Propolis Exhibits Melatonin Effect - Protects Thyroid, Liver

Protective effects of propolis are well-documented in humans and animals. This study confirms the important benefits of this particular component. Coincidentally, another study found that consuming propolis with CAPE is more effective than consuming CAPE separately. 

Protective antioxidative effects of caffeic acid phenethyl ester (CAPE) in the thyroid and the liver are similar to those caused by melatonin

Thyroid Res, 2014 June

BACKGROUND:

Whereas oxidative reactions occur in all tissues and organs, the thyroid constitutes such an organ, in which oxidative processes are indispensable for physiological functions. In turn, numerous metabolic reactions occurring in the liver create favourable conditions for huge oxidative stress. Melatonin is a well-known antioxidant with protective effects against oxidative damage perfectly documented in many tissues, the thyroid and the liver included. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, has been suggested to be also an effective antioxidant. The aim of the study was to evaluate the effects of CAPE on Fenton reaction-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) in porcine thyroid and liver, and to compare the results with protective effects of melatonin.

METHODS:

Thyroid and liver homogenates were incubated in the presence of CAPE (500; 100; 50; 10; 5.0; 1.0 μM) or melatonin (500; 100; 50; 10; 5.0; 1.0 μM), without or with addition of FeSO4 (30 μM) + H2O2 (0.5 mM). The level of lipid peroxidation was measured spectrophotometrically and expressed as the amount of MDA + 4-HDA (nmol) per mg of protein.

RESULTS:

Whereas CAPE decreased the basal LPO in a concentration-dependent manner in both tissues, melatonin did not change the basal LPO level. When antioxidants were used together with Fenton reaction substrates, they prevented - in a concentration-dependent manner and to a similar extent - experimentally-induced LPO in both tissues.

CONCLUSIONS:

Protective antioxidative effects of CAPE in the thyroid and the liver are similar to those caused by melatonin. CAPE constitutes a promising agent in terms of its application in experimental and, possibly, clinical studies.

Propolis Contains Anti-Obesity Ingredient

Propolis continues to generate surprising results. This new development determined a major component in propolis, CAPE, prevents the production of fat cells. The preventative effects of propolis continue to mount and this anti-obesity aspect will certainly merit future studies. Could this be tied to the epigenetic characteristic of propolis?

Caffeic acid phenethyl ester, a major component of propolis, suppresses high fat diet-induced obesity through inhibiting adipogenesis at mitotic clonal expansion stage

J Agric Food Chem, 2014 Mar 10

In the present study, we aimed to investigate anti-obesity effect of CAPE in vivo, and the mechanism by which CAPE regulates body weight in vitro. To confirm anti-obesity effect of CAPE in vivo, mice were fed with a high fat diet (HFD) with different concentrations of CAPE for 5 weeks. CAPE significantly reduced body weight gain and epididymal fat mass in obese mice fed a HFD.

In accordance with in vivo results, Oil red O staining results showed that CAPE significantly suppressed MDI-induced adipogenesis of 3T3-L1 preadipocytes. FACS analysis results showed that CAPE delayed MDI-stimulated cell cycle progression, thereby contributing to inhibit mitotic clonal expansion (MCE) which is prerequisite step for adipogenesis. Also, CAPE regulated expression of cyclin D1 and phosphorylation of ERK and Akt which are upstream of cyclin D1.

These results suggest that CAPE exerts anti-obesity effect in vivo, presumably through inhibiting adipogenesis at early stage of adipogenesis

Propolis Suppresses Breast Cancer Cells

The rich phenolic compounds in propolis work better together than when separated and fortunately they uncovered this important point in this review. It reinforces other studies defining the anticancer effects of propolis. They describe it as a 'honeybee-produced naturopathic formulation'. 

Propolis and its Active Component, Caffeic Acid Phenethyl Ester (CAPE), Modulate Breast Cancer Therapeutic Targets via an Epigenetically Mediated Mechanism of Action.

J Cancer Sci Ther, 2013, Oct

Abstract:

Alternative remedies for cancer treatment is a multi-billion dollar industry. In particular, breast cancer (BC) patients use alternative and natural remedies more frequently than patients with other malignancies. 

Propolis is an example of a honeybee-produced naturopathic formulation, contents of which differ by geographic location. It is readily available, affordable, and in use safely since ancient times globally. Caffeic acid phenethyl ester (CAPE) is a major active component in propolis and is thought to be responsible for its varied properties, including antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory and anticancer. CAPE is effective in many models of human cancer, including BC as we have previously shown. CAPE affects genes associated with tumor cell growth and survival, angiogenesis and chemoresistance. We demonstrate that these are related in part to CAPE's role as a histone deacetylase inhibitor, a class of drugs designated as epigenetic agents that modulate the activities of oncogenes and tumor suppressor genes.

CAPE and propolis, cause an accumulation of acetylated histone proteins in MCF-7 (ER+) and MDA-MB-231 (ER-/PR-/Her2-) cells with associated decreases in ER and PR in MCF-7 cells, and upregulation of ER and decrease in EGFR in MDA-231 cells. In addition, these products reduced activated phosphorylated Her2 protein in SKBR3 (Her2 +) cells. 

Interestingly, propolis, when normalized for CAPE content, appears to be more potent than CAPE alone similarly to the greater effects of complete foods than isolated components. These data provide a potential mechanistic basis for one of the oldest naturopathic agents used in medicine and cancer treatment.

For a complete copy of this review, click here.

Propolis Improves Bone Fracture Healing

Propolis, a natural protector for all species, works equally well both internally and externally. This study confirms yet another important aspect of one of its many flavonoids, CAPE, which strengthens the body's capacity to heal bone fractures faster, thanks to its antioxidant and anti-inflammatory properties...

Influence of caffeic acid phenethyl ester on bone healing in a rat model

J Intl Medical Research, 2013 Sep 24

OBJECTIVE:

To examine the effects of caffeic acid phenethyl ester (CAPE; a component of honey bee-hive propolis with antioxidant, anti-inflammatory, antiviral and anticancer properties) on bone regeneration and fibrotic healing in a rat model.

METHODS:

Male Sprague-Dawley rats (n = 63; mean age 7 weeks; weight 280-490 g) were randomly divided into three groups: A, cranial defect with no bone healing treatment (n = 21); B, cranial defect treated with CAPE (n = 21); C, cranial defect treated with CAPE and β-tricalcium phosphate/hydroxyl apatite (n = 21). Rats were anaesthetized with ketamine (8 mg/100 g) by intraperitoneal injection and a cranial critical size bone defect was created. Following surgery, CAPE (10 µmol/kg) was administered by daily intraperitoneal injection. Seven rats in each group were killed at days 7, 15 and 30 following surgery. Bone regeneration, fibrotic healing and osteoblast activity were evaluated by histopathology.

RESULTS:

Statistically significant differences in healing were found between all groups. There were no statistically significant within-group differences between day 7 and 15. At day 30, bone healing scores were significantly higher in groups B and C compared with group A.

CONCLUSION:

CAPE significantly improved bone-defect healing in a rat model, suggesting that CAPE has beneficial effects on bone healing.

Propolis: Adjuvant Agent for Cancer Prevention

Honeybees have been using the resin that protects tree buds from disease for preventative action in their hives. It's now recognized by humans for having therapeutic and preventative effects. I wonder what else we could learn from honey bees...

Clinical Reviews in Allergy & Immunology

June 2013, Volume 44, Issue 3, pp 262-273

Propolis, a waxy substance produced by the honeybee, has been adopted as a form of folk medicine since ancient times. It has a wide spectrum of alleged applications including potential anti-infection and anticancer effects. Many of the therapeutic effects can be attributed to its immunomodulatory functions. The composition of propolis can vary according to the geographic locations from where the bees obtained the ingredients.

Two main immunopotent chemicals have been identified as caffeic acid phenethyl ester (CAPE) and artepillin C. Propolis, CAPE, and artepillin C have been shown to exert summative immunosuppressive function on T lymphocyte subsets but paradoxically activate macrophage function. On the other hand, they also have potential antitumor properties by different postulated mechanisms such as suppressing cancer cells proliferation via its anti-inflammatory effects; decreasing the cancer stem cell populations; blocking specific oncogene signaling pathways; exerting antiangiogenic effects; and modulating the tumor microenvironment.

The good bioavailability by the oral route and good historical safety profile makes propolis an ideal adjuvant agent for future immunomodulatory or anticancer regimens. However, standardized quality controls and good design clinical trials are essential before either propolis or its active ingredients can be adopted routinely in our future therapeutic armamentarium. 

Anti-Cancer Properties Identified in Propolis

Propolis has many therapeutic applications. The phenolic compounds are numerous as are their effects, from anti-inflammatory and antifungal, to antimicrobial and antiviral. Best of all, propolis is complementary with traditional and alternative practices...

The Immunomodulatory and Anticancer Properties of Propolis

Clin RevAllergy Immunol, 2012 Jun 17

Propolis, a waxy substance produced by the honeybee, has been adopted as a form of folk medicine since ancient times. It has a wide spectrum of alleged applications including potential anti-infection and anticancer effects. Many of the therapeutic effects can be attributed to its immunomodulatory functions.

The composition of propolis can vary according to the geographic locations from where the bees obtained the ingredients. Two main immunopotent chemicals have been identified as caffeic acid phenethyl ester (CAPE) and artepillin C. Propolis, CAPE, and artepillin C have been shown to exert summative immunosuppressive function on T lymphocyte subsets but paradoxically activate macrophage function. On the other hand, they also have potential antitumor properties by different postulated mechanisms such as suppressing cancer cells proliferation via its anti-inflammatory effects; decreasing the cancer stem cell populations; blocking specific oncogene signaling pathways; exerting antiangiogenic effects; and modulating the tumor microenvironment.

 
The good bioavailability by the oral route and good historical safety profile makes propolis an ideal adjuvant agent for future immunomodulatory or anticancer regimens. However, standardized quality controls and good design clinical trials are essential before either propolis or its active ingredients can be adopted routinely in our future therapeutic armamentarium.

Propolis Suppresses Prostate Cancer Cells

Propolis is a proven, preventative solution for cancer. CAPE is one of several flavonoids which exhibit anti-tumor properties. Other flavonoids which express the same activity include chrysine, quercetin, artepillin C, Methyl caffeate, Methyl feruleate and Diterpendoid of clerodan...

Caffeic Acid Phenethyl Ester Suppresses the Proliferation of Human Prostate Cancer Cells through Inhibition of p70S6K and Akt Signaling Networks

Cancer PrevRes 2012 May 1

Abstract:

Caffeic acid phenethyl ester (CAPE) is a bioactive component derived from honeybee hive propolis. CAPE has been shown to have antimitogenic, anticarcinogenic, and other beneficial medicinal properties. Many of its effects have been shown to be mediated through its inhibition of NF-κB signaling pathways.

We took a systematic approach to uncover the effects of CAPE from hours to days on the signaling networks in human prostate cancer cells. We observed that CAPE dosage dependently suppressed the proliferation of LNCaP, DU-145, and PC-3 human prostate cancer cells. Administration of CAPE by gavage significantly inhibited the tumor growth of LNCaP xenografts in nude mice. Using LNCaP cells as a model system, we examined the effect of CAPE on gene expression, protein signaling, and transcriptional regulatory networks using micro-Western arrays and PCR arrays.

We built a model of the impact of CAPE on cell signaling which suggested that it acted through inhibition of Akt-related protein signaling networks. Overexpression of Akt1 or c-Myc, a downstream target of Akt signaling, significantly blocked the antiproliferative effects of CAPE.

In summary, our results suggest that CAPE administration may be useful as an adjuvant therapy for prostate and potentially other types of cancers that are driven by the p70S6K and Akt signaling networks.

Propolis: The Chemopreventative Anticancer Drug

The anti-tumor effects of Propolis are verified once again in detail. This protector of the beehive is the natural protector for all mankind and all in the animal kingdom... 

The Anticancer Activity of Propolis

FoliaHistochem Cytobiol, 2012 Apr
[click here for full pdf]

Abstract:

Propolis and its compounds have been the subject of many studies due to their antimicrobial and antiinflammatory activity; however, it is now known that they also possess antitumor properties.

This review aims to summarize the results of studies on the mechanism of activity of propolis and its active compounds such as CAPE and chrysin in the apoptotic process, and their influence on the proliferation of cancer cells.

Our review shows that propolis and its presented compounds induce apoptosis pathways in cancer cells. The antiproliferative effects of propolis, CAPE or chrysin in cancer cells are the result of the suppression of complexes of cyclins, as well as cell cycle arrest.

The results of in vitro and in vivo studies suggest that propolis, CAPE and chrysin may inhibit tumor cell progression and may be useful as potential chemotherapeutic or chemopreventive anticancer drugs...

Conclusion: 

With an increasing incidence rate of cancer worldwide, new anticancer agents are still required. One of the benefits of anticancer therapy is the ability to initiate apoptosis and cell cycle arrest in cancer cells. The studies presented in this review suggest that propolis and its compounds, CAPE and chrysin, may inhibit cell cycle proliferation or induce apoptosis in tumor cells...

Propolis Anti-Tumor Effect Used to Treat Neurofibromatosis

Propolis has many merits to aid human and animal species. Repeated studies show its ability to regulate cell functions and to block irregular cell functions, i.e. anti-tumor, anti-viral, anti-bacterial, immunostimulant capacities thanks to its rich flavonoid content...

Effective Neurofibromatosis Therapeutics Blocking the Oncogenic Kinase PAK1

Drug DiscovTher, 2011 Dec

Neurofibromatosis (NF) is a family of genetic diseases which are caused by dysfunction of either NF1 gene or NF2 gene. One in 3,000 people suffer from this tumor-carrying NF. NF1 gene product is a RAS GTPase activating protein (GAP) of 2,818 amino acids, which normally attenuates the GTP-dependent signal transducing activity of the G protein RAS.

Dysfunction of this GAP leads to the abnormal activation of RAS, and eventually an oncogenic kinase called PAK1 as well. NF2 gene product is ''Merlin'' which directly inactivates PAK1. Thus, dysfunction of Merlin causes the abnormal activation of PAK1. In other words, dysfunction of NF1 gene (causing type 1 NF) is basically the same as dysfunction of NF2 gene (causing type 2 NF). In fact the growth of both NF1 and NF2 tumors requires PAK1, and all PAK1 blockers, synthetic chemicals or natural products, suppress the growth of these NF tumor cells both in vitro (cell culture) and in vivo (mice).

However, until recently, no FDA-approved effective NF therapeutics is available on the market. Here a series of anti-PAK1 products shall be introduced, which would be potentially useful for the life-long treatment of NF patients in the future. These include the most potent HDAC (histone deacetylase) inhibitor FK228 (IC50: around 1 nM), that eventually blocks PAK1, the direct PAK1 inhibitor PF3758309 (IC50: around 10 nM), a CAPE (caffeic acid phenethyl ester)-based propolis extract called ''Bio 30'' from NZ (New Zealand), and an ARC (artepillin C)-based green propolis extract (GPE) from Brazil.

Although the first two drugs are potent, none of them is available on the market as yet. The last two natural (bee-made) products are available on the market, and have been used for the therapy of NF and tuberous sclerosis (TSC) as well as many PAK1-dependent solid cancers such as breast and pancreatic cancers as well as glioma, which altogether represent more than 70% of all human cancers.

Since PAK1 is not essential for the normal cell growth, propolis extracts cause no side effects.

Propolis Protects Kidneys from Cadmium Poisoning

The protective effects of Propolis are extremely important and extremely expansive. Whether you want to treat a physical ailment or to prevent something from getting started, Propolis is THE preventative ingredient to your daily intake. Protecting kidneys with a daily dose of propolis could go a long way to prevent future problems...

Protective Effect of Caffeic Acid Phenethyl Ester Against Cadmium-Induced Renal Damage in Mice

J Toxicol Sci, 2012, Jan 21

Abstract:
Cadmium (Cd) is classified as an environmental pollutant and human carcinogen. Food is the major source of Cd exposure for the general population and cigarette smoking significantly adds to the body burden of Cd (Klaassen et al., 1999). Caffeic acid phenethyl ester (CAPE), a biological active component of honeybee propolis extracts, has been used as a folk medicine with no harmful effects on normal cells.

Here we investigated the beneficial effect of CAPE on Cd-induced renal damage in mice.

Since renal damage induced by Cd (II) is related to oxidative stress, lipid peroxidation (LPO), protein carbonyl (PCO), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were evaluated. Moreover, the concentrations of Cd and zinc (Zn) in the kidney were analyzed. The intoxication of Cd (II) leads to the enhanced production of LPO and PCO, and the decrease of SOD activity and GSH level, probably due to the serious oxidative stress. However, the activities of CAT in the Cd (II)-induced group showed an elevated tendency, probably relating to an adaptive-response to the oxidative damage.

The co-administration of CAPE can attenuate the oxidative stress caused by the intoxication of Cd and restore the altered antioxidant defense system.

Based on our data, it is proposed that CAPE may involve in the protection of renal damage induced by Cd (II) owing to its antioxidant capacity and anti-inflammatory effect.

Propolis Protects Against Chemo & Radio Therapy-Induced Toxicity

Propolis protects prophylactically and preventatively ... an amazing feature that also modulates the immune system by boosting or balancing the production of healthy cells...

The Potential Usage of Caffeic Acid Phenethyl Ester (CAPE) Against Chemotherapy-Induced and Radiotherapy-Induced Toxicity

CellBiochem Funct, 2012 March 20

Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners.

Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties.

The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens.

Propolis Flavonoids Accelerate Wound Healing

Propolis flavonoids are numerous but those of great interest are CAPE (caffeic acid phenethyl ester), chrysin, kaempferol, pinocembrin, galangin and artepillin C. These vary on the geographical source of propolis, due the wide variety of polyphenols harvested by the honeybees in the region. Nonetheless, the anti-inflammatory effects have great importance for many applications...

Flavonoids in propolis acting on mast cell-mediated wound healing
Inflammapharmacology, 2012 Feb 17
Salvatore Chirumbolo, University of Verona Italy 

Barroso et al. have shown, on the latest issue of Inflammopharmacology, that the topical application of propolis on surgical wounds affected the number of mast cells recruited in these sites, and suggested two well-known anti-inflammatory components present in propolis, namely caffeic acid and artepillin C, as possible active molecules (Borelli et al. 2002; Paulino et al. 2008). It is widely acknowledged that propolis down-regulates type I allergy and inflammation by affecting mast cells, but the effective components of propolis, which cause these effects, remain still unknown.

Propolis components vary depending on the area from which they are collected, mainly because of the genetic variability among wild plants in different geographic regions; variability in phenolics composition may result in different biochemical property of the propolis, depending on the main component active in raw propolis or in its extracts. In Chinese propolis, chrysin, kaempferol and its derivative, pinocembrin and galangin were identified as main flavonoids able to act on mast cell-mediated inflammatory response, while chrysin was shown to inhibit IL-4 and MCP-1 production from antigen-stimulated RBL-2H3 basophil/mast cell lines (Nakumura et al. 2010). On the other hand, Brazilian propolis extract contains only small amounts of these flavonoids, which might suggest that variation in propolis components could affect anti-allergic and anti-inflammatory properties (Nakumura et al. 2010). Brazilian propolis contains, therefore, major percentage of phenolic acids, such as caffeic acid phenethyl ester (CAPE) and artepillin C (Park et al. 2002). 

excerpt online at SpringerLink.com

As the activity of propolis, like many natural products, may be due to the synergic effect of several bioactive components, it will be necessary to distinguish between different types of propolis and analyse its complex compositions to guarantee specific biological activities of propolis diffused worldwide (Frankland Sawaya et al. 2011). Furthermore, inflammation by mast cells can be inhibited by several flavonoids present in propolis. Recent evidence was reported showing that chrysin decreased gene expression of pro-inflammatory cytokines, such as TNF-ά, IL-1β, IL-4 and IL-6 in mast cells by a nuclear factor-κB (NF- κ B) and caspase-1 dependent mechanism (Bae et al. 2011). Genistein modulates NF- κ  B and TNF-ά expression during the early stage of wound healing (Park et al. 2011). CAPE accelerates cutaneous wound healing and its is arguable that propolis with a significant amount of this phenolic acid may exert a wound repairing property (Serarslan et al. 2007). 

The anti-inflammatory property attributed to flavonoids in propolis might suggest that these polyphenols should exert their action toward other newly discovered function of mast cells (Ng 2010), even in association with CAPE or other phenolic acids. Wound healing is a complex process of lysis and reconstitution controlled by a series of cell signaling proteins and involved tissue regeneration and angiogenesis (Hiromatsu and Toda 2003; Nienartowicz et al. 2006). Mast cells have been shown to play a significant role in the early inflammatory stage of wound healing and also influence proliferation and tissue remodeling in skin…

Propolis May Help Treat Asthmatic Children

CAPE, a predominant compound found in propolis, has been identified to possess other important capacities:
 - antiviral (König and Dustmann, 1985)

 - anti-inflammatory (Bankova et al., 1983) 
 - antimetastatic activity against mammary carcinoma (Bašic et al., 1997)
 - anti-bacterial activity on gram-positive & negative micro-organisms (Villanueva et al., 1970, Cizmarik & Matel, 1970, 1973)

The Immunoregulatory Effects of Caffeic Acid Phenethyl Ester on the Cytokine Secretion of Peripheral Blood Mononuclear Cells From Asthmatic Children

Pediatrics and Neonatology, Volume 52, Issue 6, December 2011, Pages 327-331

Background:

Asthma is a chronic inflammatory disease of the airways for which current treatments are mainly based on pharmacological interventions, such as glucocorticoid therapy. Our objective was to study the immunoregulatory effects of caffeic acid phenethyl ester (CAPE, a phytochemical synthesized from propolis) on cytokine secretion of peripheral blood mononuclear cells (PBMCs) from asthmatic children.

Methods:

PBMCs from asthmatic children (5.5 ± 3.3 years old, n = 28) and healthy children (5.6 ± 2.8 years old, n = 23) were co-cultured with CAPE in vitro with and without phorbol-12-myristate-13-acetate-ionomycin.

Results:

Our results show that predominant interleukin 4 (IL-4) and interferon-gamma secretion of cultured supernatant were detected in healthy donors compared with asthmatics. In the presence of phorbol-12-myristate-13-acetate-ionomycin, with or without CAPE treatment, the asthmatic children showed significantly decreased levels of IL-10 secretion compared with the healthy controls. However, CAPE significantly decreased IL-10 and interferon-gamma in healthy donors. There was a slight but not statistically significant reduction of IL-4 secretion in CAPE-treated PBMCs compared with untreated control PBMCs from the healthy children. Our data also shows that CAPE significantly enhanced transforming growth factor-beta 1 production from PBMCs from asthmatic children.

Conclusion:

The immunoregulatory effects of CAPE on human PBMCs may be through the induction of regulatory T cells, as evidenced by the enhanced transforming growth factor-beta 1 production from PBMCs from asthmatic children in our study.

Propolis Shows Anti-Inflammatory Action in Intestines

As usual, Propolis proves its functionality in a mucuos environment with anti-inflammatory activity. I wonder if CAPE will also exhert its anti-tumor properties at the same time...

Catechols in Caffeic Acid Phenethyl Ester are Essential for Inhibition of TNF-Mediated IP-10 Expression Through NF-κB-Dependent But HO-1- and p38-Independent Mechanisms in Mouse Intestinal Epithelial Cells

Molecular Nutritional Food Research, Oct 31 2011

Scope: 

Caffeic acid phenethyl ester (CAPE) is an active constituent of honeybee propolis inhibiting nuclear factor (NF)-κB. The aims of our study were to provide new data on the functional relevance and mechanisms underlying the role of CAPE in regulating inflammatory processes at the epithelial interface in the gut and to determine the structure/activity relationship of CAPE.

Methods and results: 

CAPE significantly inhibited TNF-induced IP-10 expression in intestinal epithelial cells. Using various analogues, we demonstrated that substitution of catechol hydroxyl groups and addition of one extra hydroxyl group on ring B reversed the functional activity of CAPE to inhibit IP-10 production. The anti-inflammatory potential of CAPE was confirmed in ileal tissue explants and embryonic fibroblasts derived from TNF(ΔARE/+) mice. Interestingly, CAPE inhibited both TNF- and LPS-induced IP-10 production in a dose-dependent manner, independently of p38 MAPK, HO-1 and Nrf2 signaling pathways.

We found that CAPE did not inhibit TNF-induced IκB phosphorylation/degradation or nuclear translocation of RelA/p65, but targeted downstream signaling events at the level of transcription factor recruitment to the gene promoter.

Conclusion: 

This study reveals the structure-activity effects and anti-inflammatory potential of CAPE in the intestinal epithelium.

Propolis Component Key in Treating Allergic Airway Disease

One of the many compounds of Propolis, CAPE has the super-hero force to aid the human condition...


Caffeic Acid Phenethyl Ester Suppresses Eotaxin Secretion and Nuclear p-STAT6 in Human Lung Fibroblast Cells
J Microbiol Immunol Infect, 2011 May 19
BACKGROUND: 

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been proven to have anti-inflammatory and antiallergic properties. We have investigated the activity of CAPE in regulating cytokine-induced eotaxin production and its related signal protein, signal transducer and activator of transcription 6 (STAT6), in human lung fibroblast.

METHODS: 

The CCD-11Lu human lung fibroblast cell line was used as an in vitro model. Cells were pretreated with CAPE followed by stimulation with interleukin-4 and tumor necrosis factor alpha. The levels of eotaxin in cultured supernatants were measured by enzyme-linked immunosorbent assay. The amounts of STAT6 and phosphorylated STAT6 in cellular nuclear protein extracts were determined by Western blot analysis. STAT6 DNA binding activities were detected by electrophoretic mobility shift assay.

RESULTS: 

Pretreated CCD-11Lu cells with noncytotoxic doses (0.1-10μM) of CAPE inhibited the production of eotaxin under stimulation of interleukin-4 (10ng/mL) and tumor necrosis factor alpha (10ng/mL). CAPE pretreatment also decreased the amount of phosphorylated STAT6 and the STAT6 DNA binding complexes in nuclear extracts.

CONCLUSION: 

CAPE inhibited the production of eotaxin protein in stimulated human lung fibroblast cells in a dose-dependent manner. This activity is, at least, through STAT6 inhibition. We suggest that CAPE is a promising agent in controlling eotaxin secretion and subsequent eosinophils influx and may therefore have a potential role to play in treating allergic airway disease

Propolis Component Inhibits Breast Cancer Tumor Growth

more promising news for the use of Propolis as an anti-tumor agent...


Caffeic Acid Phenethyl Ester (CAPE), Derived from a Honeybee Product Propolis, Exhibits a Diversity of Anti-Tumor Effects in Pre-Clinical Models of Human Breast Cancer
Cancer Letters, Article in Press

Breast cancer (BC) patients use alternative and natural remedies more than patients with other malignancies. Specifically, 63–83% use at least one type of alternative medicine and 25–63% use herbals and vitamins.

Propolis is a naturopathic honeybee product, and CAPE (caffeic acid phenethyl ester), is a major medicinal component of propolis. CAPE, in a concentration dependent fashion, inhibits MCF-7 (hormone receptor positive, HR+) and MDA-231 (a model of triple negative BC (TNBC) tumor growth, both in vitro and in vivo without much effect on normal mammary cells and strongly influences gene and protein expression.

It induces cell cycle arrest, apoptosis and reduces expression of growth and transcription factors, including NF-κB. Notably, CAPE down-regulates mdr-1 gene, considered responsible for the resistance of cancer cells to chemotherapeutic agents. Further, CAPE dose-dependently suppresses VEGF formation by MDA-231 cells and formation of capillary-like tubes by endothelial cells, implicating inhibitory effects on angiogenesis.

In conclusion, our results strongly suggest that CAPE inhibits MDA-231 and MCF-7 human breast cancer growth via its apoptotic effects, and modulation of NF-κB, the cell cycle, and angiogenesis.

Propolis Bioflavonoid Shows Anti-Cancer Activity

Effect of Propolis and Caffeic Acid Phenethyl Ester (CAPE) on NFκB Activation by HTLV-1 Tax

Antiviral Research, Article in Press

HTLV-1 is the etiological agent of an aggressive malignancy of the CD4+ T-cells, adult T-cell leukemia (ATL) and other sever clinical disorders. The viral Tax protein is a key factor in HTLV-1 pathogenicity. A major part of Tax oncogenic potential is accounted for by its capacity of inducing the transcriptional activity of the NFκB factors, which regulate the expression of numerous cellular genes. 

Propolis (PE), a natural product produced by honeybees, has been used for long time in folk medicine. One of PE active components, caffeic acid phenylethyl ester (CAPE), was well characterized and found to be a potent inhibitor of NFκB activation. Therefore, the aim of this study was to pursue the possibility of blocking Tax oncogenic effects by treatment with these natural products. 

Human T-cell lines were used in this study since these cells are the main targets of HTLV-1 infections. We tried to determine which step of Tax-induced NFκB activation is blocked by these products. 

Our results showed that both tested products substantially inhibited activation of NFκB-dependent promoter by Tax. However, only PE could efficiently inhibit also the Tax-induced activation of SRF- and CREB- dependent promoters. 

Our results showed also that PE and CAPE strongly prevented both Tax binding to IκBα and its induced degradation by Tax. However, both products did not interfere in the nuclear transport of Tax or NFκB proteins.