Combining an in silico approach with an animal experiment to investigate the protective effect of troxerutin for treating acute lung injury

Abstract

Background Troxerutin (TRX), a naturally occurring flavonoid in various fruits, has been reported to exhibit numerous pharmacological and biological activities in vitro and in vivo. However, the molecular mechanisms underlying TRX as a treatment for disease are poorly understood. Methods Using pharmacophore mapping and inverse docking, a set of potential TRX target proteins that have been associated with multiple forms of diseases was obtained. Bioinformatic analyses were performed using the Enrichr and STRING servers to analyse the related biological processes and protein-protein networks. Furthermore, we investigated the potential protective effect of TRX against lipopolysaccharide-induced acute lung injury (ALI) using a mouse model. Morphological changes in the lungs were assessed using haematoxylin and eosin staining. Inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 were investigated using ELISA. Activation of MAPK and NF-κB was detected using western blotting. Results Our network pharmacology analysis revealed the existence of multiple TRX-related chemical-target interactions and the related biological processes. We found that pretreatment with TRX protected against histological changes and obviously regulated the inflammatory cell counts and inflammatory cytokine levels in bronchoalveolar lavage fluid. Based on bioinformatic and western blot analyses, TRX may exert a protective effect against ALI by inhibiting MAPK and NF-κB signalling. Conclusions TRX can ameliorate pulmonary injury by inhibiting the MAPK and NF-κB signalling pathways and has a potential protective effect against ALI. This study may be helpful for understanding the mechanisms underlying TRX action and for discovering new drugs from plants for the treatment of ALI. Electronic supplementary material The online version of this article (10.1186/s12906-019-2515-7) contains supplementary material, which is available to authorized users.

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“…These effects of troxerutin were comparable with those of 5 mg/kg DEX. Network pharmacology analysis and in vivo experiments showed that troxerutin markedly prevented the MAPK and NF-κB signaling pathway [ 174 ].…”

Troxerutin-Mediated Complement Pathway Inhibition is a Disease-Modifying Treatment for Inflammatory Arthritis

“…It is widely reported that TXR is a phytochemical with proven health benefits. It also has very low toxicity (LD 50 of 27160 mg/kg body weight in rats) and is safe for human use ( Zhang et al, 2015a ; Zhang et al, 2015b ; Shan et al, 2018 ; Li et al, 2019 ).…”

Troxerutin-mediated C9 inhibition is a disease-modifying treatment for inflammatory arthritis.

“…It is widely reported that TXR is a phytochemical with proven health benefits. It also has a very low toxicity (LD50 of 27160 mg/kg body weight in rat) and safe for human use (38)(39)(40)(41).…”