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<p>Isoproterenol (ISO) is a synthetic β-adrenergic agonist widely used to model xenobiotic-induced cardiac injury, primarily through mechanisms involving oxidative stress, mitochondrial dysfunction, dyslipidemia, and apoptosis. Considering the growing interest in plant-derived bioactive compounds as cardioprotective agents, this study evaluated the mechanistic potential of a polyherbal formulation (PHF) composed of <i>Andrographis paniculata</i>, <i>Bauhinia variegata</i>, <i>Moringa oleifera</i>, and <i>Lantana camara</i>. GC-MS profiling of the formulation revealed several pharmacologically relevant phytoconstituents, including 3-methylmannoside, isothiourea, L-gala-L-ido-octose, β-sitosterol, heptanal, and eicosatrienoic acid methyl ester. ISO challenge in rats resulted in pronounced cardiac injury marked by elevated biomarkers, perturbed lipid metabolism, depletion of endogenous antioxidants, mitochondrial ATP loss, Ca<sup>2+</sup> overload, suppression of tricarboxylic acid cycle enzymes, and activation of Bax/caspase-3-mediated apoptosis. Pretreatment with PHF significantly attenuated these pathological changes by restoring antioxidant defenses, stabilizing lipid homeostasis, improving mitochondrial bioenergetics, enhancing TCA cycle activity, and modulating intrinsic apoptotic signalling. Additionally, PHF upregulated mitochondrial biogenesis mediators (PGC-1α, NRF1, TFAM) and promoted AMPK-PPARα-driven fatty acid oxidation while suppressing SREBP-1c-associated lipogenesis. Molecular docking further supported the multi-target nature of the phytochemicals through strong interactions with mitochondrial, lipid-regulatory, and apoptotic proteins. Collectively, these findings highlight the pharmacognostic value of PHF and demonstrate its potential as a natural cardioprotective intervention capable of modulating key metabolic and mitochondrial pathways involved in xenobiotic-induced cardiac toxicity.</p> Graphical Abstract <p></p>

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Polyherbal Formulation Attenuates Isoproterenol-Induced Cardiac Toxicity Through Regulation of Mitochondrial Bioenergetics, Lipid Toxicity, and Intrinsic Apoptotic Pathways in Rats

  • 期刊论文

  • 发表日期：

    2026年2月25日

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  • V V Sathibabu Uddandrao,
  • S. Nivetha,
  • P. Chandrasekaran,
  • S. Sengottuvelu,
  • Brahma Naidu Parim,
  • Umesh Kumar,
  • Andamuthu Yamunadevi,
  • Kaushik Das

摘要

Isoproterenol (ISO) is a synthetic β-adrenergic agonist widely used to model xenobiotic-induced cardiac injury, primarily through mechanisms involving oxidative stress, mitochondrial dysfunction, dyslipidemia, and apoptosis. Considering the growing interest in plant-derived bioactive compounds as cardioprotective agents, this study evaluated the mechanistic potential of a polyherbal formulation (PHF) composed of Andrographis paniculata, Bauhinia variegata, Moringa oleifera, and Lantana camara. GC-MS profiling of the formulation revealed several pharmacologically relevant phytoconstituents, including 3-methylmannoside, isothiourea, L-gala-L-ido-octose, β-sitosterol, heptanal, and eicosatrienoic acid methyl ester. ISO challenge in rats resulted in pronounced cardiac injury marked by elevated biomarkers, perturbed lipid metabolism, depletion of endogenous antioxidants, mitochondrial ATP loss, Ca2+ overload, suppression of tricarboxylic acid cycle enzymes, and activation of Bax/caspase-3-mediated apoptosis. Pretreatment with PHF significantly attenuated these pathological changes by restoring antioxidant defenses, stabilizing lipid homeostasis, improving mitochondrial bioenergetics, enhancing TCA cycle activity, and modulating intrinsic apoptotic signalling. Additionally, PHF upregulated mitochondrial biogenesis mediators (PGC-1α, NRF1, TFAM) and promoted AMPK-PPARα-driven fatty acid oxidation while suppressing SREBP-1c-associated lipogenesis. Molecular docking further supported the multi-target nature of the phytochemicals through strong interactions with mitochondrial, lipid-regulatory, and apoptotic proteins. Collectively, these findings highlight the pharmacognostic value of PHF and demonstrate its potential as a natural cardioprotective intervention capable of modulating key metabolic and mitochondrial pathways involved in xenobiotic-induced cardiac toxicity.

Graphical Abstract