PMID- 36881963 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20230404 IS - 2772-9508 (Electronic) IS - 2772-9508 (Linking) VI - 148 DP - 2023 May TI - Biogenic silver NPs alleviate LPS-induced neuroinflammation in a human fetal brain-derived cell line: Molecular switch to the M2 phenotype, modulation of TLR4/MyD88 and Nrf2/HO-1 signaling pathways, and molecular docking analysis. PG - 213363 LID - S2772-9508(23)00086-9 [pii] LID - 10.1016/j.bioadv.2023.213363 [doi] AB - Silver nanoparticles (AgNPs) have inconsistent findings against inflammation. Although a wealth of literature on the beneficial effects of green-synthesized AgNPs has been published, a detailed mechanistic study of green AgNPs on the protective effects against lipopolysaccharide (LPS)-induced neuroinflammation using human microglial cells (HMC3) has not yet been reported. For the first time, we studied the inhibitory effect of biogenic AgNPs on inflammation and oxidative stress induced by LPS in HMC3 cells. X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and transmission electron microscopy were used to characterize AgNPs produced from honeyberry. Co-treatment with AgNPs significantly reduced mRNA expressions of inflammatory molecules such as interleukin (IL)-6 and tumor necrosis factor-alpha, while increasing the expressions of anti-inflammatory markers such as IL-10 and transforming growth factor (TGF)-beta. HMC3 cells were also switched from M1 to M2, as shown by lower expression of M1 markers such as cluster of differentiation (CD)80, CD86, and CD68 and higher expression of M2 markers such as CD206, CD163, and triggering receptors expressed on myeloid cells (TREM2). Furthermore, AgNPs inhibited LPS-induced toll-like receptor (TLR)4 signaling, as evidenced by decreased expression of myeloid differentiation factor 88 (MyD88) and TLR4. In addition, AgNPs reduced the production of reactive oxygen species (ROS) and enhanced the expression of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), while decreasing the expression of inducible nitric oxide synthase. The docking score of the honeyberry phytoconstituents ranged from -14.93 to - 4.28 KJ/mol. In conclusion, biogenic AgNPs protect against neuroinflammation and oxidative stress by targeting TLR4/MyD88 and Nrf2/HO-1 signaling pathways in a LPS-induced in vitro model. Biogenic AgNPs could be utilized as potential nanomedicine against LPS-induced inflammatory disorders. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Sharma, Anshul AU - Sharma A AD - College of BioNano Technology, Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea. FAU - Sanjay AU - Sanjay AD - Department of Food Science and Biotechnology, Gachon University, Gyeonggi-do 13120, Republic of Korea. FAU - Jaiswal, Varun AU - Jaiswal V AD - College of BioNano Technology, Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea. FAU - Park, Miey AU - Park M AD - College of BioNano Technology, Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea; Institute for Aging and Clinical Nutrition Research, Gachon University, Gyeonggi-do 13120, Republic of Korea. FAU - Lee, Hae-Jeung AU - Lee HJ AD - College of BioNano Technology, Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea; Institute for Aging and Clinical Nutrition Research, Gachon University, Gyeonggi-do 13120, Republic of Korea; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea. Electronic address: skysea@gachon.ac.kr. LA - eng PT - Journal Article DEP - 20230303 PL - Netherlands TA - Biomater Adv JT - Biomaterials advances JID - 9918383886206676 RN - 0 (Lipopolysaccharides) RN - 0 (Myeloid Differentiation Factor 88) RN - 3M4G523W1G (Silver) RN - 0 (NF-E2-Related Factor 2) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - 0 (Toll-Like Receptor 4) RN - 0 (TLR4 protein, human) SB - IM MH - Humans MH - *Lipopolysaccharides/toxicity MH - Myeloid Differentiation Factor 88/genetics/metabolism/pharmacology MH - Molecular Docking Simulation MH - Silver/pharmacology MH - NF-E2-Related Factor 2/genetics/metabolism/pharmacology MH - Neuroinflammatory Diseases MH - Heme Oxygenase-1/genetics/metabolism/pharmacology MH - Toll-Like Receptor 4/genetics/metabolism MH - *Metal Nanoparticles/therapeutic use MH - Signal Transduction MH - Phenotype MH - Cell Line MH - Inflammation/chemically induced/metabolism MH - Brain/metabolism OTO - NOTNLM OT - Inflammation OT - Interleukin OT - Lipopolysaccharide OT - Microglia OT - Silver nanoparticles OT - Toll-like receptor COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/08 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/03/07 18:03 PHST- 2022/09/29 00:00 [received] PHST- 2023/02/23 00:00 [revised] PHST- 2023/02/25 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/03/08 06:00 [pubmed] PHST- 2023/03/07 18:03 [entrez] AID - S2772-9508(23)00086-9 [pii] AID - 10.1016/j.bioadv.2023.213363 [doi] PST - ppublish SO - Biomater Adv. 2023 May;148:213363. doi: 10.1016/j.bioadv.2023.213363. Epub 2023 Mar 3.