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This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, ß-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.
Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol , Perimenopausa , Feminino , Animais , Ratos , Ratos Sprague-Dawley , Microcirculação , Pós , Citocromo P-450 CYP1A1RESUMO
Choroidal melanoma is a devastating disease that causes visual loss and a high mortality rate due to metastasis. Luteolin, a potential anticancer compound, is widely found in natural plants. The aim of this study was to evaluate the antiproliferative, antiadhesive, antimigratory and anti-invasive effects of luteolin on choroidal melanoma cells in vitro and to explore its potential mechanism. Cell counting kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) assays, Cell adhesion, migration, and invasion assays were performed to examine the inhibitory effects of luteolin on cell cell viability, proliferation, adhesion, migration and invasion capacities, respectively. Considering the correlation between Matrix metalloenzymes and tumor metastasis, Enzyme-linked immunosorbent assays (ELISAs) were used to assess matrix metalloproteases MMP-2 and MMP-9 secretion. Western blotting was performed to detect p-PI3K P85, Akt, and p-Akt protein expression. The cytoskeletal proteins vimentin were observed with cell immunofluorescence staining. Luteolin can inhibit OCM-1â¯cell proliferation, migration, invasion and adhesion and C918â¯cell proliferation, migration, and invasion through the PI3K/Akt signaling pathway. Therefore, Luteolin may have potential as a therapeutic medication for Choroidal melanoma.
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Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias da Coroide/tratamento farmacológico , Luteolina/uso terapêutico , Melanoma/tratamento farmacológico , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Neoplasias da Coroide/enzimologia , Neoplasias da Coroide/patologia , Ensaio de Imunoadsorção Enzimática , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Melanoma/enzimologia , Melanoma/patologia , Microscopia de Fluorescência , Invasividade Neoplásica/prevenção & controle , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Vimentina/metabolismoRESUMO
BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease with a poor prognosis and a mortality rate of up to 55%. Currently, there is no standard treatment for CCS. The department of gastroenterology of our hospital admitted a patient with CCS whose symptoms improved significantly after treatment with thalidomide combined with endoscopy, and there was no obvious adverse reaction during the 2-year follow-up. CASE SUMMARY: A 47-year-old Chinese man presented with diarrhea for more than 4 mo, accompanied by loss of taste, fatigue, and weight loss. Physical examination demonstrated that the patient's skin and hands were hyperpigmented, the front edges of the nails of both hands were notably thickened and yellow, and the nails were partially atrophied. Gastrointestinal endoscopy identified a diffuse polypoid bulge, and the patient bore an albumin level of 27.3 g/L. The level of the calcium correction amount was (2.164 mM) which allowed for a comprehensive diagnosis of Cronkhite-Canada syndrome, combined with hypoalbuminemia and hypocalcemia. Thalidomide of 150 mg per day was administered to regulate immunity, and the symptoms were relieved after 1 wk. During the follow-up period, polyps were still found that had not been resolved by thalidomide treatment, and endoscopic therapy was performed. This resulted in further improvement of his condition and no particular discomfort during the 2 years of follow-up. CONCLUSION: The patient's symptoms were significantly relieved by thalidomide 2 years after treatment, proposing it as a potential treatment for CCS.
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Sub-health status, in which a person's mind and body exist in a low-quality state of being between disease and health, has become an urgent public health problem that cannot be ignored globally. One of the most apparent sub-health symptoms is fatigue, and it also shows a significant decrease in mental vitality and adaptability caused by disruption of the neuroendocrine-immune system. Dendrobium officinale (DOF) has a long history of use in China as a medicinal food with immune-regulating, anti-fatigue, anti-oxidant, and hypoglycemic effects. The ameliorative effects of Dendrobium officinale on sub-health mice are investigated in this present study, as well as its underlying mechanisms via neuroendocrine-immune (NEI) modulation. Forty male KM mice were divided into normal control group (NC), model control group (MC), and two doses of ultrafine DOF powder (DOFP) intervention groups: DOFP-L (0.1 g kg-1), DOFP-H (0.2 g kg-1) groups. Sub-health mice were induced by mimicking unhealthy human lifestyles, including cold water swimming, limbs restriction, an unhealthy diet, and sleep deprivation for seven weeks. The findings revealed that DOFP intervened sub-health mice have less bodyweight loss, normal fecal morphology, as well as lower face temperature and blood flow, which is similar to the normal mice. Moreover, sub-health mice treated with DOFP showed improved forelimb grip strength and exercise endurance in weight-loaded exhaustion swimming and cold water exhaustion swimming, combined with reduced content of lactic acid (LD), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) in the plasma, increased storage of liver glycogen (LG), and muscle glycogen (MG), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduced malondialdehyde (MDA) levels in the liver. Additionally, DOFP could increase the counts of autonomous movements of sub-health mice, minimize tail suspension time, and perform well in the elevated plus maze and open field tests, all of which are associated with anti-depression and anti-anxiety. Moreover, mechanistic investigations revealed that DOFP could alleviate plasma corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) related hormones in the HPA axis, increase the level of hypothalamic norepinephrine (NE) and plasma ß-endorphin (ß-EP) of sub-health mice, while downregulating the content of 5-hydroxytryptamine (5-HT), dopamine (DA), and the relative mRNA expression of 5-HT1A and CRH in hypothalamus, and increase immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and CD4+/CD8+ T cell ratio levels. In conclusion, DOFP can relieve symptoms such as fatigue and depression in sub-health mice by regulating the disorder of the neuroendocrine-immune network.
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Dendrobium , Camundongos , Humanos , Masculino , Animais , Pós , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Sistema Imunitário , Estilo de Vida , ÁguaRESUMO
AIM: To investigate the effects of luteolin on apoptosis, the cell cycle, and the expression and secretion of vascular endothelial growth factor (VEGF) in human choroidal melanoma cells (C918 and OCM-1). METHODS: C918 and OCM-1 cells cultured in vitro were treated with various concentrations of luteolin (0, 5, 10, 15 µmol/L). Cell growth was observed with an inverted microscope, and cell cycle arrest was detected by propidium iodide (PI) staining using flow cytometry. Apoptosis was detected by Hoechst33342 staining, and apoptosis rate was determined by Annexin V-FITC/PI experiments using flow cytometry. The expression of apoptosis-related proteins Bcl-2, Bax and VEGF was analyzed using Western blots. The levels of VEGF secreted by the cells into the supernatant was analyzed using ELISA. RESULTS: After treating with 5 to 15 µmol/L luteolin for 48h, the fusion degree of C918 and OCM-1 cells decreased, and more floating apoptotic cells appeared. Luteolin treatment increased the G0-G1 phase ratio of the C918 and OCM-1 cells, blocked cell cycle progression, and increased the apoptosis rate of the C918 and OCM-1 cells. Western blot showed that luteolin decreased the expression of Bcl-2 and VEGF in the C918 and OCM-1 cells and increased the expression of Bax protein. The ELISA results showed that 10 to 15 µmol/L luteolin decreased the cell secretion of VEGF. CONCLUSION: Luteolin may induce apoptosis by regulating the levels of apoptosis-related proteins in C918 and OCM-1 cells. Luteolin can induce cell cycle arrest, decrease the expression of VEGF.
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As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from Chrysanthemum indicum L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich Chrysanthemum indicum L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKß, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.
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BACKGROUND/AIMS: Previous studies have found that the injection of rat bone marrow mesenchymal stem cells (rBMSCs) in a mouse model of acute hepatic failure significantly relieves intestinal damage and endotoxemia. However, the mechanism of this process remains unknown. This study demonstrated the differentiation of rBMSCs into enterocyte-like cells and possible molecular mechanisms for this with the aim of finding a new treatment for intestinal epithelial injury and endotoxemia during liver failure. MATERIALS AND METHODS: rBMSCs were isolated from rat femurs and tibias. Differentiation was induced by co-culturing rBMSCs with rat intestinal epithelial cells (mIEC-6) using Transwell plates; after three, seven, and ten days of induction, expression of specific differentiation molecules were quantified. To inhibit the activity of the Mitogen-activated protein kinase 1/2 (ERK1/2) signaling pathway, an inhibitor of Mitogen-activated protein kinase kinase 1/2 (MEK1/2) was added to the co-culture medium, and western blot analysis was performed after 36 or 72 h to evaluate the expression of ERK1/2 signaling pathway markers (p-MEK1/2 and p-ERK1/2). RESULTS: The rBMSCs differentiated into enterocyte-like cells when co-cultured with mIEC-6 cells. Inhibition of ERK1/2 signaling abrogated the activity of MEK1/2, but MEK increased after 72 h, and the epithelioid differentiation of rBMSCs was consistent with the change in MEK expression. CONCLUSION: rBMSCs differentiate into intestinal epithelium after co-culture with mIEC-6 by regulation of the ERK1/2 signaling pathway. Further research is needed to elucidate the network of mechanisms.