PMID- 38057100 OWN - NLM STAT- MEDLINE DCOM- 20240130 LR - 20240206 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 47 IP - 1 DP - 2024 Jan 26 TI - Tanshinone IIA Alleviates Early Brain Injury after Subarachnoid Hemorrhage in Rats by Inhibiting the Activation of NF-kappaB/NLRP3 Inflammasome. PG - 279-291 LID - 10.1248/bpb.b23-00519 [doi] AB - The abnormal activation of the nuclear factor-kappa B (NF-kappaB)/nod-like receptor family-pyrin domain-containing 3 (NLRP3) signaling pathway is closely related to early brain injury after subarachnoid hemorrhage (SAH). Targeting the NLRP3-inflammasome has been considered an efficient therapy for the local inflammatory response after SAH. Tanshinone IIA (Tan IIA), a major component extracted from Salvia miltiorrhiza, has been reported to have anti-inflammatory effects. The aim of this study was to investigate the effect and mechanism of Tan IIA on early brain injury after SAH. In vivo SAH injury was established by endovascular perforation technique in Sprague-Dawley rats. Limb-placement test and corner turning test were used to measure the behavior. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, hematoxylin-eosin (H&E) staining, and immunofluorescence were used to evaluate the nerve damage. Real-time RT quantitative PCR (RT-qPCR) was used to quantify the levels of inflammatory factors. Western blot was performed for the activation of the NF-kappaB/NLRP3 pathway. An in vitro SAH model was used to validate the conclusion. We found that the neurobehavioral impairment and cerebral edema in SAH model rats given Tan IIA were alleviated. Further study demonstrated that Tan IIA could inhibit SAH-secondary neuronal apoptosis around hematoma and alleviate brain injury. Tan IIA down-regulated the expression of interleukin-6 (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha, and inhibited the activation of NF-kappaB. And the overexpression of pro-inflammatory factors NLRP3, IL-1beta, and IL-18 induced after SAH was also reversed by Tan IIA. In conclusions, Tan IIA could inhibit the NF-kappaB/NLRP3 inflammasome activation to protect and ameliorate SAH-followed early brain injury, and may be a preventive and therapeutic strategy against SAH. FAU - Yang, Fanhui AU - Yang F AD - Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College. FAU - Ma, Ningshuai AU - Ma N AD - Department of Ultrasonography, The Affiliated Hospital of North Sichuan Medical College. FAU - Li, Suping AU - Li S AD - Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College. FAU - Chen, Fei AU - Chen F AD - Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College. FAU - Huang, Xiaohong AU - Huang X AD - Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College. FAU - Zhao, Li AU - Zhao L AD - Department of Neurology, The Affiliated Hospital of North Sichuan Medical College. AD - Institute of Neurological Diseases, North Sichuan Medical College. FAU - Cao, Lingzhi AU - Cao L AD - Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College. LA - eng PT - Journal Article DEP - 20231206 PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Inflammasomes) RN - 0 (NF-kappa B) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 03UUH3J385 (tanshinone) RN - 0 (Abietanes) SB - IM MH - Rats MH - Animals MH - Inflammasomes/metabolism MH - NF-kappa B/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - *Subarachnoid Hemorrhage/complications/drug therapy/pathology MH - Rats, Sprague-Dawley MH - *Brain Injuries/pathology MH - *Abietanes OTO - NOTNLM OT - early brain injury OT - neuron OT - nod-like receptor family-pyrin domain-containing 3 (NLRP3) OT - nuclear factor-kappa B (NF-kappaB) OT - subarachnoid hemorrhage OT - tanshinone IIA EDAT- 2023/12/07 00:42 MHDA- 2024/01/30 12:42 CRDT- 2023/12/06 21:03 PHST- 2024/01/30 12:42 [medline] PHST- 2023/12/07 00:42 [pubmed] PHST- 2023/12/06 21:03 [entrez] AID - 10.1248/bpb.b23-00519 [doi] PST - ppublish SO - Biol Pharm Bull. 2024 Jan 26;47(1):279-291. doi: 10.1248/bpb.b23-00519. Epub 2023 Dec 6.