ArticleVeterinary research2022
DAD3 targets ACE2 to inhibit the MAPK and NF-κB signalling pathways and protect against LPS-induced inflammation in bovine mammary epithelial cells.
Article in Veterinary research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Network Pharmacology and Molecular Docking: Exploring the Mechanism of Peppermint in Mastitis Prevention and Treatment in Dairy Cows.Veterinary sciences · 2025Article
- Dandelion root extracts and taraxasterol inhibit LPS‑induced colorectal cancer cell viability by blocking TLR4‑NFκB‑driven ACE2 and TMPRSS2 pathways.Experimental and therapeutic medicine · 2024Article
- The role of SARS-CoV-2-mediated NF-κB activation in COVID-19 patients.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Small Intestinal Endocrine Cell Derived Exosomal ACE2 Protects Islet β-Cell Function by Inhibiting the Activation of NLRP3 Inflammasome and Reducing β-Cell Pyroptosis.International journal of nanomedicine · 2024Article
- The Yeast and Hypha Phases ofAnimals : an open access journal from MDPI · 2023Article
- Overexpression of ACE2 ameliorates Aβ-induced blood-brain barrier damage and angiogenesis by inhibiting NF-κB/VEGF/VEGFR2 pathway.Animal models and experimental medicine · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The protective arm of the renin-angiotensin system (RAS), the ACE 2/Ang-(1-7)/MasR axis, has become a new anti-inflammatory target. As a specific activator of ACE2, diminazene aceturate (DA) can promote anti-inflammatory effects by regulating the ACE2/Ang-(1-7)/MasR axis. However, due to the reported toxicity of DA, its application has been limited. In the current study, we synthesized a low toxicity DA derivative 3 (DAD3) and sought to determine whether DAD3 can also activate ACE2 in bovine mammary epithelial cells (BMEC) and regulate the RAS system to inhibit inflammation. We found that both DA and DAD3 can activate and promote ACE2 expression in BMEC. iRNA-mediated knockdown of ACE2 demonstrated that DAD3 activates the ACE2/Ang-(1-7)/MasR axis and plays an anti-inflammatory role in BMEC. Furthermore, the inhibitory effects of DA and DAD3 on the protein phosphorylation of MAPK and NF-κB pathways were reduced in ACE2-silenced BMEC. Our findings show that ACE2 is a target of DAD3, which leads to inhibition of the MAPK and NF-κB signalling pathways and protects against LPS-induced inflammation in BMEC. Thus, DAD3 may provide a new strategy to treat dairy cow mastitis.
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