Musk Ketone Induces Neural Stem Cell Proliferation and Differentiation in Cerebral Ischemia via Activation of the PI3K/Akt Signaling Pathway

Zhou, Zheyi; Dun, Linglu; Wei, Bing-Xin; Gan, Yanyan; Liao, Zhongling; Lin, Xiumiao; Lu, Junlei; Liu, Guocheng; Xu, Hong; Lu, Changjun; An, Hong‐Wei

doi:10.1016/j.neuroscience.2020.02.031

Cited by 28 publications

(18 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…; 1.0, 5.0 mg/100 g, i.p Reducing the histamine and S-HT contents of the inflamed tissues [ 34 ] HUVEC Muscone 37.5, 75, 150 μg/mL Decreasing expression of CAMs on HUVEC [ 49 ] IL-1β induced end-plate chondrocytes; Rat model of endplate degeneration Muscone 6.25, 12.5, and 25 lmol/L; 10 mg/kg, p.o Blocking the proinflammatory effect of IL-1β in vitro; inhibiting inflammatory cytokine expression in degenerated IVDs, and prevent IVD degeneration in vivo [ 52 ] Murine BV2 microglial cells; adjuvant inflammatory pain model Muscone 1, 2, 4, 8, 16 μM; 4, 8, 16 mg/kg Suppressing microglial activation-mediated inflammatory response through the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome; inhibiting the CFA-induced NOX4, p-JAK2/p-STAT3, and NLRP3 inflammasome expression in the spinal cord of mice [ 54 ] Neuroprotective effects Glutamate-induced PC12 cells Muscone 0.1, 1, 10 μM Attenuating ROS generation and Ca2 + influx, via NR1 and CaMKII-depended ASK-1/JNK/p38 signaling pathways [ 61 ] MCAO rat model Muscone 1 mg/kg, i.g Down-regulating the expression of EAAC1mRNA in the ischemic hippocampus [ 62 ] MCAO rat model Muscone 1 mg/kg, i.g Reducing NR1 protein expression, thereby reducing excitatory glutamate toxicity [ 63 ] MCAO rat model; oxygen–glucose deprivation cell model Muscone 0.5, 1 mg/kg, i.g. ; 0.9, 1.8 μM Activating the PI3K/Akt signaling pathway [ 67 ] In vitro blood–brain barrier model ...…”

Section: Pharmacological Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Zoology, chemical composition, pharmacology, quality control and future perspective of Musk (Moschus): a review

et al. 2021

View full text Add to dashboard Cite

Musk, the dried secretion from the musk sac gland which is located between the navel and genitals of mature male musk deer, is utilized as oriental medicine in east Asia. It has been utilized to treat conditions such as stroke, coma, neurasthenia, convulsions, and heart diseases in China since ancient times. This paper aims to provide a comprehensive overview of musk in zoology, chemical composition, pharmacology, clinical applications, and quality control according to the up-to-date literature. Studies found that musk mainly contains macrocyclic ketones, pyridine, steroids, fatty acids, amino acids, peptides, and proteins, whilst the main active ingredient is muscone. Modern pharmacological studies have proven that musk possesses potent anti-inflammatory effects, neuroprotective effects, anti-cancer effects, antioxidant effects, etc. Moreover, muscone, the main active ingredient, possesses anti-inflammatory, neuroprotective, antioxidant, and other pharmacological effects. In the quality control of musk, muscone is usually the main detection indicator, and the common analytical method is GC, and researchers have established novel and convenient methods such as HPLC-RI, RP-UPLC-ELSD, and Single-Sweep Polarography. In addition, quality evaluation methods based on steroids and the bioactivity of musk have been established. As for the identification of musk, due to various objective factors such as the availability of synthetic Muscone, it is not sufficient to rely on muscone alone as an identification index. To date, some novel technologies have also been introduced into the identification of musk, such as the electronic nose and DNA barcoding technology. In future research, more in vivo experiments and clinical studies are encouraged to fully explain the pharmacological effects and toxicity of musk, and more comprehensive methods are needed to evaluate and control the quality of musk.

show abstract

Section: Pharmacological Effectsmentioning

confidence: 99%

“…Muscone can promote neural stem cell proliferation and differentiation to protect against cerebral ischemia. This effect is attributed to the activation of the PI3K/Akt signaling pathway [ 67 ]. Cerebral ischemia is accompanied by edema, and this symptom may lead to death [ 68 ].…”

Section: Pharmacological Effectsmentioning

confidence: 99%

Zoology, chemical composition, pharmacology, quality control and future perspective of Musk (Moschus): a review

et al. 2021

View full text Add to dashboard Cite

show abstract

“…PDK1 phosphorylates Akt proteins, involved in cell growth and survival (Hers et al, 2011). PI3K/Akt signaling can be activated in response to different cues such as reactive oxygen species (ROS) (Le Belle et al, 2011), chaperone proteins (Huang and Wang 2018) or even phytochemicals (Lu et al, 2020;Zhou et al, 2020) to promote NSCs' proliferation. In low hypoxic conditions, niche components secrete vascular endothelial growth factor (VEGF) or brain derived neurotrophic factor (BDNF) that rise PI3K, Akt and JNK…”

Section: B Mapk/erk and Akt Signalingmentioning

confidence: 99%

“…Moreover, after oxygen-glucose deprivation, glucose-regulated protein 78 exercises anti-apoptotic and proliferative effects through PI3K/Akt and ERK1/2 pathways (Liu et al, 2018). Phytochemicals, such as astragalosides (Chen et al, 2019;Sun et al, 2020) and musk ketone (Zhou et al, 2020), that were known for their beneficial post-stroke effects, decrease apoptosis and enhance proliferation by regulating EGFR/MAPK and PI3K/Akt signaling. Other study identified miR-145 as an important regulator of NSCs' function after ischemia through MAPK pathway, that leads to decreased levels of Cleaved-caspase 3 and increased levels of Cyclin D1.…”

Section: Biomedicalmentioning

confidence: 99%

Neural stem cells-from quiescence to differentiation and potential clinical uses

Dobranici

Dinescu

Costache

2021

Rev. Biol. Biomed. Sci.

View full text Add to dashboard Cite

Specialised cells of the brain are generated from a population of multipotent stem cells found in the forming embryo and adult brain after birth, called neural stem cells. They reside in specific niches, usually in a quiescent, non-proliferating state that maintains their reservoir. Neural stem cells are kept inactive by various cues such as direct cell-cell contacts with neighbouring cells or by soluble molecules that trigger intracellular responses. They are activated in response to injuries, physical exercise, or hypoxia condition, through stimulation of signaling pathways that are usually correlated with increased proliferation and survival. Moreover, mature neurons play essential role in regulating the balance between active and quiescent state by realising inhibitory or activating neurotransmitters. Understanding molecular mechanisms underlying neuronal differentiation is of great importance in elucidating pathological conditions of the brain and treating neurodegenerative disorders that until now have no efficient therapies.

show abstract

“…After cerebral ischemic injury, the PI3K/AKT pathway is activated and involved in cell proliferation, differentiation ( Zhou et al, 2020 ), angiogenesis ( Chen et al, 2019 ), and survival ( Beker et al, 2019 ). The activation of the PI3K/AKT signaling pathway is related to the increase in many growth-stimulating factors, angiogenic molecules, and vascular endothelial growth factor.…”

Section: Introductionmentioning

confidence: 99%

Guhong Injection Protects Against Apoptosis in Cerebral Ischemia by Maintaining Cerebral Microvasculature and Mitochondrial Integrity Through the PI3K/AKT Pathway

et al. 2021

View full text Add to dashboard Cite

Guhong injection (GHI) can be used for the treatment of ischemic stroke. We investigated the antiapoptotic activity of GHI, its ability to repair the cerebral microvessels and mitochondria, and the PI3K/AKT signaling pathway of GHI against cerebral ischemia. Western blot and immunohistochemical analyses were used to determine the expression of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), cytochrome c (Cyt-c), basic fibroblast growth factor (BFGF), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and proteins in the PI3K/AKT signaling pathway. Transmission electron microscopy and scanning electron microscopy were used to evaluate the structures of the cerebral microvasculature and cells. Hoechst 33342 staining was used to evaluate the nuclear morphology. FITC-AV/PI double staining was used to measure the antiapoptotic effects. The fluorescent dye JC-1 was used to measure mitochondrial membrane potential. The enzyme-linked immunosorbent assay (ELISA) was used to detect the activities of matrix metalloproteinase-9 (MMP-9). Biochemical assay kits were used to detect the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA). Compared with the middle cerebral artery occlusion (MCAO) group, there was decreased infarct volume and significantly improved neurological deficits in the GHI group. In addition, the expression of Bcl-2 was significantly upregulated, while the expression of Cyt-c, Bax, and cleaved caspase-3 was notably downregulated. GHI administration attenuated the pathological change and morphology of the cerebral microvasculature, and immunohistochemical staining indicated that the expressions of BFGF, VEGF, and TGF-β1 were significantly increased. The cell morphology, cell viability, cell nuclei characteristics, and mitochondrial morphology normalized following GHI treatment, which decreased the release of Cyt-c and the mitochondrial membrane potential. The levels of LDH, MMP-9, and MDA decreased, while SOD increased. Moreover, GHI administration inhibited the activation of the PI3K/AKT signaling pathway in rat brain microvascular endothelial cells (rBMECs) following oxygen/glucose deprivation (OGD) injury. Therefore, our results show that GHI administration resulted in antiapoptosis of cerebral cells and repair of cerebral microvessels and mitochondria via the PI3K/AKT signaling pathway.

show abstract

Musk Ketone Induces Neural Stem Cell Proliferation and Differentiation in Cerebral Ischemia via Activation of the PI3K/Akt Signaling Pathway

Cited by 28 publications

References 29 publications

Zoology, chemical composition, pharmacology, quality control and future perspective of Musk (Moschus): a review

Zoology, chemical composition, pharmacology, quality control and future perspective of Musk (Moschus): a review

Neural stem cells-from quiescence to differentiation and potential clinical uses

Guhong Injection Protects Against Apoptosis in Cerebral Ischemia by Maintaining Cerebral Microvasculature and Mitochondrial Integrity Through the PI3K/AKT Pathway

Contact Info

Product

Resources

About