Hydroalcoholic extract from Origanum vulgare induces a combined anti-mycobacterial and anti-inflammatory response in innate immune cells

PLoS One. 2019 Mar 4;14(3):e0213150. doi: 10.1371/journal.pone.0213150. eCollection 2019.

Abstract

In nature, many plants or their extracted compounds have been found to possess anti-inflammatory features and therapeutic properties against infectious as well as non-infectious diseases, including cancer. In this study, we analysed the immunomodulatory effects on innate immune cells of hydroalcoholic extract from Origanum vulgare L. ssp. hirtum (HyE-Ov), a plant traditionally known for its anti-oxidative properties. The effects of HyE-Ov were tested on human monocyte derived dendritic cells (DC), type-1 (M1) and type-2 macrophages (M2) infected with M. bovis Bacille Calmette-Guérin (BCG), used as a model of persistent intracellular bacterium. DC, M1 and M2 treated with HyE-Ov significantly enhanced their mycobactericidal activity, which was associated with phagosomal acidification in M1 and M2 and increase of phagosomal, but not mitochondrial ROS production in M1, M2, and DC. Treatment of BCG-infected DC with HyE-Ov significantly reduced TNF-α and IL-12 production and increased TGF-β synthesis. Finally, experiments were repeated using eight different HPLC fractions of HyE-Ov. Results showed that the capability to activate anti-microbial and anti-inflammatory response is shared by different fractions, suggesting that diverse bioactive molecules are present within the hydroalcoholic extract. Altogether, these results show that HyE-Ov promotes anti-mycobacterial innate immunity and limits inflammatory response in vitro and suggest that this plant extract may be exploitable as phytocomplex or nutraceutical for novel host-directed therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry
  • Alcohols / pharmacology*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology
  • Healthy Volunteers
  • Humans
  • Immunity, Innate / drug effects
  • Interleukin-2 / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mycobacterium bovis / drug effects*
  • Mycobacterium bovis / pathogenicity
  • Origanum / chemistry*
  • Phagosomes / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Alcohols
  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • IL2 protein, human
  • Interleukin-2
  • Plant Extracts
  • TNF protein, human
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by grants to MF: i) Horizon 2020 Programme of European Commission, grant “EMI-TB”—grant # 643558; ii) Italian Foundation for Cystic Fibrosis, “Preclinical study of a host-directed therapy based on Metformin and bioactive liposomes for the control of multidrug resistant P. aeruginosa infection”—grant #14/2017; iii) Italian Foundation for multiple sclerosis, grant #2016/R/22. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.