Protective effects of the notoginsenoside R1 on acute lung injury by regulating the miR-128-2-5p/Tollip signaling pathway in rats with severe acute pancreatitis.

Abstract

Notoginsenoside R1 (NG-R1), the extract and the main ingredient of Panax notoginseng, has anti-inflammatory effects and can be used in treating acute lung injury (ALI). In this study, we explored the pulmonary protective effect and the underlying mechanism of the NG-R1 on rats with ALI induced by severe acute pancreatitis (SAP). MiR-128-2-5p, ERK1, Tollip, HMGB1, TLR4, IκB, and NF-κB mRNA expression levels were measured using real-time qPCR, and TLR4, Tollip, HMGB1, IRAK1, MyD88, ERK1, NF-κB65, and P-IκB-α protein expression levels using Western blot. The NF-κB and the TLR4 activities were determined using immunohistochemistry, and TNF-α, IL-6, IL-1β, and ICAM-1 levels in the bronchoalveolar lavage fluid (BALF) using ELISA. Lung histopathological changes were observed in each group. NG-R1 treatment reduced miR-128-2-5p expression in the lung tissue, increased Tollip expression, inhibited HMGB1, TLR4, TRAF6, IRAK1, MyD88, NF-κB65, and p-IκB-α expression levels, suppressed NF-κB65 and the TLR4 expression levels, reduced MPO activity, reduced TNF-α, IL-1β, IL-6, and ICAM-1 levels in BALF, and alleviated SAP-induced ALI. NG-R1 can attenuate SAP-induced ALI. The mechanism of action may be due to a decreased expression of miR-128-2-5p, increased activity of the Tollip signaling pathway, decreased activity of HMGB1/TLR4 and ERK1 signaling pathways, and decreased inflammatory response to SAP-induced ALI. Tollip was the regulatory target of miR-128-2-5p.

• Authors: Ju He, Ming-Wei Liu, Zhi-Yi Wang, Rong-Jie Shi
• Journal: Innate immunity (Innate Immun) Vol. 28 Issue 1 Pg. 19-36 (01 2022) ISSN: 1753-4267 [Electronic] United States
• PMID: 35142579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ginsenosides
• HMGB1 Protein
• Interleukin-6
• Intracellular Signaling Peptides and Proteins
• MIRN128 microRNA, rat
• MicroRNAs
• Myeloid Differentiation Factor 88
• NF-kappa B
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• tollip protein, rat
• Intercellular Adhesion Molecule-1
• NF-KappaB Inhibitor alpha
• notoginsenoside R1

Topics

• Acute Disease
• Acute Lung Injury (drug therapy, metabolism)
• Animals
• Ginsenosides
• HMGB1 Protein (metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-6 (metabolism)
• Intracellular Signaling Peptides and Proteins
• MicroRNAs (genetics, metabolism)
• Myeloid Differentiation Factor 88 (metabolism)
• NF-KappaB Inhibitor alpha (metabolism)
• NF-kappa B (metabolism)
• Pancreatitis (drug therapy)
• Rats
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)