Xin-Ji-Er-Kang protects myocardial and renal injury in hypertensive heart failure in mice

  • Phytomedicine. 2021 Oct:91:153675. doi: 10.1016/j.phymed.2021.153675.
Xin-Xin Ling  1 ,  Hua Chen  1 ,  Bei-Bei Fu  1 ,  Cheng-Shao Ruan  1 ,  Ming Pana  1 ,  Kai Zhou  1 ,  Zhi-Rui Fang  1 ,  Jun-Tang Shao  2 ,  Feng-Qin Zhu  3 ,  Shan Gao  4
Affiliations
  • 1. Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China.
  • 2. Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
  • 3. Hefei Cancer Hospital, Chinese Academy of Science, Hefei 230032, China. Electronic address: [email protected].
  • 4. Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
PMID: 34332285 DOI: 10.1016/j.phymed.2021.153675
Abstract

Background: Xin-Ji-Er-Kang (XJEK) as a herbal formula of traditional Chinese medicine (TCM) has shown the protective effects on myocardial function as well as renal function in mouse models of myocardial infarction.

Hypothesis/purpose: We investigated the effects of XJEK on cardiovascular- and renal-function in a heart failure mouse model induced by high salt (HS) and the associated mechanisms.

Study design: For the purpose of assessing the effects of XJEK on a hypertensive heart failure model, mice were fed with 8% high salt diet. XJEK was administered by oral gavage for 8 weeks. Cardiovascular function parameters, renal function associated biomarkers and XJEK's impact on renin-angiotensin-aldosterone system (RAAS) activation were assessed. To determine the underlying mechanism, the calpain1/junctophilin-2 (JP2)/sarcoplasmic reticulum CA2+ ATPase (SERCA2a) pathway was further studied in AC16 cells after angiotensin II-challenge or after calpastatin small interfering RNA (siRNA) transfection.

Results: Mice on HS-diet exhibited hypertensive heart failure along with progressive kidney injury. Similar to fosinopril, XJEK ameliorated hypertension, cardiovascular-and renal- dysfunction in mice of HS-diet group. XJEK inhibited HS-induced activation of RAAS and reversed the abnormal expression pattern of calpain1and JP2 protein in heart tissues. XJEK significantly improved cell viability of angiotensin II-challenged AC16 cells. Moreover, XJEK's impact on calpain1/JP2 pathway was partly diminished in AC16 cells transfected with calpastatin siRNA.

Conclusion: XJEK was found to exert cardiovascular- and renal protection in HS-diet induced heart failure mouse model. XJEK inhibited HS-diet induced RAAS activation by inhibiting the activity and expression of calpain1 and protected the junctional membrane complex (JMC) in cardiomyocytes.

Keywords
Calpain1; Heart failure; Junctophilin-2; Renin-angiotensin–aldosterone system; Xin-Ji-Er-Kang.
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