2. Academic Validation
  3. Berberine attenuates sunitinib-induced cardiac dysfunction by normalizing calcium regulation disorder via SGK1 activation

Berberine attenuates sunitinib-induced cardiac dysfunction by normalizing calcium regulation disorder via SGK1 activation

  • Food Chem Toxicol. 2023 Mar 26;175:113743. doi: 10.1016/j.fct.2023.113743.
Congxin Li 1,  Wenting Wu 2,  Jiahui Xing 2,  Wei Yan 1,  Jiali Zhang 2,  Jinglei Sun 2,  Zhihan Zhang 3,  Suhua Qiu 2,  Yanfang Xu 2,  Xianying Wang 4
Affiliations

Affiliations

  • 1 Department of Pharmacy, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
  • 2 Department of Pharmacology, Hebei Medical University, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
  • 3 Department of Nutrition, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050010, China.
  • 4 Department of Pharmacy, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China. Electronic address: [email protected].
PMID: 36972840 DOI: 10.1016/j.fct.2023.113743
Abstract

Sunitinib (SNT)-induced cardiotoxicity is associated with abnormal calcium regulation caused by phosphoinositide 3 kinase inhibition in the heart. Berberine (BBR) is a natural compound that exhibits cardioprotective effects and regulates calcium homeostasis. We hypothesized that BBR ameliorates SNT-induced cardiotoxicity by normalizing the calcium regulation disorder via serum and glucocorticoid-regulated kinase 1 (SGK1) activation. Mice, neonatal rat cardiomyocytes (NRVMs), and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to study the effects of BBR-mediated SGK1 activity on the calcium regulation disorder caused by SNT as well as the underlying mechanism. BBR offered prevention against SNT-induced cardiac systolic dysfunction, QT interval prolongation, and histopathological changes in mice. After the oral administration of SNT, the Ca2+ transient and contraction of cardiomyocytes was significantly inhibited, whereas BBR exhibited an antagonistic effect. In NRVMs, BBR was significantly preventive against the SNT-induced reduction of calcium transient amplitude, prolongation of calcium transient recovery, and decrease in SERCA2a protein expression; however, SGK1 inhibitors resisted the preventive effects of BBR. In hiPSC-CMs, BBR pretreatment significantly prevented SNT from inhibiting the contraction, whereas coincubation with SGK1 inhibitors antagonized the effects of BBR. These findings indicate that BBR attenuates SNT-induced cardiac dysfunction by normalizing the calcium regulation disorder via SGK1 activation.

Keywords

Berberine; Cardiac contractile dysfunction; Human-induced pluripotent stem cell-derived cardiomyocyte; Phosphoinositide 3-kinase; Serum and glucocorticoid-regulated kinase 1; Sunitinib.

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