Bioactive compounds of cyanobacterial strains possess antibacterial activity.
The wound care market is rapidly expanding due to the development of innumerable dressings that exhibit specific healing requirements for different wound types. The use of biomaterials as suitable wound dressing material is highly advantageous due to their biocompatibility, biodegradability, and non-toxicity. Cyanobacteria have been widely explored for their potential applications in wound healing, as they are the rich source of bioactive compounds with antibacterial, antitumor, antiviral, antioxidant, and antifungal activities. In recent years this group of organisms has been widely studied due to their immense potential in biomedical applications. Although their different bioactivities can support wound healing in different ways, very few forms have proven utility as a wound-healing agent. This chapter gives an insight into the potential of cyanobacteria in wound healing. Different bioactive compounds present in variable forms of cyanobacteria and their associated activities were reported to support tissue regeneration and wound healing acceleration. As the demand for cost-effective, bioactive wound care products is ever increasing, these organisms have immense potential to be utilized for the development of bioactive wound dressings. Hence, various bioactive compounds of cyanobacteria, their associated activities, and roles in wound healing have been briefly reviewed in this chapter.
- wound healing
- bioactive compounds
- antioxidant activities
Wound healing involves various interactions between cellular, molecular, biochemical, and physiological activities, making the process very complex, dynamic, and precisely programmed. Wound healing involves four phases: hemostasis, inflammation, proliferation, and remodeling to restore the structural, functional, and physiological integrities of injured tissues . This process results in the regeneration and replacement of injured tissue at the wound site . Several nutritional factors are required for proper cellular differentiation, immune functioning, and collagen formation . Any interruption, aberrance, or prolongation in the healing process would extend the tissue damage and thus prolong the repair process, contributing to chronic wound healing . In recent years there has been accelerating demand for various wound dressings, each with specific characteristics, considering the distinctive healing requirements of various wound types. Various synthetic and natural products have been widely explored for their efficiency and accelerating wound healing abilities to accomplish the need for suitable dressing for a particular wound type.
The nonabsorbent and non-biodegradable nature of synthetic products makes these products unsuitable for healing purposes . Medicinal plants are widely being explored for their utility in wound healing, and the ancient knowledge of medicinally essential plants, their increased popularity and utility further raised interest in exploring new natural products useful for the healing process. Various studies confirmed the anti-inflammatory, pro-collagen synthesis, antioxidant and antibacterial activities of natural products from plants and microbes, potentially beneficial for healing purposes. Biocompatibility and the presence of various bioactive phytochemicals in natural products efficiently promote the healing process and make them economically suitable for designing and fabricating dressings . To satisfy the demand for new natural therapeutic agents for wound healing and to decrease the average costs involved in their development, researchers are screening organisms from overlooked microbial sources having the potential to be used as effective wound healing agents such as proteobacteria, bacterioidetes, and cyanobacteria.
Cyanobacteria are ubiquitous, oxygenic photosynthetic bacteria having diverse nature and can be found in various forms like unicellular and filamentous, marine and freshwater, free-living symbiotic, edible, and poisonous. [7, 8]. This group of organisms has immense potential to produce many primary and secondary metabolites thus are known to perform potent biological activities. Produced secondary metabolites are low molecular weight, natural organic compounds, essential for average growth and development of these organisms. These metabolites have a wide range of applications in the field of medicines, industries, and biotechnology. These metabolites are a rich source of bioactive compounds, and cyanobacteria are the most promising organisms to produce them. In the last few decades, cyanobacteria have gained lots of attention for their medicinal values and wound healing properties. They are the choice of organisms due to their easy availability, fast regeneration, and huge diversity which have further expanded interest of researchers in their values as medicine and functional foods . Thus, their potential as a good source of new therapeutic lead compounds has been realized during the last two decades. Cyanobacterial secondary metabolites show different medicinally essential activities such as antitumor, antibacterial, antifungal, antiviral, anti-inflammatory, immunomodulatory effects, and protease inhibition . These biological activities are helpful to promote wound healing in different ways. Despite their potent biological activities, very few cyanobacterial forms are known to be useful in wound healing acceleration. Thus, this chapter presents an overview of bioactive compounds of cyanobacteria responsible for their various biological activities that promote the wound healing process by affecting different phases and factors of wound healing.
2. Important wound healing properties of cyanobacteria
2.1 Antibacterial activity
Antibacterial compounds are the molecules that kill or inhibit the growth of bacteria by affecting their physiological processes. Increased temperature due to inflammation caused by immune response and humidity caused by accumulation of fluid at the wound surface, make the wounds more vulnerable for bacterial infections. Once the wounded site came in contact with bacteria, they can penetrate underlying tissues, leading to life-threatening infections. To deal with such pathological conditions, effective wound management practices are essentially required. To improve the healing process and to reduce the wound bacterial colonization as well as infection at the wound site, the use of systematic antibiotics and the application of antimicrobial-loaded wound dressings are viable options to overcome the issue of infection and associated delay in healing. Considering the fact that usage of antibiotics has led to the increasing emergence of multidrug-resistant (MDR) strains of bacteria which negatively affects the healing process and worsens this issue . Thus, there is a need to develop/discover an effective wound management material which can efficiently cure wound in such conditions. Several cyanobacteria are known to produce intracellular and extracellular bioactive compounds that possess antibacterial activities. . These compounds are effective against various bacterial strains like
|Cyanobacterial Strain||Bioactive Compounds||Reference|
|Comnostin, Muscoride A, Dodecahydrophenanthrene, 4-methylchrysazin, Norharmane and 4-hydroxy-7-methylindan-1,carbamidocyclophane, Nostocarboline||[13, 16, 22]|
|Lyngbyazothrin, pahayokolide A||[26, 27]|
|Pitipeptolides, malyngolid||[29, 30]|
|hapalindole T, ambiguine-I isonitrile||[14, 18]|
2.2 Antifungal activity
Devastating chronic wound infection is a significant reason for trauma worldwide, which causes serious public health problems. Majorly bacteria are responsible for infections in wounds, but very few recent studies analyzed both fungal and bacterial communities in the microbiome of chronic wounds, suggesting the role of fungi as underappreciated agents that leads to complications at the wound site . Hard to heal wounds like diabetic foot ulcers (DFUs) are majorly infected by members of the genus
|Cyanobacterial Strain||Bioactive Compounds||Reference|
|Fontonamide, hapalindole||[38, 41]|
|Toyocamycin, Tubercidin||[42, 43]|
|Majusculamide C, Hectochlorin, Tanikolide||[24, 44, 45]|
|Nostofungicidine, Nostodione||[48, 49]|
|tolytoxin, phytoalexin, scytophycins|||
2.3 Antioxidant activity
Antioxidants are substances that prevent oxidation. They balance oxidative stress by eliminating free radicals and allowing the regeneration of tissue by repairing the cells . Respiratory burst generates oxidants during wound healing; production of these oxidants supports acceleration in healing. These produced oxidants act as a messenger and thus promote healing. However, a delicate balance between oxidants and antioxidants required to control the progress of the wound. For normal wounds, low physiology levels of reactive oxygen species and oxidative stress are required at wound sites. Whereas oxidative stress and impaired wound healing led by their overexposure. To improve the level of oxidative stress, increased level of antioxidants is expected, which further help in healing acceleration . Antioxidants also preserve and stimulate the function of immune cells against homeostatic disorders. Therefore, their increased levels can improve the immune response and accelerate wound healing . Accumulation of low molecular weight iron at the wound site also increases inflammation and microbial invasion of the wound , suggesting the requirement of a chelating agent to achieve proper healing. Production of various, chemically diverse groups of secondary metabolites from cyanobacteria established their industrial significance and made them an excellent source of antioxidants that facilitate the formation of the body’s defense mechanism against free radical induced damages to cells. Their antioxidant and metal chelating ability are reportedly due to phytonutrients and pigments present in them . Their cell-free extracts possess free radical scavenging property, metal chelating activity, and deoxyribose protection . The antioxidant properties of the cyanobacterial cell extracts are imparted by the total phenol and total flavonoid content present in the extracts. The free radical scavenging, metal chelating, and antioxidative damage protecting properties of cyanobacterial cell extracts are presumably linked with varied quantities of polyphenolics, gallic, chlorogenic, caffeic, vanillic, and ferulic acids, flavonoids, quercetin, and kaempferol present in them. Exopolysaccharides of cyanobacteria also exhibit good antioxidant and anticoagulant activities. They can also induce oxidants and antioxidant enzymes and are known as immunostimulators . Exopolymers of three strains of
2.4 Immunomodulatory and anti-inflammatory effects
Inflammation is a local, protective and physiological response to microbial invasion or injury. The magnitude of the inflammatory response is crucial: insufficient responses result in immunodeficiency, whereas excessive responses cause morbidity and mortality. Therefore, homeostasis and health are restored when inflammation is limited by anti-inflammatory responses . Natural compounds have gained lots of attention in treating various types of inflammations to reduce the reaction of the immune system against pathogens, toxic compounds, and damaged cells. The immune system actively participates in homeostasis, re-establishment, following tissue injury via multiple mechanisms, and plays a critical role throughout the wound healing process. Immune system control to promote tissue repair and regeneration is an attractive approach when designing regenerative strategies. Now a day, the multifunctional immunomodulatory properties of cyanobacteria are gaining much attention in the field of medicine. Cyanobacteria produce various metabolites with different chemical structures, including small molecules of peptides and proteins, polysaccharides, fatty acids, and their derivatives, possessing anti-inflammatory activities . Different cyanobacterial components control the release of certain cytokines from human monocytes and macrophages. Depending on the wound microenvironment, they also can reduce or activate the production of reactive oxygen species from neutrophils . Immunomodulatory effects of cyanobacteria highly induce activation of both types of immune cells which could promote wound debridement, accelerate re-epithelization, and wound closure . Edible cyanobacterial forms are known for their immune-boosting abilities, and many studies have proven their immunomodulatory and anti-inflammatory effects.
|Chemical group of bioactive compound||Bioactive Compound||Cyanobacterial Strain||References|
|Amino acids and peptides||Aeruginosin|||
|Ethyl tumonoate A|||
|Lipids||Monogalactosyl diacylglycerol, Digalactosyl diacylglycerol, Sulphoquinovosyl diacylglycerol, Phosphatidyl glycerol|||
2.5 Hemostatic activity
For people throughout the world, traumatic injuries have been a challenge. Considering technological advancements made through age’s trauma remains a leading cause of human morbidity and mortality . Excess bleeding can cause delayed wound healing, hematoma formation, infection, dehiscence, and necrosis. Patients suffering from trauma and its consequent hemorrhage essentially require the establishment of hemostasis by topical wound dressings. Constriction of blood vessels, the activation of the coagulation cascade, and the formation of blood clots are essential and significant steps of hemostasis. Therefore, any effort made to accelerate any or all phases above can help achieve hemostasis . The role of cyanobacteria and algae in hemostasis is significantly less known and identified. In the majority, their antithrombic activities useful to cure thrombosis-related diseases are reported. The antithrombic activity of Spirulan, a sulfated polysaccharide of
2.6 Wound healing effect of cyanobacteria
Specific healing requirements of a wound widen the scope of identifying more natural, economic, and effective wound healing agents, which gave extraordinary rise to the development of many synthetic and natural products useful as suitable wound healing dressing materials. Various natural products obtained by plants are widely known for their medicinal properties, facilitating wound healing. Bioactive secondary metabolites like alkaloids, essential oils, flavonoids, tannins, terpenoids, saponins, and phenolics are present in plant-based natural products. These compounds possess various activities like anti-inflammatory, antioxidant, antibacterial, procollagen synthesis, etc., and efficacy to modulate one or more phases of the wound healing process which further help in accelerated tissue regeneration during healing . Similarly, cyanobacterial bioactive compounds possess important medicinal properties like immunostimulating, antiviral, antioxidant, antibacterial, antifungal, antialgal, and anticancerous activities [38, 98] but very few are known for their wound healing potential. The blue-green microalgae
The ever-increasing demand for effective bioactive dressings suitable for different types of wounds is rapidly expanding the wound care market at diverse levels. Cyanobacteria are known for their numerous biomedical applications; thus, recently, they are a widely explored group of organisms. The cyanobacterial bioactive compounds possess antiviral, antifungal, antibacterial, antitumor, anti-inflammatory, and antioxidant activities suitable to accelerate wound healing even in chronic conditions by controlling different phases and factors of the wound. Cyanobacteria are known for the abundant availability of versatile bioactive compounds and their associated properties, but unfortunately, very few forms of cyanobacteria are known for their role in wound healing. Their easy cultivation, colossal diversity, and different biological activities can make them suitable candidates for research. Further, they can be explored more in the field of biomaterials for designing and fabrication of low-cost, biocompatible, and biodegradable wound dressings.
The authors are indebted to the Department of Science and Technology (DST), Govt. of India New Delhi, for providing opportunity and financial support (SP/YO/2019/1502) for interdisciplinary research work. The authors are also grateful to Professor Ashish Bhatnagar and Professor Monica Bhatnagar, Department of Microbiology, M.D.S. University, Ajmer, India for their support in the subject study.
Conflict of interest
The authors declare no conflict of interest.