Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.
Summary
Dendrobium aphyllum is an edible plant that is used as a functional food to improve health. We previously examined peptides and polysaccharides extracted from Dendrobium aphyllum; however, we did not investigate D. aphyllum’s alkaloid compounds and their functions. In this study, we detail the composition of alkaloids from Dendrobium aphyllum (DAA), including 2α, 3β‐dihydroxy nortropane, 1‐methyl‐2‐[(4Z,7Z)‐4,7‐tridecadienyl]‐4(1H)‐quinolone and maokonine, which were first identified by UPLC‐MS analysis. Furthermore, the anti‐inflammatory activity of DAA on LPS‐induced RAW 264.7 macrophages was examined. DAA treatment inhibited LPS‐induced NO production and decreased (P < 0.05) IL‐1, IL‐6, TNF‐α and PGE2 secretion in the RAW 264.7 macrophages. DAA treatment also inhibited COX‐2 and iNOS mRNA expression in a dose‐dependent manner, indicating that these compounds can attenuate the synthesis of the above‐mentioned molecules at the transcriptional level, tentatively confirming their anti‐inflammatory effect.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.