TY - JOUR
T1 - The therapeutic role and mechanism of 4-Methoxycinnamic acid in fungal keratitis
AU - Wang, Yuwei
AU - Yin, Min
AU - Gu, Lingwen
AU - Yi, Wendan
AU - Lin, Jing
AU - Zhang, Lina
AU - Wang, Qian
AU - Qi, Yinghe
AU - Diao, Weilin
AU - Chi, Menghui
AU - Zheng, Hengrui
AU - Li, Cui
AU - Zhao, Guiqiu
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/3
Y1 - 2023/3
N2 - Fungal keratitis is an infectious vision-threatening disease that has a poor prognosis, and the clinical therapeutic drugs have multiple limitations, such as epithelial toxicity and low bioavailability. Therefore, new antifungal treatment strategies must be developed. 4-Methoxycinnamic acid (MCA) is a widely occurring natural phenolic acid that has been proven to have multiple effects, such as antibacterial, antifungal, anti-inflammatory, neuroprotective, and inhibiting cancer. In this research, we explored the effects and underlying mechanisms of MCA on A. fumigatus keratitis and the antifungal effects of the combination of MCA and natamycin (NATA) on A. fumigatus. We found that MCA exerts antifungal effects by inhibiting the synthesis of the fungal cell wall, changing the permeability of fungal cell membranes. Moreover, the MCA-NATA combination exhibited synergy for A. fumigatus. In addition, MCA exerted an anti-inflammatory effect by downregulating the inflammatory factors (IL-1β, TNF-α, IL-6, and iNOS) in C57BL/6 mice and RAW264.7 cells. The anti-inflammatory mechanism of MCA was associated with the Mincle signal pathway. In summary, MCA acts as a potential therapeutic drug for fungal keratitis and a potential antifungal sensitizer for natamycin. MCA inhibits fungal cell wall synthesis, destroys the permeability of fungal cell membranes, and mediates the anti-inflammatory, immune response of the host.
AB - Fungal keratitis is an infectious vision-threatening disease that has a poor prognosis, and the clinical therapeutic drugs have multiple limitations, such as epithelial toxicity and low bioavailability. Therefore, new antifungal treatment strategies must be developed. 4-Methoxycinnamic acid (MCA) is a widely occurring natural phenolic acid that has been proven to have multiple effects, such as antibacterial, antifungal, anti-inflammatory, neuroprotective, and inhibiting cancer. In this research, we explored the effects and underlying mechanisms of MCA on A. fumigatus keratitis and the antifungal effects of the combination of MCA and natamycin (NATA) on A. fumigatus. We found that MCA exerts antifungal effects by inhibiting the synthesis of the fungal cell wall, changing the permeability of fungal cell membranes. Moreover, the MCA-NATA combination exhibited synergy for A. fumigatus. In addition, MCA exerted an anti-inflammatory effect by downregulating the inflammatory factors (IL-1β, TNF-α, IL-6, and iNOS) in C57BL/6 mice and RAW264.7 cells. The anti-inflammatory mechanism of MCA was associated with the Mincle signal pathway. In summary, MCA acts as a potential therapeutic drug for fungal keratitis and a potential antifungal sensitizer for natamycin. MCA inhibits fungal cell wall synthesis, destroys the permeability of fungal cell membranes, and mediates the anti-inflammatory, immune response of the host.
KW - 4-Methoxycinnamic acid
KW - A. fumigatus
KW - Antifungal
KW - Innate immune response
KW - Mincle
UR - http://www.scopus.com/inward/record.url?scp=85147212936&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2023.109782
DO - 10.1016/j.intimp.2023.109782
M3 - Article
C2 - 36731151
AN - SCOPUS:85147212936
SN - 1567-5769
VL - 116
JO - International Immunopharmacology
JF - International Immunopharmacology
M1 - 109782
ER -