RESUMO
BACKGROUND: Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients. METHODS: This study is a multi-centre, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants are assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline (before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks. DISCUSSION: The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN12746343. Registered on September 25, 2020.
Assuntos
Depressão , Medicamentos de Ervas Chinesas , Depressão/diagnóstico , Depressão/tratamento farmacológico , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Medicina Tradicional Chinesa , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Background: Depression is a stress-related disorder that seriously threatens people's physical and mental health. Xiaoyaosan is a classical traditional Chinese medicine formula, which has been used to treat mental depression since ancient times. More and more notice has been given to the relationship between the occurrence of necroptosis and the pathogenesis of mental disorders. Objective: The purpose of present study is to explore the potential mechanism of Xiaoyaosan for the treatment of depression using network pharmacology and experimental research, and identify the potential targets of necroptosis underlying the antidepressant mechanism of Xiaoyaosan. Methods: The mice model of depression was induced by chronic unpredictable mild stress (CUMS) for 6 weeks. Adult C57BL/6 mice were randomly divided into five groups, including control group, chronic unpredictable mild stress group, Xiaoyaosan treatment group, necrostatin-1 (Nec-1) group and solvent group. Drug intervention performed from 4th to 6th week of modeling. The mice in Xiaoyaosan treatment group received Xiaoyaosan by intragastric administration (0.254 g/kg/d), and mice in CUMS group received 0.5 ml physiological saline. Meanwhile, the mice in Nec-1 group were injected intraperitoneally (i.p.) with Nec-1 (10 mg/kg/d), and the equivalent volume of DMSO/PBS (8.3%) was injected into solvent group mice. The behavior tests such as sucrose preference test, forced swimming test and novelty-suppressed feeding test were measured to evaluate depressive-like behaviors of model mice. Then, the active ingredients in Xiaoyaosan and the related targets of depression and necroptosis were compiled through appropriate databases, while the "botanical drugs-active ingredients-target genes" network was constructed by network pharmacology analysis. The expressions of RIPK1, RIPK3, MLKL, p-MLKL were detected as critical target genes of necroptosis and the potential therapeutic target compounds of Xiaoyaosan. Furthermore, the levels of neuroinflammation and microglial activation of hippocampus were measured by detecting the expressions of IL-1ß, Lipocalin-2 and IBA1, and the hematoxylin and eosin (H&E) stained was used to observe the morphology in hippocampus sections. Results: After 6-weeks of modeling, the behavioral data showed that mice in CUMS group and solvent group had obvious depressive-like behaviors, and the medication of Xiaoyaosan or Nec-1 could improve these behavioral changes. A total of 96 active ingredients in Xiaoyaosan which could regulate the 23 key target genes were selected from databases. Xiaoyaosan could alleviate the core target genes in necroptosis and improve the hippocampal function and neuroinflammation in depressed mice. Conclusion: The activation of necroptosis existed in the hippocampus of CUMS-induced mice, which was closely related to the pathogenesis of depression. The antidepressant mechanism of Xiaoyaosan included the regulation of multiple targets in necroptosis. It also suggested that necroptosis could be a new potential target for the treatment of depression.
RESUMO
Five new isoprenylated flavones, artochamins A-E (1-5), together with eight known flavones (6-13), were isolated from the roots of Artocarpus chama. All structures were elucidated by spectroscopic methods. Artonin E (12) showed strong cytotoxicity against 1A9 (ovarian), significant activity against MCF-7 (breast adenocarcinoma), and moderate activity against HCT-8 (ileocecal) and MDA-MB-231 (breast adenocarcinoma) tumor cell lines. Artochamin C (3) was more potent against MCF-7, 1A9, HCT-8, and SK-MEL-2 (melanoma) than A549 (lung carcinoma), KB (epidermoid carcinoma of the nasopharynx), and its drug-resistant (KB-VIN) variant. Artocarpin (6) displayed weak but relatively broad inhibitory effects compared with 3 and 12.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Artocarpus/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Flavonoides/isolamento & purificação , Plantas Medicinais/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Humanos , Estrutura Molecular , Raízes de Plantas/química , Células Tumorais CultivadasRESUMO
Sixteen flavonoids and their derivatives isolated from Desmos spp. were evaluated for inhibition of HIV replication in H9 lymphocyte cells. 2-Methoxy-3-methyl-4,6-dihydroxy-5-(3'-hydroxy)cinnamoylbenzaldehyde (12) and lawinal (6) demonstrated potent anti-HIV activity with EC(50) values of 0.022 and 2.30 microg/mL and therapeutic indexes of 489 and 45.2, respectively. Compound 12 appears to be an excellent lead for further anti-HIV drug development.