PMID- 36388798 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221119 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 10 IP - 20 DP - 2022 Oct TI - Sodium Danshensu protects against oxygen glucose deprivation/reoxygenation-induced astrocytes injury through regulating NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome and tuberous sclerosis complex-2 (TSC2)/mammalian target of rapamycin (mTOR) pathways. PG - 1097 LID - 10.21037/atm-22-2143 [doi] LID - 1097 AB - BACKGROUND: Cerebral ischemic stroke is a serious condition with high incidence, mortality, and associated disability. Currently, effective therapeutic options are available for ischemic stroke are limited. Accumulating evidence indicates that sodium Danshensu, mono sodium compound derived from Salvia miltiorrhiza, plays protective roles in ischemic stroke. However, the underlying protective mechanism of sodium Danshensu in cerebral ischemic stroke remains unknown. METHODS: In the current study, we explored the role and mechanism of sodium Danshensu on astrocytes exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), which mimics the process of ischemia-reperfusion. The impact of sodium Danshensu on cell viability and apoptosis after OGD/R were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-dophenyl tetrazolium bromide (MTT) assay and flow cytometry. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were used to detect the expression of target messenger RNA (mRNA) and proteins associated with apoptosis and autophagy. The release of lactate dehydrogenase (LDH) was determined, and the production of proinflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: It was found that sodium Danshensu could significantly increase cell viability and decrease LDH release and apoptosis. Besides, it inhibited the production of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6. Sodium Danshensu also dose-dependently decreased protein and mRNA levels of nucleotide binding oligomerization NOD-like receptor pyrin domain containing 3 (NLRP3) and high mobility group box 1 (HMGB1), which play a crucial role in promoting ischemic stroke-induced cell injury. Moreover, sodium Danshensu dose-dependently upregulated Beclin 1 expression, downregulated P62 protein expression, and further increased LC3B-II/LC3B-I ratio through inducing autophagy in astrocytes. Additionally, we noticed that sodium Danshensu dose-dependently increased tuberous sclerosis complex-2 (TSC2) protein expression, while significantly reduced the levels of mammalian target of rapamycin (mTOR) in the presence of OGD/R insult. CONCLUSIONS: These findings suggest that sodium Danshensu protects against OGD/R-induced injury by modulating the NLRP3 inflammasome and TSC2/mTOR pathways. CI - 2022 Annals of Translational Medicine. All rights reserved. FAU - Hu, Shengzhao AU - Hu S AD - Department of Emergency, the First Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Chen, Yingli AU - Chen Y AD - Department of Hematology, Jiangxi Provincial Children's Hospital, Nanchang, China. FAU - Huang, Shipeng AU - Huang S AD - Department of Emergency, the First Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Liu, Min AU - Liu M AD - Department of Emergency, the First Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Liu, Ying AU - Liu Y AD - Department of Emergency, the First Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Huang, Shaofang AU - Huang S AD - Department of Emergency, the First Affiliated Hospital of Nanchang University, Nanchang, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC9652549 OTO - NOTNLM OT - Autophagy OT - NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3 inflammasome) OT - ischemic stroke OT - sodium Danshensu OT - tuberous sclerosis complex-2/mammalian target of rapamycin (TSC2/mTOR) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2143/coif). The authors have no conflicts of interest to declare. EDAT- 2022/11/18 06:00 MHDA- 2022/11/18 06:01 PMCR- 2022/10/01 CRDT- 2022/11/17 12:17 PHST- 2022/03/28 00:00 [received] PHST- 2022/08/31 00:00 [accepted] PHST- 2022/11/17 12:17 [entrez] PHST- 2022/11/18 06:00 [pubmed] PHST- 2022/11/18 06:01 [medline] PHST- 2022/10/01 00:00 [pmc-release] AID - atm-10-20-1097 [pii] AID - 10.21037/atm-22-2143 [doi] PST - ppublish SO - Ann Transl Med. 2022 Oct;10(20):1097. doi: 10.21037/atm-22-2143.