For centuries physicians and herbalists from various traditional systems of medicine have been using herbs and natural healing modalities to assist patients suffering from microbial infections of various forms to restore normal functions of the body. Since the discovery of penicillin in 1928, the over dependence and use of its derivatives by modern conventional medical systems, have caused these invading microorganisms to become more resilient and develop new defense mechanisms. Furthermore, the negative effects of these drugs on the human microbiome was not fully understood. The human microbiome plays an important role maintaining normal physiological functions within the body and protects healthy mucosal tissues from being prone to invading pathogenic microorganisms. Unhealthy tissues can become prone to infection by stronger invading opportunistic microorganisms which begin to develop biofilms. The biofilm is a community of microorganisms living symbiotically and shielded by a protective layer from the body’s own immune system. These factors have contributed to an increased rate of chronic infections and the development of the disease conditions associated with it. The aim of this study is to research and evaluate the physiological effects of oleo-gum-resins frankincense and myrrh and their possible uses to assist the body’s innate ability in restoring normal functions and health to the body tissues infected by biofilm enclosed pathogenic organisms. Myrrh and Frankincense are oleo-gums-resins obtained from various species of the Commiphora tree and the Boswellia tree., historical records and archeological evidence indicate they have been used extensively in ancient Egypt as well as in biblical times, being two of the three gifts offered to the infant Jesus by the magi. The third gift was gold, emphasizing the esteem and value provided to these two herbs. Boswellic acids which are a component of frankincense have been found to reduce and tackle the pathogenic biofilm’s protective layer, as well as, reduce inflammation and sooth tissues. Myrrh has been proven to show significant anthelmintic, antibacterial and antifungal properties, as well as, analgesic effects. Therefore, researching the combined physiological effects of myrrh and frankincense gum resins can offer new insights into the tools provided by plant medicine to effectively assist patients trying to overcome chronic infections and restore normal body functions.
Antibacterial resistant diseases are a serious threat to human health in today’s world, with mortality rates increasing every year. FDA approved single-target drugs are having lower success rate treating complex chronic disease conditions of the body and have an increased risk of serious side effects (Cao, et al., 2019). Natural herbal remedies and traditional healing modalities uses plants medicine, consisting of a plethora of chemicals and constituents designed and evolved in nature to work synergistically to provide a more broad-spectrum effect on the body (Buhner, 1999). Herbs when used in accordance with traditional wisdom and knowledge of a learned herbalist, causes little to no side effects, and work with the body to promote and restore normal physiological functions. (Buhner, 1999). Understanding the pathology of antimicrobial resistant diseases, will help us understand further the changes that take place within the tissues and organs of the body, in order to find solutions to intelligently assist in restoring the organism back to a state of health. Studying the role, the human microbiome plays in respect to normal physiological functions within the body will help us understand how an imbalance in that ecosystem would disturb the normal function of the body and result in a state of disease. Finding solutions using plant medicine to address these antibiotic resistant organisms and understanding their own survival and defense mechanism which prevent the body’s innate ability of restoring and maintaining homeostasis, would be of great importance today. Plants and herbs possess a much more complex chemistry than single-target antibiotic drugs, garlic for example contains more than 33 sulfur compounds and 17 amino acids and other compounds, another example is Yarrow which contains over 120 different constituents which means a person would be utilizing 120 different medicines when used (Buhner, 1999). The different constituents within herbs potentiate, enhance and mitigate each other’s effects inside the human body. Invading pathogenic bacteria find it more difficult to evade or develop resistance to this complex chemical composition. Pharmaceutical antibiotics, anthelmintic and antifungals are composed of a simple single-target substance lacking in complexity (Buhner, 1999). The intelligence of microorganisms that are living far surpasses this lack of complexity and have, as proven in a number of case studies, determined measures 5 to counteract their effect and grow more resilient as a result (Buhner, 1999). There are many herbs known throughout various traditional and modern medicine systems to be effective for antibacterial resistance infections and diseases, this list includes Grapefruit seed extract, Wormwood, Sage, Garlic, Aloe and much more (Buhner, 1999). This study aims to research, study and evaluate the combined effect of gum-resins frankincense and myrrh to assist the body to combat chronic infections, restore and maintain normal physiological functions of the body. Frankincense and myrrh are two powerful natural medicines and have been used for centuries by physicians and herbalists in many systems of medicine throughout various cultures, in the treatment of infections of tissues, organs and systems of the human body.
Material and Methods
The study employs a systemic methodology to identify, select and critically review current literature in relationship to the following topics:
• Historical and modern significance of frankincense and myrrh.
• The microbiome and human physiology.
• Pathology of antimicrobial resistant diseases.
• Understanding the role of biofilms in chronic infections.
• Chemical composition of frankincense and myrrh gum resins.
• Physiological effects of frankincense gum resin
• Physiological effects of myrrh gum resin
• Combined effects of frankincense and myrrh gum resins.
Systemic identification based on electronic databases utilized for the literature search were Google Scholar, Research Gate and Pub Med. After an initial review of the research material, the relevance of the source material was analyzed based on the established topics comprising this study. The retrieved literature published between 1898 and 2019 were selected for analysis.
I. Historical and Modern Significance of Frankincense and Myrrh
Frankincense and Myrrh are two oleo-gums-resins obtained from various species of the Commiphora tree and the Boswellia tree (Felter & Lloyd, 1898). Frankincense is a hard, gelatinous resin secreted from the trunk incisions of the various species of the Boswellia trees (e.g. Boswellia carterii, Boswellia Sacra or Boswellia Serrata), which grows in abundance in southern Arabian Peninsula, Somalia, Ethiopia and India. Frankincense is harvested by causing deep incisions into the trunk of the Boswellia tree from which the milky oleo-gum resin is secreted and then is hardened to create the translucent, brittle, white-yellow tears, which is then collected. It possesses a bitter taste and a pleasant resinous odor, which when used in incense exudes a distinct aroma (Felter & Lloyd, 1898). The Arabs who were known to harvest frankincense in southern regions of the Arabian Peninsula, called the milky sap of the boswelia tree, al lubn, from the Arabic word meaning milk. The Arabic word was then anglicized to olibanum, which is another name for frankincense. (Ben-Yehoshua, Hanus, & Borowitz, 2012). Myrrh Is an oily, gelatinous substance obtained from the various species of the Commiphora tree (e.g. Commiphora myrrha, Commiphora molmol), which grows in tropical and subtropical areas such as Somalia, Ethiopia and southern Arabian Peninsula. The Myrrh gum is created naturally without the need for incisions, as the soft and paleyellow juice flows naturally from the Commiphora tree, it becomes hard, dark and redder as it dries. The size of the gum can vary in size from a pea to the size of a large walnut (Felter & Lloyd, 1898). Myrrh gum resin has a bitter taste, its name is derived from the Hebrew word ‘murr’, meaning bitter (Ben-Yehoshua, Hanus, & Borowitz, 2012).
The gum bearing trees, Commiphora and Boswellia, were known to grow in forbidding mountainous regions in the horn of Africa and south of the Arabian Peninsula, the dangerous journey into inhospitable terrain one must take to obtain these resins further elevated their significance. These valuable items were standard gifts to honor a king or 8 a deity in the ancient world. Archaeological evidence of trade routes and expeditions to harvest these resins, emphasizes the economic significance of frankincense and myrrh for the regions where they grow (Ben-Yehoshua, Hanus, & Borowitz, 2012).
Myrrh and Frankincense are two of the most significant and renown resins in the ancient world. They are mentioned with esteem in historical and religious texts going back centuries. The oldest known scientific records, the Ebens papyrus, dating back to the 16th century B.C. mentioned Frankincense. The Hebrew religious scrolls dating back 1500 B.C. mentions Myrrh and puts it as a primary ingredient in the anointing oil (Ben-Yehoshua, Hanus, & Borowitz, 2012). Their significance is evident through the various historical texts, archeological findings and temple hieroglyphs discovered from the ruins of ancient civilizations and cultures. The Greeks, Romans, Egyptians, Israelites and numerous other cultures used frankincense and myrrh as part of their religious ceremonies. Egyptian and Sumerian hieroglyphs indicate that frankincense and myrrh were considered sacred and presented as offering to the gods in the form of burning incense (Ben-Yehoshua, Hanus, & Borowitz, 2012).
In biblical times, the sacred and divine nature of frankincense and myrrh were further emphasized as being two of the three gifts offered to the infant Jesus by the three magi’s or wise men. The divine aroma and smoke of these resins permeated through the halls of ancient temple, and their universal appeal remained throughout the ages as a testimony of the value of these two legendary resins. Frankincense and Myrrh were widely used in the ancient world as incense in religious and cultural ceremonies. It is now proven that the smoke from burning these resins repels mosquitoes, protecting people and animals from mosquito borne illnesses, such as malaria, West Nile virus, and dengue fever (Ben-Yehoshua, Hanus, & Borowitz, 2012). They were incorporated by ancient Egyptians in their embalming preparations, large quantities of frankincense and myrrh were used to treat the dead body and preserve it from decay and deterioration. The antibacterial properties of these resins were important in preserving the body from putrefaction.
The Ebers papyrus cites the use of frankincense in cases of throat and larynx infections, stopping bleeding, reducing phlegm, asthmatic attacks, and stopping vomiting. Frankincense was also used in wound healing, as the ancient cultures discovered its antimicrobial properties (Ben-Yehoshua, Hanus, & Borowitz, 2012).9 Use of frankincense in China was first mentioned in the 6th Century C.E. in the Mingyi Bielu and was used in memorial ceremonies. Frankincense is used in Chinese herbal medicine in a similar way to myrrh, to increase blood circulation and relieve pain. An ancient Chinese prescription, Qi Li San, is prescribed for all Injuries and is made up of dragon’s blood, catechu, myrrh, frankincense, carthamus, cinnabar, musk, and borneol. This ointment is the base for Yunnan Bai Yao, a popular remedy today, reputedly carried by the Vietcong during the Vietnam War to stop bleeding from wounds, with apparently amazing success. Chinese herbal doctors often use frankincense together with myrrh, as they are considered to have complementary actions, The frankincense acts on the tendons, reducing stiffness, while the myrrh activates the circulation of blood. An example of which in Chinese herbal medicine is called Qi Li San, a resinous mixture containing myrrh, frankincense, and six other resins (BenYehoshua, Hanus, & Borowitz, 2012). The oleo-gum resin obtained from the Boswellia serrata has been used extensively by the Ayurveda Indian system of medicine to treat various conditions such as arthritis, asthma, ulcers and skin diseases, and currently being used in the treatment of inflammatory related conditions (Raja, et al., 2011). The infused oil of frankincense was used in traditional Ayurveda medicine in India for arthritic and inflammatory condition, gastric disorders, pulmonary diseases, and skin ailments.
Myrrh was used for skin conditions and as an anti-inflammatory. Ibn Sina (Avicenna) in his Canon of Medicine of the tenth century recommended frankincense for tumours, ulcers, vomiting, dysentery, and fevers. (Ben-Yehoshua, Hanus, & Borowitz, 2012) Frankincense and Myrrh were components of European pharmacopoeia, however, with the dawning of the era of synthetic drugs by the twentieth century, their use have diminished since then. They are still used therapeutically in various regions ranging from North Africa to China, and in India as both resins are have a long history of use in the Ayurvedic system of medicine (Lumenih & Teketay, 2003). In modern times, research on frankincense has focused primarily on the anti-inflammatory and anti-cancer effects of extracts and some of the chemical constituents of the resin. They have also studied the anti-ulcer, memory 10 enhancement and anti-oxidation effects of Frankincense (Cao, et al., 2019). The pharmacological effects of myrrh have also been studied in modern times, with focus on its anti-inflammatory, anticancer, analgesic and antibacterial effects. It’s antimicrobial effects against the bacteria staphylococcus has been found to be eight times as effective as Norfloxacin, a pharmaceutical antibiotic drug (Cao, et al., 2019). Frankincense is increasingly becoming a popular remedy for arthritic problems, due to growing concerns over the safety of conventional anti-inflammatory drugs (Chevallier, Herbal Remedies, 2007). Frankincense is also used in other inflammatory conditions such as asthma, ulcerative colitis, and multiple sclerosis, it is also used to treat brain tumors and Alzheimer’s disease (Chevallier, Herbal Remedies, 2007). Myrrh has been used traditionally and currently in mouth and throat remedies due to its astringent and antiseptic properties (Chevallier, Encyclopedia of Herbal Medicine, 2016). It is used as a mouth wash in the form of a tincture or diluted essential oil for sore throats, canker sores and gingivitis (Chevallier, Encyclopedia of Herbal Medicine, 2016). Ayurvedic medicine uses myrrh as a tonic and aphrodisiac and blood cleanser (Chevallier, Encyclopedia of Herbal Medicine, 2016).
II. Pathology of Antimicrobial Resistant Diseases
In 1993, infectious disease specialist Dr. Cynthia Gilbert informed her long-term kidney infection patient, that after nine months of trying every antibiotic available to treat an infection, she is unable to eradicate this infection. 9 years prior to this incident, this bacterial infection was easily cured, however, it has now become resistant to antibiotics (Buhner, 1999). The patient weakened by disease was not able to fight off the pathogenic bacteria that has become unsusceptible to pharmaceuticals, and days later succumbed to an infection of the blood and heart (Buhner, 1999). More and more people are being admitted to hospitals with difficult to treat infections, and a considerable 1 Boswellia is a close relative of frankincense (Boswellia Sacra). This study does not distinguish between both and the differences between both in potency and composition of the active constituents is not put into consideration for the purpose of this study.11 percentage of patients are being infected while visiting hospitals. Marc Lappe of the university of Illinois College of Medicine, a pathologist and author, was quoted as saying “by conservative estimate, such infections are responsible for at least a hundred thousand deaths a year, and the toll is mounting”. Mankind now must deal with a threat of infectious diseases of epidemic proportion which are increasingly stronger and more resilient (Buhner, 1999). In 1928, penicillin was discovered, and commercial production began. During this time new antibiotics were being discovered daily. There were however voices of concern and amongst them was the man who discovered penicillin Alexander Fleming, who wrote in the British Journal of Experimental Pathology in 1929, that several bacteria were already developing resistance to the drug he had discovered, and in 1945 he again issued a warning in a New York Times interview that improper use of penicillin would inevitably lead to the development of resistant bacteria. An example of this phenomenon would be with the Staphylococcus aureus bacteria, in 1945 14% of which developed resistance, then in 1950 this percentage grew to 59% and in 1995 the percentage grow to an alarming 95% (Buhner, 1999). The microbiome and host immunity go hand in hand, and this is a dynamic relationship that develops over time. Factors that affect this relationship are microbial exposure, environmental exposure, local host factors and general host factors. Microbial exposure can be from multiple sources including inhaled through air, ingested with food or via skin contact. These microorganisms interact with human mucosal and skin surfaces, affecting the microbiome and the immune system over time. Environmental factors can be through interpersonal contact, climate, urban or rural environment, air and food quality. Host factors affecting this relationship is the genetic makeup, age and adaptive immunity and local factors such as the anatomy, organ specific disease conditions or defects (Hakansson, Orihuela, & Bogaert, 2018). The resilience of the human microbiome is largely related to the diversity of the various species of microorganisms inhabiting this community, and the presence of specific species with an inherent immune defense mechanism against specific pathogens (Hakansson, Orihuela, & Bogaert, 2018). When the host mucosal surface and microbial environment are in balance, the mucosa is free from damage and 12 inflammation (Hakansson, Orihuela, & Bogaert, 2018). Therefore, it is evident that the human microbiome plays an essential role in human physiology. When this balance is negatively affected by environmental factors, the diversity of the microbiome decreases, epithelial inflammation can occur, and dysbiosis can be developed as a result. When this dysbiosis occur, the human body is no longer functioning as it is intended by design, and a cascade of disease conditions can soon manifest, including viral infections, inflammatory triggers, resulting in increased potential of the colonization of pathogenic organisms and reduced barrier integrity allowing for further pathogenic invasion of the human body (Hakansson, Orihuela, & Bogaert, 2018). Therefore, learning about the factors that negatively affect the relationship between the host’s innate intelligence and the microbiome inhabiting various systems of the human body, is of great importance, in understanding the human physiology and pathology of chronic infections.
Living cells have within them the vital force, these cells combine to form tissues, which forms organs and organs unite to form the various systems throughout the human body. The harmonious function of these several parts is the expression of the vital force. An infection of any part of the human anatomy by an organism which does not work in harmony with the normal ecological system, results in an interference with the normal function of the body and thus the organism is in a state of disease. It is now evident that the human body is composed of a diverse ecosystem of microorganisms that make up the human microbiome, these include bacteria, fungi, parasites and viruses.
Most of these organisms live as part of the digestive system and is essential in the development of the mucosal barrier function, healthy immune system, nutritional assimilation and offers crucial resistance to infectious disease (Hakansson, Orihuela, & Bogaert, 2018). When a disruption occurs in the ecosystem of these microorganisms, it causes a state known as dysbiosis, where the normal function of these organisms within our body is affected and a lack of harmony between the host and the microbiome occurs resulting in a variety of infectious, inflammatory conditions and consequently a state of disease manifests (Hakansson, Orihuela, & Bogaert, 2018).
Certain species of beneficial organisms’ part of the human microbiome plays a critical role in creating a healthy environment within the human body, while other species if their population grows beyond certain limits can contribute to a disfunction and dysbiosis. The overuse of antibiotics can contribute to dysbiosis, for example 13 selectively targeting the population of healthy lactobacillus bacteria, while allowing for pathogens not affected by the specific antibacterial agent, i.e. fungi, to overgrow and significantly cause and contribute to dysbiosis within the human microbiome (Hakansson, Orihuela, & Bogaert, 2018). This disequilibrium at the mucosal tissues could be the causative factor in the development of infections and the ability for new biofilms to form inhabiting colonies of microorganism which are not functioning in harmony with cells, tissues, organs and systems where these pathogens attach to (Hakansson, Orihuela, & Bogaert, 2018).
An important factor when understanding the pathology of chronic infections is the emerging antibiotic resistance, which is believed to be partially caused by the formation of biofilm enclosed communities of pathogenic organisms that alters normal physiological functions within the body. Once the pathogens develop late stages of the biofilm, antibiotic drugs forms of penicillin do little to tackle the pathogenic bacteria, while indiscriminately attacking the beneficial microbiome which is essential to our immunity and assisting the body in tackling the pathogenic microorganisms.
This approach have proven to be unsuccessful in treating chronic infectious diseases such that of the respiratory system (Hakansson, Orihuela, & Bogaert, 2018), and thus the purpose of this study is to further investigate the combined effects of boswellic acids found in frankincense gum and the chemical constituents within myrrh gum resin to tackle these difficult cases of chronic infections, when the intelligent response, wisdom and traditional knowledge of natural herbal medicine can provide the solution to this emerging global problem.
III. The Microbiome and Human Physiology
Physiology can be defined as the scientific study of the functions of the body. It can be studied from a cellular, tissue, organ and body system level. Physiological mechanisms are made possible by the intelligent design and relationships of the various body parts and levels that carry out each of the functions required to maintain homeostasis within the body. Homeostasis is the ability of a cell or organism to regulate its internal conditions to maintain health, the normal function of all tissues of the body (Sherwood & Ward, 2019). 14 The body systems maintain homeostasis, the maintenance by intelligent, coordinated and regulated functions of the body systems of relatively stable chemical and physical conditions in the internal environment of the body’s cells (Sherwood & Ward, 2019). Homeostasis is essential for survival of cells and cells make up the body systems. The body cells can live and function only when the extracellular environment is compatible with their survival, for example, chemical properties such as pH must be within a specific physiological range for the survival of the cell. Therefore, Homeostasis is essential for the survival of each cell, and each cell, through its specific function, contributes as part of the body system to maintain the internal environment within the physiological range as shared by all cells (Sherwood & Ward, 2019). Homeostasis is also a considered a dynamic state where change can occur but this is minimized by equilibrium adjustment mechanisms (Sherwood & Ward, 2019), providing scientific evidence to the concept of the vital force or innate intelligence within living cells which have been understood and taught by herbalists throughout various traditional medicine systems. All 11 body systems contribute to maintaining homeostasis and normal function of the body, for example, the digestive system breaks down food into small nutrients that can be absorbed into the blood plasma for distribution to body cells, and it also transfers water and minerals from the external environment to the internal environment. And it eliminates undigested food material to the external environment as feces (Sherwood & Ward, 2019). An important element often overlooked when studying human physiology and energy homeostasis is the gut microbiome. Human friendly bacteria within the gastrointestinal tract represents 1-3% of total body mass, it is a highly active and growing population. It likely contributes significantly to the body’s total energy usage and it processes certain ingested food material and molecules to create new compounds that can be used by the body’s cells. It can also be considered as a virtual endocrine organ as they secrete compounds that affect other cells within the body and their ability to respond to stress (Sherwood & Ward, 2019). When a human being is born and begins the natural process of nursing, human-friendly bacteria begins to colonize the newborn baby skin through skin interaction and the gastrointestinal tract from the mother’s milk. A mature human being will have 1 to 2 pounds of billions of bacteria living in healthy symbiosis inside and on the body. We cannot live without many essential nutrients that are produced by these microorganisms, and it is now evident that 15 many of these human-friendly bacteria protects us from dangerous pathogenic bacteria and maintains balance within our complex ecological system. This symbiotic human-friendly ecological system of microorganism is known today as the human microbiome. (Buhner, 1999). The human microbiome starts to grow and develop during and after birth and is inherited from the mother’s microbiome. In the respiratory tract for example, the bacteria found after birth is like that of other bodily systems such as the skin and the digestive system. The method of birth whether it is vaginally delivered or through caesarean section, also affects the type of bacteria which begins to inhabit the body, as there is a vast spectrum of different species of these beneficial bacteria which inhabit and colonize tissues within different systems throughout the body. For example, lactobacillus is found predominantly in the gut and the female reproductive organs, whereas, Staphylococcus spp. is typical inhabiting the skin. Environmental factors after birth and during early infancy can have a significant role in the development of the microbiome throughout the human body, and an increasingly complex and diverse communities emerge which is now being suggested to be an important aspect of the human physiology (Hakansson, Orihuela, & Bogaert, 2018). Contrary to previous theories the microbiome is found in many systems throughout the body, including the respiratory system. Therefore, it is an essential part of human physiology as it is an essential component of good health, by allowing the normal function of the tissue units of the body to function in a normal manner. The function of the microbiome within the respiratory system is to maintain mucosal integrity and prevent airway infections, when a dysbiosis occurs in this system it can lead to acute or chronic inflammation, mucosal dysfunction and infectious diseases (Hakansson, Orihuela, & Bogaert, 2018). The respiratory system is a group of organs allied together to bring atmospheric air containing oxygen to a place where it can be readily absorbed by the blood during inspiration and take undesired gases containing carbon dioxide from the blood and exhaust them to the outside during expiration. That is the normal function of this system. As air enters the upper respiratory tract through the nasal cavity, pharynx, larynx and reaches the lower respiratory tract consisting of the trachea, bronchi and finally reached the alveoli where the exchange of gases occurs. The pharynx 16 is a cone-shaped tube of musculo-membranous tissue and with the broad end connects to the mouth and nose cavity, while the narrow end of this cone shaped tissue connects with the esophagus. It is a common pathway for the digestive system and the respiratory system. It is suggested that the microbiome inhabiting the tissues of the pharynx when functioning normally protects against bacterial pathogens by the process of intrinsic competitive colonization resistance, through the production of mucus and antimicrobial peptides, and promoting tight junction integrity which shields the respiratory and digestive system tracts with the blood (Hakansson, Orihuela, & Bogaert, 2018). In is also believed that a healthy microbiome regulates immune system response by differentiating between harmful and beneficial organisms and thus contribute to immune system maturation over time (Hakansson, Orihuela, & Bogaert, 2018) IV. Understanding the Role of Biofilms in Chronic Infections Biofilm can be defined as a community of organisms attached to a surface material which can harbor living organisms and submerged in a slimy extracellular matrix. The organisms living within this community possess genetic diversity and can survive throughout many environmental challenges and conditions in relationship to the free flouting planktonic form of bacteria organisms (Maric & Vranes, 2007). Biofilm organisms are resistant to negative environmental effects and is also resistant to antibiotic agents, in fact biofilm bacteria are 10 – 1000 times more resistant to antibiotics than planktonic bacteria cells (Maric & Vranes, 2007). Biofilm can be detrimental or beneficial, it has been estimated that 65% of microbial infections are associated with biofilm formation. The structural nature of the biofilm serves as protection and a shield offering multiple antimicrobial resistance (AbdelAziz & A, 2014). Bacteria is widely argued to be the most successful form of life on our planet, in terms of total biomass and the diverse environments and habitats colonized, the reason being lies in its adaptability to its growth conditions. An example of such bacterial species are the Pseudomonas aeruginosa, which were studied to further understand the mechanism of biofilm, and it has been found that the mature biofilm this species of bacteria develops protects it 17 from adverse environmental conditions and from biological and chemical antibacterial agents. (Costerton, Lewandowski, Caldwel, Korber, & Lappin-scott, 1995) The structure of biofilms were studied and examined using digital imaging devices, and it has been found that mixed species biofilm showcased differences in structural chemistry in different locations within the same biofilm resulting in different electrochemical properties, Biofilm bacteria has been found to produce and maintain chemical microenvironments within the biofilm, which allows for the bacteria to control pH levels and oxygen and other chemical properties, permitting the growth of numerous and diverse species of bacteria with a limited range of metabolic capabilities, such as the habitation of both aerobic and anaerobic organisms within the biofilm matrix.. Evidence also suggests cell-cell communication which further enhances the complexity and resilience of mixed species biofilms (Costerton, Lewandowski, Caldwel, Korber, & Lappin-scott, 1995). Such complexity and diversity provides the strength and resilience of this type of biofilm and it can be predicted that once such a formation of mixed species biofilm of infectious species of organisms finds a suitable surface environment to grow inside the human body, it can provide a serious challenge to the body’s own natural defenses and vital force to restore the organism back to a state of health. Biofilm formation lifecycle: 1) Free-floating, or planktonic, bacteria encounter a suitable surface can become attached. They begin to produce slimy extracellular polymeric substances (EPS) and to colonize the surface. 2) EPS production allows the emerging biofilm community to develop a complex, three-dimensional structure that is influenced by a variety of environmental factors. Biofilm communities or microcolonies can develop soon after. 3) Biofilms can propagate through detachment of small or large clumps of cells, or by a type of "seeding dispersal" that releases individual cells. Either type of detachment allows bacteria to attach to a surface or to a biofilm downstream of the original community (O'Toole, Kaplan, & Kolter, 2000). Biofilms are also beneficial for us. They line the digestive tract, especially the lower intestines, and the skin. Healthy biofilms contain many different species of bacteria working in harmony with living cells. They are an essential part 18 of our anatomy and physiology. Many trillions of organisms protect us from pathogens and toxins, help boost our immune system, keep our digestive system working, steer us away from disease, and could improve cognitive function as well [Rose, 2011]. All body fluids provide enough organic material for optimum bacterial growth; therefore, it can be predicted that all plastic and metal surfaces of medical devices could contain bacterial biofilms when bacteria are present in these fluids. The development of biofilms inhabiting infectious organisms has been evident in medical devices and is an ongoing challenge at hospitals and medical facilities to tackle. Once such a biofilm is established, it’s natural resistance to natural surfactants, phagocytosis and antibiotic therapy allows it to remain resilient living environment long after the planktonic organism has been killed by the host defense factors and by antibacterial agents (Costerton, Lewandowski, Caldwel, Korber, & Lappin-scott, 1995). Comparing the microenvironment of a bacterial cell in a biofilm to that of a planktonic cell of the same organism, following adhesion to a surface the bacterial cell alters many of its structural molecules and properties, resulting in the developing of microcolonies enclosed in dense slime and attached to the colonized surface. The microcolony is the basic unit of biofilm growth, just as the tissue is the basic unit of growth of a more complex organism. Bacterial cell within a microcolony has been observed to have a degree of homeostasis and cooperative organisms, as well as, an effective method of exchanging nutrients and metabolites (Costerton, Lewandowski, Caldwel, Korber, & Lappin-scott, 1995). The microcolonies can consist of 10-25% of cells and 79 – 90% an extracellular polysaccharide matrix which protects the biofilm cells from negative environmental conditions such as ultraviolet radiation, changes in the pH values and other factors such as antibiotic agents. Water channels within the biofilm has been observed to serve as highways connecting the microcolonies for the transportation and distribution of nutrients and harmful metabolites. Biofilm has also been found to adapt to changes in nutrients level which it can utilize, an important relationship has been observed with the level of glucose. The more glucose is available the more growth of the biofilm matrix is observed, while lower levels of glucose yielded a smaller biofilm matrix. (Maric & Vranes, 2007). 19 In a recent study, the effect of penicillin which is an indiscriminate antibacterial agent, has been observed and it has been found that after treatment on a bacterial culture, there was a remaining planktonic bacterial cells which persisted after the treatment, which was dealt with the host’s immune system. This can be observed in cases of acute short-term infections. However, biofilm persisting organisms were not affected by the host’s immune system and were protected by their extracellular polysaccharide matrix. Furthermore, the persisting biofilm bacteria would then begin to create new planktonic cells when the concentration of the antimicrobial agent reduces. This dynamic relationship is the reason why patients dealing with chronic infections due to biofilm formation will experience relapse of symptoms (Maric & Vranes, 2007). Natural endothelial surfaces within a living complex organism are more resilient to bacterial adhesion and consequently biofilm formation, in comparison to medical devices, due to natural antibacterial components of the tissue surface antibodies which can kill planktonic bacteria as they approach the tissue surface, and cellular immunity is active on tissue surfaces. The tissue surface of a complex living organism is covered by thick biofilms of native beneficial bacteria, such as lactobacilli in the vagina, and therefore the tissue surface is protected from the adhesion of external opportunistic organisms. Another important example is the intestinal tract which is abundant in organic nutrients, however, it is covered by a thick layer of mucous, and contains vast species of beneficial organisms which are part of the normal human being’s physiology, which makes the colonization and biofilm formation by infectious organisms rather difficult (Costerton, Lewandowski, Caldwel, Korber, & Lappin-scott, 1995). However, in cases where there is a disruption or abnormality in normal physiological function of these tissue surfaces, which could be a result of excessive use of strong antibacterial agents such as penicillin or another factor which affects the physiological function and state of these tissue surfaces, then it can be determined that colonization and biofilm formation by infectious undesirable species of bacteria can take place, and in such cases as evident in this study and observation of the resilience and fortitude of complex biofilms, the ability of the host organism to effectively combat and eradicate this infection can be quite challenging and could require the utilization of mother nature’s powerful healing herbs, wisdom and natural medicine as tools to assist the organism to selectively combat the infectious biofilm and restore health, balance and vitality to the organism. Certain plants and trees have for millennials grown to adapt and evolve alongside beneficial and disease-causing microorganisms, 20 and the wisdom and knowledge to tackle such biofilm harboring infectious and opportunistic organisms could reside within their essence and chemical composition. The relationship between a host such as a human being and the native community of microorganisms, maintaining normal physiological conditions, is well balanced. A disruption of this relationship can create the conditions necessary for infectious diseases, and according to the National Institutes of Health, over 60% of all microbial infections are caused by biofilm. An example of disease conditions in human beings caused by this are: Cystic fibrosis pneumonia, biliary tract infection and urinary catheter cystitis (Abdel-Aziz & A, 2014). Viral infections whether acute or chronic have been shown to cause a disruption of the microbiome in the tissues affected, and reduction of microbiome diversity (Hakansson, Orihuela, & Bogaert, 2018). This action can lead to conditions where pathogenic microorganism find the opportunity to inhabit host tissue and create biofilms which then lead to chronic infections and further exacerbate the disease condition within the human body. V. Chemical Composition of Frankincense and Myrrh When studying the chemical composition of herbs, it is important to distinguish between the perspective of a scientist who sees a plant’s constituents as a “crude chemical brew”, searching for an identifiable “active principle”. And the perspective of an herbalist who has a holistic approach at understanding and valuing the sum of an herb’s constituents (Pengelly, 2004). Knowledge of individual constituents can be of benefit for the purpose of quality control, extraction procedures and further understanding the pharmacological activity and pharmacokinetics, and offer a more holistic understanding of a herb’s action (Pengelly, 2004). Frankincense and Myrrh are oleo-gum-resins, which are milky exudates composed of a gum which is partly or wholly soluble in water, and a resin which is partly or wholly soluble in alcohol. When triturated and mixed with water, gum-resins yield emulsions, the gum part dissolves while the resin is suspended within the solution (Green, 2000). 21 Frankincense The key constituents of frankincense (Boswellia) are triterpene acids (including beta-boswellic acid), essential oil, terpenols, monosaccharised, uronic acids, sterols and tannins (Chevallier, Encyclopedia of Herbal Medicine, 2016). The major chemical components of the oleo-gum resin Frankincense can be divided into three groups, volatile oils (lower terpenoids), higher terpenoids, and carbohydrates. The higher terpenoids consists of β-boswellic acids along with 11-keto- β-boswellic acids and their acetates. 11-keto- β-boswellic acids has been found to be beneficial in large number of inflammatory diseases, cancer, arthritis, chronic colitis, ulcerative colitis, Crohn’s disease and bronchial ashma (Raja, et al., 2011). The oil portion contains 62.1% ester, 15.4% alcohol, 9.9% monoterpene hydrocarbons and 7.1% diterpenes (Lumenih & Teketay, 2003). The oil constituents have shown to contain α-pinene, α-thujene, β-pinene, camphene, myrcene, o-methylanisole, α-terpinene, methoxytoluene, hexyl acetate, limonene, 1, 8-cineole, n-octanol, linalool, octyl acetate, bornyl acetate, cembrene A, incensole, incensole acetate, sabinene, o-cymene, ρ-cymene, 1,8- cineole, cis-β-ocimene, trans-β-ocimene, ϒ-terpinene, 1-octanol, terpinolene, linalool, 1-decanol, terpinen-4-ol, αterpineol, 1-octyl acetate, citronellyl acetate, neryl acetate, geranyl acetate, hexyl hexanoate, 1-decyl acetate, hexyl octanoate, α-campholenic aldehyde, caproic acid, oenanthic acid, caprylic acid, pelargonic acid, lauric acid, and verbenone (Lumenih & Teketay, 2003). The gum portion was found to contain 2 polysaccharides (Lumenih & Teketay, 2003). The terpenoid portion contains boswellic acids and albanoresin. The boswellic acids components are the most widely studied and attributed to the vast therapeutic effects of Frankincense (Lumenih & Teketay, 2003). Boswellic acids are further known to contain β-boswellic acid, acetyl-α-boswellica acid, and acetyl-β-boswellic acid, 22 and associated 3-acetyl-11-hrdroxy-β-boswellic acid and 11-keto-β-boswellic acid acetate chemicals (Lumenih & Teketay, 2003). Today, extracts for frankincense are typically standardized to contain 37.5–65% boswellic acids (Lumenih & Teketay, 2003). Myrrh The main constituents of the oleo-gum-resin myrrh are resin 35-40%, gum 60%, volatile oil 2.5-8% along with a bitter principle (Pengelly, 2004). The alcohol soluble resins are commiphoric acids, commiphorinic acid, heeraboresene, heerabomurrhols and commiferin (Lumenih & Teketay, 2003). the resins were found to contain α-, β-, and γ-commiphoric acids, commiphorinic acid, α- and β-herrabomyyhols, heerboresene, commiferin, kertosteroids, compesterol, β-sitosterol, cholestrerol, α-amyrone and 3-epi-α-amyrin. (Lumenih & Teketay, 2003). The water-soluble gum or mucilage fraction is composed mainly of acidic polysaccharide with galactose, xylose, 4- 0-methyl-glucuronic acid and arabinose (Lumenih & Teketay, 2003). The volatile oil fraction contains different terpenes, sesquiterpenes, esters, elemol, cinnamaldehyde, cuminaldehyde, cumicalcohol, eugenol, heerabolene, limonine, dipentene, pinene, m-cresol, cadinene and numereous furanosesquiterpenes myrcene and α- camphorarene; steroids including Z-guggulsterol, and I, II, III guggulsterol aldehydes and alcohols (Lumenih & Teketay, 2003). VI. Physiological Effects of Frankincense 23 Frankincense gum resin possess anti-inflammatory, antiseptic and astringent properties (Chevallier, Encyclopedia of Herbal Medicine, 2016). Frankincense is also considered to be a stimulant (King, Felter, & Lloyd, 1898). Frankincense and Inflammatory Diseases Frankincense’s anti-inflammatory effect combats extensive or too-painful occurrence of inflammation, a degree of inflammation is a necessary process in healing (Green, 2000). Inflammation is a natural response of body tissues to irritations, injuries, infections or abnormal conditions of the immune system such as autoimmune diseases. Inflammation causes the patient to experience pain, swelling, redness and in some cases loss of normal physiological functions. Frankincense has been used in traditional medicine to help restore normal functions to many patients dealing with various inflammatory diseases, and is today it is used in both complementary and alternative medicine for the treatment of some chronic inflammatory conditions (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Body cells produce a chemical called Leukotrienes which can cause inflammation by increasing free radical damages, abnormal function of the immune system, cell adhesion and migrations of the cells causing inflammation to the inflamed area. Example of inflammatory conditions where Leukotriene production is associated with are asthma, colitis, rheumatism, arthritis and psoriasis (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Boswellia has been shown to affect physiological functions and inhibit inflammation, through its action of blocking the synthesis of leukotrienes. The inhibition of inflammation induced by the physiological effects of Boswellia causes the inflamed tissue to shrink and the patient is therefore relieved of the pain and discomfort (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). The constituents of the frankincense gum resin which is responsible in this anti-inflammatory effect are the Boswellic acids (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). 24 Boswellic acids are major constituents of the oleo-gum resin Frankincense, harvested from the Boswellia tree. The two main boswellic acids are known as β-bowsellic acids and 11-keto-β-boswellic acids. These acids are known for their significant anti-inflammatory properties and have been used in the treatment of many conditions including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn’s disease and bronchial asthma. (Raja, et al., 2011) Frankincense and the Heart Frankincense strengthens the heart and promotes healthy circulation and blood flow due to its stimulant effects. A stimulate warms the body, quicken circulation, and breaks up obstructions and congestion (Green, 2000). Certain inflammatory conditions of the body can cause the buildup of plaque inside the blood vessels and consequently cause hardening of arteries, this is a major factor in coronary heart disease. Certain boswellic acids within the frankincense gum has been found to inhibit a specific function within the body which is found to be a major factor in the development of chronic inflammatory conditions, and therefore, can be of great benefit in the prevention of certain coronary heart diseases due to its anti-inflammatory effects as well (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Frankincense and the Respiratory System The physiological effects of frankincense on the respiratory system has been appreciated traditionally, it has been used in steam inhalations, baths and massages to treat cough, catarrh, bronchitis and asthma. Due to the effect of boswellic acids on the biosynthesis of leukotrienes and the anti-inflammatory response this action induces, it can reduce and prevent chronic inflammatory diseases of the respiratory system such as asthma (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). A patient study was conduction to evaluate the effects of Boswellia on chronic bronchial asthma and results showed significant improvement in 70% of the patients who took 300 mg of a Boswellia Serrata preparation three times per day for 6 weeks (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). 25 Frankincense and the Skin Frankincense has been found to induce a soothing effect on irritated skin due to the pentacyclic triterpene structure shared within difference boswellic acid compounds. Frankincense has been used for this purpose in traditional Chinese medicine for centuries as a skin remedy for bruises and infected sores (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Frankincense and the Digestive System The anti-inflammatory effect boswellic acids possess and its soothing effect on irritated tissues has brought frankincense recognition as an excellent remedy for patients who are dealing with inflammatory bowel diseases (IBD). IBD is the condition where inflammation of the intestines occur and can cause two chronic diseases, ulcerative colitis and Crohns disease. Pathologist have yet to fully understand the causes of inflammatory bowel disease, however, there are two factors are being investigated, the first is immune abnormality caused by genetic or environmental factors and the second is abnormal gastrointestinal tract factors such as the microbiome, oxidative stress and intestinal permeability which is the abnormal function of tight junctions between the cells lining the gastrointestinal tract (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Since leukotrienes has been attributed to keep inflammation active in chronic inflammatory diseases of the digestive tract, and the effects of boswellic acids on inhibiting a key enzyme of leukotrienes, frankincense gum resin can play an important role in the reduction of the occurrences of such inflammatory conditions of the digestive tract. In addition to its antiinflammatory effect Traditional Iranian Medicine system employs the gum resins of Boswellia serrata and Boswellia carterri as a remedy to be used by patients dealing with inflammatory bowel diseases. (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). The results of a study where patients dealing with ulcer colitis grade II and III were given 350 mg dosage of 26 Boswellia serrate three times per day for 6 weeks showed that 80% of patients were in remission. The study concluded that the efficacy of frankincense was like that of sulfasalazine, which is a chemical drug used in the treatment of IBD (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Frankincense and Cancer Gum resin harvested from various species of the Boswellia tree, has been found to possess antitumor properties due to triterpenoids present within the chemical constituents of this oleo-gum resin. Further studies were performed to evaluate the effects of four triterpenic acids within frankincense gum and it has been found to inhibit the synthesis of DNA, RNA and protein in human leukemia cells in a dose dependent manner (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Furthermore, boswellic acid acetates have been found to induce apoptosis or death of six human myeloid leukemia cell within certain conditions. The anticancer properties of certain boswellic acids are attributed to the physiological effect of inhibiting cell proliferation and the induction of apoptosis in tumor cells (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Boswellic acids have been found to inhibit a serine/threonine protein kinase which is a major factor in many types of cancer and the survival of these cells (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). The effects of frankincense have also been studied in the difficult case of brain cancer, which is the condition where malignant tumor cells develop within the brain. This type of cancer is particularly difficult for the patient as the tumor cells grow fast and invade surrounding tissues, which causes difficulty for surgical intervention to remove these cells before treating the underlining condition and begin to provide the proper recommendations to assist the body to restore normal functions of the body and cell growth (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). The anti-inflammatory effect of boswellic acids have shown promise as a powerful tool to be used by patients dealing with brain cancer. This effect was evaluated in a study where a preparation of Boswellia serrata extract using ethanol as a solvent, and results showed that within 7 days a reduction in peritumoral brain edema of 22- 48% was observed and cells of the treated tumor tissue showed no tendency to proliferate within 2 weeks, in 27 relation to untreated patients (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Antiseptic and Antimicrobial Effect of Frankincense Frankincense possess antiseptic effects which prevents or eliminates sepsis, infectious destructive condition of tissue (Green, 2000). The essential oil obtained from the gum resin of the Boswellia carterri tree has been found to possess antimicrobial effect against a wide range of microorganisms such as fungi and bacterial strains, in clinical studies (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). The efficacy of antimicrobial agents is strongly related to the effect it has on the barrier created by the biofilm which is a multilayered community of bacterial cells and studying this is crucial in understanding the pathology of chronic infections caused by biofilm formations (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). Effects of boswellic acids on biofilm. The antibiotic resistance of pathogens involved in nosocomial infections, which are infections originating from hospitals, have become a serious worldwide health problem. Such pathogens as staphylococcus aureus, streptococcus pneumonia and Enterococcus faecalis have been identified as posing a significant threat due to the formation of biofilm on medical devices and damaged tissues, which contributes to the significant difficulty in eradicating these infections. (Raja, et al., 2011) The antibacterial properties of boswellic acids have been studied and the acetyl-11-keto-β-boswellic acids or AKBA has been found to be the most potent of the boswellic acids studied in vitro, and therefore was chosen to study further its effectiveness when combating stronger strains of organisms where biofilm formation is present (Raja, et al., 2011). Furthermore, the post antibiotic effect of AKBA was studied versus a pharmaceutical antibiotic called ciprofloxacin and was found to be more effective against the S. aureus. (Raja, et al., 2011)28 The biofilm inhibition and reduction of the boswellic acid, acetyl-11-keto-β-boswellic acid, was studied and determined to be significant based on the laboratory results (Raja, et al., 2011). The antibacterial properties of Boswellia dry extract has been found to be highly effective against selected aerobic and anaerobic bacteria such as Streptococcus, Corynebacteria, C. perfringens and P. acnes, whereas keto-β-boswellic acids did not possess the same properties (Raja, et al., 2011). Further tests were also performed to study the effect of AKBA on the bacterial cell membrane, which showcased that the AKBA altered the cell membrane structure resulting in a disruption of the permeability barrier of microbial structures. However, AKBA demonstrated a lack of antibacterial properties against gram-negative bacteria (Raja, et al., 2011). The antimicrobial effect of boswellic acids was studied against oral cavity pathogens, and the results demonstrated a strong antibacterial effect by certain boswellic acids found in frankincense gum resin against all the bacterial strains in this study (Hamidpour, Hamidpour, Hamidpour, & Shahlari, 2013). VII. Physiological Effect of Myrrh Myrrh possess antimicrobial, astringent, carminative, expectorant, anticatarrhal, antiseptic and vulnerary properties (Ebadi, 2007). Furthermore, Myrrh exerts a stimulant effect, especially on mucosal tissues, and has been used traditionally as a vermifuge. Smaller dosage of myrrh has been known to aid digestion, while larger doses accelerate the pulse, increase body heat, induce sweating and is counter indicated in cases where internal inflammations is present. It is used in cases of weakness, excessive mucous secretion, chronic gonorrhea, chronic catarrh, laryngitis, bronchitis, humoral asthma and in respiratory disorders (Felter & Lloyd, 1898). Guggulsterones, a steroid found within the chemical constituents of myrrh lowers blood cholesterol and triglycerides through stimulation of the thyroid function (Pengelly, 2004). • Myrrh’s astringent effect contracts, firms and strengthens body tissues by precipitating proteins, and can 29 reduce excess secretions and discharge (Green, 2000). The astringent and antiseptic properties of myrrh is the reason why this herb is used in form of a tincture to treat mouth ulcers and tighten weak gums and loose teeth (Chevallier, Encyclopedia of Herbal Medicine, 2016). • Myrrh’s carminative effect excite peristalsis, promote the expulsion of gas and soothe the stomach, supporting healthy digestion (Green, 2000). • Myrrh’s expectorant effect supports the respiratory system by assisting it to remove excess mucus (Green, 2000). • Myrrh’s anticatarrhal effect counteracts the build-up of excess mucus and inflammation in sinus or other upper respiratory parts (Green, 2000).
• Myrrh’s antiseptic effect prevents or eliminates sepsis, infectious destructive condition of tissue (Green, 2000).
• Myrrh’s vulnerary effect assists the body to heal wounds, externally (Green, 2000). Antimicrobial Effect of Myrrh. Myrrh’s antimicrobial effects (antiviral, anthelmintic, antibacterial and antifungal) helps the body’s immune system destroy or resist the proliferation of pathogenic micro-organisms (Green, 2000). The anthelmintic activity of myrrh has been studied extensively in recent times. Clinical trials proved its efficacy against various stages of the parasitical organism schistosoma mansoni, which causes a disease condition affecting the liver cells. Myrrh showed significant activity against this parasitical organism, as well as, results showed a reduction in the degenerative disease condition affecting the liver (Bone & Mills, 2013).
In veterinary studies, the efficacy of myrrh as an anthelmintic agent has been evaluated through several uncontrolled trials. Sheep were tested and myrrh proved to be successful with sometimes a 100% cure rates (Bone & Mills, 2013). In clinical studies, it was observed that myrrh stimulated the body’s natural immune response against the parasites 30 rather than exerting a direct anti parasite effect (Bone & Mills, 2013). Indicating the difference between using a synthetic anthelmintic drug and using an herb which exert a physiological effect assisting the vital force within the cells to function normally and restore a state of health in the body. Clinical trials conducted in Egypt for the disease conditions Schistosomiasis and Fascioliasis, caused by resilient parasitical infections, and myrrh demonstrated in these clinical trials a strong efficacy with 90% cure rate in fascioliasis and 100% in schistosomiasis (Bone & Mills, 2013). An important factor when discussing the efficacy of anthelmintic agents whether they are of pharmaceutical origin or natural herbs, is their safety through studying the toxicology of these agents. Numerous studies have been performed to evaluate the safety of Myrrh in comparison to pharmaceutical anthelmintic agents, an example of such agents is Praziquantel. It was determined that Praziquantel is hepatotoxic, genotoxic and carcinogenic, while myrrh proved to have no adverse effects on the liver and kidneys. Like many herbal and botanical products, myrrh is safe to the human body (Abdul-Ghani, Loutfy, & Hassan, 2009). The antifungal properties of myrrh have also been studied and results confirmed the efficacy of myrrh in this regards (Dolara, Cerbai, Pugliese, & Menichetti, 2000). The results of this experiment agrees with historical uses of myrrh by herbalists and physicians of several medical systems to treat wounds which are prone to developing infections, in embalming, as a mouth wash and treatments of gastrointestinal disorders (Dolara, Cerbai, Pugliese, & Menichetti, 2000). Analgesic Effects of Myrrh. Myrrh’s analgesic effect relieves pain when administered orally or externally (Green, 2000). Myrrh has been used historically as a pain relieving agent, in recent years clinical trials on mice found two compounds within myrrh that exerts an analgesic effect through interaction with the brain opioid mechanism (Dolara, Cerbai, Pugliese, & Menichetti, 2000). 31 VIII. Combined Effects of Frankincense and Myrrh Various studies have been published and reviewed supporting the traditional use of Frankincense and Myrrh together to treat infectious disease conditions and restore harmony and health to the human body as a result. The earliest record of their combined use is the Papyrus Ebers, an ancient Egyptian formulary of prescriptions dating to 1500 BC, and they were both prescribed to treat wounds and skin sores. Furthermore, frankincense and myrrh were used with other herbs such as opium and red ochre to treat pruritus and infections of burn wounds (de Rapper, Van Vuuren, Kamatou, Viljoen, & Dagne, 2012). The Persian physician and philosopher Avicenna used frankincense as an antimicrobial agent as early as the 11th century, he also used it to treat inflammation and infections of the urinary tract and internally the oil was used for treatment of throat and larynx infections, respiratory infections and some stomach and liver conditions (de Rapper, Van Vuuren, Kamatou, Viljoen, & Dagne, 2012). In 1100 BC the Sumerians used myrrh to treat infected teeth and as an anthelmintic, and the Egyptians used it for embalming which indicates its proficiency in keeping pathogens intending to decompose the decaying and dead human tissues at bay for centuries. The oil of myrrh has also been used to treat wounds on skin and fungal infections caused by Candida Albicans and Tinea pedis (de Rapper, Van Vuuren, Kamatou, Viljoen, & Dagne, 2012). In modern times, in vitro study was designed to evaluate the independent and combined effect of frankincense oils and myrrh oils, obtained from various regions, as antimicrobial agents. The results conclude that all these oils demonstrated significant antimicrobial efficacy, and combined effects of both oils together demonstrated a more broad-spectrum effect against several species of microbial organisms. Therefore, the synergy of both of these resin oils is evident and further justifies the historical records and the herbalists and physicians who studied and used frankincense and myrrh together to treat various infectious diseases (de Rapper, Van Vuuren, Kamatou, Viljoen, & Dagne, 2012). Studies have determined that when combining Frankincense and Myrrh, the chemical constituents are not simply 32 added to each other but rather the actual chemical composition changes, causing significant changed to the pharmacological effects. The synergistic effect of combining these two resins changes the physiological effect on the human body, exerting synergistic anti-inflammatory, synergistic anticancer, synergistic analgesic, synergistic antibacterial and synergistic blood activating effects. In laboratory studies, it has been found that their synergistic effect provides a better penetration-promoting effect, which would enhance the potency when used in transdermal applications for skin infections or wounds prone to bacterial infections with biofilms to develop. In vitro experiments have proved that the combination of the essential oils of frankincense and myrrh have exerted the most significant antimicrobial effect against the Bacillus cereus, in comparison with other drug combinations, further proving the efficacy of the new chemical constituents formed in synergy when combining the essential oils of myrrh and frankincense (Cao, et al., 2019).
The first objective of this study was to research the historical and modern significance of frankincense and myrrh gum resins. Historical data on the esteem and value allocated to these gum resins by early civilizations and traditional systems of medicines from various cultures, was incontrovertible. From renown physicians such as Avicenna to kings and queens of ancient civilizations, frankincense and myrrh were highly sought and used for various purposes.
Traditional medicine systems and physicians used them to assist the body to heal from disease conditions affecting almost every system of the body. Kings, queens and religious leaders used them as incense and offerings to their gods or deity. Oils used in religious ceremonies and rituals such as the anointing oil in biblical times, incorporated them as one of the main ingredients. The use and esteem of frankincense and myrrh throughout the ages and across cultures is well documented and the research presented in this study offers only a small reflection into the majesty and legendary status of Frankincense and Myrrh. The main goal of this study is to research the physiological actions of frankincense and myrrh and their combined effect to assist the body’s innate ability to tackle chronic infections and antimicrobial resistant diseases. The first 33 step was to study and understand this pathology, and the reason why it is difficult for the body to eradicate these invading organisms and restore normal functions of the body.
A correlation between the emergent excessive use of penicillin derived single target drugs and the growing resilience of these invading organisms has been established through recent historical data and research findings. These new forms of invading organisms can more easily evade the body’s immune system due to their growing resistance, and when in the presence of mucosal tissues which are prone to harboring these microbial organisms, they begin to inhabit and form biofilms. This led us to research and understand biofilms which are essentially a community of microorganisms that live synergistically together and create an extra cellular polymeric substance which shields and protects these microorganisms from the outside environment. It has been determined as one of the main reasons behind the chronic and recurring nature of these infections, as the body is unable to completely eradicate these invading organisms due to its inability to effectively penetrate this protective shield and deliver the antimicrobial agent whether it be created by the body’s own immune system or antibiotic drugs taken internally by the patients. In order to fully understand why such invading organism can inhabit the body tissues and establish these biofilms, an understanding of the human microbiome and its role in maintaining normal physiological functions of the body had to be studied. The many functions of the human strains of beneficial organisms indicated that they are an essential part of human physiology and act as a virtual organ or system within the body itself. Therefore, the modern use of antibiotics which indiscriminately reduce the population of these healthy beneficial organisms are a secondary factor to why invading organisms can find suitable tissues within the body that lack the protection which our beneficial microbiome offers us. This is an important factor in understanding the pathology of chronic infections and the causes which lead to it. The chemical constituents within frankincense and myrrh are complex and they potentiate, enhance and mitigate each other’s effects inside the human body. The invading pathogenic organisms find it more difficult to evade and develop resistance to their complex chemical composition and physiological effects on the immune system. Research indicated that boswellic acids within the frankincense gum resin has been proven in clinical trials and experiments to reduce the density of biofilms and the protective layer, allowing for the body’s immune system 34 assisted by myrrh’s antimicrobial effects to penetrate and destroy the pathogenic organisms within the biofilm. While the chemical composition of both frankincense and myrrh have a plethora of components and compounds which are proven to be antibacterial, anthelmintic and antifungal, while having little to no side effects to the human body. Furthermore, boswellic acids exerts strong anti-inflammatory effects to the body tissues which is important as infections can cause irritation and inflammation in the tissues and organs they are affecting. Therefore, as the boswellic acids are reducing and tackling the biofilms created by these resilient invading microorganisms the antibacterial, anthelmintic and antifungal properties from compounds of both resins begin to assist the body to remove these harmful organisms, and the boswellic acids exert anti-inflammatory effects which can assist the body tissues to begin to heal and allow for the beneficial microorganisms to grow and restore harmony and balance within the body. The synergistic effect of combining these two leo-gum-resins changes the physiological effect on the human body, exerting synergistic anti-inflammatory, synergistic anticancer, synergistic analgesic, synergistic antibacterial and synergistic blood activating effects. This combined effect can assist the body’s innate ability in restoring normal functions and health to the body tissues infected by biofilm enclosed pathogenic organisms.
The current study concludes the following:
• The use of frankincense and myrrh have been recorded throughout various cultures, and modern research has proven the efficacy of these gum resins for the purposes that they were used for.
• Frankincense and myrrh have been used by physicians and herbalists from various traditional systems of medicine to treat wounds, digestive ailments, inflammatory conditions, arthritis and infections of oral and body tissues.
• Frankincense and myrrh have been used by kings, queens and religious figures for cultural ceremonies and religious rituals and were highly prized.
• Boswellic acids within frankincense gum resin exerts strong anti-inflammatory effects on the body, and posses’ strong antibacterial properties as well.
• Boswellic acids have been proven in recent studies and clinical trials to tackle and reduce biofilms in oral cavities.
• Myrrh has been used in embalming preparations which protects dead human tissues from decaying and harboring the organisms associated with decay.
• Myrrh has been proven in recent years to possess strong anthelmintic, antifungal and antibacterial properties.
• A correlation between the use of penicillin and the rise in antimicrobial resistant diseases and chronic infections has been established through research and recent historical data.
• The pathology of antimicrobial resistant diseases was studied, and these major factors has been noted: o The growing resistance of invading microorganism as they learn to adapt and evade the single target antibiotic drugs used in conventional medicine since the discovery of penicillin.
o The lack of understanding of the role the human microbiome plays in normal physiological functions of the body, has led to the overuse of pharmaceutical antibiotics which indiscriminately kill and reduce the population of these healthy beneficial microorganisms. o The disturbance to the human microbiome these and other external factors can cause, results in unhealthy tissue which are prone to harbor these invading microorganisms.
• The synergistic effect of combining frankincense and myrrh changes the physiological effect on the human body, exerting synergistic anti-inflammatory, synergistic anticancer, synergistic analgesic, synergistic antibacterial and synergistic blood activating effects.
• It has been found that their synergistic effect provides a better penetration-promoting effect, which would enhance the potency when used in transdermal applications for skin infections or wounds prone to bacterial infections with biofilms to develop.
• Frankincense and myrrh can offer great value for herbalists who are assisting patients dealing with chronic infections. The chemical compounds within both exert physiological effects on the body which could help 36 restore normal functions and maintain homeostasis in the body of patients who are dealing with chronic infections of various forms.
Abdel-Aziz, S. M., & A, A. (2014, July 18). Bacterial Biofilm: Dispersal and Inhibition Strategies. SAJ Biotechnology, 37 1(1), 1-9. Abdul-Ghani, R. A., Loutfy, N., & Hassan, A. (2009). Myrrh and trematodoses in Egypt: An overview of safety, efficacy and effectiveness profiles. Parasitology International, 58, 210-214. doi:doi:10.1016/j.parint.2009.04.006 Ben-Yehoshua, S., Hanus, L., & Borowitz, C. (2012, September). Frankincense, Myrrh, and Balm of Gilead: Ancient Spices of Southern Arabia and Judea. Horticultural reviews, 39(1), 1-79. Bone, K., & Mills, S. (2013). Principles and Practice of Phytotherapy: Modern Herbal Medicine (Second ed.). Edinburgh: Churchill Livingstone Elsevier. Buhner, S. H. (1999). Herbal Antibiotics: Natural alternatives for treating drug-resistant bacteria. (D. Balmuth, Ed.) North Adams, MA, USA: Storey Publishing. Cao, B., Wei, X.-C., Xu, X.-R., Zhang, H.-Z., Luo, C.-H., Feng, B., . . . Zhang, D.-K. (2019). Seeing the Unseen of the Combination of Two Natural Resins, Frankincense and Myrrh: Changes in Chemical Constituents and Pharmacological Activities. (D. J. Atanas G. Atanasov, Ed.) Molecules(24), 1-27. doi:doi:10.3390/molecules24173076 Chevallier, A. (2007). Herbal Remedies (1st ed.). New York: DK Publishing . Chevallier, A. (2016). Encyclopedia of Herbal Medicine (3rd ed.). (T. Mann, Ed.) New York: DK Publishing. Costerton, W., Lewandowski, Z., Caldwel, D. E., Korber, D. R., & Lappin-scott, H. (1995). Microbial Biofilms (Vol. 49). Annual Reviews Inc. Retrieved from https://doi.org/10.1146/annurev.mi.49.100195.003431 de Rapper, S., Van Vuuren, S., Kamatou, G., Viljoen, A., & Dagne, E. (2012). The additive and synergistic antimicrobial effects of selected frankincense and myrrh oils - a combination from the pharaonic pharmacopoeia. Letters in Applied Microbiology, 54, 352-359. doi:10.1111/j.1472-765X.2012.03216.x Dolara, P., Cerbai, E., Pugliese, A. M., & Menichetti, S. (2000). Local Anaesthetic, Antibacterial and Antifungal Properties of Sesquiterpenes from Myrrh. Planta Medica(66), 356-358. doi:DOI: 10.1055/s-2000-8532 Dolara, P., Luceri, C., Ghelardini, C., Monserrat, C., Aiolli, S., & Lodovici, M. (1996). Analgesic Effects of Myrrh. Nature, 379, 29. Ebadi, M. (2007). Pharmacodynamic basis of herbal medicine (2nd ed.). New York: Taylor & Francis Group. Felter, H., & Lloyd, J. U. (1898). King's American Dispensatory. Green, J. (2000). The Herbal Medicine-Maker's Handbook. New York: Crossing Press. Hakansson, A. P., Orihuela, C. J., & Bogaert, D. (2018). Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection. Physiological Reviews, 781-811. doi:10.1152/physrev.00040.2016 Hall-Stoodley, L., Costerton, J. W., & Stoodley, P. (2004, February). Bacterial Biofilm: From the natural environment to infectious disease. Natural Reviews Microbiology, 2. doi:10.1038/nrmicro821 Hamidpour, R., Hamidpour, S., Hamidpour, M., & Shahlari, M. (2013). Frankincense (乳香 Rǔ Xiāng; Boswellia Species): From the Selection of Traditional Applications to the Novel Phytotherapy for the Prevention and 38 Treatment of Serious Diseases. Journal of Traditional and Complementary Medicine, 3(4), 221-226. doi:10.4103/2225--4110.119723 Iram, F., Khan, S. A., & Husain, A. (2017). Phytochemistry and potential therapeutic actions of Boswellic acids. Asian Pacific Journal of Tropical Biomedicine, 7(6), 513-523. doi:http://dx.doi.org/10.1016/j.apjtb.2017.05.001 King, J., Felter, H. W., & Lloyd, J. U. (1898). King's American Dispensatory. Cincinnati: The Ohio Valley Company. Lumenih, M., & Teketay, D. (2003). Frankincense and Myrrh resources of Ethiopia: Medicinal and Industrial uses. Ethiopian Journal of Science, 26(2), 161-172. Maraghehpour, B., Khayamzadeh, M., Najafi, S., & Kharazifard, M. (2017). Traditionally used herbal medicines with antibacterial effect on Aggegatibacter actinomycetemcomitans: Boswellia serrate and Nigella sativa. Journal of Indian Society of Periodontology, 197-161. doi:10.4103/jisp.jisp_12_17 Maric, S., & Vranes, J. (2007). Characteristics and significance of microbial biofilm. PERIODICUM BIOLOGORUM, 109(2). O'Toole, G., Kaplan, H. B., & Kolter, R. (2000). Biofilm formation as microbial development. Journal of Microbiology, 54, 49 - 79. Pengelly, A. (2004). The Constituents of Medicinal Plants: An introduction to the chemistry & therapeutics of herbal medicines (2nd ed.). Cambridge: Sunflower Herbals. Raja, A. F., Ali, F., Khan, I. A., Shawl, A. S., Arora, D. S., Shah, B. A., & Taneja, S. C. (2011). Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-B-Boswellic acid from Boswellia Serrata. BMC Microbiology, 1-9. Retrieved from http://www.biomedcentral.com/1471-2180/11/54 Rose, J. B. (2011, December 2). Biofilm: The Good and the Bad. Retrieved from Water and Health: http://waterandhealth.org/safe-drinking-water/drinking-water/biofilms-good-bad-2/ Sherwood, L., & Ward, C. (2019). Human Physiology: From Cells to Systems (4th ed.). Toronto: Nelson Education Ltd. Tadesse, W., Desalegn, G., & Alia, R. (2007, Dec). Natural gum and resin bearing species of Ethiopia and their potential applications. Forest Systems, 16(3), 211 221. Retrieved October 21, 2019