Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages

Fitoterapia. 2016 Jul;112:104-15. doi: 10.1016/j.fitote.2016.05.008. Epub 2016 May 20.

Abstract

Inflammatory response plays an important role in the activation and progress of many debilitating diseases. Natural products, like cannabidiol, a constituent of Cannabis sativa, and moringin, an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucomoringin present in Moringa oleifera seeds, are well known antioxidants also endowed with anti-inflammatory activity. This is due to a covalent-based mechanism for ITC, while non-covalent interactions underlie the activity of CBD. Since these two mechanisms are distinct, and the molecular endpoints are potentially complementary, we investigated in a comparative way the protective effect of these compounds alone or in combination on lipopolysaccharide-stimulated murine macrophages. Our results show that the cannabidiol (5μM) and moringin (5μM) combination outperformed the single constituents that, at this dosage had only a moderate efficacy on inflammatory (Tumor necrosis factor-α, Interleukin-10) and oxidative markers (inducible nitric oxide synthase, nuclear factor erythroid 2-related factor 2, nitrotyrosine). Significant upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3 was observed in cells treated with cannabidiol-moringin combination. Treatment with the transient receptor potential vanilloid receptor 1 antagonist was detrimental for the efficacy of cannabidiol, while no effect was elicited by cannabinoid receptor 1 and cannabinoid receptor 2 antagonists. None of these receptors was involved in the activity of moringin. Taken together, our in vitro results testify the anti-inflammatory, antioxidative, and anti-apoptotic effects of the combination of cannabidiol and moringin.

Keywords: Anti-inflammation; Cannabidiol; Combination therapy; LPS; Macrophages; Moringin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis Regulatory Proteins / metabolism
  • Cannabidiol / pharmacology*
  • Cytokines / metabolism
  • Isothiocyanates / pharmacology*
  • Lipopolysaccharides
  • Macrophages / drug effects*
  • Mice
  • Moringa / chemistry
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Cytokines
  • Isothiocyanates
  • Lipopolysaccharides
  • moringin
  • Cannabidiol
  • isothiocyanic acid
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse