Protective effect and mechanism of ginsenoside Rg1 on H2O2 induced hippocampal neurons aging due to down-regulate NOX2 mediated NLRP1 inflammasome activation in vitro

OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1(Rg1) on H_2O_2-induced hippocampal neurons aging in vitro.METHODS The primary culture hippo.campal neurons(7 d) were randomly placed into six groups:normal control group,H_2O_2(200 μM) treat.ment group,and H_2O_2+Rg1(1,5 and 10μM) groups.The neurons were with Rg1(1,5 and 10 μmol·L^(-1))for 6 h.H_2O_2(200 μmol · L-1) was added to the medium and incubate for 18 h.The Dihydroethidium(DHE) staining was performed for ROS production assessment.The LDH release and Hoechst 33258 were performed to examine the neuronal damage and apoptosis.The immunoblot was used to deter.mine the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons.The ELISA was performed to detect the levels of IL-1β and IL-18 released in the supernatant in hippocampal neurons.RESULTS Rg1(5 and 10 μmol·L^(-1)) significantly reduced the ROS production,attenuated H_2O_2-induced neuronal damage and apoptosis(P<0.05,P<0.01).The immunoblot results showed that Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons(P<0.05,P<0.01).Additionally,Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased IL-1β and IL-18 release in the supernatant.CONCLUSION The protective effect of Rg1 in H_2O_2-induced hippocampal neurons aging may be due to inhibit NOX2-NLRP1 activation.

Michael Acceptor Pyrrolidone Derivatives and Their Activity against Diffuse Large B-cell Lymphoma

Objective This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma(DLBCL),a common and heterogeneous malignancy of the adult lymphohematopoietic system.Given the limitations of current therapies,there is a pressing need to develop new and effective drugs for DLBCL treatment.Methods A series of pyrrolidone derivatives were synthesized,and their antitumor activities were assessed,particularly against DLBCL cell lines.Structure-activity relationship(SAR)analysis was conducted to identify key structural components essential for activity.The most promising compound,referred to as compound 7,was selected for further mechanistic studies.The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting,and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis.Results The compound 7 exhibited good antitumor activity among the synthesized derivatives,specifically in DLBCL cell lines.SAR analysis highlighted the critical role ofα,β-unsaturated ketones in the antitumor efficacy of these compounds.Mechanistically,compound 7 was found to induce significant DNA damage,trigger an inflammatory response,cause mitochondrial dysfunction,and disrupt cell cycle progression,ultimately leading to apoptosis of DLBCL cells.Conclusion The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death.These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL.