|Year : 2018 | Volume
| Issue : 24 | Page : 200-207
Use of medicinal plants in the treatment of erysipelas: A review
Ivanise Brito da Silva1, Rafaela Damasceno Sá2, Danielle Patrícia Cerqueira Macêdo2, Karina Perrelli Randau3
1 Therapeutic Innovation Postgraduate Program, Federal University of Pernambuco, Recife, Brazil
2 Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Brazil
3 Therapeutic Innovation Postgraduate Program; Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Brazil
|Date of Web Publication||12-Oct-2018|
Dr. Karina Perrelli Randau
Professor Arthur De Sá Avenue, S/N, University City, 50740-521, Recife
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Erysipelas infection is caused by Gram-positive bacteria, in particular, β-hemolytic Streptococcus pyogenes streptococci (B, C, and G). Typically treated with benzathine penicillin, the bacterial resistance and entry points in the skin favor disease recurrence. The use of herbs is a widespread traditional practice in the general population as an alternative method for curing diseases and symptoms with subsequent improvement in quality of life. It represents a more affordable treatment for the lower-class population. This article reviews the use of medicinal plants in the treatment of erysipelas. A review was conducted identifying medicinal plants that can be used for the treatment of erysipelas. The search was conducted from publications from 1980 to 2016 by combining the search terms “medicinal plant” and “erysipelas.” The databases used in the research were PubMed, Web of Science, Google Scholar, Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Health Sciences, Cochrane Library, Scopus, and ScienceDirect. Data from the included articles are summarized in two tables with ethnopharmacological and pharmacological information. In this review, 30 articles were included. The selected plants have different popular indications of use, for example, to combat fever, inflammatory processes, and skin problems. The pharmacological studies evaluate the anti-inflammatory, antimicrobial, antioxidant, toxicological, immunomodulatory, and antiprotozoal properties of plants using in vitro and in vivo methods. The plants mentioned in this study are reported as viable possibilities for the treatment of erysipelas. Future research may be carried out to elucidate the active principles, mechanisms of action, and pharmacodynamic aspects and thus propose a new treatment.
Keywords: Erysipelas, ethnopharmacology, medicinal plants, treatment
|How to cite this article:|
da Silva IB, Sá RD, Cerqueira Macêdo DP, Randau KP. Use of medicinal plants in the treatment of erysipelas: A review. Phcog Rev 2018;12:200-7
|How to cite this URL:|
da Silva IB, Sá RD, Cerqueira Macêdo DP, Randau KP. Use of medicinal plants in the treatment of erysipelas: A review. Phcog Rev [serial online] 2018 [cited 2019 Jul 23];12:200-7. Available from: http://www.phcogrev.com/text.asp?2018/12/24/200/243199
| Introduction|| |
Erysipelas is an infection that involves the superficial layers of the skin caused by Gram-positive bacteria, such as group A streptococcus: Streptococcus pyogenes, β-hemolytic streptococci (B, C, and G), and S. aureus, and the Gram-negative Pseudomonas aeruginosa. Popularly known as Fire-of-Santo-Antônio, it was considered as a bacterial infection of high mortality in the preantibiotic era. It is a frequent disease in clinical practice, which presents a high rate of recurrence of approximately 23%–29% of the cases treated. Although it is considered a common disease, the etiology is still not well established, and it presents a differential diagnosis with Wells Syndrome, contact dermatitis, and deep venous thrombosis. In most cases, it is related to the presence of S. pyogenes. The virulence of such microorganisms is based on the secretion of surface proteins, particularly protein M, and on structures that directly or indirectly prevent phagocytosis involved in adhesion and carbohydrate metabolism or induce the release of pro-inflammatory cytokines.
The disease usually affects lower limbs and the face. It shows the following clinical symptoms: fever, pain, located redness, and swelling. However, the disease may worsen forming vesicles and/or blisters with a serous content, bleeding involving lymph vessels, acute glomerulonephritis, sepsis, septic arthritis, and endocarditis. The acute complications of disease are abscess and/or necrosis. The complications of a general nature are toxidermia and bacteremia/septicemia. Recurrences represent the late complication more frequent, being responsible for the high morbidity rate. It may cause death.
The treatment is performed using injectable antibiotics, such as benzathine penicillin, erythromycin, or clindamycin. However, many microorganisms are resistant to this treatment, making the therapy more difficult. In addition, the use of the isolated antibiotic does not promote wound healing, thereby enabling a gateway into the diseased skin and consequently the appearance of opportunistic infections.
The search for medicinal plants as an alternative treatment for skin diseases is an ancient practice, especially when related to diseases with difficult healing. Normally, the potential of drugs made from medicinal plants is associated with the promotion of angiogenesis. The formation of new vessels is important during the healing process since it ensures the supply of nutrients to sustain cell metabolism, as well as facilitate the elimination of toxic substances through circulation.
The use of medicinal plants in tissue reconstruction has evolved over the years from simple applications using herbs on the site to an improvement of sophisticated technologies in pharmaceutical industrial production. Were identified countries that take an interest in developing research investigating the wound healing potential of medicinal plants. Among these countries, Brazil had the largest number of publications, followed by India, United States, Cuba, Turkey, China, Peru, Japan, and Thailand.
Scientific studies report the need for the discovery of new drugs for the treatment of erysipelas. Currently, the clinical approach is made using penicillin, empirically. Considering the difficulties related to the treatment and the convenience of discovering new herbal or plant drugs that are safe for patients and that are effective in treatment, thereby reducing recurrence, this study aims to investigate the literature on the use of medicinal plants for the treatment of erysipelas.
| Materials and Methods|| |
A review was performed identifying medicinal plants used for the treatment of erysipelas. This type of research allows for the analysis and inference by a researcher on the issues of interest.
The search was conducted from publications combining the search terms “medicinal plant” and “wrysipelas” with Boolean operators “and.” The databases used in the research were PubMed, Web of Science, Google Scholar, Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Health Sciences, Cochrane Library, Scopus, and ScienceDirect. Inclusion criteria were original papers published between 1986 and 2016, written in English, Portuguese, or Spanish, which presented medicinal plants with indication for the treatment of erysipelas. Exclusion criteria were articles that present treatment with nonherbal materials, book chapters, short communication, review articles, historical articles, and papers without available full-text.
Data from the included articles are summarized in two tables with ethnopharmacological and pharmacological information. The species are organized in alphabetical order. The site The Plant List (www.theplantlist.org) was used to validate the scientific names and synonyms of the botanical taxa. In addition, plants that obtained more than one citation had their characteristics described.
| Results and Discussion|| |
In this review, 30 articles on ethnopharmacology and pharmacology were included. [Table 1] shows 18 ethnopharmacological articles selected. In these papers, 54 species were cited belonging to 37 different botanical families. Leaves were the part of the plant that was most cited for use, followed by flowers.
|Table 1: Ethnopharmacological medicinal plants used for the treatment of erysipelas|
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These works present the species that are also used for the treatment of erysipelas. However, no work that aimed to investigate medicinal plants popularly used only for erysipelas treatment was verified among the studies evaluated. The authors cite the ethnopharmacological use of the species and among the indications is the treatment of erysipelas.
The selected plants have different popular indications of use, for example, to combat fever, inflammatory processes, skin problems, or scarring was seen in ethnopharmacological articles. However, erysipelas is an infectious disease that causes pain, edema, fever, and skin wounds. The population chooses the plant species that have the capacity to decrease the symptoms of the disease.
Biodiversity, especially in developing countries, needs to be explored since the use of medicinal plants is a strategy that has a lower cost when compared with treatments with synthetic drugs. The investment in researches with medicinal plants can help the countries that have an ethnopharmacological potential. Brazil and India are the countries with the highest number of publications among the selected manuscripts.
Brazil has a wide biodiversity and many classes of active compounds have been isolated from Brazilian medicinal plants. Moreover, the tradition of the use of medicinal plants has called the attention of Brazilian researchers and has accelerated the interest in natural products, both from academia and pharmaceutical companies. India has the Council of Medical Research on medicinal plants that encourages the development of quality standards for pharmacopeial bodies and the drug industry with the intention of generating high-quality traditional or herbal drugs, a fact that would increase the country's scientific production.
The researches on pharmacological properties of medicinal plants with indication of use for the treatment of erysipelas are compiled. Twelve pharmacological articles were selected. In these papers, 16 species were cited belonging to 10 different botanical families [Table 2]. These studies evaluate anti-inflammatory, antimicrobial, antioxidant, toxicological, immunomodulatory, and antiprotozoal properties of plants using in vitro and in vivo methods. Brazil and India appear with the highest numbers of publications, followed by China. The rich diversity of medicinal plants in China provides an important source of medicinal raw materials, both for traditional medicine systems and for the pharmaceutical industry.
|Table 2: Pharmacological activities of medicinal plants used to treat erysipelas|
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The absence of articles aimed at the treatment of erysipelas, of ethnopharmacological or pharmacological origin, suggests that the subject is not well explored in the academic environment and reveals the need for further studies. Academic and pharmaceutical investment in research is required for the development of herbal formulations that can be used as an alternative treatment. The use of herbal preparations in replacing benzathine penicillin will mean quality of life for patients and the possibility of a different clinical management of the disease.
The antimicrobial evaluation of the ethanolic extract of Portulaca quadrifolia L. through the disc diffusion technique revealed that the extract has activity against the species Shigella dysenteriae with inhibitory growth between 10 and 20 mm. This study was conducted to evaluate Indian plants used in traditional medicine. The aim of this work was to identify the ability of the alcoholic extracts from 45 species for inhibiting bacterial and fungal growth. In addition, the authors did a phytochemical study of the species. P. quadrifolia is the only species among the selected ones that has been used for erysipelas. However, the extract tested only inhibited the growth of a bacterial strain and showed no secondary compounds in its chemical constitution.
The antimicrobial activity of the ethanolic extract the strains Portulaca pilosa L. obtaining inhibition of the growth of P. aeruginosa and S. aureus. Minimal inhibitory concentration (MIC) by the broth microdilution method showed that the crude ethanolic extract of Peperomia pellucida against S. aureus and P. aeruginosa had a MIC of 62.5 mg/mL. The resin glycosides from Ipomoea wolcottiana Rose increased the effect of the antibiotics against multidrug-resistant strains. However, the assay was performed only against of Escherichia coli, Salmonella enterica serovar Typhi, and Shigella flexneri.
Amazon Waiapi Indians treat malaria with an inhalation of vapor obtained from leaves of Virola surinamensis. The bark resin from the species is used in folk medicine for the treatment of erysipelas. The presence of sesquiterpene nerolidol is related to the antimalarial activity of the plant. The treatment, in vitro, of Plasmodium falciparum with 100 mg/mL of nerolidol over 48 h caused 100% inhibition in the development of young trophozoite. The antiulcerogenic activity of the resin extract of this species was also verified, through different models of lesion in mice. Besides, the authors report that the species is used as a natural form of treatment for different gastritis, inflammation, and erysipelas.
The increase of antioxidant substances in the healing process is important because in granulation tissues these antioxidants hasten the process of wound healing by destroying the free radicals. Free radicals can alter the functioning of many molecular complexes, leading to loss of form and function. Antioxidants can protect against the damage induced by free radicals acting at various levels. The inflammatory phase of the healing period generates a situation known as oxidative burst, caused by the cells involved in the inflammatory process. This stress increases the consumption of oxygen, resulting in the production of reactive oxygen and nitrogen derivatives. Antioxidant compounds, in this way, have an important role in promoting healing. The effect of antioxidant prevents cell damage and increases collagen fibrillary endurance. Evaluating the antioxidant effect of plants is important when investigating their potential for healing. The antioxidant potential of the species: Castanea seguinii Dode, Castanea mollissima Blume, Podophyllum hexandrum Royle, Forsythia suspensa (Thunb.) Vahl., and Acacia leucophloea (Roxb.) Willd. was verified in the pharmacological studies, by in vitro and in vivo tests.
The antioxidant power of methanolic extracts of plants used in Chinese medicine was also evaluated. The authors identified the concentration required to eliminate 50% of 2,2-diphenyl-1-picrylhydrazyl (DPPH). C. mollissima Blume (IC50 0.319 ± 0.018) and C. seguinii Dode (IC50 0.345 ± 0.022) used the same methodology, to verify the antioxidant capacity of the oil isolated from F. suspensa (Thunb.) Vahl. leaves. In addition to DPPH, the β-carotene bleaching test was also evaluated. The authors had results of IC50 of 22.35 and 29.51 mg/mL, respectively. The authors relate the antioxidant capacity of plants to chemical composition, due to the presence of phenolic compounds. The antioxidant capacity of the acetone extract from stem bark of A. leucophloea was determined by the gene expression of antioxidant enzymes. The study demonstrated that A. leucophloea extract inhibited H2O2-mediated oxidative stress by regulating the expression of enzymes/manganese, catalase, and glutathione peroxidase. The activity was dose dependent (25, 50, and 75 μg/mL); the authors suggest future studies to relate mechanisms of action and chemical components.
These pharmacological assays are not sufficient to establish a relationship between the plants and the treatment of erysipelas. The plant species are cited as a possibility for the treatment of erysipelas, but there is no concrete scientific evidence to assure this use. Antimicrobial activities are important; however, they need to ensure that plant present activities against the microorganisms found in the lesions of patients with erysipelas. Antioxidant assay needs to be associated with anti-inflammatory and healing, through in vivo and in vitro evaluations. Identification of the antimicrobial profile, evaluations of immunomodulatory, anti-inflammatory, and healing activities, cytotoxicity models in vitro and in vivo are necessary to correctly establish the use of these species for the treatment of erysipelas.
| Characteristics of the Most Cited Plants for Use in Treatment of Erysipelas|| |
The most cited plants in ethnopharmacological and pharmacological articles were briefly described their characteristics although no work with these species directly related to the treatment of erysipelas was found. The species were: Aloe vera (L.) Burm. f.; Sambucus nigra L; Stachytarpheta cayennensis (Rich.) Vahl., and Virola surinamensis (Rol. ex Rottb.) Warb.
Aloe vera (L.) Burm. f.
A. vera (Xanthorrhoeaceae) is an herbaceous, succulent plant, which grows up to 1 m high, and is probably of African origin. It has thick, succulent leaves attached to a short stem. It is a medicinal plant with different properties, being ascribed to the inner colorless gel and to the exudates from the outer layers. A. vera is a natural cleaner that has the power to penetrate in the tissues. The species has strong antibiotic, virucidal, fungicidal, and anti-inflammatory properties, presenting an absorption by the skin greater than the water and chemical constituents with an action on the immune system.
In vitro studies indicated that A. vera leaf gel can inhibit the growth of bacteria strains: S. aureus, Enterococcus faecalis,Bacillus cereus (MTCC 1272), E. coli (MTCC 1687), P. aeruginosa (MTCC 1688), Salmonella typhi (MTCC 531), Klebsiella pneumoniae (MTCC 530), S. flexneri and S. pyogenes. A study exploited the usage of A. vera plant extract as a reducing agent to synthesize silver nanoparticles (AgNP) to evaluate its efficiency in antimicrobial activity. The results showed that the enhanced and synergetic activity of the plant extract was obtained when it combined with AgNP. The inhibition of growth was verified in the following strains : S. aureus, B. cereus, Micrococcus luteus, E. coli, and K. pneumoniae.
Studies have shown that treatment with A. vera gel extracts resulted in faster healing of wounds. Polysaccharides from the plant promote both the proliferation of fibroblasts and the production of hyaluronic acid, and hydroxyproline in the fibroblasts acts on the healing process. Besides polysaccharides, there are in the chemical constitution antioxidant substances, including α-tocopherol (Vitamin E), carotenoids, ascorbic acid (Vitamin C), flavonoids, and tannins. The presence of anthraquinones, which is a structural analog of tetracycline, as an active compound, is related to the antibacterial activity from the species. The anthraquinones act like tetracycline which inhibits bacterial protein synthesis by blocking the ribosome.
An in vitro study demonstrated that A. vera ethanolic extract showed cytotoxic activity against fibroblasts at the concentration of 50 μg/mL, according to the MTT test. However, fibroblast migration analysis at this concentration demonstrated that after 72 h of treatment, there was an improvement in cell proliferation and migration. The authors suggest that stimulating cell proliferation and migration may cause the extract to aid in the healing process.
The acute toxicity of the hydroalcoholic extracts of A. vera leaves was tested in chicks using concentrations (40–1.280 mg/kg). The results showed that it can be considered safe since they caused neither lethality nor adverse changes in their general behavior. An in vitro study showed that toxicity of the gel and the whole leaf materials from A. vera are safe to use on skin tissue. Toxicological tests are important for guiding research that aims to develop drugs because they guarantee the safety of use, corroborating with ethnopharmacological knowledge.
Sambucus nigra L.
S. nigra (Adoxaceae) is large shrub or tree of 3–4 m in height and presents an irregular and many-branched canopy, with tortuous trunk and fissured bark, native of South America. Phytochemical studies of the aerial parts of the plant showed compounds, such as glycosides, flavonoids (rutin and quercetin), tannins, essential oils, triterpene acids, and reducing sugars.
Pharmacological studies have shown evidence of the following properties for S. nigra: anti-inflammatory, anti-Helicobacter pylori, and antioxidant.
The presence of these chemical compounds imparts anti-inflammatory, antioxidant, and expectorant properties in the species. Studies showed the power of the fruits of S. nigra L. in lower of the inflammatory response. This action is related to the presence of immune modulating components, including anthocyanins, flavonols, and phenolic acids.
In vitro anti-inflammatory assay of aqueous extract of S. nigra L. fruit in co-cultured intestinal epithelial cells and lipopolysaccharide (LPS)-stimulated macrophages showed that in concentration (1 mg/mL) the extract has the ability to inhibit proinflammatory pathway in LPS-stimulated macrophages by downregulating the expression of proinflammatory genes.
A study with S. nigra extracts evaluated its ability against bacterial and viral strains. There was a reduction in the growth of microorganisms of human clinical importance, at concentrations of 5%, 10%, 15%, and 20%. Furthermore, the authors suggest that the concentrations tested were not toxic to cells by the MTT assay.
The anti-inflammatory, antiseptic, and healing properties of S. nigra were assessed in experimental model of thermal skin burns, in Wistar rats. 1% silver sulfadiazine cream and cold-cream group were compared with cold-cream containing 10% vegetal extract. Rats treated with cold-cream containing 10% S. nigra extract of leaves showed a good epithelization, the wound healing being almost complete for 21 days. The inflammatory reaction and edema were smaller. The authors suggest that the presence of flavonoids and tannins compounds of the cold-cream with 10% extract is responsible for accelerating the repair of rat skin.
Another study evaluated the healing effect of different leaf extracts of Sambucus ebulus L. on rats and mice using incision and excision model of healing. The extracts were incorporated into a 1% concentration ointment base. The positive control was done with Madecassol® ointment. The methanolic extract of S. ebulus leaves was found to be remarkably active on in vivo wound models. The compound quercetin 3-O-glucoside was isolated from the methanolic extract as one of the active wound-healing ingredients. However, the extract presented a better action than the isolated compound, which suggests that the activity is related to the synergism of the compounds present in the crude extract.
An in vitro study evaluated the cytotoxic potential of aqueous extracts of the fruits of S. nigra. The authors concluded that in concentration (1 mg/ml), there was no cytotoxic, genotoxic, and mutagenic activity. Therefore, the use of fruits as functional food components could be postulated; however, further in vivo studies should also be conducted to confirm the health benefits of aqueous extract.
Stachytarpheta cayennensis (Rich.) Vahl
S. cayennensis (Verbenaceae) is an annual or perennial subbush, erect, branched, grows to 70–100 cm high, has few flowers, blue in color, and is a plant native to Brazil. Phytochemical screenings reveal that plants of the genus Stachytarpheta contain terpenes, flavonoids, arylpropanoids, iridoids, carbohydrates, glycosides, saponins, alkaloids, terpenoids, and steroids.
Stachytarpheta jamaicensis is widely known for its high medicinal importance in traditional and folk medicinal systems in various countries. This plant has been reported to possess pharmacological effects due to the presence of various bioactive phytochemicals. It demonstrates analgesic, antimalarial, and anti-inflammatory effects. S. cayennensis is used popularly in antiallergic, bronchodilatory, digestion stimulating, antacid and antidiarrheal, anti-inflammatory, antioxidant, and antimicrobial treatments.
An in vitro study evaluated the antimicrobial activity of organic extracts of roots of the species. It showed activity against Bacillus subtilis, Staphylococcus saprophyticus, Staphylococcus epidermidis, S. aureus, and S. pyogenes. The methanol extract of the leaves of S. cayennensis can have potent immunomodulatory effect on both humoral-mediated and cell-mediated immune responses. The authors emphasized that the presence of flavonoids increases the helper T-cells, interleukin 2, interferon, and macrophages; it is thus useful against several diseases of immune dysfunction. Pharmacological studies showed evidence of the anti-inflammatory, antinociceptive, antiparasitic, and antioxidant capacity of the species. In addition, low toxicity provides safe therapeutic use.,,
Virola surinamensis (Rol. ex Rottb.) Warb
V. surinamensis (Myristicaceae) is a tree with a pyramidal shape, 25–35 m high, has a cylindrical trunk, simple leaves, and small yellow flowers. It is native of alagadic forests of the Amazon region. Phytochemical research demonstrates the presence of steroids, flavonoids, lignans, and polyketides. There are studies in the literature mentioning several activities of this species, such as larvicide, antinociceptive, anti-inflammatory, antitumor, gastroprotective, and trypanocidal activities.,,
A study in vivo with mice showed that the ethanolic extract (500 mg/kg) demonstrated gastroprotective activity. The authors have evidenced the action of epicatechin present in its composition, which activated the defense mechanism of the gastric mucosa against aggressive factors, but its use demands great care because toxicological symptoms are mentioned by the population.
A study carried out with lignan (grandisin) associated the antinociceptive and anti-inflammatory effects of the species with the presence of this composition, corroborating the use in popular medicine of plants rich in grandisin for the treatment of symptoms caused by the inflammatory process, such as pain and edema. Besides this, the authors suggested that the mechanism of action of the molecule involves inhibition of the prostaglandin formation and/or activity through mechanisms of inhibition of cyclooxygenase activity or prostaglandin receptor antagonist action. The use of this species for the treatment of erysipelas may be related to the presence of lignin, a molecule that has anti-inflammatory action, which reduces symptoms such as edema, pain, heat, and flushing at the lesion site.
| Conclusion|| |
Erysipelas is a disease with clinical importance, especially when considering the consequences of its acute and late complications. However, it is poorly studied. It is thus not possible to clarify the disease mechanisms and develop new drugs, especially from medicinal plants. The usual treatment is conducted through an intramuscular administration of benzathine penicillin. Research involving the search for alternative treatments is scarce.
Popular use of plants without scientific evidence should be carefully evaluated as this can lead to complications to the health of the individual. This use must be validated through scientific research to be recognized as a possibility of treatment. Ethnopharmacological articles only cite the different uses of species, among which is the treatment of erysipelas. It was not possible to find any ethnopharmacological articles that approached integrally the popular plants for the treatment of erysipelas.
Articles with pharmacological activities evaluate antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory capacities of the plant species, most of them being in vitro. This shows, therefore, the need for research that evaluates healing, immunomodulatory and antibacterial activities. In vitro and in vivo preclinical tests, involving disease causing pathogens, identification of active principles to combat these microorganisms, cytotoxic assays, should be performed.
The plants mentioned in this study are reported as viable possibilities for the treatment of erysipelas. Future research may be carried out to elucidate the active principles, mechanisms of action, and pharmacodynamic aspects and thus propose a new treatment with changes in the clinical management of the disease.
We are grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]