Neferine ameliorates hypertensive vascular remodeling modulating multiple signaling pathways in spontaneously hypertensive rats

Background: Neferine exhibits therapeutic effects on anti-hypertension. However, the effect of neferine on hypertensive vascular remodeling remains unexplored. Therefore, the current study was to investigate the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms.Methods: Total 30 male spontaneously hypertensive rats (SHRs) were divided randomly into five groups, including SHR, Neferine-L (2.5 mg/kg/day), Neferine-M (5 mg/kg/day), Neferine-H (10 mg/kg/day), and Valsartan (10 mg/kg/day) groups (n = 6 for each group). Wistar Kyoto (WKY) rats were set as control group (n = 6). Noninvasive blood pressure system, ultrasound, hematoxylin and eosin staining, masson trichrome staining were used to detect the blood pressure, pulse wave velocity (PWV), pathological changes and collagen content in abdominal aortas of SHRs. RNA-sequencing and immunohistochemistry(IHC) analyses were used to identify and verify the differentially expressed transcripts and activation of associated signaling pathways in SHRs.Results: Various concentrations of neferine or valsartan treatment substantially reduced the elevation of blood pressure, PWV, and abdominal aortic thickening of SHRs. RNA-sequencing and KEGG analyses recognized 441 differentially expressed transcripts and several enriched pathways (including PI3K/AKT and TGF-beta/Smad2/3 signaling pathways) after neferine treatment. Masson trichromatic staining and IHC analysis demonstrated that neferine treatment decreased the collagen content and down-regulated the protein expression of PCNA, collagen I & III, and fibronectin, as well as p-PI3K, p-AKT, TGF-beta 1 and p-Smad2/3 in abdominal aortic tissues of SHRs. Conclusion: Neferine treatment exhibits therapeutic effects on anti-hypertension and reduces vascular remodeling, as well as suppresses the abnormal activation of multiple signaling pathways, including PI3K/AKT and TGF beta 1/Smad2/3 pathways.

Automated summary

This study investigates the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms. The results demonstrate that neferine can effectively reduce blood pressure, pulse wave velocity, and abdominal aortic thickening in hypertensive rats. It also suppresses the abnormal activation of PI3K/AKT and TGF-beta/Smad2/3 signaling pathways.