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. 2022 Mar 3;22(1):55.
doi: 10.1186/s12906-022-03540-1.

Anti-inflammatory effects of flavonoids and phenylethanoid glycosides from Hosta plantaginea flowers in LPS-stimulated RAW 264.7 macrophages through inhibition of the NF-κB signaling pathway

Li Yang  1 , Junwei He  2
Affiliations

Anti-inflammatory effects of flavonoids and phenylethanoid glycosides from Hosta plantaginea flowers in LPS-stimulated RAW 264.7 macrophages through inhibition of the NF-κB signaling pathway

Li Yang et al. BMC Complement Med Ther. .

Abstract

Background: The flower of Hosta plantaginea (Lam.) Aschers has traditionally been used in China as an important Mongolian medicine for the treatment of inflammatory diseases with limited scientific evidence. In previous studies, 16 flavonoids and 3 phenylethanoid glycosides (1-19) were isolated from the ethanolic extract of H. plantaginea flowers. Nevertheless, the anti-inflammatory effects of these constituents remain unclear. In the present study, the anti-inflammatory effects of these 19 constituents and their underlying mechanisms were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.

Methods: The viability of RAW 264.7 macrophages was detected by Cell Counting Kit-8 (CCK-8) assay. Meanwhile, nitric oxide (NO) production was measured by Griess assay, while the secretion of tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), interleukin 1β (IL-1β) and IL-6 in LPS-induced macrophages was determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, the protein expression of nuclear factor kappa B (NF-κB) p65 and phosphorylated NF-κB p65 was evaluated by Western blot analysis.

Results: All constituents effectively suppressed excessive NO production at a concentration of 40 μM with no toxicity to LPS-induced RAW 264.7 macrophages. Among them, five flavonoids (1, 4-6 and 15) and one phenylethanoid glycoside (17) remarkably prevented the overproduction of NO with median inhibitory concentration (IC50) values in the range of 12.20-19.91 μM. Moreover, compounds 1, 4-6, 15 and 17 potently inhibited the secretion of TNF-α, PGE2, IL-1β and IL-6, and had a prominent inhibitory effect on the down-regulation of the phosphorylated protein level of NF-κB p65.

Conclusion: Taken together, compounds 1, 4-6, 15 and 17 may be useful in managing inflammatory diseases by blocking the NF-κB signaling pathway and suppressing the overproduction of inflammatory mediators.

Keywords: Anti-inflammatory; Flavonoid; Hosta plantaginea flowers; NF-κB; Phenylethanoid glycoside.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Effects of 16 flavonoids (1–16) and 3 phenylethanoid glycosides (17–19) on NO production in LPS-stimulated RAW 264.7 macrophages. All data from three independent experiments are expressed as mean ± SD. ##p < 0.01 vs. culture medium-only control group; **p < 0.01 vs. LPS-only model group. One-way ANOVA, followed by Tukey’s test using GraphPad Prism 6
Fig. 2
Fig. 2
Dose-response curves for compounds 1, 4–7, 11, 13–15 and 17 in the NO inhibition assay (n = 3)
Fig. 3
Fig. 3
Effects of compounds 1, 4–6, 15 and 17 on the production of TNF-α (A), PGE2 (B), IL-1β (C) and IL-6 (D) in LPS-stimulated RAW 264.7 macrophages. All data from three independent experiments are expressed as mean ± SD. ##p < 0.01 vs. culture medium-only control group; **p < 0.01 vs. LPS-only model group. One-way ANOVA, followed by Tukey’s test using GraphPad Prism 6
Fig. 4
Fig. 4
Effects of compounds 1, 4–6, 15 and 17 on NF-kB activation (A-phosphorylated p65 and B-total p65) in LPS-stimulated RAW 264.7 macrophages. All data from three independent experiments are expressed as mean ± SD. ##p < 0.01 vs. culture medium-only control group; **p < 0.01 vs. LPS-only model group. One-way ANOVA, followed by Tukey’s test using GraphPad Prism 6
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