Natural Substances as Valuable Alternative for Improving Conventional Antifungal Chemotherapy: Lights and Shadows

Abstract

Fungi are eukaryotic organisms with relatively few pathogenic members dangerous for humans, usually acting as opportunistic infections. In the last decades, several life-threatening fungal infections have risen mostly associated with the worldwide extension of chronic diseases and immunosuppression. The available antifungal therapies cannot combat this challenge because the arsenal of compounds is scarce and displays low selective action, significant adverse effects, and increasing resistance. A growing isolation of outbreaks triggered by fungal species formerly considered innocuous is being recorded. From ancient times, natural substances harvested from plants have been applied to folk medicine and some of them recently emerged as promising antifungals. The most used are briefly revised herein. Combinations of chemotherapeutic drugs with natural products to obtain more efficient and gentle treatments are also revised. Nevertheless, considerable research work is still necessary before their clinical use can be generally accepted. Many natural products have a highly complex chemical composition, with the active principles still partially unknown. Here, we survey the field underlying lights and shadows of both groups. More studies involving clinical strains are necessary, but we illustrate this matter by discussing the potential clinical applications of combined carnosic acid plus propolis formulations.

Keywords: antifungal agents; carnosic acid (CA); chemotherapy; essential oils (EO); natural products (NP); propolis (PP).

Figure 1

Scheme of a fungal cell showing the cellular targets for the main three families utilized in antifungal chemotherapy (blue background) and for best studied NPs (light yellow background). The corresponding mechanisms of action are outlined. Dashed lines indicate inhibition.