PMID- 36670940 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230201 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 12 IP - 1 DP - 2022 Dec 29 TI - Ishige okamurae Attenuates Neuroinflammation and Cognitive Deficits in Mice Intracerebroventricularly Injected with LPS via Regulating TLR-4/MyD88-Dependent Pathways. LID - 10.3390/antiox12010078 [doi] LID - 78 AB - Neuroinflammation is one of the critical causes of neuronal loss and cognitive impairment. We aimed to evaluate the anti-neuroinflammatory properties of Ishige okamuae using mice intracerebroventricularly injected with lipopolysaccharides (LPS) and LPS-treated C6 glioma cells. We found that the short- and long-term memory deficits of LPS-injected mice were improved by oral administration of Ishige okamurae extracts (IOE). LPS-induced neuronal loss, increase in amyloid-beta plaque, and expression of COX-2 and iNOS were restored by IOE. In addition, LPS-induced activation of Toll-like receptor-4 (TLR-4) and its downstream molecules, such as MyD88, NFkappaB, and mitogen-activated protein kinases (MAPKs), were significantly attenuated in the brains of mice fed with IOE. We found that pretreatment of IOE to C6 glioma cells ameliorated LPS-induced expression of TLR-4 and its inflammatory cascades, such as MyD88 expression, reactive oxygen species production, MAPKs phosphorylation, and NFkappaB phosphorylation with consequent downregulation of COX-2, iNOS, proinflammatory cytokines, and nitric oxide expression. Furthermore, IOE (0.2 microg/mL) was found to have equivalent efficacy with 10 muM of MyD88 inhibitor in preventing LPS-induced inflammatory responses in C6 glioma cells. Taken together, these results strongly suggest that IOE could be developed as a promising anti-neuroinflammatory agent which is able to control the TLR-4/MyD88-dependent signaling pathways. FAU - Kwon, Oh-Yun AU - Kwon OY AD - Department of Nano-Bioengineering, Incheon National University, 119 Academy-ro, Incheon 22012, Republic of Korea. FAU - Lee, Seung-Ho AU - Lee SH AUID- ORCID: 0000-0002-9941-4195 AD - Department of Nano-Bioengineering, Incheon National University, 119 Academy-ro, Incheon 22012, Republic of Korea. LA - eng GR - Incheon Nation University research grant in 2021/Incheon National University/ PT - Journal Article DEP - 20221229 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC9854571 OTO - NOTNLM OT - Ishige okamurae OT - MyD88 OT - TLR-4 OT - cognitive deficits OT - lipopolysaccharide OT - neuroinflammation COIS- The authors declare no conflict of interest. EDAT- 2023/01/22 06:00 MHDA- 2023/01/22 06:01 PMCR- 2022/12/29 CRDT- 2023/01/21 01:04 PHST- 2022/12/07 00:00 [received] PHST- 2022/12/22 00:00 [revised] PHST- 2022/12/26 00:00 [accepted] PHST- 2023/01/21 01:04 [entrez] PHST- 2023/01/22 06:00 [pubmed] PHST- 2023/01/22 06:01 [medline] PHST- 2022/12/29 00:00 [pmc-release] AID - antiox12010078 [pii] AID - antioxidants-12-00078 [pii] AID - 10.3390/antiox12010078 [doi] PST - epublish SO - Antioxidants (Basel). 2022 Dec 29;12(1):78. doi: 10.3390/antiox12010078.