Broadleaf Mahonia attenuates granulomatous lobular mastitis‑associated inflammation by inhibiting CCL‑5 expression in macrophages

Int J Mol Med. 2018 Jan;41(1):340-352. doi: 10.3892/ijmm.2017.3246. Epub 2017 Nov 9.

Abstract

Granulomatous lobular mastitis (GLM) is a type of chronic mammary inflammation with unclear etiology. Currently systematic corticosteroids and methitrexate are considered as the main drugs for GLM treatment, but a high toxicity and risk of recurrence greatly limit their application. It is therefore an urgent requirement that safe and efficient natural drugs are found to improve the GLM prognosis. Broadleaf Mahonia (BM) is a traditional Chinese herb that is believed to have anti‑inflammatory properties according to ancient records of traditional Chinese medicine. The present study investigated this belief and demonstrated that BM significantly inhibited the expression of interleukin‑1β (IL‑1β), IL‑6, cyclooxygenase‑2 and inducible nitric oxide synthase in RAW264.7 cells, but had little influence on the cell viability, cell cycle and apoptosis. Meanwhile, the lipopolysaccharide‑induced elevation of reactive oxygen species and nitric oxide was also blocked following BM treatment, accompanied with decreased activity of nuclear factor‑κB and MAPK signaling. A cytokine array further validated that BM exhibited significant inhibitory effects on several chemoattractants, including chemokine (C‑C motif) ligand (CCL)‑2, CCL‑3, CCL‑5 and secreted tumor necrosis factor receptor 1, among which CCL‑5 exhibited the highest inhibition ratio in cell and clinical GLM specimens. Collectively, the results show that BM is a novel effective anti‑inflammatory herb in vitro and ex vivo, and that CCL‑5 may be closely associated with GLM pathogenesis.

MeSH terms

  • Animals
  • Chemokine CCL5 / genetics*
  • Drugs, Chinese Herbal / administration & dosage*
  • Drugs, Chinese Herbal / chemistry
  • Female
  • Gene Expression Regulation / drug effects
  • Granulomatous Mastitis / drug therapy*
  • Granulomatous Mastitis / genetics
  • Granulomatous Mastitis / pathology
  • Humans
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Mahonia / chemistry
  • Mice
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Ccl5 protein, mouse
  • Chemokine CCL5
  • Drugs, Chinese Herbal
  • Reactive Oxygen Species