In Vitro and In Vivo Anti-Inflammatory Effects of Cannabis sativa Stem Extract

With growing scientific interest in cannabinoids, a number of studies have focused on biological activities of cannabidiol and its major source, inflorescence and leaf of Cannabis sativa plant. However, recent analytical chemistry studies have reported the pharmacological significance of non-cannabinoid phytochemicals that are rich in other parts of the plant. Thus, the objective of this study was to investigate the anti-inflammatory effects of Cannabis extracts from plant parts of shelled seeds, roots, and stems containing no or trace amounts of cannabinoids. Among water and ethanol extracts from three plant parts, Cannabis stem ethanol extract (CSE) had the most potent free radical scavenging activities and suppressive effects on the production of nitric oxide from macrophages. In further studies using macrophages, CSE effectively inhibited lipopolysaccharide (LPS)-induced inflammatory responses by suppressing proinflammatory cytokines, nuclear factor-kappa B and mitogen-activated protein kinase phosphorylations, and cellular accumulation of reactive oxygen species. Moreover, in mice exposed to LPS, CSE reduced tumor necrosis factor-alpha production and normalized activations of proapoptotic proteins in the liver, kidney, and spleen. Gas chromatography/mass spectrometry analyses of CSE showed several active compounds that might be associated with its antioxidant and anti-inflammatory effects. Collectively, these findings indicate that CSE counteracts LPS-induced acute inflammation and apoptosis, suggesting pharmaceutical applications for the stem part of C. sativa.