PMID- 34706808 OWN - NLM STAT- MEDLINE DCOM- 20211029 LR - 20211029 IS - 1550-7033 (Print) IS - 1550-7033 (Linking) VI - 17 IP - 10 DP - 2021 Oct 1 TI - Protective Effect of Ginsenoside Rb1 Nanoparticles Against Contrast-Induced Nephropathy by Inhibiting High Mobility Group Box 1 Gene/Toll-Like Receptor 4/NF-kappaB Signaling Pathway. PG - 2085-2098 LID - 10.1166/jbn.2021.3163 [doi] AB - With the progress made in the widespread application of interventional radiology procedures, there has been an increasing number of patients who suffer from cardiovascular diseases and go through imaging and interventional treatment with iodine contrast medium (ICM) year by year. In turn, there has been an increasing amount of concern over acute kidney injury (AKI) brought about by ICM. As evidenced by numerous studies, the initiation of inflammatory response plays a critical role in the development of ICM-induced AKI. Correspondingly, the strategy of targeting renal inflammatory response and cytokine release could provide an effective solution to mitigating the ICM-induced AKI. Moreover, Ginsenoside Rb1 (GRb1) constitutes one of the major active components of ginseng and features a wide range of vital biological functions. Judging from the research findings, GRb1 could impose antioxidant and anti-inflammatory effects on cardiovascular diseases, in addition to lung, liver and kidney diseases. However, reports on whether GRb1 could impose a protective effect against contrast-induced nephropathy (CIN) are absent. In this study, we have examined the therapeutic effects imposed by GRb1 as well as the potential molecular mechanism by establishing an in vivo and in vitro model of CIN. In addition, we have set up a mouse model of CIN through sequential intravenous injection of indomethacin, N(omega)-nitro-Larginine methyl ester (L-NAME), and iopromide. To further enhance the bioavailability of GRb1, we have encapsulated GRb1 with polyethylene glycol (PEG)/poly lactic-co-glycolic acid (PLGA) nanocarriers to generate GRb1 nanoparticles (NPs) conducting the in vivo experiments. During the in vitro experiments, we have adopted GRb1 to treat NRK-52E cells or cells transfected with the high mobility group box 1 gene (HMGB1) overexpression plasmid. As shown by the in vivo experimental results, GRb1 NPs could evidently improve the renal dysfunction in CIN, diminish the extent of apoptosis of tubular epithelial cells, and reduce the expression of high mobility group box 1 (HMGB1) and cytokines (tumor necrosis factor (TNF-alpha), interleukin (IL) 6 and IL-1beta). In addition, GRb1 NPs are found to be capable of preventing the activation of Toll-like receptor 4 (TLR4)/NF-kappaB signaling pathway triggered by contrast medium. The in vitro experimental results have exactly confirmed the findings of the in vivo experiments. In the meantime, through the observation of the in vitro assays, overexpression of HMGB1 can partially counteract the beneficial effects imposed by GRb1. Judging from our research data, GRb1 could impose a protective effect against CIN by inhibiting inflammatory response via HMGB1/TLR4/NF-kappaB pathway, whereas HMGB1 constitutes a critical molecular target of GRb1. FAU - Zhou, Shuai AU - Zhou S AD - Cardiology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China. FAU - Lu, Shan AU - Lu S AD - Emergency Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China. FAU - Guo, Sen AU - Guo S AD - Cardiology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China. FAU - Zhao, Luosha AU - Zhao L AD - Cardiology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China. FAU - Han, Zhanying AU - Han Z AD - Cardiology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China. FAU - Li, Zhenzhen AU - Li Z LA - eng PT - Journal Article PL - United States TA - J Biomed Nanotechnol JT - Journal of biomedical nanotechnology JID - 101230869 RN - 0 (Ginsenosides) RN - 0 (NF-kappa B) RN - 0 (RB1 protein, human) RN - 0 (Retinoblastoma Binding Proteins) RN - 0 (Toll-Like Receptor 4) RN - 7413S0WMH6 (ginsenoside Rb1) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Animals MH - Ginsenosides MH - Humans MH - *Kidney Diseases MH - Mice MH - NF-kappa B/genetics/metabolism MH - *Nanoparticles/toxicity MH - Retinoblastoma Binding Proteins MH - Signal Transduction MH - Toll-Like Receptor 4/metabolism MH - Ubiquitin-Protein Ligases EDAT- 2021/10/29 06:00 MHDA- 2021/10/30 06:00 CRDT- 2021/10/28 05:35 PHST- 2021/10/28 05:35 [entrez] PHST- 2021/10/29 06:00 [pubmed] PHST- 2021/10/30 06:00 [medline] AID - 10.1166/jbn.2021.3163 [doi] PST - ppublish SO - J Biomed Nanotechnol. 2021 Oct 1;17(10):2085-2098. doi: 10.1166/jbn.2021.3163.