Elucidating the role of Rhodiola rosea L. in sepsis-induced acute lung injury via network pharmacology: emphasis on inflammatory response, oxidative stress, and the PI3K-AKT pathway

Abstract

Context

Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects.

Objective

This study elucidates the molecular mechanisms of RR against sepsis-induced ALI.

Materials and methods

The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 μg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 μg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation.

Results

We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED₅₀) = 18.98 μg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results.

Discussion and conclusion

This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.

Keywords:

• Rhodiola rosea L
• sepsis-induced acute lung injury
• pulmonary fibrosis
• inflammation
• network pharmacology
• molecular docking
• experimental verification
• PI3K-AKT signalling pathway

Author contributions

The authors confirm contribution to the paper as follows: Conceptualization: LJ and LZ; Data curation, Formal analysis, Investigation and Methodology: DY, ZZ and LX; Funding acquisition: LZ. Project administration, Resources and Supervision: LX, QJ and YT; Software: ZZ, YT and LJ; Validation: QJ and DY; Visualization and Writing-original draft: LJ; Writing-review & editing: LZ. All authors reviewed the results and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [LZ], upon reasonable request.

Additional information

Funding

This work was supported by the [The project of science and technology plan of traditional Chinese medicine in Zhejiang Province] under Grant [number 2021ZB103] and [The research project of Zhejiang Chinese Medical University] [number 2022JKZKTS28].