RESUMEN
OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
Asunto(s)
Antidepresivos , Medicamentos Herbarios Chinos , Proteínas Quinasas Activadas por AMP/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Adiponectina/metabolismo , Animales , Antidepresivos/farmacología , China , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Glucosa , Hipotálamo/metabolismo , Ratones , Receptores de Adiponectina/metabolismoRESUMEN
OBJECTIVE: High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assessed the anti-NAFLD effect of SLBZP in vivo. METHODS: Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array. RESULTS: SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues. CONCLUSION: SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1ß release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Hígado , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Polvos , Ratas , Receptor Toll-Like 4 , Microtomografía por Rayos XRESUMEN
To systematically evaluate the efficacy of traditional Chinese medicine(TCM) compounds combined with levodopa medicine in the treatment of Parkinson's disease(PD), and screen basic herbs to provide certain evidence-based medical proof and program for better guidance on clinical drug use. Six databases were searched to screen out the randomized controlled trial on the TCM compounds combined with levodopa medicine in the treatment of PD. Literature quality of the included studies was evaluated by improved Jadad rating scale, and the Meta-analysis was performed by RevMan 5.3 software. After the data of the basic TCM compounds involved were sorted out, the strong association rules were found by using Apriori algorithm of SPSS Modeler 18.0 software, and then the basic herbs for the treatment of PD could be picked out. A total of 20 studies were eventually included, involving 1 784 patients. Ten studies were of high-quality literature, Jadad score≥4 points. Meta-analysis showed that efficacy of TCM combined with levodopa medicine was better than levodopa medicine alone in lowering Unified Parkinson's Disease Rating Scale(UPDRS) score: UPDRS â (MD=-0.43, 95%CI[-0.62,-0.24], P<0.000 1), UPDRS â ¡(MD=-2.72, 95%CI[-3.24,-2.21], P<0.000 01), UPDRS â ¢(MD =-1.97, 95%CI[-2.69,-1.25], P<0.000 01), UPDRS â £(MD=-0.28, 95%CI[-0.46,-0.11], P=0.002). And the improvement in UPDRS score reduction rate of TCM combined with levodopa medicine was better than that in levodopa medicine alone: effective rate(OR=4.81, 95%CI[3.50, 6.62], P<0.000 01). Data mining results showed that the basic prescription for treating PD consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Gastrodiae Rhizoma in general. According to each part of UPDRS, the basic prescription for treating mentation, behavior and mood(UPDRS â ) consists of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Among which Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle might have unique efficacy. The basic prescriptions for treating UPDRS â ¡ and UPDRS â ¢ consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata, or Chuanxiong Rhizoma-Angelicae Sinensis Radix(two drug combinations). However, in the treatment of UPDRS â £, the drugs were scattered. But due to the limitations in the quantity and quality of clinical studies, the results obtained still need further research and clinical confirmation of its efficacy.