1. The flavonoid-enriched extract from the root of Smilax china L. inhibits inflammatory responses via the TLR-4-mediated signaling pathway.
- Author
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Feng H, He Y, La L, Hou C, Song L, Yang Q, Wu F, Liu W, Hou L, Li Y, Wang C, and Li Y
- Subjects
- Animals, Catalase metabolism, Cytokines metabolism, Glutathione metabolism, Inflammation metabolism, Interleukin-1beta metabolism, Male, NF-kappa B metabolism, Rats, Rats, Wistar, Superoxide Dismutase metabolism, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents pharmacology, Flavonoids pharmacology, Inflammation drug therapy, Inflammation Mediators metabolism, Plant Extracts pharmacology, Signal Transduction drug effects, Toll-Like Receptor 4 metabolism
- Abstract
Ethnopharmacological Relevance: Smilax china L. has been used clinically to treat various inflammatory disorders with a long history., Aim of the Study: To investigate the mechanisms underlying anti-inflammatory action of the extract from the herb., Materials and Methods: The extract was identified and quantified using the Ultra Performance Liquid Chromatography-Photo Diode Array-Mass Spectrometer method. The anti-inflammatory activities were examined in xylene-induced mouse ear edema and cotton ball-induced rat granuloma. The inflammatory mediators, pro-inflammatory cytokines and TLR-4-mediated signals in LPS-stimulated RAW264.7 macrophages were determined using ELISA, real-time PCR, Western blot and/or immunofluorescence, respectively., Results: The extract was found to enrich flavonoids (44.3%, mainly astilbin, engeletin, isoastilbin, cinchonain Ia, quercetin-3-O-a-L-rhamnopyranoside and chlorogenic acid). The flavonoid-enriched extract (FEE) inhibited xylene-induced mouse ear edema and cotton ball-induced rat granuloma, and suppressed LPS-induced over-release and/or overexpression of tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1β and interleukin-6 in RAW264.7 macrophages. Mechanistically, FEE suppressed protein overexpression of TLR-4 and its downstream signals, MyD88 protein, phosphorylated inhibitory κB-α, NF-κB-P65 and MAPK p38, as well as phosphorylation of phosphoinositide 3-kinase (PI3K) p85α at Tyr
607 and Akt at Ser473 in LPS-stimulated macrophages. The mode of the anti-inflammatory action of FEE was similar to that of TAK-242 (a selective TLR-4 inhibitor)., Conclusions: The present results demonstrate that FEE inhibit inflammatory responses via the TLR-4-mediated signaling pathway. Our findings go a new insight into the mechanisms underlying anti-inflammatory action of the herb, and provide a better understanding of its use for inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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