HER2-positive breast cancer patients now have a better prognosis thanks to trastuzumab. However, the drug can also cause HF or left ventricular dysfunction during therapy. The SGLT2i dapagliflozin had positive effects on the heart and kidneys. The sodium-glucose cotransporter 2 inhibitor dapagliflozin helped patients with HF, and the low ejection fraction in the DAPA-HF trial lowered their chance of developing worsening HF episodes and dying from cardiovascular causes. A nutritional supplement called berberine enhanced heart function and myocardial apoptosis while reducing the extent of myocardial infarcts and the incidence of ventricular arrhythmia.

Human fetal cardiomyocytes (HFC cell line) were given subclinical doses of trastuzumab (200 nM) alone, in conjunction with berberine (200 mM), dapagliflozin (50 nM), or both, during a 48-hour period. Researchers tested for cell viability, apoptosis, NLRP3 expression, methylglyoxal, and leukotrienes-B4 after incubation. In addition, a western blot was used to detect pAMPK and IL-6 expression.

Cardiomyocytes exposed to Trastuzumab had considerably higher cell viability after taking berberine and dapagliflozin. The cell viability of cardiac cells was improved synergistically when Berberine and Dapagliflozin were coupled (P<0.001 versus Trastuzumab). Berberine, dapagliflozin, and both together decreased cell apoptosis by 32.5, 41.8, and 72.7%, respectively (vs. trastuzumab group). In comparison to untreated cells, methylglyoxal was significantly decreased. Berberine and Dapagliflozin clearly induced pAMPK, as shown by a Western blot study. The expression of leukotriene B4 did not alter much. For berberine, dapagliflozin, and both together, IL-6 levels were decreased by 46.3, 62.7, and 86.3%, respectively (vs. trastuzumab group).

In cardiac cells exposed to the HER2-bloking agent Trastuzumab, Berberine and Dapagliflozin had strong cardioprotective benefits. By lowering heart failure and apoptotic biomarkers, berberine and dapagliflozin together cause myocardial cells to exhibit an anti-inflammatory phenotype.

Reference: annalsofoncology.org/article/S0923-7534(22)01892-0/fulltext