Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination.

Abstract

Schisandra chinensis, as a Chinese functional food, is rich in unsaturated fatty acids, minerals, vitamins, and proteins. Hence, this study was intended to elucidate the effects and biological mechanism of Schisandrin A from Schisandra chinensis in DN. C57BL/6 mice were fed with a high-fat diet and then injected with streptozotocin (STZ). Human renal glomerular endothelial cells were stimulated with 20 mmol/L d-glucose for DN model. Schisandrin A presented acute kidney injury in mice of DN. Schisandrin A reduced oxidative stress and inflammation in model of DN. Schisandrin A reduced high glucose-induced ferroptosis and reactive oxygen species (ROS-)-mediated pyroptosis by mitochondrial damage in model of DN. Schisandrin A directly targeted AdipoR1 protein and reduced LPS+ATP-induced AdipoR1 ubiquitination in vitro model. Schisandrin A activated AdipoR1/AMPK signaling pathway and suppressed TXNIP/NLRP3 signaling pathway in vivo and in vitro model of DN. Conclusively, our study revealed that Schisandrin A from Schisandra chinensis attenuates ferroptosis and NLRP3 inflammasome-mediated pyroptosis in DN by AdipoR1/AMPK-ROS/mitochondrial damage. Schisandrin A is a possible therapeutic option for DN or other diabetes.

• Authors: Xiaohu Wang, Qin Li, Bangzhi Sui, Maodi Xu, Zhichen Pu, Teng Qiu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 5411462 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35996380 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Xiaohu Wang et al.

Chemical References

• ADIPOR1 protein, human
• Cyclooctanes
• Inflammasomes
• Lignans
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Polycyclic Compounds
• Reactive Oxygen Species
• Receptors, Adiponectin
• schizandrin A
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Cyclooctanes
• Diabetes Mellitus
• Diabetic Nephropathies (metabolism)
• Endothelial Cells (metabolism)
• Ferroptosis
• Humans
• Inflammasomes (metabolism)
• Lignans
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Polycyclic Compounds
• Pyroptosis
• Reactive Oxygen Species (metabolism)
• Receptors, Adiponectin (metabolism)
• Schisandra (metabolism)
• Ubiquitination