In Vitro and In Vivo Inhibitory Activity of Limonene against Different Isolates of Candida spp.

Abstract

Commensal yeast from the genus Candida is part of the healthy human microbiota. In some cases, Candida spp. dysbiosis can result in candidiasis, the symptoms of which may vary from mild localized rashes to severe disseminated infections. The most prevalent treatments against candidiasis involve fluconazole, itraconazole, miconazole, and caspofungin. Moreover, amphotericin B associated with prolonged azole administration is utilized to control severe cases. Currently, numerous guidelines recommend echinocandins to treat invasive candidiasis. However, resistance to these antifungal drugs has increased dramatically over recent years. Considering this situation, new therapeutic alternatives should be studied to control candidiasis, which has become a major medical concern. Limonene belongs to the group of terpene molecules, known for their pharmacological properties. In this study, we evaluated in vitro the limonene concentration capable of inhibiting the growth of yeast from the genus Candida susceptible or resistant to antifungal drugs and its capacity to induce fungal damage. In addition, intravaginal fungal infection assays using a murine model infected by Candida albicans were carried out and the fungal burden, histopathology, and scanning electron microscopy were evaluated. All of our results suggest that limonene may play a protective role against the infection process by yeast from the genus Candida.

Journey of Limonene as an Antimicrobial Agent

“…Results of the study showed the protective role of limonene against Vulvovaginal candidiasis causing fungal isolates, as a low fungal burden in mice was observed after the treatment with limonene in comparison to untreated mice. Electron microscopy also revealed that limonene treatment caused dramatic structural changes in fungal cells including cell wall rupture 92 . Limonene is also found to inhibit the intracellular and extracellular enzymes such as cellulase and pectin methyl esterase present in some fungal isolates such as A. niger, P. digitatum, F. oxysporium and R. solani 93 .…”

Biomaterials for the Prevention of Oral Candidiasis Development

“…These antifungal agents can be administered either locally or systemically, in various forms ranging from oral suspensions, ointments, creams, gels, and troches, to tablets, pastilles, and even intravenous infusions. However, due to their toxicity, adverse side effects, and acquired resistance, these therapeutics action is often hindered [7,8,15,19,22,27,[33][34][35]. [19,47] Conventional local oral delivery formulations usually exhibit an initial burst release that rapidly decreases to subtherapeutic concentrations [8], whereas regular antifungal systemic drugs result in severe side effects [48].…”

“…In immunocompromised patients, it becomes overgrown, causing opportunistic infections, with symptoms varying from mild localized rashes to severe disseminated infections. Candida infections are known as candidiasis (sometimes found in the literature as candidosis), the Candida infections localized in the oral cavity being generally termed oral candidiasis [4][5][6][7][8].…”

“…Nonetheless, the efficiency of this approach is impaired by the emergence of drug-resistant Candida species. Hence, new therapeutic strategies have to be developed [7].…”

Mechanism of Antifungal Activity by 5-Aminoimidazole-4-Carbohydrazonamide Derivatives against Candida albicans and Candida krusei

“…are responsible for the majority of the yeast-like systemic mycosis [1,2]. In the last few decades, the increment of fungal infections, particularly nosocomial, and resistance to antifungal agents has stimulated the search for new antifungal agents [3,4].…”