Primary forms of oral candidiasis .
Due to the resistance of Candida sp. to the usual antifungal, the demand for active principles found in the plants has been the target of diverse studies around the world. There are few in vivo and human studies on the antifungal activity of medicinal plants in the mouth. Native and imported medicinal plants, used by the Brazilian population for traditional medicine use, are the subject of study in this chapter. Thirty-eight Brazilian plants were related to information on species, family, name, used part, and medical indication of popular use. All the species mentioned had their extracts tested in vitro against C. albicans, C. tropicalis, C. krusei, C. parapsilosis, among other species that occur more frequently in the mouth. In the articles consulted, there is a great variation in Candida species tested and in minimum inhibitory concentration. The in vitro studies serve as information for the continuity of studies on the best performing plants, validate the popular belief about the use, and provide subsidies for the development of new products that are effective in the control of oral and systemic candidiasis and that are cheap and accessible for the population.
- Brazilian medicinal plants
- Candida sp.
- oral candidiasis
- minimum inhibitory concentration
1. Oral candidiasis—by Elizete Maria Rita Pereira/Vagner Rodrigues Santos
The most common fungal pathogens detected from the oral cavity are
The type of
1.1. Main types, diagnosis, and treatment of oral candidiasis
Candidiasis is an acute or chronic infection produced by
|Primary forms of oral candidiasis||Characteristics|
|Pseudomembranous candidiasis (oral thrush)||Confluent white plaques with epithelial desquamation and accumulation of keratin, fibrin, necrotic tissue, and fungal hyphae [5, 11]|
|Acute erythematous oral candidiasis|
|Chronic erythematous oral candidiasis|
|Chronic hyperplastic candidiasis (candida leukoplakia)|
Diagnosis of oral candidiasis is established by identification of clinical signs and symptoms in conjunction with the presence of Candida organisms in the examination of an injury smear, biopsy examination containing hyphal form in the epithelium (Schiff’s Periodic Acid), or positive culture and serological tests [11, 12, 13].
Generally, the drugs of choice for localized, uncomplicated candidiasis in patients with normal immune function are topical antifungal agents (Figure 1). These agents can achieve elevated levels of concentration in the oral epithelium . Azoles act inhibiting the lanosterol 14-α-demethylase (enzyme involved in ergosterol biosynthesis) activity 14-α-demethylase (enzyme involved in ergosterol biosynthesis) and disrupt the cell membrane. The resistance to azole, generally, can be observed in HIV/AIDS patients receiving treatment for pre-HAART oral or esophageal candidiasis, for example. The resistance mechanisms of
Polyenes act by direct binding to ergosterol within the membranes of fungal cells, therefore, inducing the leakage of cytoplasmic content and leading to the death of microorganism. Formulations of nystatin or amphotericin B are used for 4 weeks [11, 14]. Resistance was observed in case reports of cancer patients on chemotherapy and those who have received long-term prophylactic therapy. The mechanism of Candida resistence to the polyenes are not yet known, but seem to involve changes in the cell membrane composition .
Echinocandins are noncompetitive inhibitors of the β-1,3 glucan synthase encoded by the FKS1 gene of
Antifungal systemic agents are indicated in fungemia when found in low immunity or immunodeficiency, high agranulocytosis, cancer patients or patients with intravenous catheters . Worldwide, an increase in the number of antifungal resistant yeasts is recognized. An important factor in contribution to human candidiasis is the ability of
The search for new antifungal agents and the characterization of new targets that are more appropriate and efficient have been proposed . Potential alternative therapies include the use of new active principles obtained from different general sources, such as natural products, in particular, the plants that contain several components that are important sources of biologically active molecules .
2. Brazilian medicinal plants tested against
Candidaspp.—by Vagner Rodrigues Santos
The search for therapeutic applications of medicinal plants and their derivatives has grown in the past years throughout the world. Several studies have been carried out in order to evaluate new biological properties from the biodiversity. The discovery of new antimicrobial components is of great relevance, particularly for dentistry, since bacterial and fungal infections of the oral cavity are a relatively common problem:
These are examples of infectious conditions of the mouth, and the resistance to antimicrobials in clinical cases has stimulated the search for natural agents as alternative treatments for the mouth infectious conditions. In Brazil, local communities use plants and their extracts for different medicinal purposes and take advantage of the availability of these plants and the low cost for product preparation. Plants have been used as antimicrobial, anti-inflammatory, wounds scarring, and antihemorrhagic agents, just to mention a few .
Medicinal plants continue to be widely used in rural and urban areas of Brazil. However, the intense miscegenation of crops over the last few centuries has more popularized the use of exotic native Brazilian plants and plants imported from other countries in popular medicine, especially in the southcentral part of the country. Most of these species were introduced by the Europeans and Africans, and are usually used according to the traditions of their places of origin [15, 16]. The growth of the pharmaceutical industry during the second half of the last century also distanced the Brazilian population from traditional medicine based on native plants. In the mid-1970s, for example, commercial pharmacies had lost their importance as the pharmaceutical industry completely dominated the drug market. This period was also marked by intense repression of mysticism, including the traditional use of medicinal plants. These facts are aggravated also by the continuous destruction of the rich Brazilian ecosystems, a process initiated with the exploration of Brazilwood by the Portuguese. As a consequence, remedies prepared with native plants, especially those of Amerindian origin, are now little known or used .
The Brazilian territory has about 20% of the world’s biodiversity, including plants, which serve as raw materials for the production of herbal medicines and other products. The great cultural and ethnic diversity of Brazil is responsible for the knowledge transmitted over generations on the management and use of medicinal plants . The high frequency of infections by the
Several plants have been studied in Brazil based on popular use, mainly by rural communities .
The antifungal activity observed in some plants may be related to the presence of flavonoid glycosides and tannins, components that have antimicrobial and anti-inflammatory properties . There is a growing interest in the use of tannins as antimicrobial agents. The activity of tannins against bacteria and yeasts can be measured by their action on the membranes, since they can cross the cell wall, composed of polysaccharides and proteins, and bind to its surface .
Studies with natural products generate difficulties regarding the comparison of results. This situation is due to the different presentations of the products used as tincture, ethanolic extract, aqueous extract, essential oil, among others, as well as the various methodological criteria employed  and also the different forms of phytotherapic presentation, among them, oral solutions, gel, and tea by decoction. The greater or lesser biological activity of the essential oils has been shown to be dependent on the composition of their chemical constituents, such as citral, pinene, cineole, caryophyllene, elemeno, furanodiene, limonene, eugenol, eucalyptol, and carvacrol. These constituents are responsible for the antiseptic, antibacterial, antifungal, and antiparasitic properties .
The mode of extraction of the active principles can influence significantly the antimicrobial activity. Biosynthesis of the constituents of a plant is strongly affected by the environment, harvest and postharvest, rainfall, temperature, luminosity, and humidity .
The mechanisms of action of medical plant extents on
The most common microbiological methods for testing plant-derived products such as extracts, resins, and essential oils are agar diffusion tests and liquid-liquid tests such as macrodilution and microdilution . The techniques of application of the plant antimicrobial substance in the diffusion method are by means of disc, stainless steel, or glass cylinders and agar perforation. The agar diffusion test, also called plaque diffusion, is a physical method in which a microorganism is challenged against a biologically active substance in solid culture medium and relates the size of the growth inhibition zone of the challenged microorganism [25, 26]. The application of the diffusion method is limited to fast-growing microorganisms, which are aerobic or anaerobic. The evaluation is comparative against a reference biological standard (positive control), and the zone or halo of inhibition of growth is measured starting from the circumference of the disc or well, to the margin where there is growth of microorganisms . According to the size of the halo, the microorganisms can be classified as: sensitive, when the diameter of the zone of inhibition is greater or no more than 3 mm less than the positive control; moderately sensitive, halo greater than 2 mm, but smaller than the positive control of more than 3 mm; and resistant, diameter equal to or less than 2 mm. As a positive control, a standard antimicrobial is used, and as a negative control, the solvent is used for the dissolution of the extracts [28, 29, 30, 31, 32]. The recommended incubation conditions are 35–37°C for bacteria for 24 to 48 hours and for fungi from 25 to 27°C for 48 to 72 hours [33, 34, 35, 36, 37, 38, 39]. These tests serve to define the minimum inhibitory concentration that quantifies the lowest concentration of the product capable of inhibiting the growth of microorganisms [40, 41, 42, 43, 44, 45, 46] (Table 3).
Table 2 shows the species, families, popular names, and used parts of plants for the various applications in traditional medicine.
|Herbs||Family||Local popular name||Used source||Medical use||Ref.|
|[38, 60, 61]|
|Digestive, emetic, febrifuge, hepatic, antioxidant,|
|Euphorbiaceae||Canopy, velame||Oil, barks,|
|Myrtaceae||Pitanga||Leaves||Diarrhea, fever, diabetes, inflammation,|
|Barks, leaves, resin||Antimicrobial|
|Verbenaceae||Rosemary-pepper, Alecrim-pimenta||Leaves, barks||Antinociceptive,|
|Celastraceae||Holy Thorn, Espinheira santa||Sheets||Antiseptic,|
|[87, 97, 98]|
|Lamiaceae||Peppermint, H ortelã--pimenta||Sheets||Expectorant,|
|Myrtaceae||Guava tree goiabeira||Leaves,|
|[20, 101, 102]|
|Anacardiaceae||Aroeira||Fruits, leaves, stem bark,|
|[108, 109, 110]|
|[87, 111, 112]|
|Rhamnaceae||Juazeiro||Leaves, fruits, bark, root.||Anti-inflammation, antimicrobial, healing||[87, 113]|
|Herbs||Active compounds||Microorganism||MIC: μg//mL||Ref.|
allistatin, allicin, ajoene
saponins, flavonoids amentoflavone
|1.50||[114, 49, 50]|
|Tannins, flavonoids||0.031||[115, 51, 52]|
|Isoscutellarein, 6-hydroxyluteolin, hispidulin, scutellarein, luteolin, apigenin; anthocyanins, coumarins, flavonoids, saponins, tannins, triterpenes||0.007/0.015||[55, 56, 102]|
|Nimonol, mahmoodin, naheedin||1000/500||[58, 117, 118]|
|Artepillin C, baccharin, kaempferide, drupanin, p-coumaric acid, culifolin, caffeic acid phenethyl ester, chlorogenic acid, kaempferol, pinocembrin, naringenin, chrysin||0.350|
|[24, 38, 92, 119]|
|Flavonoids, phenolic acids, quercetin, luteolin, nepetin or eupafolin, apigenin, hispidulin, phytoalexin||2.0||[120, 121]|
|Quercetin, hyperosides, α-cadinol, gamma-cadinene, 1,2,3-cadinatriene, α-muurolol||11.0 a 30||[64, 65]|
|Quercetin, ruthin, kaferol, gallic acid, chlorogenic acid, elagenic acid, caffeic acid||0.2||[66, 67]|
|Erytaurin, gentiopicrin, erytro-centaurin||10.5||[49, 68]|
|Decanal, trans-2-decenal, 2-decen-1-ol, cyclodecane, mono- and sesquiterpene hydrocarbons||0.007|
|[60, 92, 122]|
|5.25||[49, 123, 124]|
|Tannins, 4-O-methyl—catechin; epicatechin-3-O-gallate; 4-O-methyl-catechin-3-O-gallate||15.6|
|[79, 80, 128]|
Eugiflorins D1 and D2,
afzelin, myricitrin, quercetin, myricetin, betulinic acid, centelloside C
|[129, 81, 82, 130]|
|Flavonoids, phenolic acids, alkaloids, phytosterols, tannins, and triterpenoids||0.78–3.12||[131, 132]|
|Triterpenic saponins, glycyrrhizin,|
coumarins, quinones, flavonoids, tannins, triterpenes, steroids, alkaloids
|Ellagic acid||4.40||[60, 92]|
|Isoborneol, bornyl acetate,|
|[69, 93, 94]|
|Tannins, nepeticin, rigidenol,|
11-Î ± −hydroxygliquidone,
|8-cineole, neomenthol, menthol, carvone, acetato de metila, trans-cariofileno e viridiflorol menthol, menthone||0.73||[87, 97, 98]|
|[87, 99, 135]|
|Tannins, piperidine alkaloids, polyphenols, oxalic acid, malic acid, ascorbic acid, estrone punicic acid, punicalagin||20|
|[136, 69, 81]|
|[137, 138, 139]|
z-salven, β- pinene,
|[105, 106, 142]|
|[49, 143, 144]|
|4.25||[108, 110, 145]|
|Betulinic acid, oleanolic acid, caffeine, amphibine D, jujubogenin||0.625|
|[87, 92, 112, 146]|
3. Oral candidiasis clinical trial studies
There are few clinical studies in humans on the efficacy of extracts from Brazilian plants in the treatment of oral candidiasis. More recently, human effectiveness of Brazilian green propolis derived from
In this chapter, there is information about the most used Brazilian species of plants against
The authors thank Ms. Lorena de Melo Santos for the English revision.
Photo Credits (alphabetical order of Latin names): 1 Allium sativum, alho; 2