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

Frontiers in Medicine

Ru Chen¹  Zhen-feng Hou²  Ren-shuang Cao³  Xiao-xuan Chen³  Fan Yang³  Hao-yue Zhu³  Wei Zhang⁴  GuoDong Zang⁴  Wan-yang Li⁵  Yu-xuan Li⁶ 

[1] Biomedical Research Institute of Fudan University, Shanghai, China;College of Life Sciences, Shandong Normal University, Jinan, China;College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China;Department of Pulmonary Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China;School of Public Health, Xiangya Medical College, Central South University, Changsha, China;Second School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China;

关键词: D-limonene;    coronavirus disease 2019;    coronavirus disease related pulmonary fibrosis;    severe acute respiratory syndrome;    PI3K/Akt signaling pathway;   

DOI  :  10.3389/fmed.2021.591830

来源: Frontiers

【 摘 要 】

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 d-limonene in the COVID-PF treatment. The differentially expressed genes of COVID-PF were downloaded from the GeneCards database, and their pathways were analyzed. d-Limonene was molecularly docked with related proteins to screen its pharmacological targets, and a rat lung fibrosis model was established to verify d-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 d-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 d-limonene has a potential therapeutic value for COVID-PF.

【 授权许可】

CC BY