RESUMO
BACKGROUND: Aconitine is well-known for its potential analgesic, anti-inflammatory, and circulation promoting effects and has been widely used as a folk medicine in South Korea. Owing to its extremely toxic nature and relatively low safety margin, intoxication is sometimes fatal. The toxic compound mainly affects the central nervous system, heart, and muscle, resulting in cardiovascular complications. PURPOSE: To determine the exact relationship between blood concentration of aconitine and clinical manifestation. BASIC PROCEDURES: The National Forensic Service (NFS) was commissioned to assist in a quantitative analysis of highly toxic aconitine and corresponding blood concentrations by analyzing the body fluids of three patients who were suspected of aconitine poisoning. MAIN FINDINGS: Aconitine blood values tested by the NFS showed that patients with a blood concentration below a certain level developed symptoms slowly and showed a high severity of clinical manifestation. There was no correlation between blood concentration and symptoms or ECG results. CONCLUSIONS: In case of suspected aconitine poisoning, an emergency care department should be visited, even with symptomatic improvement, and the patient should be monitored for at least 24 h, depending on the level of recovery and changes in ECG results.
Assuntos
Aconitina/sangue , Aconitina/intoxicação , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Serviço Hospitalar de Emergência , Feminino , Medicina Legal , Humanos , Masculino , Pessoa de Meia-Idade , República da CoreiaRESUMO
Epigallocatechin gallate (EGCG) is the principal bioactive ingredient in green tea and has been reported to have many health benefits. EGCG influences multiple signal transduction pathways related to human diseases, including redox, inflammation, cell cycle, and cell adhesion pathways. However, the molecular mechanisms of these varying effects are unclear, limiting further development and utilization of EGCG as a pharmaceutical compound. Here, we examined the effect of EGCG on two representative transmembrane signaling receptors, integrinαIIbß3 and epidermal growth factor receptor (EGFR). We report that EGCG inhibits talin-induced integrin αIIbß3 activation, but it activates αIIbß3 in the absence of talin both in a purified system and in cells. This apparent paradox was explained by the fact that the activation state of αIIbß3 is tightly regulated by the topology of ß3 transmembrane domain (TMD); increases or decreases in TMD embedding can activate integrins. Talin increases the embedding of integrin ß3 TMD, resulting in integrin activation, whereas we observed here that EGCG decreases the embedding, thus opposing talin-induced integrin activation. In the absence of talin, EGCG decreases the TMD embedding, which can also disrupt the integrin α-ß TMD interaction, leading to integrin activation. EGCG exhibited similar paradoxical behavior in EGFR signaling. EGCG alters the topology of EGFR TMD and activates the receptor in the absence of EGF, but inhibits EGF-induced EGFR activation. Thus, this widely ingested polyphenol exhibits pleiotropic effects on transmembrane signaling by modifying the topology of TMDs.
Assuntos
Antioxidantes/metabolismo , Catequina/análogos & derivados , Receptores ErbB/metabolismo , Integrina beta3/metabolismo , Bicamadas Lipídicas/metabolismo , Modelos Moleculares , Transdução de Sinais , Substituição de Aminoácidos , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Células CHO , Catequina/química , Catequina/metabolismo , Catequina/uso terapêutico , Cricetulus , Suplementos Nutricionais , Dimerização , Receptores ErbB/agonistas , Receptores ErbB/química , Receptores ErbB/genética , Humanos , Integrina alfa2/química , Integrina alfa2/genética , Integrina alfa2/metabolismo , Integrina beta3/química , Integrina beta3/genética , Ligantes , Bicamadas Lipídicas/química , Mutação , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/agonistas , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/química , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Talina/antagonistas & inibidores , Talina/química , Talina/metabolismoRESUMO
DW1029M is a botanical extract consisting of Morus bark and Puerariae radix, produced by Dong-Wha Pharmaceutical, for nephroprotective drug development; it has been in phase II clinical trials in Korea. In our mechanistic investigations, we found that DW1029M inhibits advanced glycation end products (AGEs), rat lens aldose reductase (RLAR), and transforming growth factor (TGF)-ß1 signaling, all of which are implicated in diabetic complications such as diabetic nephropathy and diabetic retinopathy. DW1029M inhibits AGE formation via Fe(2+) chelation. The extract contains 13 active constituents that inhibit AGE formation, 8 active constituents that inhibit RLAR activity, and 1 inhibitor of TGF-ß1 signaling. Our results suggest DW1029M protects against diabetic nephropathy via blockade of AGE formation, RLAR activity, and TGF-ß1 signaling.