7-Deoxy-<i>trans</i>-dihydronarciclasine Isolated from <i>Lycoris chejuensis</i> Inhibits Neuroinflammation in Experimental Models

Zhao, Dong; Gu, Ming-Yao; Zhang, Li Jun; Jeon, Hyo Jin; Cho, Yong-Baik; Yang, Hyun Ok

doi:10.1021/acs.jafc.9b03307

Cited by 8 publications

(19 citation statements)

References 44 publications

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“…Our data showed that E144 decreased the secreted level of TNF-α, ruling out the possibility that E144 might cause putative side-effects by increasing TNF-α. Instead, E144 significantly decreased LPS-induced TNFα level, consistent with a recent report regarding the anti-inflammatory effect of E144 [45]. These results indicated that while E144 activated ADAM17 towards certain substrate such as Mca-KPLGL-Dpa-AR, it also inhibited ADAM17 towards another substrate, thereby reducing the secreted TNFα.…”

Section: Discussionsupporting

confidence: 90%

Substrate-Specific Activation of α-Secretase by 7-Deoxy-Trans-Dihydronarciclasine Increases Non-Amyloidogenic Processing of β-Amyloid Protein Precursor

et al. 2020

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Accumulation of β-amyloid (Aβ) in the brain has been implicated in the pathology of Alzheimer’s disease (AD). Aβ is produced from the Aβ precursor protein (APP) through the amyloidogenic pathway by β-, and γ-secretase. Alternatively, APP can be cleaved by α-, and γ-secretase, precluding the production of Aβ. Thus, stimulating α-secretase mediated APP processing is considered a therapeutic option not only for decreasing Aβ production but for increasing neuroprotective sAPPα. We have previously reported that 7-deoxy-trans-dihydronarciclasine (E144), the active component of Lycoris chejuensis, decreases Aβ production by attenuating APP level, and retarding APP maturation. It can also improve cognitive function in the AD model mouse. In this study, we further analyzed the activating effect of E144 on α-secretase. Treatment of E144 increased sAPPα, but decreased β-secretase products from HeLa cells stably transfected with APP. E144 directly activated ADAM10 and ADAM17 in a substrate-specific manner both in cell-based and in cell-free assays. The Lineweaver–Burk plot analysis revealed that E144 enhanced the affinities of A Disintegrin and Metalloproteinases (ADAMs) towards the substrate. Consistent with this result, immunoprecipitation analysis showed that interactions of APP with ADAM10 and ADAM17 were increased by E144. Our results indicate that E144 might be a novel agent for AD treatment as a substrate-specific activator of α-secretase.

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Section: Discussionsupporting

confidence: 90%

Substrate-Specific Activation of α-Secretase by 7-Deoxy-Trans-Dihydronarciclasine Increases Non-Amyloidogenic Processing of β-Amyloid Protein Precursor

et al. 2020

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“…The inhibitory activity of all the isolated compounds on nitric oxide (NO) release was tested by the method described in previous reports , with minor modifications. In short, 100 μL medium containing 4 × 10 4 BV-2 cells was transferred to each well of the 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

Quassinoids from Picrasma chinensis with Insecticidal Activity against Adults and Larvae of Diaphorina citri Kuwayama and Neuroprotective Effect

Fan

Han

Deng

et al. 2022

J. Agric. Food Chem.

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Eleven new tetracyclic quassinoids, picrachinensin A−K (1−11), along with six known congeners, were isolated from the stems and leaves of Picrasma chinensis. Their structures were elucidated by integrated multiple spectroscopic techniques, singlecrystal X-ray diffraction analysis, and electronic circular dichroism. Notably, compounds 3 and 4 are a pair of undescribed epimers, and 8 and 9 are unusual quassinoids with a hydroxymethyl group at C-13. Biologically, compound 7 exhibited insecticidal activity on both adults and larvae of Diaphorina citri Kuwayama even more effectively than the positive control (abamectin), with an LD 50 of 55.69 mg/L for adults and a corrected mortality rate of 30.42 ± 2.78% for larvae (100 mg/L). According to preliminary structure− activity relationship investigations, the hydroxymethyl at the C-13 position of quassinoids was beneficial for their insecticidal activity. In addition, compounds 1, 4, and 12 exhibited excellent neuroprotective effect against H 2 O 2 -induced oxidative injury on SH-SY5Y cells, with more potent activity than the positive control (Trolox), and all the compounds exhibited no cytotoxicity to SH-SY5Y and BV-2 cells at the indicated concentrations.

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“…A colorimetric assay was performed to detect cell metabolic ability according to a previously reported protocol ( Zhao et al ., 2019 ). BV-2 microglial cells were cultured with DMEM/F12 medium (Gibco) in 96-well plates (1×10 4 cells/well) for 24 h. Then, Cells were treated for 12 h with various concentrations of SA in the presence or absence of 100 ng/mL LPS.…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability was measured by a colorimetric assay to detect cell metabolic ability according to a previously reported protocol (Zhao et al, 2019). BV-2 microglial cells were cultured in DMEM/F12 medium (Gibco) in 96-well plates (1×10 4 cells/well) for 24 hours.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…For the preparation of mouse brain samples as described previously (Zhao et al, 2019), the mouse cerebral cortex was collected, stored at -80°C and then homogenized with PRO-PREP protein extraction buffer (iNtRON, Seongnam-si, Republic of Korea) supplemented with 1× PIC set III (Sigma-Aldrich, St. Louis, MO, USA). The homogenates were then centrifuged (13,000 rpm) for 20 min at 4°C.…”

Section: Total Protein Isolation From Bv-2 Cellsmentioning

confidence: 99%

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Sinapic Acid Attenuates the Neuroinflammatory Response by Targeting AKT and MAPK in LPS-Activated Microglial Models

Huang

Zhao

Lee

et al. 2022

Biomol Ther (Seoul)

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Sinapic acid (SA) is a phenolic acid that is widely found in fruits and vegetables, which has various bioactivities, such as antidiabetic, anti-in ammatory, anticancer and anxiolytic functions. Overactivated microglial cells play a major role in the development of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The objective of this study was to investigate the effect and mechanism of sinapic acid in microglia-derived neuroin ammatory models. Our results demonstrated that SA inhibited production of the nitric oxide (NO) pro-in ammatory factor, induced nitric oxide synthase (iNOS), induced interleukin (IL)-6 and enhanced the release of IL-10 in a dose-dependent manner. Subsequently, a mechanistic study revealed that SA remarkably attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, administration of SA regulated the production of in ammation-related cytokines and inhibited the phosphorylation of MAPK cascades and Akt in the mouse cerebral cortex. These results suggested that SA may offer a possible treatment for antiin ammatory activity by targeting the AKT/MAPK signaling pathway.

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7-Deoxy-trans-dihydronarciclasine Isolated from Lycoris chejuensis Inhibits Neuroinflammation in Experimental Models

Cited by 8 publications

References 44 publications

Substrate-Specific Activation of α-Secretase by 7-Deoxy-Trans-Dihydronarciclasine Increases Non-Amyloidogenic Processing of β-Amyloid Protein Precursor

Substrate-Specific Activation of α-Secretase by 7-Deoxy-Trans-Dihydronarciclasine Increases Non-Amyloidogenic Processing of β-Amyloid Protein Precursor

Quassinoids from Picrasma chinensis with Insecticidal Activity against Adults and Larvae of Diaphorina citri Kuwayama and Neuroprotective Effect

Sinapic Acid Attenuates the Neuroinflammatory Response by Targeting AKT and MAPK in LPS-Activated Microglial Models

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