RESUMO
OBJECTIVE: To elucidate the chemical profile and the pharmacological mechanism by which Jinlingzi powder (, JLZP) treats bile reflux gastritis (BRG). METHODS: A BRG model was established in rats by oral administration of the model solution. JLZP was orally administered for 35 d. Residual gastric rate and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and gastrin levels in the serum were measured, and stomach tissues were collected for histopathological analysis. We used ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry to identify the chemical ingredients in JLZP. Then, protein-protein interaction and herb-compound-target networks were constructed to screen potential bioactive compounds and targets. Kyoto Encyclopedia of Genes and Genomes pathway analysis was then performed to elucidate the pathway involved in the JLZP-mediated treatment of BRG. After constructing the core compound-target-pathway interaction network, molecular docking was performed to study the binding free energy of core bioactive compounds and two candidate targets [RAC-alpha serine/threonine-protein kinase (AKT1) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)]. RESULTS: JLZP extracts significantly promoted gastric emptying, regulating the release of cytokines (TNF-α and IL-6) and improving gastrin secretion and mucosal repair. Fifty-six compounds were tentatively characterized in JLZP. Moreover, the network pharmacology and molecular docking results showed that alkaloids and flavonoids might be the bioactive compounds in JLZP that treat BRG. JLZP might improve mucosal repair during BRG progression by modulating the phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B, hypoxia inducible factor-1, mitogen-activated protein kinase, forkhead box O, TNF, and IL-17 signaling pathways. CONCLUSIONS: We elucidated the chemical constituents and the pharmacological mechanism of JLZP in treating BRG and provided a basis for clinical application.
Assuntos
Refluxo Biliar , Medicamentos de Ervas Chinesas , Gastrite , Animais , Ratos , Gastrinas , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Farmacologia em Rede , Pós , Gastrite/tratamento farmacológico , Fator de Necrose Tumoral alfa , FosfatidilinositóisRESUMO
One candidate preparation of human sequence recombinant transforming growth factor-ß3 (TGF-ß3) was formulated and lyophilized at NIBSC prior to evaluation in a collaborative study for its suitability to serve as an international standard. The preparation was tested by 8 laboratories using in vitro bioassays and immunoassays. The candidate preparation 09/234 was judged suitable to serve as an international standard based on the data obtained for biological activity and stability. On the basis of the results reported here, the preparation coded 09/234 was established by the WHO Expert Committee on Biological Standardisation (ECBS) as the WHO 1st IS for human TGF-ß3 with an assigned value for TGF-ß3 activity of 19,000 IU/ampoule.
Assuntos
Fator de Crescimento Transformador beta3/normas , Bioensaio/métodos , Bioensaio/normas , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Padrões de ReferênciaRESUMO
The central feature of drug addiction is compulsive drug use--loss of control over apparently voluntary acts of drug seeking and drug taking. Drug addiction, as a chronic brain disease, may result from abnormal engagement of long-term associative memory. Addiction and memory are likely to share much in common in the aspects of neural adaptations, synaptic plasticity, and related molecular mechanisms. This paper reviews the possible roles of learning mechanisms in the development of relapse, sensitization, and drug addiction, abnormal associative learning and compulsive behavior, addiction memory and addiction, multiple memory systems and the development of addiction, and emphasize the importance of synaptic plasticity and addiction memory in drug addiction. Addiction is characterized by the involvement of specific learning patterns of information. Addiction is closely related to the disorder of associate learning that depends on dopamine. Hippocampus may play a key role in addiction. At last, we put forward the future directions for research.