Wild Bitter Melon Extract Abrogates Hypoxia-Induced Cell Death via the Regulation of Ferroptosis, ER Stress, and Apoptosis in Microglial BV2 Cells.

Chih-Hung Lin,Valeria Chiu,Chou-Chin Lan,Po-Chun Hsieh,Chan-Yen Kuo,Jiunn-Sheng Wu,Zhiqian Zhang

doi:10.1155/2022/1072600

Abstract

Microglial cells are well-known phagocytic cells that are resistant to the central nervous system (CNS) and play an important role in the maintenance of CNS homeostasis. Activated microglial cells induce neuroinflammation under hypoxia and typically cause neuronal damage in CNS diseases. In this study, we propose that wild bitter melon extract (WBM) has a protective effect on hypoxia-induced cell death via regulation of ferroptosis, ER stress, and apoptosis. The results demonstrated that hypoxia caused microglial BV-2 the accumulation of lipid ROS, ferroptosis, ER stress, and apoptosis. In this study, we investigated the pharmacological effects of WBM on BV-2 cells following hypoxia-induced cell death. The results indicated that WBM reversed hypoxia-downregulated antiferroptotic molecules Gpx4 and SLC7A11, as well as upregulated the ER stress markers CHOP and Bip. Moreover, WBM alleviated hypoxia-induced apoptosis via the regulation of cleaved-caspase 3, Bax, and Bcl-2. Our results suggest that WBM may be a good candidate for preventing CNS disorders in the future.

Highlights

Microglial cells are the main neuroimmune cells that play a central role in maintaining efficient central nervous system (CNS) homeostasis [1]
Accumulating evidence has shown that intracerebral hemorrhage (ICH) causes microglial cells to migrate into the damaged brain area to regulate the homeostasis of Fe (II) and toxic hydroxyl radicals, resulting in oxidative stress, lipid reactive oxygen species (ROS) overproduction, and ferroptosis [9–11]
Results showed that hypoxia significantly downregulated the antiferroptotic molecules glutathione peroxidase 4 (Gpx4) and SLC7A11 (Figure 1(d)), as well as upregulated the endoplasmic reticulum (ER) stress molecules CHOP and Bip by western blotting (Figure 1(e))

Summary

Introduction

Microglial cells are the main neuroimmune cells that play a central role in maintaining efficient central nervous system (CNS) homeostasis [1]. Microglial cells are activated under ischemia and polarize into proinflammatory (M1) and anti-inflammatory (M2) phenotypes in response to stimulation associated with stroke [3]. Qin and Crews reported that activated M1-type microglia promote reactive oxygen species (ROS) overproduction via NADPH oxidase upregulation, increase the production of proinflammatory factors, and cause neuronal damage [4]. Erefore, targeting and promoting anti-inflammatory microglia in ischemic stroke may Evidence-Based Complementary and Alternative Medicine increase the functional recovery from neural injury and neurogenesis [5]. Accumulating evidence has shown that intracerebral hemorrhage (ICH) causes microglial cells (macrophages) to migrate into the damaged brain area to regulate the homeostasis of Fe (II) and toxic hydroxyl radicals, resulting in oxidative stress, lipid ROS overproduction, and ferroptosis [9–11]. Taken together, targeting ferroptosis in I/R-induced neural damage should consider the antiferroptosis effect to achieve optimal outcomes

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Discussion

Conclusion