Cardioprotective effects of 3-N-Butylphthalide in diabetic cardiomyopathy: focus on balanced mitochondrial dynamics and pyroptosis pathways
- 1Department of Cardiology, Shaanxi Provincial Hospital of Chinese Medicine Xi'an 710003 China
- 2Department of Zoology, College of Science, King Saud University Riyadh 11451 Saudi Arabia
- 3Department of Biochemistry, Sri Krishnadevaraya University, Anantapur 515003 India
Abstract
Diabetic cardiomyopathy (DCM) is a severe complication of diabetes, marked by myocardial dysfunction due to mitochondrial dysfunction and pyroptosis. 3-N-Butylphthalide (NBP), known for cardioprotective effects, remains unstudied in DCM. We evaluated NBP’s therapeutic potential in a rat model of type 2 DCM, focusing on mitochondrial dynamics, mitophagy, and pyroptosis. Male Sprague–Dawley rats with DCM, induced by a high-fat diet and streptozotocin, were divided into five groups: control, DCM, DCM + NBP (100 mg/kg/day for 14 days’ post-diabetes), DCM + Mdivi-1 (1.2 mg/kg/day), and DCM + NBP + Mdivi-1. Cardiac function was assessed by echocardiography; myocardial injury, histopathology, inflammasome-pyroptosis activation, mitophagy, mitochondrial dynamics, and function were analyzed via ELISA, hematoxylin and eosin staining, transmission electron microscopy, Western blot, and biochemical assays. DCM rats showed reduced ejection fraction and fractional shortening, increased left ventricular end-diastolic and systolic diameters, elevated cTnI and BNP, and histopathological damage. Inflammasome and pyroptosis markers (NLRP3, cleaved-caspase-1, ASC, GSDMD-N, IL-1β, LDH) increased, mitophagy (PINK1, Parkin) decreased, and mitochondrial function (ROS up, ATP down) worsened in DCM group. NBP improved cardiac function, reduced injury markers, and histopathology by suppressing inflammasome-pyroptosis, enhancing mitophagy, and restoring mitochondrial function and dynamics (Mfn2 up, Drp1 modulated). Co-treatment with Mdivi-1 attenuated these effects, indicating reliance on balanced mitochondrial dynamics. NBP mitigates DCM by enhancing mitochondrial homeostasis and inhibiting pyroptosis, but its efficacy diminishes with excessive fission inhibition. These findings suggest NBP’s potential as a DCM therapy, meriting further clinical exploration.
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BibTeX
@article{xie2026cardioprotective,
title = {{Cardioprotective effects of 3-N-Butylphthalide in diabetic cardiomyopathy: focus on balanced mitochondrial dynamics and pyroptosis pathways}},
author = {Huaning Xie and Shaik Althaf Hussain and Narendra Maddu and Jing An},
journal = {The Korean Journal of Physiology \& Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology},
year = {2026},
month = nov,
doi = {10.4196/kjpp.25.294},
url = {https://doi.org/10.4196/kjpp.25.294},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Cardioprotective effects of 3-N-Butylphthalide in diabetic cardiomyopathy: focus on balanced mitochondrial dynamics and pyroptosis pathways
AU - Huaning Xie
AU - Shaik Althaf Hussain
AU - Narendra Maddu
AU - Jing An
PY - 2026
DA - 2026/11/01
JO - The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
DO - 10.4196/kjpp.25.294
UR - https://doi.org/10.4196/kjpp.25.294
AB - Diabetic cardiomyopathy (DCM) is a severe complication of diabetes, marked by myocardial dysfunction due to mitochondrial dysfunction and pyroptosis. 3-N-Butylphthalide (NBP), known for cardioprotective effects, remains unstudied in DCM. We evaluated NBP’s therapeutic potential in a rat model of type 2 DCM, focusing on mitochondrial dynamics, mitophagy, and pyroptosis. Male Sprague–Dawley rats with DCM, induced by a high-fat diet and streptozotocin, were divided into five groups: control, DCM, DCM + NBP (100 mg/kg/day for 14 days’ post-diabetes), DCM + Mdivi-1 (1.2 mg/kg/day), and DCM + NBP + Mdivi-1. Cardiac function was assessed by echocardiography; myocardial injury, histopathology, inflammasome-pyroptosis activation, mitophagy, mitochondrial dynamics, and function were analyzed via ELISA, hematoxylin and eosin staining, transmission electron microscopy, Western blot, and biochemical assays. DCM rats showed reduced ejection fraction and fractional shortening, increased left ventricular end-diastolic and systolic diameters, elevated cTnI and BNP, and histopathological damage. Inflammasome and pyroptosis markers (NLRP3, cleaved-caspase-1, ASC, GSDMD-N, IL-1β, LDH) increased, mitophagy (PINK1, Parkin) decreased, and mitochondrial function (ROS up, ATP down) worsened in DCM group. NBP improved cardiac function, reduced injury markers, and histopathology by suppressing inflammasome-pyroptosis, enhancing mitophagy, and restoring mitochondrial function and dynamics (Mfn2 up, Drp1 modulated). Co-treatment with Mdivi-1 attenuated these effects, indicating reliance on balanced mitochondrial dynamics. NBP mitigates DCM by enhancing mitochondrial homeostasis and inhibiting pyroptosis, but its efficacy diminishes with excessive fission inhibition. These findings suggest NBP’s potential as a DCM therapy, meriting further clinical exploration.
SN - 1226-4512
SN - 2093-3827
ER -