AUTHOR=Li Dai-Di , Fan Hong-Xia , Yang Rong , Li Ying-Ying , Zhang Feng , Shi Jing-Shan 

TITLE=Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.846541

DOI=10.3389/fphar.2022.846541

ISSN=1663-9812

ABSTRACT=Alzheimer’s disease (AD) is a neurodegenerative disorder recognized as a global public health priority. Although available treatments temporarily relieve the symptoms, they could not prevent the progression of cognitive decline. Natural compounds have traditionally been rich sources for drug discovery. Dendrobium nobile Lindl. alkaloid (DNLA) is the main active compound in Dendrobium nobile Lindl, a traditional Chinese herbal medicine. Recent studies indicated that DNLA produced neuroprotection. However, the mechanisms underlying DNLA-generated neuroprotection remain unknown. To investigate neuroprotection and the underlying mechanisms of DNLA, mouse hippocampus injection of lipopolysaccharide (LPS)-induced neuronal damage was performed. DNLA protected hippocampus neurons and working memory disorder against LPS-induced neurotoxicity. In addition, DNLA suppressed cell undergoes membrane lysis and cell swelling and inhibited the essential mediator of pyroptosis GSDMD-N expressions. Furthermore, DNLA-mediated neuroprotection was dependent on the inhibition of microglial NLRP3 inflammasome activation, as evidenced by fact that DNLA reduced pro-inflammatory factors (IL-18 and IL-1β) production and further DNLA-exerted neuroprotection against LPS-induced neuronal damage and cognitive impairment was not observed at NLRP3 knockout mice. Together, this study suggests that DNLA attenuated NLRP3-mediated pyroptosis to generate neuroprotection against LPS-induced neuronal damage and cognitive impairment.