ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2018
Anti-inflammatory effect and mechanism of the spirocyclopiperazinium salt compound LXM-15 in rats and mice.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
- Article
- Therapeutic Targeting ofPharmacological reviews · 2021Review
- Malyngamide F Possesses Anti-Inflammatory and Antinociceptive Activity in Rat Models of Inflammation.Pain research & management · 2021Article
- Anti-arthritic Effect of the Spirocyclopiperazinium Salt Compound LXM-15 in Rats and Its Underlying Mechanism.Inflammation · 2020Article
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6 authors at 2 institutions in 1 country.
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Abstract
objectiveThis study aimed to investigate the anti-inflammatory effects of a novel spirocyclopiperazinium salt compound LXM-15, and explore the underlying mechanisms.
methodsXylene-induced mouse ear oedema and carrageenan-induced rat paw oedema tests were used to evaluate the anti-inflammatory effects of LXM-15. The protein levels of TNF-α, IL-6, phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were detected by ELISA or Western blot analysis. Additionally, receptor blocking test was performed to explore the possible target.
resultsIntragastric administration with LXM-15 (2, 1, 0.5 mg/kg in mice, and 6, 3, 1.5 mg/kg in rats) produced distinct anti-inflammatory effects in vivo, the highest inhibition percentage was 60 and 52%, respectively (P < 0.01). Following treatment with LXM-15 (6 mg/kg, i.g.), the levels of TNF-α and IL-6 in the rats paws were attenuated by 40 and 41%; and the phosphorylation of JAK2 and STAT3 was restrained by 35 and 45%, respectively (P < 0.01). All effects of LXM-15 were blocked by pretreatment with methyllycaconitine citrate or tropicamide.
conclusionThis study provides the first report that the spirocyclopiperazinium salt compound LXM-15 displays considerable anti-inflammatory effects. The underlying mechanism may be through activating the peripheral α7 nicotinic acetylcholine receptor and M4 muscarinic acetylcholine receptor, leading to the inhibition of the JAK2/STAT3 signalling pathway, eventually resulting in the reduction of TNF-α and IL-6.
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