Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways

Kang, Shaolei; Li, Jinglin; Yao, Zhihui; Liu, Jiaxin

doi:10.3389/fncel.2021.654340

Cited by 25 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SIRT1 is the main regulator of neurogenesis and plays a neuroprotective role in neurological diseases [ 38 ]. Previous studies showed that activation of SIRT1 reversed nerve damage in different neurological diseases by augmenting hippocampal neurogenesis [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

et al. 2021

View full text Add to dashboard Cite

Neuroinflammation plays important roles in the pathogenesis and progression of altered neurodevelopment, sensorineural hearing loss, and certain neurodegenerative diseases. Hyperoside (quercetin-3-O-β-D-galactoside) is an active compound isolated from Hypericum plants. In this study, we investigate the protective effect of hyperoside on neuroinflammation and its possible molecular mechanism. Lipopolysaccharide (LPS) and hyperoside were used to treat HT22 cells. The cell viability was measured by MTT assay. The cell apoptosis rate was measured by flow cytometry assay. The mRNA expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by quantitative reverse transcription polymerase chain reaction. The levels of oxidative stress indices superoxide dismutase (SOD), reactive oxygen species (ROS), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were measured by the kits. The expression of neurotrophic factor and the relationship among hyperoside, silent mating type information regulation 2 homolog-1 (SIRT1) and Wnt/β-catenin, and sonic hedgehog was examined by western blotting. In the LPS-induced HT22 cells, hyperoside promotes cell survival; alleviates the level of IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; and increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF. In addition, hyperoside upregulated the expression of SIRT1. Further mechanistic investigation showed that hyperoside alleviated LPS-induced inflammation, oxidative stress, and apoptosis by upregulating SIRT1 to activate Wnt/β-catenin and sonic hedgehog pathways. Taken together, our data suggested that hyperoside acts as a protector in neuroinflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The notion that SIRT1 controls mammalian cell growth and survival under stress is widely recognized; however, this effect has been reported as either a promoter or suppressor depending on the cell types studied, ranging from immortalized cell lines of various lineages to cancer cells and neural stem cells. A recent study showed that CBD induced autophagy in SH-SY5Y cells, which protected the cell from mitochondrial dysfunction by upregulating SIRT1 and inhibiting NF-KB and Notch pathways [ 59 ]. Our study showed that CBD increased neurite outgrowth and spine density via SIRT1.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol induces autophagy and improves neuronal health associated with SIRT1 mediated longevity

et al. 2022

View full text Add to dashboard Cite

Autophagy is a catabolic process to eliminate defective cellular molecules via lysosome-mediated degradation. Dysfunctional autophagy is associated with accelerated aging, whereas stimulation of autophagy could have potent anti-aging effects. We report that cannabidiol (CBD), a natural compound from Cannabis sativa, extends lifespan and rescues age-associated physiological declines in C. elegans. CBD promoted autophagic flux in nerve-ring neurons visualized by a tandem-tagged LGG-1 reporter during aging in C. elegans. Similarly, CBD activated autophagic flux in hippocampal and SH-SY5Y neurons. Furthermore, CBD-mediated lifespan extension was dependent on autophagy genes (bec-1, vps-34, and sqst-1) confirmed by RNAi knockdown experiments. C. elegans neurons have previously been shown to accumulate aberrant morphologies, such as beading and blebbing, with increasing age. Interestingly, CBD treatment slowed the development of these features in anterior and posterior touch receptor neurons (TRN) during aging. RNAi knockdown experiments indicated that CBD-mediated age-associated morphological changes in TRNs require bec-1 and sqst-1, not vps-34. Further investigation demonstrated that CBD-induced lifespan extension and increased neuronal health require sir-2.1/SIRT1. These findings collectively indicate the anti-aging benefits of CBD treatment, in both in vitro and in vivo models, and its potential to improve neuronal health and longevity.

show abstract

“…The antioxidants are the first defense to detoxify ROS [ 14 ]. Identification of effective antioxidant active chemical components from plants or natural products, eliminating active oxygen and maintaining homeostasis, is one of the hotspots of the current research [ 18 , 19 ]. NGR1 has been reported to treated neurological complications [ 8 , 9 ]; in addition, NGR1 has anti-inflammatory and antioxidative stress effects [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we found that NGR1 has an effect on mitochondrial dysfunction and Ca 2+ concentration. When mitochondria are damaged, activated PINK1 aggregates on the outer mitochondrial membrane and induces mitochondrial autophagy through direct/indirect activated Parkin [ 29 ], thereby protecting mitochondrial DNA from reactive oxygen species and stimulating the self-repair process of mitochondria [ 19 ]. In this study, we found that NGR1 treatment activates the PINK1/Parkin pathway and upregulates Parkin expression.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protective Effect of NGR1 against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells by Upregulating the SIRT1/Wnt/β-Catenin Pathway

Wang¹,

Gao

Yang³

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Notoginsenoside R1 (NGR1) is an active compound isolated from Panax notoginseng. Despite the NGR1 having been used as a traditional medicine, little is known about the neuroprotective effects. In this study, we investigate the protective effects of NGR1 against glutamate-induced cytotoxicity in HT22 cells and its possible molecular mechanism. We assessed the toxicity of NGR1 and the protective activity by MTT assay. The levels of oxidative stress indices superoxide dismutase (SOD), glutathione (GSH), and mitochondrial membrane potential (MMP) were measured by the kits. The levels of reactive oxygen species (ROS) and Ca2+ concentration were measured by flow cytometry. Furthermore, we determined the expression of mitochondrial dysfunction related protein PINK1, Parkin, silent mating type information regulation 2 homolog-1 (sirtuin 1; SIRT1), and Wnt/β-catenin by Western blotting. Here, we discovered that glutamate treatment led to cell viability loss, apoptosis facilitation, Ca2+ upregulation, MMP fluorescence intensity downregulation, and ROS generation of HT22 cells. In parallel, expression of Parkin was declined by glutamate. While, NGR1 treatment alleviated all the above phenomena. We further clarified that NGR1 alleviated glutamate-induced oxidative stress, apoptosis, and mitochondrial dysfunction by upregulating SIRT1 to activate Wnt/β-catenin pathways. These findings demonstrate that NGR1 alleviated glutamate-induced cell damage, and NGR1 may play a protective role in neurological complications.

show abstract

Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways

Cited by 25 publications

References 33 publications

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

Cannabidiol induces autophagy and improves neuronal health associated with SIRT1 mediated longevity

Protective Effect of NGR1 against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells by Upregulating the SIRT1/Wnt/β-Catenin Pathway

Contact Info

Product

Resources

About