Authors: Alessandra Ulivieri, Luca Lavra, Fiorenza Magi, Alessandra Morgante, Eugenio Martinelli, and Leila B. Salehi
Scientific Reports, 10 February 2026
Researchers use the Maestro MEA platform with LEAP to show baicalin protects against doxorubicin-induced electrophysiological dysfunction in human iPSC-cardiomyocytes.
Doxorubicin is an effective chemotherapeutic agent, but its use is limited by cardiotoxic side effects that can impair cardiac function. In this study, researchers investigated whether baicalin, a natural compound with antioxidant and anti-inflammatory properties, could protect human iPSC-derived cardiomyocytes from doxorubicin-induced damage—particularly at the electrophysiological level, where data have been limited.
Using Axion BioSystems’ Maestro Pro MEA platform, the team assessed both acute and long-term effects of doxorubicin exposure, with and without baicalin treatment. Functional recordings revealed that doxorubicin disrupted key electrophysiological parameters, while baicalin treatment (10–25 µM) mitigated these effects, stabilizing corrected field potential duration (FPDc), action potential duration (APD), beat rate, spike amplitude, and conduction velocity.
Importantly, the researchers leveraged LEAP (Local Extracellular Action Potential) technology to capture high-resolution action potential waveforms alongside conduction velocity mapping. These results demonstrate that baicalin provides measurable protection against doxorubicin-induced electrophysiological dysfunction and highlight the value of combining MEA recordings with LEAP-enabled insights to better understand cardiotoxicity and cardio-protection in human-relevant models.
Researcher Insights
An interview with authors Alessandra Ulivieri, PhD and Luca Lavra, PhD
Laboratorio di Ricerca Biomedica, Fondazione Università Niccolò Cusano per la Ricerca Medico-Scientifica
What motivated your team to investigate baicalin as a potential cardioprotective compound in a human iPSC-derived cardiomyocyte model of doxorubicin-induced cardiotoxicity?
"Doxorubicin is an extremely effective anticancer drug, but its clinical use is often limited by cardiotoxicity. In our Laboratory of Foundation Niccolò Cusano, we study the cardioprotective effects of natural compounds, and we are interested in identifying compounds that could protect the heart without interfering with the anticancer effects of antineoplastic drugs. Baicalin caught our attention because previous studies had suggested antioxidant and anti-apoptotic properties, but evidence in human-relevant cardiac models was still limited. Human iPSC-derived cardiomyocytes provide a physiologically relevant human model that allows the simultaneous evaluation of molecular, structural, and electrophysiological changes associated with cardiotoxicity. Using human iPSC-derived cardiomyocytes allowed us to investigate whether baicalin could protect human cardiac cells from doxorubicin-induced damage and, importantly, whether it could preserve cardiac function as well as cell survival."
Your study combines cytotoxicity, apoptosis, oxidative stress, sarcomere organization, and MEA-based electrophysiology. Why was it important to evaluate both structural and functional endpoints?
"Cardiotoxicity is a multifaceted process. A compound may improve cell viability while failing to preserve normal cardiac function, or structural alterations may occur before overt cell death becomes evident. Therefore, evaluating a single cellular process can provide only a partial description of the overall cardiotoxic response. We aimed to analyze different levels of cellular injury. Cytotoxicity, apoptosis, and oxidative stress measurements allowed us to assess the mechanisms underlying doxorubicin-induced damage. Sarcomere organization provided information about the integrity of the contractile apparatus, which is critical for cardiomyocyte performance. At the same time, electrophysiological MEA measurements enabled us to evaluate the functional consequences of these processes. By combining these results, we were able to demonstrate not only whether baicalin improved cell survival, but also whether it helped maintain the structural and electrical properties that are essential for normal cardiac function."
What did MEA-based electrophysiology reveal about doxorubicin-induced cardiotoxicity that would have been difficult to capture using viability or imaging assays alone?
"MEA recordings provided information about the effects of Doxorubicin on the electrophysiological function of cardiomyocytes in real time. Our data indicated that electrophysiological alterations could be detected in the absence of iPSC-CM death. This suggests that functional impairment may occur before overt cell death, highlighting that MEA technology is important for the analysis of electrophysiological parameters and for identifying early signs of cardiotoxicity."
Your study measured repolarization-related readouts such as FPDc and APD90, as well as tissue-level parameters such as conduction velocity. How did combining these MEA-based functional readouts help you interpret doxorubicin-induced cardiotoxicity and baicalin-mediated protection in the hiPSC-CM model?
"Each analyzed parameter reflects a specific aspect of cardiac electrophysiology. FPDc and APD90 provide information about repolarization, while conduction velocity reflects how efficiently electrical signals propagate through the cardiomyocyte, which is strictly related to the structural integrity of the iPSC-CM monolayer. The concomitant analysis of these parameters allowed us to demonstrate that, rather than affecting a single mechanism, doxorubicin disrupted multiple cardiomyocytes' functional properties. Moreover, we demonstrated that baicalin attenuated the majority of these alterations, suggesting that its action extends beyond simple cytoprotection and includes preservation of electrophysiological function."
How did the ability to monitor electrophysiological changes over time contribute to your understanding of acute versus longer-term doxorubicin effects?
"One of the major strengths of MEA technology is that it allows repeated, non-invasive measurements on the same cultures over time. This approach was extremely important to distinguish early functional disturbances from later manifestations of cellular injury. Some electrophysiological alterations emerged before extensive structural damage became apparent, suggesting that electrical dysfunction may represent an early indicator of cardiotoxicity. Moreover, continued monitoring also enabled us to evaluate how effectively baicalin preserved cardiac function throughout the exposure period."
For researchers studying cardiotoxicity or cardioprotective compounds, what value do you see in combining hiPSC-derived cardiomyocytes with MEA-based functional assays?
"We believe this combination offers one of the most informative platforms currently available for cardiotoxicity research. Human iPSC-derived cardiomyocytes provide a clinically relevant model, while MEA technology adds a non-invasive, real-time functional analysis that is fundamental to long-term toxicity studies. Together, they enable researchers to assess not only whether human cardiomyocytes survive but also whether they preserve their normal electrophysiological function. This is particularly important when evaluating cardioprotective strategies, where preserving cardiac function is ultimately the key goal."
What's next for your lab, and what future questions are you most excited to explore based on this work?
"This study raises several important questions for future investigation. In particular, further work is needed to elucidate the molecular mechanisms underlying the cardioprotective effects of baicalin, with a focus on oxidative stress modulation, mitochondrial function, and calcium handling dynamics. In addition, it would be of interest to evaluate other natural compounds with potential cardioprotective properties, either alone or in combination with baicalin. Taken together, we believe these efforts will contribute to the development of translational strategies aimed at reducing chemotherapy-induced cardiotoxicity while preserving antitumor efficacy, with the long-term goal."
