The mechanism of galanthamine regulating IL-1β/IL-1RA ratio to ameliorate inflammatory microenvironment

doi:10.5246/jcps.2022.10.067

Abstract

Abstract:

In the present study, we aimed to evaluate the anti-inflammatory mechanism of galanthamine, a classic therapeutic drug for Alzheimer’s disease (AD). The co-culture system of hippocampal nerve cell line HT-22 and microglial cell line BV-2 was established to observe the effect of galanthamine on the expressions of inflammatory factors induced by lipopolysaccharide (LPS). MTT method was used to observe the protective effect of galanthamine on neurons. ELISA and qPCR methods were used to detect the expressions of interleukin-1β (IL-1β) and IL-1 receptor antagonist (IL-1RA) at the protein and mRNA levels, respectively. IL-1β and IL-1RA were evaluated by the ELISA method after pretreating with galanthamine and α7 nAChR blocker α-bungarotoxin (α-bun), mAChR blocker atropine (Atr), PI3K inhibitor LY294002, IKKβ inhibitor SC514, or MEK inhibitor PD98059, respectively. The results showed that galanthamine significantly inhibited LPS-induced increased IL-1β and IL-1RA expressions and maintained the ratio of IL-1β/IL-1RA. α-Bun could block the regulatory effect of galanthamine on IL-1β and IL-1RA. As PI3K and NF-κB pathways were blocked, the regulatory effect of galanthamine on the IL-1β expression was significantly inhibited. Blocking PI3K and MEK pathways could significantly inhibit the regulation of galanthamine on IL-1RA expression. In summary, galanthamine regulated the inflammatory activity of the IL-1 subfamily to play an anti-inflammatory role mediated by α7 nAChR and PI3K/NF-κB/MAPK pathways, which probably provided a new strategy for AD treatment.

Key words: Galanthamine, Interleukin-1β, IL-1 receptor antagonist, Lipopolysaccharide, Inflammatory response

Supporting:

Jingting Kang, Chao Ji. The mechanism of galanthamine regulating IL-1β/IL-1RA ratio to ameliorate inflammatory microenvironment[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(10): 773-781.

Figures/Tables 8

Table 1. Sequences of primers.

References 15

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