1. Academic Validation
  2. Mastoparan M promotes functional recovery in stroke mice by activating autophagy and inhibiting ferroptosis

Mastoparan M promotes functional recovery in stroke mice by activating autophagy and inhibiting ferroptosis

  • Biomed Pharmacother. 2024 May:174:116560. doi: 10.1016/j.biopha.2024.116560.
Qian Wang 1 Chaojie Liu 1 Mingran Chen 1 Jie Zhao 1 Dexiao Wang 1 Pengfei Gao 2 Chenggui Zhang 3 Hairong Zhao 4
Affiliations

Affiliations

  • 1 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China.
  • 2 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China; National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China.
  • 3 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China; National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China. Electronic address: [email protected].
  • 4 Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China; National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China. Electronic address: [email protected].
Abstract

Neuronal Ferroptosis and Autophagy are crucial in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Mastoparan M (Mast-M), extracted from the crude venom of Vespa magnifica (Smith), comprises 14 amino acid residues. Previous studies suggested that Mast-M reduces neuronal damage following global CIRI, but its protective mechanisms remain unclear. The present study examined the effect of Mast-M on middle cerebral artery occlusion/reperfusion (MCAO/R) induced neurological deficits using Grip, Rotarod, Longa test, and TTC staining, followed by treating the mice for three days with Mast-M (20, 40, and 80 μg/kg, subcutaneously). The results demonstrate that Mast-M promotes functional recovery in mice post-ischemic stroke, evidenced by improved neurological impairment, reduced infarct volume and neuronal damage. Meanwhile, the level of iron (Fe2+) and malonyldialdehyde was decreased in the ischemic hemisphere of MCAO/R mice at 24 hours or 48 hours by Mast-M (80 μg/kg) treatment, while the expression of NRF2, x-CT, GPX4, and LC3B protein was increased. Furthermore, these findings were validated in three models-oxygen-glucose deprivation/ reoxygenation, H2O2-induced peroxidation, and erastin-induced ferroptosis-in hippocampal neuron HT22 cells or primary neurons. These data suggested that Mast-M activates Autophagy as well as inhibits Ferroptosis. Finally, Autophagy inhibitors were introduced to determine the relationship between the Autophagy and Ferroptosis, indicating that Mast-M alleviates Ferroptosis by activating Autophagy. Taken together, this study described that Mast-M alleviates cerebral infarction, neurologic impairment, and neuronal damage by activating Autophagy and inhibiting Ferroptosis, presenting a potential therapeutic approach for CIRI.

Keywords

Autophagy; Ferroptosis; GPX4; Mastoparan M; NRF2.

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