The flavonoid-enriched extract from the root of Smilax china L. inhibits inflammatory responses via the TLR-4-mediated signaling pathway

  • J Ethnopharmacol. 2020 Jun 28;256:112785. doi: 10.1016/j.jep.2020.112785.
Haixing Feng  1 ,  Yanling He  2 ,  Lei La  3 ,  Chuqi Hou  4 ,  Luyao Song  5 ,  Qin Yang  6 ,  Fuling Wu  7 ,  Wenqin Liu  8 ,  Lianbing Hou  9 ,  Yan Li  10 ,  Chunxia Wang  11 ,  Yuhao Li  12
Affiliations
  • 1. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 2. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Pharmacy, Guangzhou Women and Children's Medical Center, Guangzhou, 510623, China. Electronic address: [email protected].
  • 3. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 4. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 5. Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. Electronic address: [email protected].
  • 6. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 7. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 8. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 9. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 10. Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, 2000, Australia. Electronic address: [email protected].
  • 11. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 12. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, 2000, Australia. Electronic address: [email protected].
PMID: 32222576 DOI: 10.1016/j.jep.2020.112785
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 Tyr607 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.

Keywords
Flavonoids; Inflammation; Smilax china L.; TLR-4.
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