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Dermatology
The skin is the largest organ of the animal and human body and protects the internal organs from a variety of injuries as well as infectious agents. The microbiota of the skin is composed of bacteria, fungi, and viruses. Together, they form a complex ecosystem that plays a role in the defence against pathogens and in the development of the host’s immune system. Once the skin barrier is breached, the originally commensal bacteria become pathogens. They cause persistent inflammation and delay healing, leading to the development of chronic wounds typical of diabetics, immobile patients, and the elderly.
- antibacterial
- anti-inflammatory
- skin
- wound healing
1. Introduction
In ancient times, herbal substances were used singly or in combination with animal products, such as honey, to treat wounds. Over the centuries, therapeutic approaches were optimized until it was found that the most important thing was to prevent bacterial contamination, to maintain a moist environment in the wound, but at the same time, to absorb the exudate and exchange gases [2]. Therefore, various forms of wound dressings, such as films, hydrocolloids, hydrogels, and micro-/nanofibers, have been developed from natural and synthetic biomaterials that have the desired properties [3]. Nowadays, considerable attention is paid to the development of innovative wound dressings loaded with natural substances with therapeutic properties, such as demulsifying, emollient, re-epithelializing, astringent, antimicrobial, antioxidant, and anti-inflammatory activities, to accelerate and improve the wound healing process [2].
2. Microenvironment of Skin Wounds
In the uninjured skin, the epidermis is the outer impermeable layer that withstands the harsh external environment. Skin repair requires the intricate synchronization of several different cell types in sequential steps [5]. Immediately after injury, an inflammatory phase (1), together with aggregation and coagulation (2), restores homeostasis, stops bleeding, and prevents infection. In the first two days, mainly neutrophils are recruited to phagocytose cell debris and bacteria. They also release the growth factors. The healing process continues with the proliferation and matrix repair phase (3), which is controlled by lymphocytes, fibroblasts, macrophages, and endothelial cells. The final phase, the longest, is epithelialisation and remodelling of scar tissue (4) [5,6,7]. This healing process can be disrupted by bacteria in many ways. Contamination of the wound alters the lactate deposition, pH, and expression of proinflammatory cytokines, leading to a persistent inflammatory state with excessive levels of ROS (reactive oxygen species), toxins, and proteases [8]. The healing process is delayed as fibroblasts, growth factors, and matrix components (collagen, elastin, and fibrin) are degraded due to this adverse environment. The relationship between microbial colonisation and delayed wound healing is not yet fully understood [9], but bacterial colonisation is considered a major cause of chronic inflammation [10]. Chronic wounds, that is, those that have a biological or physiological reason for impaired healing, account for 60–80% of all infectious diseases in humans [9].
3. Microbiology of Skin Wounds
Microbes play an important role in influencing the wound microenvironment and, thus, wound healing. The typical sign of an infected wound is the massive proliferation of bacteria and the initiation of a host response [11]. The majority of infected wounds are contaminated with bacteria from the surrounding environment, that is, the commensal microbiota present on the skin [10]. Usually, skin infections are caused by S. aureus, including MRSA (methicillin-resistant Staphylococcus aureus). Staphylococci constitute a major group of bacteria inhabiting the skin, skin glands, and mucous membranes of humans, other mammals, and birds [12]. Other pathogens include Streptococcus pyogenes [13], Pseudomonas aeruginosa, Escherichia coli, Acinetobacter spp., and coagulase-negative staphylococci, including Staphylococcus epidermidis and Staphylococcus lugdunensis [9]. The first colonisers are obviously staphylococci, as their optimum growth is at a pH of around 7. Later, the wound is colonised by bacteria that can survive in a wider pH range (e.g., P. aeruginosa and Enterococcus faecalis). Peptostreptococci occur in more alkaline chronic wounds [14]. Malassezia spp. are the most common colonising fungal species identified on healthy skin, in contrast to Candida spp., which are most common in patients with immunodeficiency or diabetes or those taking antibiotics [1]. Biofilms are a serious complication of chronic wounds. This aggregated form of variable microbiota causes delayed healing. Compared with acute wounds, it is composed of anaerobic bacteria and fungi [8]. In skin wounds, the greatest biofilm formation potential has been found in Pseudomonas, Staphylococcus, Bacillus, and Moraxella spp. [9].
4. Bacterial Skin Infections in Livestock
Most bacterial skin infections in animals are caused by the genus Staphylococcus [15]. Livestock has been significantly exposed to excessive amounts of antibiotics [16] and has thus become a reservoir for bacterial resistance genes. The current threat is livestock-associated MRSA, which is transmissible to humans [17,18]. Efforts are being made worldwide to limit the use of common antibacterial agents and to offer alternatives, such as phytochemicals, for the treatment of bacterial skin diseases in livestock. As in vitro studies have shown, the plants most commonly used for healing belong to the Fabaceae and Asteraceae families [19]. One of the most common diseases treated with herbs is mastitis in dairy cows.
Bovine Mastitis
This is a very common disease of dairy cattle caused by physical injury or by pathogenic microorganisms. It manifests itself in the form of inflammation and destruction of milk-producing tissues, resulting in reduced milk yield and poor-quality milk. The pathogens responsible for mastitis are primarily S. aureus, streptococci, and Gram-negative bacteria, such as E. coli and Klebsiella pneumoniae [20,21,22], so the established treatment is still based on antibiotic therapy [23]. S. aureus produces degradative enzymes and toxins that irreversibly damage milking tissues. However, it does not trigger an immune response in the cow as strong as other bacteria or endotoxins; it causes milder infections, leading to chronic mastitis that lasts a few months [21,24]. In addition to evolved resistance, S. aureus forms biofilms that protect the bacterial community from effective treatment when antibiotics cannot reach the MIC [25]. Factors such as economic losses associated with treatment, culling of animals, reduced milk production, the risk of increasing antibiotic resistance, and antimicrobial residues in milk are putting pressure on the dairy industry to focus on alternative therapies to prevent and treat bovine mastitis [21,26]. Unfortunately, the multietiological nature of the disease makes new therapeutic approaches difficult, and for example, the use of vaccines has been declared ineffective [27].
5. Therapeutic Strategies of Skin Infections and Wound Healing
In fact, impaired vascular function, ischaemia, superficial debris, and necrosis are the main factors causing inadequate immune response and, consequently, contaminated chronic wounds. Excessive bacterial proliferation and biofilm formation lead to a chronic and self-perpetuating inflammatory state that alters the wound microenvironment (e.g., moisture, pH, metalloproteinases, and reactive oxygen species. Therapeutic strategies then include managing as many aspects of the microenvironment as possible [8]. Nature is considered a rich source of potential therapeutics. Secondary metabolites may help to overcome pathological wound healing through pharmacological effects directed at multiple targets. Phenolics, alkaloids, essential oils (EOs), diterpenes, triterpenes, carotenoids and saponin steroids, polyunsaturated fatty acids (PUFA), glucosinolates, and polysaccharides have been reported to have anti-inflammatory, antioxidant, antibacterial, collagen-synthesis-promoting, and skin-cell-regeneration-supporting properties [28,29,30]. These phytochemicals affect one or more phases of the healing process, generally have low toxicity and good bioavailability in the skin, and are therefore widely used in wound care [28]. The advantage of treatment with natural extracts is not only the multitarget effect, but also the synergy, for example, the potentiation of the effect of the individual compounds, which can be of natural origin, but also conventional medicines. Synergistic interaction between natural products has been reported for antibacterial, antioxidant, and anti-inflammatory activities. In summary, a natural compound should ideally fulfil the four actions considered important for the treatment of skin and soft tissue infections (antimicrobial, antioxidant, anti-inflammatory, and wound healing) [31]. Widespread practice to combat infections is based on controlling the bacterial load, which is achieved by regular cleansing of the wound and the use of antiseptics, specific antibiofilm agents, and antibiotics, mostly with a local effect. Systemic antibiotics are usually not used as they are hardly available in poorly perfused tissue [32]. Nowadays, intensive research is being conducted to develop wound dressings that prevent microbes from entering wounds and have a bactericidal effect. In recent studies, plant extracts and secondary metabolites have been incorporated into various wound dressings and tested against different Gram-positive/negative bacteria. Promising active natural agents include henna (Lawsonia inermis), St. John’s wort (Hypericum perforatum), EOs, curcumin, Aloe vera, and thymol [10]. Some of them have even been tested in clinical trials alone or incorporated into nanoparticles. Examples include honey, various EOs, sunflower seed oil, and tea tree oil [3].
This entry is adapted from the peer-reviewed paper 10.3390/molecules27144491
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