artepillin-c and caffeic-acid-phenethyl-ester

Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.

Topics: Animals; Anti-Anxiety Agents; Antineoplastic Agents; Antioxidants; Brazil; Caffeic Acids; Humans; New Zealand; Phenylethyl Alcohol; Phenylpropionates; Propolis

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.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Caffeic Acids; Cell Line, Tumor; Humans; Immunologic Factors; Neoplasms; Neoplastic Stem Cells; Oncogene Proteins; Phenylethyl Alcohol; Phenylpropionates; Propolis; Signal Transduction; T-Lymphocyte Subsets; Tumor Microenvironment

Topics: Animals; Bees; Caffeic Acids; Phenylethyl Alcohol; Propolis

There is an increasing evidence that the oncogenic kinase PAK1 is responsible not only for malignant transformation, but also for several other diseases such as inflammatory diseases (asthma and arthritis), infectious diseases including malaria, AIDS, and flu, as well as a series of neuronal diseases/disorders (neurofibromatosis, tuberous sclerosis, Alzheimer's diseases, Huntington's disease, epilepsy, depression, learning deficit, etc.) which often cause premature death. Interestingly, a few natural PAK1-blockers such as curcumin, caffeic acid (CA) and rosmarinic acid (RA) extend the lifespan of the nematode Caenorhabditis elegans or fruit flies. Here, to explore the possibility that C. elegans could provide us with a quick and inexpensive in vivo screening system for a series of more potent but safe (non-toxic) PAK1-blocking therapeutics, we examined the effects of PAK1-deficiency or down-regulation on a few selected functions of this worm, including reproduction, expression of HSP16.2 gene, and lifespan. In short, we found that PAK1 promotes reproduction, whereas it inactivates HSP16.2 gene and shortens lifespan, as do PI-3 kinase (AGE-1), TOR, and insulin-like signalling /ILS (Daf-2) in this worm. These findings not only support the "trade-off" theory on reproduction versus lifespan, but also suggest the possibility that the reduced reproduction (or HSP16.2 gene activation) of this worm could be used as the first indicator of extended lifespan for a quick in vivo screening for PAK1-blockers.

Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Caffeic Acids; Down-Regulation; Green Fluorescent Proteins; Heat-Shock Proteins; Longevity; p21-Activated Kinases; Phenylethyl Alcohol; Phenylpropionates; Protein Kinase Inhibitors; Recombinant Fusion Proteins; Reproduction; Signal Transduction

There are mainly three types of propolis whose major anticancer ingredients are entirely different: (1) CAPE (caffeic acid phenethyl ester)-based propolis in Europe, Far East and New Zealand, (2) artepillin C (ARC)-based Brazilian green propolis and (3) Brazilian red propolis. It was shown previously that NF (neurofibromatosis)-associated tumors require the kinase PAK1 for their growth, and CAPE-based propolis extracts such as Bio 30 suppress completely the growth of NF tumors in vivo by blocking PAK1 signaling. Also it was demonstrated that ARC suppresses angiogenesis, suggesting the possibility that ARC also blocks oncogenic PAK1 signaling. Here it is shown for the first time that both ARC and green propolis extract (GPE) indeed block the PAK1 signaling selectively, without affecting another kinase known as AKT. Furthermore, it was confirmed that ARC as well as GPE suppress almost completely the growth of human NF tumor xenografts in mice, as does Bio 30. These results suggest that both CAPE-based and ARC-based propolis extracts are natural anti-PAK1 remedies and could be among the first effective NF therapeutics available on the market. Since more than 70% of human cancers such as breast and prostate cancers require the kinase PAK1 for their growth, it is quite possible that GPE could be potentially useful for the treatment of these cancers, as is Bio 30.

Topics: Animals; Antineoplastic Agents; Caffeic Acids; Cell Line, Tumor; Female; Mice; Mice, Nude; Neoplasms, Experimental; Neurofibromatoses; p21-Activated Kinases; Phenylethyl Alcohol; Phenylpropionates; Propolis; Proto-Oncogene Proteins c-akt; Signal Transduction; Xenograft Model Antitumor Assays

The xanthine oxidase (XOD) inhibitory activity of propolis from China and Brazil was measured. The propolis from both place were seen to have XOD inhibitory activity. However, a stronger tendency was shown in the propolis from China. The compounds in each the propolis were measured quantitatively. A great deal of chrysin, galangin, and caffeic acid phenetyl ester were found in the propolis from China, an abundance of p-coumaric acid and artepillin C in the propolis from Brazil. Therefore it was revealed that the propolis compounds are very different depending on their place of origin. The XOD inhibitory activity of these five compounds was measured. Caffeic acid phenetyl ester had the strongest activity, with chrysin and galangin next; p-coumaric acid and artepillin C showed weak XOD inhibitory activity. We evaluated the hypouricemic effect of propolis from China on hyperuricemia induced by the uricase inhibitor, oxonic acid (500 mg/kg p.o., 1 h before the test drugs), and measured plasma uric acid values in rats. Oral propolis had a hypouricemic effect 2 h after its administration to oxonate-pretreated rats. These results suggested that a continuous intake of propolis may be effective for the prevention and the treatment of gout and hyperuricemia.

Topics: Animals; Anti-Infective Agents; Brazil; Caffeic Acids; China; Coumaric Acids; Disease Models, Animal; Flavonoids; Gout; Hyperuricemia; Male; Oxonic Acid; Phenylethyl Alcohol; Phenylpropionates; Propionates; Propolis; Rats; Rats, Sprague-Dawley; Uric Acid; Xanthine Oxidase