Therapeutic effects of Gunryeong-tang on the cardio-renal axis in an animal model of pulmonary hypertension

Abstract

Background: In the realm of cardiovascular and renal health, the modulation of oxidative stress and inflammation within the cardio-renal axis plays a pivotal role. This study investigates the therapeutic potential of Gunryeong-tang (GRT), a traditional Korean herbal formula combining Oryeongsan (Wulingsan) and Sagunza-tang (Sijunzi-tang), specifically in addressing cardio-renal axis dysfunction induced by pulmonary arterial hypertension (PAH-r). Methods: PAH-r models were induced through intraperitoneal injection of monocrotaline (MCT) at a daily dose of 50 mg/kg for 5 days to simulate pulmonary hypertension, a common cause of cardio-renal syndrome. The primary focus is on evaluating its anti-fibroinflammatory effects and its ability to modulate oxidative stress and inflammation. The treatment group received oral administration of GRT (100 mg/kg/day). Results: Various parameters were assessed, including right ventricular (RV) enlargement and fibrosis, lung weight, pulmonary fibrosis, expression of cardiac hypertrophy markers, and involvement of specific pathways (TGF-β/p-Smad2 and HMGB-1/TLR4/MyD88/NF-κB). Renal dysfunction markers, such as blood urea nitrogen (BUN), creatinine clearance rate (Ccr), glomerular dilatation, tubular fibrosis, and protein expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), were evaluated to highlight the formula's anti-fibroinflammatory effects. Treatment resulted in significant improvements in the PAH-r group. It alleviated RV enlargement and fibrosis, suppressed lung weight increase, and mitigated pulmonary fibrosis. The administration downregulated cardiac hypertrophy markers (CTGF, TGF-β, and α-SMA mRNA levels) and inhibited the TGF-β/p-Smad2 and HMGB-1/TLR4/MyD88/NF-κB pathways, showcasing GRT's anti-fibroinflammatory properties. Additionally, the treatment ameliorated renal dysfunction, as evidenced by reduced BUN and Ccr levels, improved glomerular dilatation, and reduced protein expression of KIM-1 and NGAL. GRT demonstrates significant therapeutic potential in managing cardio-renal axis dysfunction induced by PAH-r, emphasizing its multifaceted benefits in modulating oxidative stress and inflammation within this axis. Conclusions: This study provides valuable insights into the underlying mechanisms, highlighting the modulation of cardiac hypertrophy markers and specific pathways. These findings underscore the promising role of GRT as a viable treatment option for cardio-renal axis dysfunction associated with PAH-r.