What is Propolis? and What We Know About it.

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Overview

Propolis is made by honey bees from beeswax, saliva, and tree resins. The resulting product is a dark, sticky, and resinous material with earthy notes. Propolis has recently attracted attention due to its impressive health benefits, documented in numerous scientific studies. It comes in different types and varieties depending on the environment and location where it is produced and the plant sources used by the bees. All kinds of Propolis share a similar chemical composition, giving this natural product exceptional therapeutic properties. 

Propolis comprises various natural materials, including resinous, balsamic, gummy compounds, waxes, essential oils, and pollen from different plants. It is highly rich in polyphenols and is considered a valuable source of important minerals such as magnesium, calcium, iodine, potassium, sodium, copper, zinc, manganese, and trace amounts of iron. Additionally, Propolis contains several essential vitamins such as thiamin, riboflavin, vitamins B6, C, E, D, and provitamin A, making it highly nutritious and beneficial.

Research has demonstrated that the natural resinous substance known as Propolis can potentially aid in reducing obesity caused by a diet high in fat. This is attributed to the presence of caffeic acid in Propolis. Numerous studies have also confirmed that Propolis possesses numerous therapeutic properties, including but not limited to antibacterial, antiviral, anti-inflammatory, anticancer, antifungal, and antitumor effects. Additionally, Propolis has shown promising results in supporting individuals with diet-induced obesity and diabetes.

This review aims to comprehensively explain Propolis, covering its various types, chemical composition, bioactive compounds, digestion process, and potential health benefits concerning obesity and diabetes. Additionally, we will explore possible drug interactions, recommended dosage, and safety considerations.

Introduction

Propolis is a Greek word, where ‘pro’ means ‘the entrance of,’ and ‘polis’ means ‘city.’ Propolis acts as a natural glue and defender of beehives, guarding against deadly microorganisms. With its natural antibacterial and antifungal effects, Propolis protects the hive, preventing harmful microorganisms from entering and causing infections. Bees meticulously combine beeswax and saliva enzymes to create Propolis, a dark and resinous substance with valuable properties. The unique blend of plant resins, waxes, and essential oils in Propolis varies based on location, season, and available plant sources, resulting in different colors and textures.

Propolis acts as a potent natural shield against bacteria and viruses, protecting bees and potentially offering health benefits to humans. It has been documented throughout history as a natural remedy for various treatments, and recent scientific research has confirmed its efficacy as a powerful antimicrobial agent. Propolis has many potential health benefits, from boosting the immune system to treating wounds and infections.

According to various studies, Propolis exhibits potent anti-inflammatory, anticancer, antifungal, and antitumor effects. This natural ingredient has shown immense potential in promoting overall well-being. It may serve as a valuable addition to conventional healthcare practices.

It is widely used as an ingredient in conventional medicine to boost health and protect the body from inflammation and conditions like diabetes, cardiovascular diseases, and cancer. Propolis can be found in different forms, such as tablets, capsules, toothpaste, mouthwash, facial creams, ointments, and solutions.

Many propolis products are obtainable in today’s market, and their popularity continues to increase. Among all the propolis products, those that concentrate on oral health and wound recovery and those that desire to improve immunity are the most sought after. Many researchers have conducted comprehensive studies on Propolis’s wholesome health effects and bioactivity, published in numerous scientific papers.

The present review seeks to comprehensively understand the various aspects of Propolis, including its chemical composition, physical characteristics, and biological properties. Additionally, the review will delve into the potential drug interactions, optimal dosage, and safety considerations associated with Propolis. Moreover, the review will primarily focus on the impact of Propolis on human health, with a particular emphasis on its anti-obesity and anti-diabetes effects.

Different Types of Propolis

Propolis is an intriguing substance with a highly complex structure. It comprises diverse natural ingredients, including 50% resin and vegetable balsam, 30% wax, 10% essential and different oils, 5% pollen, and 5% other substances, such as organic debris. These diverse ingredients merge to create a distinctive and valuable product used for centuries in orthodox medicine and natural remedies.

The substance in question contains diverse chemical compounds, including but not limited to polyphenols such as flavonoids, phenolic acids, phenolic aldehyde, and alcohols. These compounds have been found to have anti-inflammatory and remedial properties. Additionally, the substance contains terpenoids, steroids, and amino acids.

Propolis is packed with different minerals, including iron, iodine, potassium, sodium, copper, zinc, calcium, manganese, and magnesium. It is also abundant in thiamin, riboflavin, and vitamins A, B6, C, D, and E, essential for maintaining good health. Besides, Propolis contains various polysaccharides like starch, glucose, fructose, ribose, rhamnose, talose, gulose, and saccharose, which significantly support a healthy immune system.

Propolis contains over 300 different compounds. Its chemical complexity is due to its diverse geographic origin, other bee species, and diverse plant sources. To thoroughly understand propolis’ chemical elements, it is necessary to analyze its geographic origin and the plant source it comes from. Such an analysis can provide a valuable understanding of its unique properties and benefits.

Propolis boasts four different types based on its geographical origin, plant source, and chemical composition: poplar, green, red, and Macaranga. Poplar-type Propolis can be found in Europe, North America, Asia, and Oceania non-tropic territories. The collection zone for green Propolis is Southeast Brazil, while Northeast Brazil is known for its red Propolis. Each kind of Propolis has a unique chemical composition, affecting its medicinal properties.

Several types of Propolis can be collected from different geographic locations, including Japan, Taiwan, Hawaii, and the Solomon Islands. One of these types is called Macaranga propolis, which is sourced from Macaranga tanarius plants. Other types of Propolis, such as those collected in Brazil and Argentina, come from plants like Baccharis dracunculifolia and Dalbergia ecastaphyllum, respectively. Each Propolis has unique characteristics and properties, depending on the plant source and geographic location.

For instance, poplar propolis consists of flavonoids, phenolic acid, and their esters. In contrast, green Propolis contains prenylated p-coumaric acids and diterpenes. Besides, red Propolis is rich in isoflavonoids and polyprenylated benzophenones, whereas Macaranga propolis is known for its prenylated flavanones. These chemical compounds are the primary components that give each type of Propolis its distinct characteristics and benefits.

Poplar-type Propolis is a rich source of various compounds, among which caffeic acid phenethyl ester (CAPE) is a significant bioactive compound. CAPE exhibits many biological activities that make it a valuable natural product. For instance, it has been found to induce apoptosis of cells associated with breast cancer, enhance insulin sensitivity, and possess radioprotective properties. The presence of CAPE in poplar-type Propolis makes it a promising candidate for therapeutic applications in various fields of medicine.

 Besides containing CAPE, poplar-type Propolis is also known to contain some other beneficial flavonoids, including chrysin, galangin, pinobanksin, and pinocembrin. Recent studies have shown that chrysin exhibits cytotoxic and anti-inflammatory properties, while galangin and pinocembrin help improve insulin resistance. On the other hand, the Brazilian green Propolis is primarily composed of artepillin C (ArtC), known for its anti-parasitic features, especially against Leishmania parasites, and its gastroprotective properties.

 Red Propolis is a unique propolis that distinguishes itself from other types, such as poplar-type and green Propolis, due to the presence of isoflavonoids. The therapeutic potential of red Propolis has been extensively studied through various pharmacological investigations, highlighting its significant role in treating specific human ailments such as dental caries, candidiasis, cancer, skin wounds, and complications caused by oxidative stress. Moreover, red Propolis has antimicrobial properties, making it a potent natural remedy for various infections.

Macaranga-type propolis contains prenylated flavonoids as its primary components, which have been scientifically established to have various pharmacological effects. These include but are not limited to antioxidant, antibacterial, antiangiogenic, and anticancer properties, as demonstrated by multiple in studies conducted in the field.

How Our Body Digest Propolis

As we explore the potential of food materials as sources of antioxidants, we must consider the availability and concentration of these beneficial compounds in the human gastrointestinal system. However, Propolis is known to have a complex molecular structure, with a high molecular weight that makes it difficult for the body to absorb and employ its antioxidant properties. Thus, it is important to be mindful of Propolis’s limitations in terms of bioavailability and absorption.

When it comes to the effectiveness of polyphenols, certain factors play a crucial role in determining their bioavailability. The form in which polyphenols are administered, such as natural fruit, juice, or extract, can immensely impact their effectiveness. Additionally, other polyphenolics can give rise to synergistic effects that enhance their bioavailability. However, several elements can hinder the bioavailability of polyphenols, including digestive instability, poor transcellular efflux in intestinal cells, and fast metabolism and excretion. These factors can significantly affect the ability of polyphenols to exert their beneficial effects in the body.

Polyphenols are a group of plant compounds in different forms, such as esters, polymers, or glycosylated forms. However, due to their tough nature, they cannot be easily absorbed by the body and require hydrolysis by the intestinal enzymes or the colonic microflora. This process helps break down the polyphenols into smaller phenolic acids, which are more readily absorbed by the body. The activity of the colonic microbiota plays a crucial role in this process. It is increasingly being viewed as an individual difference. Therefore, microbiota’s impact on polyphenols’ bioavailability has recently gained more attention.

Despite the researchers’ efforts to eliminate the residual amounts of Propolis in plasma, the levels remained high. This was attributed to Propolis’s higher initial content than other food materials like fruits and vegetables, making eliminating it more difficult.

Currently, limited research is available on how much the body can absorb and utilize the beneficial plant-based compounds in bee products. Particularly, there needs to be more information on the bioavailability of minerals in honey, polyphenols in Propolis, and the disposition and metabolism of chrysin. Further studies in these areas could provide valuable insights into the potential health benefits of consuming bee products.

According to a group of professors, the ethanolic extracts of propolis samples from different geographical areas displayed total phenolic and flavonoid content values ranging from 85–283 to 16–136 mg/g. Propolis continues to garner curiosity among researchers due to its diverse biological properties, making it a highly valued functional food.

Health Benefits of Propolis

Propolis contains phytochemicals that offer a diverse range of health benefits. These phytochemicals are responsible for a variety of health-promoting properties such as antioxidant, anti-inflammatory, antibacterial, antifungal, antivirus, antimicrobial, antitumoral, immunomodulatory, anti-allergic, antidiabetic, neuroprotective, renoprotective, dermal protective, gastroprotective, and hepatoprotective activities. In summary, Propolis is a powerful natural ingredient that can help protect and improve your health.

According to Anvarifard and colleagues, various studies on humans and animals have suggested that Propolis can enhance glycemic status, alleviate oxidative stress, mitigate renal tissue damage, and improve renal function. This has led to increased interest in the potential medicinal applications of Propolis in COVID-19.

Additional research is required to establish the root causes of the effects. However, this broad analysis elaborates on Propolis’s positive impacts on treating diabetes and obesity.

Diabetes and Propolis

Type 2 diabetes is a serious and long-lasting health condition that occurs when the body is unable to control glucose metabolism properly. This metabolic condition can lead to various difficulties, both on a small and large scale. According to global projections, the number of people affected by diabetes is expected to rise to an alarming number close to 600 million by the year 2035. Therefore, researchers are focusing on identifying controllable factors in our lifestyle, especially dietary habits, that can help reduce the incidence of this condition.

There has been a growing interest in consuming foods rich in polyphenols as a dietary factor. These polyphenols, found in various sources such as coffee, guava tea, whortleberry, olive oil, Propolis, chocolate, red wine, grape seed, and cocoa, have been suggested to be effective in lowering the risk of type 2 diabetes. Several studies have demonstrated that consuming these polyphenols can reduce insulin resistance, HbA1c, and glucose absorption in the gut. Furthermore, they have been shown to promote glucose uptake in tissues, glucose metabolism, and vascular function, making them a promising dietary strategy for individuals with type 2 diabetes.

Propolis has been found to have potential therapeutic effects on diabetic complications. In particular, propolis treatment is effective in reducing the risk of complications such as nephropathy, retinopathy, foot ulcers, and non-alcoholic fatty liver disease in diabetic patients. Studies suggest that Propolis has the potential to be used as a natural supplement to complement conventional diabetic treatments and improve patient outcomes. 

Research has also found that both Chinese Propolis and Brazilian Propolis can alleviate symptoms of diabetes in rats, and this beneficial effect may be attributed, at least in part, to the antioxidant properties of these bee products.

Recent studies have also shown that Propolis contains an element called CAPE that has the potential to prevent the damaging effects of oxidative stress caused by diabetes. This is because Propolis possesses potent antioxidant properties that can inhibit the SOD and CAT pathways, which are typically activated in response to oxidative stress. 

It is a known fact that diabetes can have a detrimental effect on the cardiovascular system, making people with diabetes more prone to heart diseases. However, recent studies have shown that Propolis helps reduce the risk of heart disease in people with diabetes. This is a promising discovery in alternative medicine, which can offer a safer and more natural way to manage diabetes and its associated complications.

Studies have been conducted to study the potential benefits of Iranian Propolis in treating type 2 diabetes. In these studies, patients were given varying doses of Iranian Propolis over different durations in randomized, double-blind, placebo-controlled trials. The results of these trials have shown that Iranian Propolis can significantly reduce fasting blood glucose levels, hemoglobin A1c (HbA1c), and insulin concentration. For instance, some of the doses used in the studies included 900 mg/day Iranian propolis for 12 weeks, 1 g/day Iranian propolis (total phenolic content: 28%) for 90 days, and 1.5 g/day Iranian propolis for eight weeks.

A recent systematic review and meta-analysis of six studies conducted up to 2018 has found that Propolis may help manage type 2 diabetes. The review has revealed that propolis intake is linked to a significant reduction in fasting blood glucose and HbA1c levels in patients with type 2 diabetes. HbA1c, a long-term marker of blood sugar levels, reflects the average blood glucose concentration over the past 2-3 months in individuals with diabetes. 

The studies included in the analysis varied in the duration and dose of propolis intake. Still, the overall findings suggest that Propolis may be a safe and effective natural intervention for managing blood sugar levels in individuals with type 2 diabetes. Propolis’s antidiabetic properties are believed to be attributed to its high content of flavonoids, phenolic acids, and other bioactive compounds. 

Despite these promising results, more research is needed to establish propolis intake’s optimal dose, duration, and safety in individuals with type 2 diabetes. Nonetheless, Propolis has the potential to be a valuable and natural addition to the existing treatment options for managing diabetes.

Zakerkish et al. conducted a study to evaluate the effect of propolis intake on diabetic patients. The study found that consuming 1000 mg of Propolis daily for 90 days significantly increased the patients’ high-density lipoprotein (HDL-C) levels. This finding suggests that Propolis may be beneficial for managing diabetes and improving cardiovascular health.

There have been some clinical trials conducted on the anti-diabetes effects of Brazilian green Propolis in patients who have type 2 diabetes. These randomized, double-blind, placebo-controlled trials used varying doses of Propolis and were conducted for different durations. However, unlike studies conducted with Iranian Propolis, these trials did not demonstrate a significant decrease in fasting blood glucose or blood HbA1c levels. Nonetheless, they did reveal that Brazilian green Propolis can inhibit hyperuricemia and impairment of glomerular filtration.

Obesity and Propolis

Obesity is an acute health matter that impacts people all around the world, regardless of age or gender. Due to the consumption of high-fat or unhealthy diets, obesity cases are rapidly growing in both adults and children. However, recent studies have shown that natural products, rich in polyphenols, can prevent and treat obesity. Specifically, these natural products can hinder adipocyte lipid accumulation, reducing the risk of obesity-related complications.

Propolis has been known to possess many health benefits for centuries. It is rich in anti-inflammatory and antioxidant compounds, making it a potent nutraceutical. Besides, recent studies have shown that propolis extracts can help combat obesity by regulating adipogenesis (fat cell formation), controlling adipokine secretion (hormones that regulate metabolism), and modulating food intake and energy expenditure. These findings suggest that Propolis could be a promising therapeutic agent for managing obesity and related metabolic conditions.

Propolis has been shown to have an anti-obesity effect. Research has found that CAPE can regulate the expression of cyclin D1, which is involved in the early stages of fat cell formation (adipogenesis) in response to a high-fat diet. By doing so, CAPE can limit visceral adipose tissue accumulation, which is the type of fat associated with increased health risks. In addition, propolis treatment has also been shown to promote thermogenesis in adipose tissue, which is the process of generating heat and burning calories. This can ultimately lead to reduced body weight gain and improved metabolic health.

The repeated intraperitoneal injection of extracts obtained from Brazilian Propolis at a dosage of 100 mg/kg twice a week for 12 weeks has significantly reduced mesenteric adipose tissue mass. However, the same treatment did not affect epididymal and inguinal adipose tissue. In a separate study, obese mice were administered an ethanolic extract of 100 mg/kg Brazilian green propolis intraperitoneally for 2 and 12 weeks. The results showed a significant reduction in visceral adipose tissue weight, indicating the potential therapeutic benefits of propolis extracts in managing obesity-related health complications.

According to a recent study on mice with diet-induced obesity, the oral administration of 50 mg/kg Brazilian green propolis extract for 10 days has effectively reduced the increase in body weight and visceral adipose tissue weight. The same study also revealed that the oral administration of 25 mg/kg propolis ethanol extract successfully attenuated body-weight gain in pre-existing obese mice. Furthermore, the study also demonstrated that after 14 weeks of oral administration of 2% ethanolic extract of Brazilian Propolis (with a high-fat diet), there was a significant reduction in weight gain and body fat accumulation. The ArtC content of this extract was noted to be 6.1%.

 Research conducted on CAPE (cinnamyl alcohol dehydrogenase) and chrysin, two critical components of Propolis, have revealed promising results in weight reduction. Studies conducted on mice fed with a high-fat diet containing CAPE (0.02−0.5%) and chrysin (100 mg/kg) have shown a significant decrease in body weight. In addition, the research has indicated a reduction in the importance of epididymal white adipose tissue, inhibition of pancreatic lipase, and an increase in voluntary exercise. These findings suggest that CAPE and chrysin may have the potential to be used as a natural remedy for weight loss.

CAPE, a compound found in Propolis, may play a significant role in the anti-obesity effects of this natural substance. However, it remains to be seen which specific factors contribute to this effect or how it works mechanistically. Further research is needed to understand the potential benefits of Propolis in obesity management fully.

According to recent reports, Propolis’s impact varies depending on the type of fatty tissue it is applied to. Visceral adipose tissue, in particular, is more responsive to Propolis’s effects than subcutaneous adipose tissue. Propolis has also been shown to regulate dyslipidemia, which makes it a potential solution for obesity management from a lipid metabolism perspective.

Dosage and Safety

Currently, ongoing research is being conducted to determine the optimal propolis dosage. However, clinical studies conducted on mice and humans indicate that Propolis and its various components are generally well-tolerated and non-toxic, provided they are not administered in massive amounts.

According to Burdock, a renowned expert in the field of toxicology, it is recommended that humans should not consume more than 1.4 mg per kilogram of body weight per day, or around 70 mg per day, as a safe dose of Propolis. It has been observed that doses of up to 300 mg daily have been safely used for ten months. However, avoiding higher amounts of Propolis is advisable as there is no conclusive evidence of their safety. Since there is a lack of human clinical studies on Propolis, it is important to consider its dosage. It should be noted that there are insufficient studies on the acute and chronic toxicity of Propolis, and more research is required in this aspect to determine its long-term effects on human health.

Research on mice and humans has revealed that Propolis has no harmful or toxic effects. In experimental animals, the administration of Propolis at doses of 200 and 5000 mg/kg body weight/day did not cause any poisonous fatalities and was deemed safe. However, it is worth noting that the composition of Propolis contains over 26 allergenic substances, which may trigger allergic reactions in some individuals.

Individuals with hypersensitivity may experience a contact allergic reaction due to esters of caffeic acid and cinnamic acid obtained from poplar buds, which are the most common cause of allergic reactions. These esters can also lead to cross-allergic reactions when present in other materials. The lethal dose 50 (LD50) value in mice varies from 2–7.3 g/kg, indicating the amount that would cause death in 50% of the tested mice.

 Studies conducted on mice and rats have shown that a dose of over 1470 mg/kg/day at 60 days and over 2470 mg/kg/day at 90 days, respectively, did not cause any adverse effects. However, in humans, toxic effects have been observed at doses as high as 15 g/day. It has been noted that high dosages of this substance may have pro-oxidant effects, which are different from the antioxidant effects. As of now, there is no clear indication of the safety of using this substance during pregnancy and lactation, and therefore, it is recommended to avoid its use during these periods.

It’s important to remember that while Propolis can have many benefits, excessive use can lead to adverse effects such as dermatitis. Additionally, Propolis can cause allergic reactions, particularly in those already allergic to other bee products. It’s worth noting that using propolis lozenges can also lead to irritation and mouth ulcers, so it’s important to use them cautiously.

While Propolis has been traditionally used for various medicinal purposes, recent studies have shown that its consumption can increase the risk of bleeding in people with bleeding disorders, as well as during and after surgery. Therefore, patients with these conditions need to be mindful and avoid consuming Propolis at least two weeks before undergoing surgery to avert any potential complications.

Drug Interactions of Propolis

It is essential to know that Propolis can interact with certain medicines. The drugs that have been observed to interact with Propolis include duloxetine, warfarin, praziquantel, donepezil, levodopa, metformin, anticancer drugs, and antimicrobial drugs. While Propolis negatively affects the effectiveness of duloxetine and warfarin, it has positive effects on the other drugs. In some cases, combining certain medications with Propolis has been found to yield better outcomes for treatment. Therefore, it is advisable to discuss the use of Propolis with your healthcare provider if you are taking any medication.

Studies have suggested combining raw, water-soluble Propolis with chemotherapeutic agents could reduce post-chemotherapeutic reactions, enhance immunity, and increase treatment effectiveness. However, there is still a lack of clearness on whether Propolis interacts with chemotherapeutic drugs, and its use during chemotherapy is still a topic of discussion.

Incorporating Propolis along with metformin therapy may yield favorable outcomes. Propolis’s beneficial effects can be attributed to its ability to safeguard pancreatic β-cells from free radicals and prevent oxidative or inflammatory damage. This results in the efficient production of insulin, which enhances insulin sensitivity and leads to lower glucose levels in the bloodstream.

Conclusion

Throughout history, people have depended on the healing properties of natural products to maintain their health and well-being. Propolis has been used for centuries as a natural remedy for various conditions. It contains multiple bioactive compounds, including flavonoids and phenols, contributing to its therapeutic effects. Propolis has been shown to have anti-inflammatory, antioxidant, and antimicrobial properties, making it a promising treatment for infected wounds and other skin conditions. In addition, studies suggest that Propolis may have the potential to prevent and manage chronic diseases such as diabetes, cancer, and cardiovascular disorders.

Propolis is known to possess antioxidant and anti-inflammatory properties, which have been observed to contribute to the promotion of good health. However, despite the available evidence, there is a need for further clinical and human trials to establish a deeper understanding of the chemical composition and physiological effects of Propolis. Once this is achieved, it would be possible to develop specific guidelines for tailored dosages that can be used to manage various diseases.

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