PMID- 37562086 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20231127 IS - 1532-2785 (Electronic) IS - 0143-4179 (Linking) VI - 102 DP - 2023 Dec TI - Protective effects of Zishen Huoxue recipe against neuronal injury in the neurovascular unit of rats with vascular dementia by interfering with inflammatory cascade-induced pyroptosis. PG - 102358 LID - S0143-4179(23)00039-2 [pii] LID - 10.1016/j.npep.2023.102358 [doi] AB - OBJECTIVE: Chinese herbal formulas show considerable therapeutic benefits in dementia. This study specifically explored the protective action of Zishen Huoxue recipe on the neurovascular unit (NVU) of rats with vascular dementia (VD). METHODS: VD rat models were established by permanent bilateral common carotid artery occlusion and treated with Zishen Huoxue recipe. In vitro glucose‑oxygen deprivation (OGD)-injured NVU models were established and treated with miR-124-3p agomir or rat medicated serum. The neurological damage, histopathological changes, and neuronal injury in the rat hippocampus were assessed using Morris water maze test and histological stainings. Expression of miR-124-3p was determined using RT-qPCR. The blood-brain barrier/NVU injury, cell pyroptosis, NLRP3 inflammasome activation, and release of inflammatory factors were analyzed mainly by immunofluorescence analysis, TUNEL staining, Western blot, and ELISA. QS-21 (an NLRP3 activator) was used to verify the role of miR-124-3p/NLRP3. RESULTS: Zishen Huoxue recipe ameliorated the learning/memory deficits, neuronal injury, NVU insults, cell pyroptosis, activation of NLRP3 inflammasome, and extensive secretion of lactate dehydrogenase/IL-1beta/IL-18 in VD rats. miR-124-3p was downregulated in VD rats but upregulated after treatment of this recipe. miR-124-3p overexpression ameliorated NVU insults, reduced cell pyroptosis, lowered NLRP3 inflammasome activation, and suppressed inflammatory responses in OGD-injured NVU models. NLRP3 inflammasome activation partly counteracted the amelioration effect of miR-124-3p on pyroptosis. Zishen Huoxue recipe could upregulate miR-124-3p to suppress pyroptosis and protect NVU function. CONCLUSION: Zishen Huoxue recipe can upregulate miR-124-3p expression to repress the inflammatory cascade-evoked pyroptosis, thereby protecting against neuronal injury in the NVU of VD rats. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Yao, Ting AU - Yao T AD - Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. FAU - Xie, Le AU - Xie L AD - Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. FAU - Xie, Yao AU - Xie Y AD - Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. FAU - Jiang, Jinlin AU - Jiang J AD - Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. FAU - Deng, Qian AU - Deng Q AD - Teaching and Residency Program Office, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. FAU - Wang, Jie AU - Wang J AD - Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. FAU - Liu, Lu AU - Liu L AD - Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. FAU - Wu, Dahua AU - Wu D AD - Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China. Electronic address: Dahuawuu@163.com. LA - eng PT - Journal Article DEP - 20230626 PL - Netherlands TA - Neuropeptides JT - Neuropeptides JID - 8103156 RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (MicroRNAs) RN - 0 (MIRN124 microRNA, rat) SB - IM MH - Rats MH - Animals MH - Inflammasomes/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Pyroptosis MH - *Dementia, Vascular/drug therapy MH - *MicroRNAs/metabolism OTO - NOTNLM OT - 0 OT - Co-culture system OT - Inflammatory cascade response OT - NLRP3 inflammasome OT - Neurovascular unit OT - Vascular dementia OT - Zishen Huoxue recipe OT - miR-124-3p COIS- Declaration of Competing Interest The authors have no conflicts of interest to declare. EDAT- 2023/08/10 18:41 MHDA- 2023/11/27 12:43 CRDT- 2023/08/10 18:00 PHST- 2023/03/31 00:00 [received] PHST- 2023/06/12 00:00 [revised] PHST- 2023/06/25 00:00 [accepted] PHST- 2023/11/27 12:43 [medline] PHST- 2023/08/10 18:41 [pubmed] PHST- 2023/08/10 18:00 [entrez] AID - S0143-4179(23)00039-2 [pii] AID - 10.1016/j.npep.2023.102358 [doi] PST - ppublish SO - Neuropeptides. 2023 Dec;102:102358. doi: 10.1016/j.npep.2023.102358. Epub 2023 Jun 26.