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

A reference to TNF which still has to be determined if reducing TNF will help stroke patients.
Dr. Tobinick could have solved this TNF question years ago if he had only actually run clinical tests on etanercept.
http://www.sciencedirect.com/science/article/pii/S0367326X16301150

• Thangavelu Soundara Rajan^a,
• Sabrina Giacoppo^a,
• Renato Iori^b,
• Gina Rosalinda De Nicola^b,
• Gianpaolo Grassi^c,
• Federica Pollastro^d,
• Placido Bramanti^a,
• Emanuela Mazzon^{a, ,}

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doi:10.1016/j.fitote.2016.05.008

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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 (5 μM) and moringin (5 μM) 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.