AUTHOR=Yang Fan , Chen Ru , Li Wan-yang , Zhu Hao-yue , Chen Xiao-xuan , Hou Zhen-feng , Cao Ren-shuang , Zang GuoDong , Li Yu-xuan , Zhang Wei 

TITLE=D-Limonene Is a Potential Monoterpene to Inhibit PI3K/Akt/IKK-α/NF-κB p65 Signaling Pathway in Coronavirus Disease 2019 Pulmonary Fibrosis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.591830

DOI=10.3389/fmed.2021.591830

ISSN=2296-858X

ABSTRACT=<p>At the time of the prevalence of coronavirus disease 2019 (COVID-19), pulmonary fibrosis (PF) related to COVID-19 has become the main sequela. However, the mechanism of PF related to COVID (COVID-PF) is unknown. This study aimed to explore the key targets in the development of COVID-PF and the mechanism of <sc>d</sc>-limonene in the COVID-PF treatment. The differentially expressed genes of COVID-PF were downloaded from the GeneCards database, and their pathways were analyzed. <sc>d</sc>-Limonene was molecularly docked with related proteins to screen its pharmacological targets, and a rat lung fibrosis model was established to verify <sc>d</sc>-limonene's effect on COVID-PF-related targets. The results showed that the imbalance between collagen breakdown and metabolism, inflammatory response, and angiogenesis are the core processes of COVID-PF; and PI3K/AKT signaling pathways are the key targets of the treatment of COVID-PF. The ability of <sc>d</sc>-limonene to protect against PF induced by bleomycin in rats was reported. The mechanism is related to the binding of PI3K and NF-κB p65, and the inhibition of PI3K/Akt/IKK-α/NF-κB p65 signaling pathway expression and phosphorylation. These results confirmed the relationship between the PI3K–Akt signaling pathway and COVID-PF, showing that <sc>d</sc>-limonene has a potential therapeutic value for COVID-PF.</p>