Rosmarinic Acid Eases Fungal Eye Infection by Boosting Immune Cell Cleanup

Jim Crocker
27th May, 2024

Rosmarinic Acid Eases Fungal Eye Infection by Boosting Immune Cell Cleanup

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at The Affiliated Hospital of Qingdao University found that rosmarinic acid (RA) reduces inflammation in fungal keratitis (FK) by lowering proinflammatory cytokine levels
  • RA promotes autophagy in cells, helping to clear damaged components and reduce inflammation during FK
  • RA restores mitochondrial health and reduces harmful reactive oxygen species (ROS) in macrophages, aiding in inflammation management
  • RA induces macrophages to adopt an anti-inflammatory state and directly limits fungal growth, making it a dual-action treatment for FK
Fungal keratitis (FK) is a severe eye infection that can lead to significant vision impairment and even blindness. The condition is exacerbated by the virulence of the fungal pathogen and the body's inflammatory response. A recent study conducted by researchers at The Affiliated Hospital of Qingdao University has explored the potential therapeutic effects of rosmarinic acid (RA), a compound extracted from Rosmarinus officinalis, on FK[1]. This study aims to shed light on how RA can modulate macrophage autophagy and reduce inflammation in FK. The research team discovered that RA significantly reduced the expression of proinflammatory cytokines and lessened the recruitment of inflammatory cells in FK. Cytokines are small proteins that are crucial in cell signaling, and their overproduction can lead to excessive inflammation. By reducing cytokine levels, RA helps to mitigate the inflammatory response that contributes to the severity of FK. One of the key findings of this study is the upregulation of autophagy markers such as LC3 and Beclin-1 in RAW 264.7 cells and FK. Autophagy is a cellular process that helps in the degradation and recycling of damaged cellular components, which is essential for maintaining cellular health. The upregulation of these markers indicates that RA promotes autophagy, which in turn helps to resolve inflammation during fungal infection. This aligns with earlier findings where flavopiridol was shown to alleviate inflammation in fungal keratitis by activating autophagy[2]. The study also found that RA restored mitochondrial membrane potential (MMP) to normal levels in macrophages. MMP is a critical indicator of mitochondrial health, and its restoration suggests that RA helps in maintaining mitochondrial function. Additionally, RA reduced the production of both intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS) in macrophages. ROS are highly reactive molecules that can cause significant cellular damage, and their reduction is beneficial in managing inflammation. Furthermore, RA induced macrophages to adopt the M2 phenotype, which is associated with anti-inflammatory responses. This was evidenced by the downregulation of mRNA expression of proinflammatory cytokines such as IL-6, IL-1β, and TNF-α. The effects of RA were counteracted by the autophagy inhibitor 3-Methyladenine (3-MA), highlighting the importance of autophagy in RA's mechanism of action. In addition to its anti-inflammatory properties, RA also exhibited antifungal activities. It promoted the phagocytosis of RAW 264.7 cells and inhibited spore germination, biofilm formation, and conidial adherence. These findings suggest that RA not only helps in reducing inflammation but also directly limits fungal growth. This dual action is particularly valuable in treating FK, as it addresses both the infection and the inflammatory response. These findings are consistent with previous studies that have explored other compounds for FK treatment. For instance, dimethyl fumarate (DMF) was found to limit fungal growth and attenuate corneal inflammation by suppressing inflammatory cell accumulation and downregulating cytokine expression[3]. Similarly, pseudolaric acid B (PAB) was shown to inhibit A. fumigatus growth and reduce inflammation by modulating macrophage activity[4]. Additionally, oxidized chondroitin sulfate (OCS) demonstrated both antifungal and anti-inflammatory properties, improving the prognosis of FK in mice[5]. In conclusion, the study conducted by The Affiliated Hospital of Qingdao University provides compelling evidence that rosmarinic acid (RA) has significant therapeutic potential for treating fungal keratitis. By promoting autophagy, reducing oxidative stress, and exhibiting antifungal properties, RA addresses both the infection and the inflammatory response associated with FK. These findings contribute to the growing body of research aimed at developing effective treatments for this debilitating condition.

MedicineHealthMycology

References

Main Study

1) Rosmarinic acid alleviates fungal keratitis caused by Aspergillus fumigatus by inducing macrophage autophagy.

Published 24th May, 2024

https://doi.org/10.1016/j.exer.2024.109944

Related Studies

2) Flavopiridol Protects against Fungal Keratitis due to Aspergillus fumigatus by Alleviating Inflammation through the Promotion of Autophagy.

https://doi.org/10.1021/acsinfecdis.2c00427

3) Dimethyl fumarate ameliorates fungal keratitis by limiting fungal growth and inhibiting pyroptosis.

https://doi.org/10.1016/j.intimp.2023.109721

4) Pseudolaric Acid B Ameliorates Fungal Keratitis Progression by Suppressing Inflammation and Reducing Fungal Load.

https://doi.org/10.1021/acsinfecdis.2c00536

5) Oxidized chondroitin sulfate eye drops ameliorate the prognosis of fungal keratitis with anti-inflammatory and antifungal effects.

https://doi.org/10.1039/d2tb00114d


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