ReferenceID 6430
Neuroprotective Effects of Trilobatin, a Novel Naturally Occurring Sirt3 Agonist from Lithocarpus polystachyus Rehd., Mitigate Cerebral Ischemia/Reperfusion Injury: Involvement of TLR4/NF-κB and Nrf2/Keap-1 Signaling
Antioxid Redox Signal
Aims: Neuroinflammation and oxidative stress are deemed the prime causes of brain injury after cerebral ischemia/reperfusion (I/R). Since the silent mating-type information regulation 2 homologue 3 (Sirt3) pathway plays
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 6430
- Evidence Id
- 23020
- Core Evidence Id
- 23020
- Source Reference Id
- 6140
- Herb2 Reference Id
- HBREF006937
- Subject Paper Key
- HBIN047106_32212827
- Pubmed Id
- 32212827
- Doi
- 10.1089/ars.2019.7825
- Paper Title
- Neuroprotective Effects of Trilobatin, a Novel Naturally Occurring Sirt3 Agonist from Lithocarpus polystachyus Rehd., Mitigate Cerebral Ischemia/Reperfusion Injury: Involvement of TLR4/NF-κB and Nrf2/Keap-1 Signaling
- Paper Abstract
- Aims: Neuroinflammation and oxidative stress are deemed the prime causes of brain injury after cerebral ischemia/reperfusion (I/R). Since the silent mating-type information regulation 2 homologue 3 (Sirt3) pathway plays an imperative role in protecting against neuroinflammation and oxidative stress, it has been verified as a target to treat ischemia stroke. Therefore, we attempted to seek novel Sirt3 agonist and explore its underlying mechanism for stroke treatment both in vivo and in vitro. Results: Trilobatin (TLB) not only dramatically suppressed neuroinflammation and oxidative stress injury after middle cerebral artery occlusion in rats, but also effectively mitigated oxygen and glucose deprivation/reoxygenation injury in primary cultured astrocytes. These beneficial effects, along with the reduced proinflammatory cytokines via suppressing Toll-like receptor 4 (TLR4) signaling pathway, lessened oxidative injury via activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, in keeping with the findings in vivo. Intriguingly, the TLB-mediated neuroprotection on cerebral I/R injury was modulated by reciprocity between TLR4-mediated neuroinflammatory responses and Nrf2 antioxidant responses as evidenced by molecular docking and silencing TLR4 and Nrf2, respectively. Most importantly, TLB not only directly bonded to Sirt3 but also increased Sirt3 expression and activity, indicating that Sirt3 might be a promising therapeutic target of TLB. Innovation: TLB is a naturally occurring Sirt3 agonist with potent neuroprotective effects via regulation of TLR4/nuclear factor-kappa B and Nrf2/Kelch-like ECH-associated protein 1 (Keap-1) signaling pathways both in vivo and in vitro. Conclusion: Our findings indicate that TLB protects against cerebral I/R-induced neuroinflammation and oxidative injury through the regulation of neuroinflammatory and oxidative responses via TLR4, Nrf2, and Sirt3, suggesting that TLB might be a promising Sirt3 agonist against ischemic stroke.
- Journal
- Antioxid Redox Signal
- Publish Year
- 2020
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Neuroinflammation; Brain Injury; Ischemic Stroke; Stroke; Middle Cerebral Artery Occlusion; Ischemia Stroke; Cerebral Ischemia
- Paper Title Cn
- Paper Title En
- Neuroprotective Effects of Trilobatin, a Novel Naturally Occurring Sirt3 Agonist from Lithocarpus polystachyus Rehd., Mitigate Cerebral Ischemia/Reperfusion Injury: Involvement of TLR4/NF-κB and Nrf2/Keap-1 Signaling
- Bilingual Status
- semi_complete