JYYS Granule Mitigates Renal Injury in Clinic and in Spontaneously Hypertensive Rats by Inhibiting NF- κB Signaling-Mediated Microinflammation

Abstract

Introduction

Hypertensive renal damage is a chronic and life-threatening kidney disease all over the world. The traditional Chinese medicine Jiang Ya Yi Shen (JYYS) granule has been a perfect drug for patients with hypertensive renal injury in clinic for 20 years in China. However, the molecular mechanism of JYYS granule remains unknown in treatment of this disease.

Methods

The clinic data were from this study's patients. The clinical symptoms of patients were indicated by (N-Acetyl- β-D-Glucosaminidase) NAG, (albumin) Alb, and ( β2-microglobin) β2-MG content in urinary of patients, and renal artery's hemodynamic parameters including (pulse index) PI, mean velocity of the arterial blood (Vm), minimum velocity of the diastolic stage (Vdmin) and peak velocity of the systolic wave (Vsmax). To further observe the effect of JYYS granule on renal damage, the rats were included in six groups: normal rats (WKY), spontaneously hypertensive rats (SHR), positive drug-treated rats (Benazepril), low dose JYYS (L), middle dose JYYS (M), and high dose JYYS (H). Then, we observed the effect of JYYS on renal function, renal tubules, inflammatory cell infiltration, and small artery thickening, and we explored the potential mechanism of JYYS in treatment of renal injury.

Results

JYYS significantly improved the clinic symptoms of patients with hypertensive nephropathy by downregulating NAG, Alb, and β2-MG content in urinary of patients and by decreasing renal artery's hemodynamic parameters including PI, Vm, Vdmin, and Vsmax. In SHR, JYYS significantly improved renal function including creatinine clearance rate, urinary albumin/creatinine, β2-MG/creatinine and arteria caudalis pressure in SHR. Secondly, light and electron microscopic examinations told that after administration of JYYS and Benazepril, the mesangial region exhibited no hyperplasia and renal capsule did not expanded, and there no abnormalities were observed in renal tubules, inflammatory cell infiltration and small artery thickening in SHR. Thirdly, JYYS exhibited its protective role by inhibiting nuclear factor kappa beta signaling-mediated micro-inflammation cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF- α), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein 1 (MCP-1) in SHR.

Conclusion

JYYS is a promising prescription of Chinese medicine for patients with hypertension and hypertensive renal damage.