Pingyang Jiangya Fang pretreatment reduces the blood pressure of spontaneously hypertensive rats with Liver-Yang hyperactivity syndrome via ROS/Akt oxidative stress pathway

Ann Palliat Med. 2021 Feb;10(2):1904-1919. doi: 10.21037/apm-20-1371. Epub 2020 Dec 16.

Abstract

Background: ROS/Akt pathway oxidative stress refers to a procedural response that activates various stress-sensitive signaling pathways in the cell thereby inducing insulin resistance (IR), and is closely related to high blood pressure. This study aims to investigate the effects of Pingyang Jiangya Fang (PYJYF) on the ROS/Akt pathway oxidative stress response in spontaneously hypertensive rats (SHRs) with Liver-Yang hyperactivity syndrome.

Methods: Except for the Wistar-Kyoto (WKY) and SHR groups, the other groups' rats were administered with Fuzi Decoction, to duplicated the model of hyperactivity of Liver-Yang. These rat's scleral color of deepens and become red, and rat's degree of irritability reached to above II degree. Compared with control group, rat's water consumption increased significantly, rotation tolerance time reduced significantly, pain threshold reduced significantly, rat tail vein systolic blood pressure (SBP) increased significantly. It shows that the model rats with hyperactivity of Liver-Yang have successfully replicated. Then, the corresponding drugs in the positive medicine group (candesartan cilexetil tablets) and the high, middle, and low dose groups of PYJYF (PYJYF-H, PYJYF-M, PYJYF-L) were administered. This work detected and analyzed behavior, SBP, renin-angiotensin system (RASS), expression of skeletal muscle angiotensin II type 1 receptor/angiotensin II type 2 receptor (AT1R/AT2R), IR index, renal/renal vascular/skeletal muscle tissue damage in each group. Moreover, we identified the target effect of point composition in the ROS/Akt signaling pathway.

Results: Unlike the WKY and SHR groups, the model group exhibited the phenotype of Liver-Yang hyperactivity syndrome, markedly increased SBP, hyper-RASS system, increased urine N-acetyl-β-Dglucosidase (NAG) and microalbuminuria (m-ALB), increased AT1R/AT2R ratio of skeletal muscle, IR, concomitant renal and skeletal muscle damage, as well as significant upregulation in the expression of ROS/ Akt signaling factor. PYJYF-H and PYJYF-M improved Liver-Yang hyperactivity syndrome, reduced SBP, the RASS system, urine NAG and m-ALB, AT1R/AT2R ratio, IR index, repair renal, renal vascular, and skeletal muscle tissue injury, as well as downregulated the expression of ROS/Akt signal factor.

Conclusions: PYJYF reduces blood pressure by inhibiting ROS/Akt pathway oxidative stress and reducing IR.

Keywords: Pingyang Jiangya Fang (PYJYF); ROS/Akt pathway; insulin resistance (IR); oxidative stress; systolic pressure.

MeSH terms

  • Animals
  • Blood Pressure
  • Liver
  • Oxidative Stress*
  • Proto-Oncogene Proteins c-akt*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Reactive Oxygen Species

Substances

  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-akt