaling. Various therapeutic agents targeting CSCs are now being considered for the treatment of various malignancies. However, conventional therapies are associated with various side effects. Therefore, current therapeutic approaches are witnessing a paradigm shift towards natural compounds. To this end, dietary polyphenols are considered promising drug candidates for their both preventive as well as therapeutic properties. In this chapter, the non-flavonoid polyphenols are discussed in the context of their ability to target CSCs and their role in attenuation of fundamental pathways involved in the maintenance of CSCs such as Wnt/β-catenin, hedgehog, notch, and induction of programmed cell death pathways has been explored. The overview of this chapter will help the oncologist to devise more efficacious combinatorial therapies, utilizing naturally occurring non-flavonoid polyphenols and their derivatives along with chemotherapeutic drugs, which will offer the advantage of eliminating both the CSCs and other malignant cells in the heterogeneous tumor mass as a multipronged approach. The traditional knowledge of phytomedicines along with the current advancements of molecular and precision medicine and suitable delivery system hold a great promise to combat cancer and exterminate it from the root.

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Topics: Cancer stem cell (61%)

1 Citations


Journal ArticleDOI: 10.1007/S11010-021-04263-6
Abstract: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the synthesis of the CFTR protein, a chloride channel. The gene has approximately 2000 known mutations and all of them affect in some degree the protein function, which makes the pathophysiological manifestations to be multisystemic, mainly affecting the respiratory, gastrointestinal, endocrine, and reproductive tracts. Currently, the treatment of the disease is restricted to controlling symptoms and, more recently, a group of drugs that act directly on the defective protein, known as CFTR modulators, was developed. However, their high cost and difficult access mean that their use is still very restricted. It is important to search for safe and low-cost alternative therapies for CF and, in this context, natural compounds and, mainly, caffeic acid phenethyl ester (CAPE) appear as promising strategies to assist in the treatment of the disease. CAPE is a compound derived from propolis extracts that has antioxidant and anti-inflammatory activities, covering important aspects of the pathophysiology of CF, which points to the possible benefit of its use in the disease treatment. To date, no studies have effectively tested CAPE for CF and, therefore, we intend with this review to elucidate the role of inflammation and oxidative stress for tissue damage seen in CF, associating them with CAPE actions and its pharmacologically active derivatives. In this way, we offer a theoretical basis for conducting preclinical and clinical studies relating the use of this molecule to CF.

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Open accessJournal ArticleDOI: 10.3390/PH14111146
11 Nov 2021-Pharmaceuticals
Abstract: The wound-healing capacity of ointments based on bee products was investigated in vivo on three experimental models of incision, excision and heat burn. For this purpose, four ointments were prepared with propolis, honey, apilarnil (drone brood homogenate) and a mixture of these three apitherapy products. The ointments were applied topically for 21 days. Clinical and macroscopic evaluation was performed throughout the experiment, with the recording of the re-epithelialization period and determination of the wound contraction rate on days 6 and 9. The histopathological examination was performed on days 1, 3, 12 and 21 of the treatment. The topical formulations were also characterized from a rheological point of view in order to verify their stability. HPLC analysis of propolis revealed the presence of phenolic compounds, particularly ferulic acid and p-coumaric which were found in high amounts. All ointments had beneficial effects on wound contraction and the re-epithelialization period, but the most significant result, both macroscopically and especially in terms of histological architecture, was presented by the ointment that contains all three apitherapy products, due to their synergistic effect.

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Topics: Apitherapy (59%)
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116 results found


Open accessJournal ArticleDOI: 10.1038/NATURE01322
Lisa M. Coussens1, Zena Werb1Institutions (1)
19 Dec 2002-Nature
Abstract: Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

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Topics: Cytokine (54%), Inflammation (52%), Innate immune system (52%)

11,085 Citations


Journal ArticleDOI: 10.1038/NM0603-669
01 Jun 2003-Nature Medicine
Abstract: Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. VEGF has also been implicated in pathological angiogenesis associated with tumors, intraocular neovascular disorders and other conditions. The biological effects of VEGF are mediated by two receptor tyrosine kinases (RTKs), VEGFR-1 and VEGFR-2, which differ considerably in signaling properties. Non-signaling co-receptors also modulate VEGF RTK signaling. Currently, several VEGF inhibitors are undergoing clinical testing in several malignancies. VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration.

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8,400 Citations


Journal ArticleDOI: 10.1038/386671A0
Werner Risau1Institutions (1)
17 Apr 1997-Nature
Abstract: After the developing embryo has formed a primary vascular plexus by a process termed vasculogenesis, further blood vessels are generated by both sprouting and non-sprouting angiogenesis, which are progressively pruned and remodelled into a functional adult circulatory system. Recent results, particularly from the study of mice lacking some of the signalling systems involved, have greatly improved our understanding of the molecular basis underlying these events, and may suggest new approaches for treating conditions such as cancer that depend on angiogenesis.

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Topics: Sprouting angiogenesis (70%), Intussusceptive angiogenesis (61%), Vasculogenesis (58%) ... show more

5,581 Citations


Journal ArticleDOI: 10.1038/NRC745
Mikala Egeblad1, Zena Werb1Institutions (1)
Abstract: Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion and metastasis. This provided the rationale for clinical trials of MMP inhibitors, unfortunately with disappointing results. We now know, however, that the MMPs have functions other than promotion of invasion, have substrates other than components of the extracellular matrix, and that they function before invasion in the development of cancer. With this knowledge in hand, can we rethink the use of MMP inhibitors in the clinic?

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Topics: Matrix metalloproteinase (51%)

5,568 Citations


Journal ArticleDOI: 10.1146/ANNUREV.IMMUNOL.16.1.225
Abstract: ▪ Abstract The transcription factor NF-κB, more than a decade after its discovery, remains an exciting and active area of study. The involvement of NF-κB in the expression of numerous cytokines and adhesion molecules has supported its role as an evolutionarily conserved coordinating element in the organism's response to situations of infection, stress, and injury. Recently, significant advances have been made in elucidating the details of the pathways through which signals are transmitted to the NF-κB:IκB complex in the cytosol. The field now awaits the discovery and characterization of the kinase responsible for the inducible phosphorylation of IκB proteins. Another exciting development has been the demonstration that in certain situations NF-κB acts as an anti-apoptotic protein; therefore, elucidation of the mechanism by which NF-κB protects against cell death is an important goal. Finally, the generation of knockouts of members of the NF-κB/IκB family has allowed the study of the roles of these protein...

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Topics: IκB kinase (60%), CHUK (55%), Proto-Oncogene Proteins c-rel (54%) ... show more

5,174 Citations


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