학술논문
Atractylodes lancea (Thunb.) DC. [Asteraceae] rhizome-derived exosome-like nanoparticles suppress lipopolysaccharide-induced inflammation in murine microglial cells.
Document Type
Academic Journal
Author
Kawada K; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Department of Clinical Pharmacy Practice Pedagogy, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Ishida T; Department of Pharmacy, Kochi Medical School Hospital, Kochi, Japan.; Morisawa S; Department of Pharmacy, Kochi Medical School Hospital, Kochi, Japan.; Jobu K; Department of Pharmacy, Kochi Medical School Hospital, Kochi, Japan.; Higashi Y; Department of Pharmacology, Kochi Medical School, Kochi University, Kochi, Japan.; Aizawa F; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.; Yagi K; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, Tokushima, Japan.; Izawa-Ishizawa Y; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Department of General Medicine, Taoka Hospital, Tokushima, Japan.; Niimura T; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, Tokushima, Japan.; Abe S; Department of Clinical Pharmacy Practice Pedagogy, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Goda M; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.; Miyamura M; Center for Regional Sustainability and Innovation, Kochi University, Kochi, Japan.; Ishizawa K; Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, Tokushima, Japan.; Department of General Medicine, Taoka Hospital, Tokushima, Japan.
Source
Publisher: Frontiers Media] Country of Publication: Switzerland NLM ID: 101548923 Publication Model: eCollection Cited Medium: Print ISSN: 1663-9812 (Print) Linking ISSN: 16639812 NLM ISO Abbreviation: Front Pharmacol Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1663-9812
Abstract
Background: Exosome-like nanoparticles (ELNs) mediate interspecies intercellular communications and modulate gene expression.
Hypothesis/purpose: In this study, we isolated and purified ELNs from the dried rhizome of Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR-ELNs), a traditional natural medicine, and investigated their potential as neuroinflammatory therapeutic agents.
Methods: ALR-ELN samples were isolated and purified using differential centrifugation, and their physical features and microRNA contents were analyzed through transmission electron microscopy and RNA sequencing, respectively. BV-2 microglial murine cells and primary mouse microglial cells were cultured in vitro , and their ability to uptake ALR-ELNs was explored using fluorescence microscopy. The capacity of ALR-ELNs to modulate the anti-inflammatory responses of these cells to lipopolysaccharide (LPS) exposure was assessed through mRNA and protein expression analyses.
Results: Overall, BV-2 cells were found to internalize ALR-ELNs, which comprised three microRNAs (ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p) that could have anti-inflammatory activity. Pretreatment of BV-2 cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide, interleukin-1β, interleukin-6, and tumor necrosis factor-α. Notably, the mRNA levels of Il1b, Il6, iNos, ccl2 , and cxcl10 in BV-2 cells, which increased upon LPS exposure, were significantly reduced following ALR-ELN treatment. Moreover, the mRNA levels of heme oxygenase 1, Irf7, ccl12 , and Irg1 also increased significantly following ALR-ELN treatment. In addition, pretreatment of primary mouse microglial cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide.
Conclusion: Our findings indicate that ALR-ELNs exhibit anti-inflammatory effects on murine microglial cells. Further validation may prove ALR-ELNs as a promising neuroinflammatory therapeutic agent.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Kawada, Ishida, Morisawa, Jobu, Higashi, Aizawa, Yagi, Izawa-Ishizawa, Niimura, Abe, Goda, Miyamura and Ishizawa.)
Hypothesis/purpose: In this study, we isolated and purified ELNs from the dried rhizome of Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR-ELNs), a traditional natural medicine, and investigated their potential as neuroinflammatory therapeutic agents.
Methods: ALR-ELN samples were isolated and purified using differential centrifugation, and their physical features and microRNA contents were analyzed through transmission electron microscopy and RNA sequencing, respectively. BV-2 microglial murine cells and primary mouse microglial cells were cultured in vitro , and their ability to uptake ALR-ELNs was explored using fluorescence microscopy. The capacity of ALR-ELNs to modulate the anti-inflammatory responses of these cells to lipopolysaccharide (LPS) exposure was assessed through mRNA and protein expression analyses.
Results: Overall, BV-2 cells were found to internalize ALR-ELNs, which comprised three microRNAs (ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p) that could have anti-inflammatory activity. Pretreatment of BV-2 cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide, interleukin-1β, interleukin-6, and tumor necrosis factor-α. Notably, the mRNA levels of Il1b, Il6, iNos, ccl2 , and cxcl10 in BV-2 cells, which increased upon LPS exposure, were significantly reduced following ALR-ELN treatment. Moreover, the mRNA levels of heme oxygenase 1, Irf7, ccl12 , and Irg1 also increased significantly following ALR-ELN treatment. In addition, pretreatment of primary mouse microglial cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide.
Conclusion: Our findings indicate that ALR-ELNs exhibit anti-inflammatory effects on murine microglial cells. Further validation may prove ALR-ELNs as a promising neuroinflammatory therapeutic agent.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Kawada, Ishida, Morisawa, Jobu, Higashi, Aizawa, Yagi, Izawa-Ishizawa, Niimura, Abe, Goda, Miyamura and Ishizawa.)