At present, Aspergillus and Fusarium are still the main pathogenic fungi of fungal keratitis (FK). The incidence of FK is increasing and the rate of blindness is high. If improperly or untimely treated, it can cause corneal injury, resulting in substantial vision loss [1], [2]. However, the limited availability of effective antifungal drugs, the high toxicity and poor permeability of drugs make the treatment of FK difficult [3].

In FK, after adhesion of the fungus to the corneal epithelium and acquisition of a beneficial microenvironment, the conidia swell and begin to germinate, followed by the production of fungal hyphae [4]. Studies have shown that the forms of hyphae are well suited to invade and destroy tissue [5].Dectin-1 responded in a specific manner to β-glucan which is enriched in the A. fumigatus cell wall. Its expression increased in response to the invasion of A. fumigatus, and leading to increased secreting of inflammatory cytokines as well as mobilization of neutrophils [6], [7]. Previous studies suggested that activation of p38 MAPK may be associated with activation of Dectin-1 [8]. The p38 pathway is also closely associated with immune inflammatory reaction, and β-ionone improves FK in mice by reducing inflammation through the p38 MAPK pathway [9]. In addition, excessive inflammatory response leads to extensive stromal damage and corneal ulcer [10]. Therefore, treatment of FK requires both antifungal and immunomodulatory effect.

Resveratrol (RES) is a naturally occurring phenolic compound present in various foods like blueberries and peanuts [11]. Studies showed that RES had widespread attention for its numerous healthful pharmacological activities, for instance, antioxidant [12], anti-inflammatory [13], and anti-fungal effects [14]. RES inhibited MAPK signaling pathway and lowered TNF-α and IL-1β expression to suppress inflammatory response in mice mastitis [15]. RES could damage dormant conidia of gray mold at the ultrastructural level [16]. In addition, RES also had repairing effect on optic nerve injury and nerve injury after cerebral ischemia–reperfusion [17], [18]. These evidences suggested that RES could improve FK by exerting antifungal, anti-inflammatory and neuroprotective potential.

In this study, we indicated that RES could inhibit the growth of A. fumigatus, affect membrane integrity and disrupt hyphae morphology. Moreover, it down-regulates the levels of inflammatory factors in vitro and in vivo through suppressing the Dectin-1/p38 MAPK pathway. RES reduces FK severity by decreasing clinical scores, lowering fungal load, as well as suppressing inflammatory cell infiltration in the mice model of FK. RES could increase corneal nerve density and improve mechanical sensitivity.