2. Academic Validation
  3. Xinbao pill attenuated water retention by regulating the CaSR/AQP2 pathway in LAD-induced chronic heart failure rats

Xinbao pill attenuated water retention by regulating the CaSR/AQP2 pathway in LAD-induced chronic heart failure rats

  • J Tradit Complement Med. 2024 Jul 2;15(5):495-508. doi: 10.1016/j.jtcme.2024.07.002.
Shiqi Li 1,  Yuanping Wang 1 2,  Xulan Cui 3,  Xiaoyu Tian 4,  Ziwei Huang 4,  Rong Zhang 4,  Yuanyuan Cheng 4,  Zhongqiu Liu 4,  Dawei Wang 1 5
Affiliations

Affiliations

  • 1 Shunde Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, Guangdong, 528333, China.
  • 2 Guangdong Provincial Second Hospital of Traditional, Chinese Medicine, Guangzhou, Guangdong, 510095, China.
  • 3 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
  • 4 Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
  • 5 The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510415, China.
PMID: 40979484 DOI: 10.1016/j.jtcme.2024.07.002
Abstract

Background: Water retention is one of the important factors in the development and exacerbation of chronic heart failure (CHF). Xinbao Pill (XBP) is widely used as an Adjuvant therapy for CHF. However, the therapeutic effect of XBP on water retention in CHF remains unclear.

Purpose: Our research was aimed to investigate the effect and mechanism of XBP on water retention in CHF.

Methods: Male Sprague-Dawley (SD) rats underwent left anterior descending (LAD) artery ligation to establish the CHF model and were subsequently administrated with different doses of XBP or Qili Qiangxin (QLQX). Cardiac functions were assessed using M-mode echocardiography. Cardiac remodeling and myocardial fibrosis were observed using HE and Masson staining. Additionally, the expression of the CaSR/AQP2 signaling pathway in the renal was detected using western blotting analysis, quantitative PCR analysis, immunofluorescence staining, immunohistochemistry, and co-immunoprecipitation assays. Furthermore, CaSR inhibitor NPS2143 was used to confirm the role of CaSR on the effect of XBP for water retention.

Results: In the LAD-induced CHF rat model, XBP improved EF (ejection fraction) and LVFS (fractional shortening), and alleviated cardiac fibrosis. Importantly, XBP significantly increased the 24-h urine volume and decreased urinary protein level after CHF. Further mechanism studies showed that XBP treatment could decrease the expression of renal AQP2 at the protein and mRNA levels. Moreover, XBP promoted renal AQP2 ubiquitination by upregulating CaSR and p-p38-MAPK expression. Meanwhile, XBP suppressed the expression of p-CREB to inhibit the mRNA expression of AQP2 in the renal tissue. However, NPS2143 blocked the beneficial effects of XBP on cardiac function and water retention, even stopped the inhibitory effect on AQP2 expression by XBP.

Conclusion: Our study revealed that XBP improved water retention against CHF via promoting CaSR/p38-MAPK-mediated AQP2 ubiquitination and regulating CaSR/CREB-mediated AQP2 transcription.

Keywords

Aquaporin2; Calcium-sensing receptor; Chronic heart failure; Water retention; Xinbao pill.

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