RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica Sinensis Radix (ASR) is a commonly used Chinese medicine known for its effects on tonifying blood, promoting blood circulation, and alleviating pain associated with menstrual regulation. Additionally, it has been used in the treatment of vascular cognitive impairment (VCI). The primary pharmacodynamic agent within ASR is volatile oil of Angelica Sinensis Radix (VOASR), which has demonstrated efficacy in combating cognitive impairment, although its mechanism remains unclear. OBJECTIVE: This study aimed to elucidate the potential molecular mechanisms underlying VOASR's improvement of cognitive function in cerebral ischemic mice. METHODS: A model of cerebral ischemic mice was established through unilateral common carotid artery occlusion (UCCAO) surgery, followed by intervention with VOASR. Cognitive function was assessed using the Morris water maze (MWM) test, while RT-qPCR was utilized to measure the differential expression of miR-301a-3p in the hippocampus. To evaluate cognitive function and hippocampal protein differences, wild-type mice and miR-301a-3p knockout mice were subjected to the MWM test and iTRAQ protein profiling. The relationship between miR-301a-3p and potential target genes was validated through a Dual-Luciferase Reporter experiment. RT-qPCR and Western blot were employed to determine the differential expression of Ppp2ca and synaptic plasticity-related proteins in the mouse hippocampus. RESULTS: Intervention with VOASR significantly improved cognitive impairment in cerebral ischemic mice and reduced the expression of miR-301a-3p in the hippocampus. Our findings suggest that miR-301a-3p may regulate cognitive function by targeting Ppp2ca. Furthermore, VOASR intervention led to an increase in the expression of Ppp2ca and synaptic plasticity-related proteins. CONCLUSION: Our study indicates that VOASR may be involved in regulating cognitive function by inhibiting miR-301a-3p, consequently increasing the expression of Ppp2ca and synaptic plasticity proteins. These results provide a new target and direction for the treatment of cognitive dysfunction.
Asunto(s)
Angelica sinensis , Isquemia Encefálica , MicroARNs , Aceites Volátiles , Ratones , Animales , MicroARNs/genética , MicroARNs/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/genética , CogniciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Spleen-invigorating pills (SIP) are composed of Codonopsis, fried Atractylodes, tangerine peel, Fructus aurantii immaturus (fried), fried hawthorn, and colored malt. SIP strengthens the spleen and increases appetite and is often used as a chemotherapy adjuvant. AIM OF THE STUDY: We aimed to explore the protective effects and mechanism of action for SIP on mouse bone marrow stromal cells (OP9) injured by 5-fluorouracil (5-FU). MATERIALS AND METHODS: The effects of SIP on OP9 cells injured by 5-FU were evaluated, and high-performance liquid chromatography (HPLC) was used as a quality control method. The experiments were divided into a control group, a model group, an epidermal growth factor (EGF) treatment group, and an SIP treatment group. The cell survival rate, apoptotic cell morphology, cell apoptosis rate, and the contents of caspase 3 were evaluated to determine the protective effects of SIP in OP9 cells injured by 5-FU. Network pharmacology was used to predict the mechanism through which SIP mediates anti-chemotherapy damage. The nitric oxide (NO) and nitric oxide synthase (iNOS) levels and the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) and p62 protein were detected to explore the mechanism through which SIP mediates anti-chemotherapy damage through the regulation of oxidative stress. RESULTS: Cell counting kit-8 (CCK8) detection showed that 5-FU reduced OP9 cell survival, and SIP blocked the inhibition of OP9 cell growth induced by 5-FU. When OP9 cells were treated with both SIP (10 g L-1) and 5-FU (2.5 × 10-2 g L-1) for 24 h, compared with the model group, the early apoptosis rates significantly decreased, and the activity of caspase 3 was significantly reduced. The results of network pharmacology and Western blot showed that compared with the model group, in the SIP group, the NO levels decreased, iNOS release decreased, and the expression of Nrf2 and p62 proteins increased. CONCLUSION: The protective effects of SIP on OP9 cells injured by 5-FU were significant. SIP may play a cytoprotective role by mediating changes in oxidative stress-related proteins. The specific mechanism of action through which SIP mediates these effects remains to be further studied.
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Medicamentos Herbarios Chinos/farmacología , Fluorouracilo/toxicidad , Células Madre Mesenquimatosas/efectos de los fármacos , Bazo/efectos de los fármacos , Animales , Antimetabolitos Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Células Madre Mesenquimatosas/patología , Ratones , Farmacología en Red , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Bazo/citología , Bazo/patologíaRESUMEN
We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3ß(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.
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Apoptosis/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/tratamiento farmacológico , Sitoesteroles/farmacología , Animales , Encéfalo/citología , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Glucosa/metabolismo , Glucógeno Sintasa Quinasa 3/biosíntesis , Glucógeno Sintasa Quinasa 3 beta , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/biosíntesis , Oxígeno/metabolismo , Podofilotoxina/análogos & derivados , Podofilotoxina/farmacología , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores de Somatomedina/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
PURPOSE: the study aimed to compare the quality of life (QOL) and radiotherapy complications among Chinese nasopharyngeal carcinoma (NPC) patients at different 3-dimensional conformal radiotherapy (3DCRT) stages adjusting for other variables. METHODS: 511 NPC patients at different 3DCRT stages were enrolled. They were interviewed regarding SF-36, complications and socio-demographic variables and cancer- or treatment- related variables. Analysis of covariance (ANCOVA) based on SF-36, complications scores as dependent variables, 3DCRT stages as independent variables, and other variables as covariate were established. RESULTS: The influencing factors of PCS included 3DCRT stages and age group. The influencing factors of MCS included 3DCRT stages and income. Most QOL scores of NPC patients were significantly associated with 3DCRT stage, after accounting for other variables. QOL scores of the patients receiving 3DCRT were the lowest, QOL scores of people after 3DCRT gradually increased. PCS scores of people greater than 5 years after 3DCRT was improved to or even better than the level before 3DCRT. The complications with significantly different scores of patients at different 3DCRT status included xerostomia, throat ache, hypogeusia, caries, hearing loss, snuffles. CONCLUSIONS: Clinicians should pay more attention to older NPC patients and patients with lower income. When patients receive 3DCRT, measures should be taken to reduce radiation injury to improve the patients' QOL.
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Imagenología Tridimensional , Neoplasias Nasofaríngeas/radioterapia , Calidad de Vida , Traumatismos por Radiación/etiología , Radioterapia Conformacional/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Pronóstico , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
Three compounds were isolated from Citrus medica L. var. sarcodactylis (Noot) Swingle. The structures were identified as limettin(I), stigmasta-5, 22-dien-3-ol(II) and palmilic acid(III) on the basis of UV, MS, IR, 1HNMR, 13CNMR and DEPT.