Therapeutic mechanism exploration of polysaccharides from Dendrobium officinale on unilateral ureteral obstruction operation-induced renal fibrosis based on improving oxidative stress injury mediated by AhR/NOX4 pathway.

Dendrobium officinale polysaccharides (DOP) has been reported to possess remarkable effects on improving renal function, oxidative stress damage and fibrotic diseases. However, the role and mechanism of DOP in preventing and treating renal fibrosis remain unclear. The purpose of this paper was to explore the therapeutic effects and underlying mechanisms of DOP on renal fibrosis. Firstly, renal fibrosis model was induced by unilateral ureteral obstruction operation (UUO) in male BALB/c mice. Subsequently, the anti-renal fibrosis effect of DOP was evaluated. It turned out that DOP significantly attenuated UUO induced renal fibrosis. The beneficial effects of DOP on renal fibrosis were concretely manifested in the relief of clinical symptoms, improvement of renal function, reduction of extracellular matrix collagen aggregation, attenuation of structural damage and inflammation, and decrement of profibrotic factors secretion. Meanwhile, DOP could also alleviate oxidative stress injury and inhibit the AhR/NOX4 pathway proteins expression. Furthermore, multivariate statistical analysis, AhR interference and overexpression experiments showed that the effect of DOP on alleviating renal fibrosis was closely related to the improvement of oxidative stress injury mediated by the AhR/NOX4 pathway. Overall, the data in the present paper indicated that DOP could alleviate renal fibrosis through improving AhR/NOX4 mediated oxidative stress injury.

Mechanism exploration of 6-Gingerol in the treatment of atherosclerosis based on network pharmacology, molecular docking and experimental validation.

BACKGROUND: The 6-Gingerol has significant anti-inflammatory, anti-oxidative and hypolipidemic activities and is widely used for treating cardiac-cerebral vascular diseases. However, the multi-target mechanism of 6-Gingerol in the treatment of atherosclerosis remains to be elucidated. METHODS: Firstly, the therapeutic actions of 6-Gingerol anti-atherosclerosis were researched based on an atherosclerotic ApoE-deficient mice model induced by high-fat feed. Then, network pharmacology and molecular docking were employed to reveal the anti-atherogenic mechanism of 6-Gingerol. Finally, the target for these predictions was validated by target protein expression assay in vitro and in vivo experiments and further correlation analysis. RESULTS: Firstly, 6-Gingerol possessed obvious anti-atherogenic activity, which was manifested by a significant reduction in the plaque area, decrease in the atherosclerosis index and vulnerability index. Secondly, based on network pharmacology, 14 predicted intersection target genes between the targets of 6-Gingerol and atherogenic-related targets were identified. The key core targets of 6-Gingerol anti-atherosclerosis were found to be TP53, RELA, BAX, BCL2, and CASP3. Lipid and atherosclerosis pathways might play a critical role in 6-Gingerol anti-atherosclerosis. Molecular docking results also further revealed that the 6-Gingerol bound well and stable to key core targets from network pharmacological predictions. Then, the experimental results in vivo and in vitro verified that the up-regulation of TP53, RELA, BAX, CASP3, and down-regulation of BCL2 from atherosclerotic ApoE-deficient mice model can be improved by 6-Gingerol intervention. Meanwhile, the correlation analysis further confirmed that 6-Gingerol anti-atherosclerosis was closely related to these targets. CONCLUSION: The 6-Gingerol can markedly improve atherosclerosis by modulating key multi-targets TP53, RELA, BAX, CASP3, and BCL2 in lipid and atherosclerosis pathways. These novel findings shed light on the anti-atherosclerosis mechanism of 6-Gingerol from the perspective of multiple targets and pathways.