Ni W

References (9)

Title : Elamipretide alleviates pyroptosis in traumatically injured spinal cord by inhibiting cPLA2-induced lysosomal membrane permeabilization - Zhang_2023_J.Neuroinflammation_20_6
Author(s) : Zhang H , Chen Y , Li F , Wu C , Cai W , Ye H , Su H , He M , Yang L , Wang X , Zhou K , Ni W
Ref : J Neuroinflammation , 20 :6 , 2023
Abstract : Spinal cord injury (SCI) is a devastating injury that may result in permanent motor impairment. The active ingredients of medications are unable to reach the affected area due to the blood-brain barrier. Elamipretide (SS-31) is a new and innovative aromatic cationic peptide. Because of its alternating aromatic and cationic groups, it freely crosses the blood-brain barrier. It is also believed to decrease inflammation and protect against a variety of neurological illnesses. This study explored the therapeutic value of SS-31 in functional recovery after SCI and its possible underlying mechanism. A spinal cord contusion injury model as well as the Basso Mouse Scale, footprint assessment, and inclined plane test were employed to assess how well individuals could function following SCI. The area of glial scarring, the number of dendrites, and the number of synapses after SCI were confirmed by HE, Masson, MAP2, and Syn staining. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were employed to examine the expression levels of pyroptosis-, autophagy-, lysosomal membrane permeabilization (LMP)- and MAPK signalling-related proteins. The outcomes showed that SS-31 inhibited pyroptosis, enhanced autophagy and attenuated LMP in SCI. Mechanistically, we applied AAV vectors to upregulate Pla2g4A in vivo and found that SS-31 enhanced autophagy and attenuated pyroptosis and LMP by inhibiting phosphorylation of cPLA2. Ultimately, we applied asiatic acid (a p38-MAPK agonist) to test whether SS-31 regulated cPLA2 partially through the MAPK-P38 signalling pathway. Our group is the first to suggest that SS-31 promotes functional recovery partially by inhibiting cPLA2-mediated autophagy impairment and preventing LMP and pyroptosis after SCI, which may have potential clinical application value.
ESTHER : Zhang_2023_J.Neuroinflammation_20_6
PubMedSearch : Zhang_2023_J.Neuroinflammation_20_6
PubMedID: 36609266

Title : A Multifunctional (-)-Meptazinol-Serotonin Hybrid Ameliorates Oxidative Stress-Associated Apoptotic Neuronal Death and Memory Deficits via Activating the Nrf2\/Antioxidant Enzyme Pathway - Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
Author(s) : Zhao F , Zhao L , Zhou Y , Tan X , Yang Y , Ni W , Zheng W , Chen H , Qiu Y , Li J
Ref : Oxid Med Cell Longev , 2023 :6935947 , 2023
Abstract : The pathogenesis of Alzheimer's disease (AD) involves multiple pathophysiological processes. Oxidative stress is a major cause of AD-associated neuronal injury. The current research was designed to examine whether a novel (-)-meptazinol-serotonin hybrid (Mep-S) with potent antioxidant activity and additional inhibitory properties for acetylcholinesterase (AChE) activity could attenuate oxidative neuronal damage and cognitive deficits. In human SH-SY5Y cells, Mep-S suppressed H(2)O(2)-induced apoptosis by restoring mitochondrial membrane potential and inhibiting caspase-3 activation. Meanwhile, it attenuated oxidative stress elicited by H(2)O(2) through lessening generation of reactive oxygen species as well as enhancing production of glutathione (GSH) and activity of superoxide dismutase (SOD). Mechanistically, Mep-S promoted nuclear translocation of a transcription factor nuclear factor E2-related factor-2 (Nrf2) in H(2)O(2)-challenged cells. This effect was accompanied by reduction in Kelch-like ECH-associated protein-1 (Keap1) levels as well as augmentation of Akt phosphorylation and expression of heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO-1). Molecular docking analysis revealed that Mep-S may disrupt the protein-protein interactions between Keap1 and Nrf2. In an in vivo mouse model, Mep-S attenuated scopolamine-caused cognitive deficits with inhibition of apoptotic neuronal death and brain AChE activity. Furthermore, the scopolamine-induced impairment of total antioxidant capacity and reduction in SOD1, SOD2, and gamma-glutamate-cysteine ligase expression in the brain were counteracted by Mep-S, accompanied by decreased Keap1 levels, increased Akt catalytic subunit and Nrf2 phosphorylation, and decreased Nrf2, HO-1, and NQO-1 expression. Collectively, our results suggest that Mep-S ameliorates apoptotic neuronal death and memory dysfunction associated with oxidative stress by regulating the Nrf2/antioxidant enzyme pathway through inactivating Keap1 and phosphorylating Nrf2 via Akt activation. Therefore, Mep-S may be a potential lead for multitarget neuroprotective agents to treat AD-like symptoms.
ESTHER : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedSearch : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedID: 36819782

Title : Corrigendum to Acylphloroglucinols with acetylcholinesterase inhibitory effects from the fruits of Eucalyptus robusta. [Bioorg. Chem. 103 (2020) 104127] -
Author(s) : Liu H , He XZ , Feng MY , Zeng Y , Rauwolf TJ , Shao LD , Ni W , Yan H , Porco JA, Jr. , Hao XJ , Qin XJ , Liu HY
Ref : Bioorg Chem , 108 :104579 , 2020
PubMedID: 33493929

Title : Polymethylated acylphloroglucinols from Rhodomyrtus tomentosa exert acetylcholinesterase inhibitory effects - Qin_2020_Bioorg.Chem__104519
Author(s) : Qin XJ , Liu H , Li PP , Ni W , He L , Khan A , Hao XJ , Liu HY
Ref : Bioorg Chem , :104519 , 2020
Abstract : Chemical investigation of the twigs and leaves of Rhodomyrtus tomentosa led to the isolation and structural identification of a novel polymethylated phloroglucinol meroterpenoid (PPM) featuring a 6/6/6/6 tetracyclic system, rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs) with a rare bis-furan framework, rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two beta-triketone units, rhotomentosone F (7), as well as five known analogues (8-12). Their structures and absolute configurations were unambiguously determined by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. All isolates were evaluated for their anti-inflammatory and acetylcholinesterase (AChE) inhibitory activities. Compound 6 displayed significant AChE inhibitory effect with an IC(50) value of 8.68 M. Further molecular docking studies of 6 revealed that the interactions with AChE residues Ser125, Glu202, and Tyr133 are crucial for AChE inhibitory activity. The current study not only enriches the chemical diversity of phloroglucinols in Myrtaceae species, but also provides potential lead compounds for the further design and development of new AChE inhibitors to treat Alzheimer's disease.
ESTHER : Qin_2020_Bioorg.Chem__104519
PubMedSearch : Qin_2020_Bioorg.Chem__104519
PubMedID: 33293058

Title : Acylphloroglucinols with acetylcholinesterase inhibitory effects from the fruits of Eucalyptus robusta - Liu_2020_Bioorg.Chem_103_104127
Author(s) : Liu H , He XZ , Feng MY , Yuan Z , Rauwolf TJ , Shao LD , Ni W , Yan H , Porco JA, Jr. , Hao XJ , Qin XJ , Liu HY
Ref : Bioorg Chem , 103 :104127 , 2020
Abstract : Eleven new acylphloroglucinols, including six new formylated phloroglucinol-monoterpene meroterpenoids, eucalyprobusals A-F (1-6), one monomeric acylphloroglucinol, eucalyprobusone B (7), and four dimeric acylphloroglucinols, eucalyprobusones C-F (8-11) were purified from the fruits of Eucalyptus robusta. The establishment of the structures of 1-11 was achieved by a combination of NMR and HRESIMS data analyses, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Compounds 6, 8, and an inseparable mixture of 10 and 11 were found to be potent AChE inhibitors with IC(50) values of 3.22 +/- 0.36, 3.82 +/- 0.22, and 2.55 +/- 0.28 microM, respectively. Possible interaction sites of 6, 8, 10, and 11 with AChE were investigated by means of molecular docking studies, and the results revealed that AChE residues Asn87, Ser125, Thr83, Tyr133, Tyr124, Tyr337, and Tyr341 played crucial roles in the observed activity of the aforementioned compounds.
ESTHER : Liu_2020_Bioorg.Chem_103_104127
PubMedSearch : Liu_2020_Bioorg.Chem_103_104127
PubMedID: 32745755

Title : Design, Synthesis, and Biological Evaluation of Orally Available First-Generation Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer's Disease - Mao_2018_ACS.Chem.Neurosci_9_328
Author(s) : Mao F , Wang H , Ni W , Zheng X , Wang M , Bao K , Ling D , Li X , Xu Y , Zhang H , Li J
Ref : ACS Chem Neurosci , 9 :328 , 2018
Abstract : Through drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized, and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for Alzheimer's disease (AD). Among these derivatives, 1p and 1w exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier (BBB) penetrability. Importantly, 1w.Cit (citrate of 1w) could reverse the cognitive dysfunction of scopolamine-induced AD mice and exhibited an excellent effect on enhancing cAMP response element-binding protein (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic plasticity. Moreover, the molecular docking simulations of 1w with hAChE and hPDE5A confirmed that our design strategy was rational. In summary, our research provides a potential selective dual-target AChE/PDE5 inhibitor as a good candidate drug for the treatment of AD, and it could also be regarded as a small molecule probe to validate the novel AD therapeutic approach in vivo.
ESTHER : Mao_2018_ACS.Chem.Neurosci_9_328
PubMedSearch : Mao_2018_ACS.Chem.Neurosci_9_328
PubMedID: 29068218

Title : Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) - Ni_2018_ACS.Chem.Neurosci_9_1625
Author(s) : Ni W , Wang H , Li X , Zheng X , Wang M , Zhang J , Gong Q , Ling D , Mao F , Zhang H , Li J
Ref : ACS Chem Neurosci , 9 :1625 , 2018
Abstract : On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of Alzheimer's disease (AD), and the lead compound 2 has proven this method was feasible in AD mouse models. In this study, our work focused on exploring alternative novel tadalafil derivatives (3a-s). Among the 19 analogues, compound 3c exhibited good selective dual-target AChE/PDE5 inhibition and good blood-brain barrier (BBB) permeability. Moreover, its citrate (3c.Cit) possessed improved water solubility and good effects against scopolamine-induced cognitive impairment with inhibition of cortical AChE activities and enhancement of cAMP response element-binding protein (CREB) phosphorylation ex vivo.
ESTHER : Ni_2018_ACS.Chem.Neurosci_9_1625
PubMedSearch : Ni_2018_ACS.Chem.Neurosci_9_1625
PubMedID: 29616790

Title : Eucalyptusdimers A-C, Dimeric Phloroglucinol-Phellandrene Meroterpenoids from Eucalyptus robusta - Qin_2018_Org.Lett_20_5066
Author(s) : Qin XJ , Feng MY , Liu H , Ni W , Rauwolf T , Porco JA, Jr. , Yan H , He L , Liu HY
Ref : Org Lett , 20 :5066 , 2018
Abstract : Eucalyptusdimers A-C, three dimeric phellandrene-derived meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate, (+/-)-eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. Their structures and absolute configurations were elucidated using spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. The isolated meroterpenoids were evaluated for their anti-inflammatory, acetylcholinesterase inhibitory, and protein tyrosine phosphatase 1B inhibitory effects.
ESTHER : Qin_2018_Org.Lett_20_5066
PubMedSearch : Qin_2018_Org.Lett_20_5066
PubMedID: 30088934

Title : Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents - Li_2016_J.Med.Chem_59_8326
Author(s) : Li X , Wang H , Lu Z , Zheng X , Ni W , Zhu J , Fu Y , Lian F , Zhang N , Li J , Zhang H , Mao F
Ref : Journal of Medicinal Chemistry , 59 :8326 , 2016
Abstract : Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, 5r, IC50 = 0.204 muM, SI > 196; 5t, IC50 = 0.067 muM, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced Abeta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound 5r displayed appropriate blood-brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of scopolamine-induced amnesia mice. The multifunctional profiles of 5r and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease.
ESTHER : Li_2016_J.Med.Chem_59_8326
PubMedSearch : Li_2016_J.Med.Chem_59_8326
PubMedID: 27552582