Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation
Diabetic peripheral neuropathy (DPN) is caused by hyperglycemia, which induces oxidative stress and inflammatory responses that damage nerve tissue. Excessive generation of reactive oxygen species (ROS) and NOD-like receptor protein 3 (NLRP3) inflammasome activation trigger the inflammation and pyro...
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MDPI AG
2020-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/1948 |
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| author | Yu-Chi Cheng Li-Wen Chu Jun-Yih Chen Su-Ling Hsieh Yu-Chin Chang Zen-Kong Dai Bin-Nan Wu |
| author_facet | Yu-Chi Cheng Li-Wen Chu Jun-Yih Chen Su-Ling Hsieh Yu-Chin Chang Zen-Kong Dai Bin-Nan Wu |
| author_sort | Yu-Chi Cheng |
| collection | DOAJ |
| description | Diabetic peripheral neuropathy (DPN) is caused by hyperglycemia, which induces oxidative stress and inflammatory responses that damage nerve tissue. Excessive generation of reactive oxygen species (ROS) and NOD-like receptor protein 3 (NLRP3) inflammasome activation trigger the inflammation and pyroptosis in diabetes. Schwann cell dysfunction further promotes DPN progression. Loganin has been shown to have antioxidant and anti-inflammatory neuroprotective activities. This study evaluated the neuroprotective effect of loganin on high-glucose (25 mM)-induced rat Schwann cell line RSC96 injury, a recognized in vitro cell model of DPN. RSC96 cells were pretreated with loganin (0.1, 1, 10, 25, 50 μM) before exposure to high glucose. Loganin’s effects were examined by CCK-8 assay, ROS assay, cell death assay, immunofluorescence staining, quantitative RT–PCR and western blot. High-glucose-treated RSC96 cells sustained cell viability loss, ROS generation, NF-κB nuclear translocation, P2 × 7 purinergic receptor and TXNIP (thioredoxin-interacting protein) expression, NLRP3 inflammasome (NLRP3, ASC, caspase-1) activation, IL-1β and IL-18 maturation and gasdermin D cleavage. Those effects were reduced by loganin pretreatment. In conclusion, we found that loganin’s antioxidant effects prevent RSC96 Schwann cell pyroptosis by inhibiting ROS generation and suppressing NLRP3 inflammasome activation. |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:57:22Z |
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| series | Cells |
| spelling | doaj.art-e9d1021e10e74595b587b4c56eba91c92023-11-20T11:05:57ZengMDPI AGCells2073-44092020-08-0199194810.3390/cells9091948Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome ActivationYu-Chi Cheng0Li-Wen Chu1Jun-Yih Chen2Su-Ling Hsieh3Yu-Chin Chang4Zen-Kong Dai5Bin-Nan Wu6Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Nursing, and Department of Cosmetic Application and Management, Yuh-Ing Junior College of Health Care and Management, Kaohsiung 80776, TaiwanDivision of Neurosurgery, Fooyin University Hospital, Pingtung 92847, TaiwanDepartment of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDepartment of Pharmacology, Graduate Institute of Medicine, College of Medicine, Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Pharmacology, Graduate Institute of Medicine, College of Medicine, Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDiabetic peripheral neuropathy (DPN) is caused by hyperglycemia, which induces oxidative stress and inflammatory responses that damage nerve tissue. Excessive generation of reactive oxygen species (ROS) and NOD-like receptor protein 3 (NLRP3) inflammasome activation trigger the inflammation and pyroptosis in diabetes. Schwann cell dysfunction further promotes DPN progression. Loganin has been shown to have antioxidant and anti-inflammatory neuroprotective activities. This study evaluated the neuroprotective effect of loganin on high-glucose (25 mM)-induced rat Schwann cell line RSC96 injury, a recognized in vitro cell model of DPN. RSC96 cells were pretreated with loganin (0.1, 1, 10, 25, 50 μM) before exposure to high glucose. Loganin’s effects were examined by CCK-8 assay, ROS assay, cell death assay, immunofluorescence staining, quantitative RT–PCR and western blot. High-glucose-treated RSC96 cells sustained cell viability loss, ROS generation, NF-κB nuclear translocation, P2 × 7 purinergic receptor and TXNIP (thioredoxin-interacting protein) expression, NLRP3 inflammasome (NLRP3, ASC, caspase-1) activation, IL-1β and IL-18 maturation and gasdermin D cleavage. Those effects were reduced by loganin pretreatment. In conclusion, we found that loganin’s antioxidant effects prevent RSC96 Schwann cell pyroptosis by inhibiting ROS generation and suppressing NLRP3 inflammasome activation.https://www.mdpi.com/2073-4409/9/9/1948Schwann cellloganinhigh glucosereactive oxygen speciesNLRP3 inflammasomepyroptosis |
| spellingShingle | Yu-Chi Cheng Li-Wen Chu Jun-Yih Chen Su-Ling Hsieh Yu-Chin Chang Zen-Kong Dai Bin-Nan Wu Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation Cells Schwann cell loganin high glucose reactive oxygen species NLRP3 inflammasome pyroptosis |
| title | Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation |
| title_full | Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation |
| title_fullStr | Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation |
| title_full_unstemmed | Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation |
| title_short | Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation |
| title_sort | loganin attenuates high glucose induced schwann cells pyroptosis by inhibiting ros generation and nlrp3 inflammasome activation |
| topic | Schwann cell loganin high glucose reactive oxygen species NLRP3 inflammasome pyroptosis |
| url | https://www.mdpi.com/2073-4409/9/9/1948 |
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