RESUMEN
BACKGROUND: The 6-Gingerol has significant anti-inflammatory, anti-oxidative and hypolipidemic activities and is widely used for treating cardiac-cerebral vascular diseases. However, the multi-target mechanism of 6-Gingerol in the treatment of atherosclerosis remains to be elucidated. METHODS: Firstly, the therapeutic actions of 6-Gingerol anti-atherosclerosis were researched based on an atherosclerotic ApoE-deficient mice model induced by high-fat feed. Then, network pharmacology and molecular docking were employed to reveal the anti-atherogenic mechanism of 6-Gingerol. Finally, the target for these predictions was validated by target protein expression assay in vitro and in vivo experiments and further correlation analysis. RESULTS: Firstly, 6-Gingerol possessed obvious anti-atherogenic activity, which was manifested by a significant reduction in the plaque area, decrease in the atherosclerosis index and vulnerability index. Secondly, based on network pharmacology, 14 predicted intersection target genes between the targets of 6-Gingerol and atherogenic-related targets were identified. The key core targets of 6-Gingerol anti-atherosclerosis were found to be TP53, RELA, BAX, BCL2, and CASP3. Lipid and atherosclerosis pathways might play a critical role in 6-Gingerol anti-atherosclerosis. Molecular docking results also further revealed that the 6-Gingerol bound well and stable to key core targets from network pharmacological predictions. Then, the experimental results in vivo and in vitro verified that the up-regulation of TP53, RELA, BAX, CASP3, and down-regulation of BCL2 from atherosclerotic ApoE-deficient mice model can be improved by 6-Gingerol intervention. Meanwhile, the correlation analysis further confirmed that 6-Gingerol anti-atherosclerosis was closely related to these targets. CONCLUSION: The 6-Gingerol can markedly improve atherosclerosis by modulating key multi-targets TP53, RELA, BAX, CASP3, and BCL2 in lipid and atherosclerosis pathways. These novel findings shed light on the anti-atherosclerosis mechanism of 6-Gingerol from the perspective of multiple targets and pathways.
Asunto(s)
Aterosclerosis , Medicamentos Herbarios Chinos , Animales , Ratones , Simulación del Acoplamiento Molecular , Caspasa 3 , Farmacología en Red , Proteína X Asociada a bcl-2 , Aterosclerosis/tratamiento farmacológico , Alcoholes Grasos/farmacología , Apolipoproteínas E , Modelos Animales de EnfermedadRESUMEN
BACKGROUND Curcumol is a hydrogenated austenitic compound with hemiketal. In this study we evaluated the effects of curcumol on local inflammatory response, cell proliferation, and metastasis in endometriosis, and elucidated the underlying mechanisms. MATERIAL AND METHODS Ectopic endometrial stromal cells were treated with increasing doses of curcumol. The MTT assay was used to assess cell viability. FITC-labeled annexin-V/PI double-staining method and flow cytometry were used to determine cell apoptosis. Cell migration was evaluated using a wound healing assay. ELISA kits were used to detect the levels of TNF-alpha, IL-6, and IL-1ß. Western blot assay was used to examine the phosphorylation degree of JAK2 and STAT3 and the expression of Bax, Bcl2, and caspase-3 proteins. Autologous endometrial transplantation was used to establish a rat model to assess the anti-EMS effect of curcumol in vivo. RESULTS Curcumol can inhibit the proliferation of ectopic endometrial stromal cells, promote cell apoptosis, and weaken cell migration ability. Curcumol can reduce the expression of Bax and caspase-3 protein and increase the expression of Bcl2 protein. Curcumol also can inhibit the secretion of inflammatory cytokines, including tumor necrosis cytokines (TNF)-alpha, interleukin (IL)-6, and IL-1ß, by ectopic endometrial stromal cells. In addition, curcumol can also inhibit the phosphorylation of JAK2 and STAT3. In vivo experiments also proved that curcumol could inhibit the growth of ectopic lesions in EMS model rats. CONCLUSIONS Curcumol can inhibit the JAK2/STAT3 pathway, reduce the inflammatory cytokines secreted by ectopic endometrial stromal cells, inhibit cell proliferation and migration, and reduce the volume of ectopic lesions.
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Apoptosis , ADN/genética , Endometriosis/genética , Janus Quinasa 2/genética , Factor de Transcripción STAT3/genética , Sesquiterpenos/farmacología , Útero/metabolismo , Adulto , Proliferación Celular , Supervivencia Celular , Medicamentos Herbarios Chinos/farmacología , Endometriosis/tratamiento farmacológico , Endometriosis/metabolismo , Femenino , Humanos , Janus Quinasa 2/biosíntesis , Estudios Retrospectivos , Factor de Transcripción STAT3/biosíntesis , Transducción de Señal , Útero/patología , Adulto JovenRESUMEN
In this work, a new strain of Bacillus amyloliquefaciens SY07 isolated from a traditional fermented soybean food was reported to possess remarkable α-glucosidase inhibitor-producing ability. Different culture media were applied for the proliferation of B. amyloliquefaciens SY07, and it was found that fermented okara broth presented the highest α-glucosidase inhibitory activity, while Luria-Bertani medium showed a negative effect. The extract from fermented okara broth acted in a dose-dependent manner to inhibit α-glucosidase activity, with an IC50 value of 0.454 mg/mL, and main inhibitors in the fermentation extract presented a reversible, uncompetitive pattern according to Lineweaver-Burk plots. Moreover, 1-deoxynojirimycin, a recognized α-glucosidase inhibitor, was found in the extract. Results indicated that B. amyloliquefaciens SY07 could utilize okara, a by-product from the soy processing industry, to generate α-glucosidase inhibitors effectively, and be regarded as a novel excellent microbial candidate for safe, economical production of potential functional foods or ingredients with hypoglycemic effect.
Asunto(s)
Bacillus amyloliquefaciens/metabolismo , Fermentación , Glycine max/metabolismo , Inhibidores de Glicósido Hidrolasas/metabolismo , Proteínas de Plantas/metabolismo , Polisacáridos/metabolismo , 1-Desoxinojirimicina/metabolismo , 1-Desoxinojirimicina/farmacología , Reactores Biológicos , Alimentos Funcionales , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Alimentos de Soja/microbiología , Glycine max/microbiología , alfa-Glucosidasas/metabolismoRESUMEN
Long noncoding RNA forkhead box D3 antisense RNA 1 (FOXD3AS1) functions as an oncogenic regulator in several types of cancer, including breast cancer, glioma and cervical cancer. However, the effects and mechanisms underlying FOXD3AS1 in cervical cancer (CC) are not completely understood. The present study aimed to investigate the biological functions and potential molecular mechanisms underlying FOXD3AS1 in CC progression. Reverse transcriptionquantitative PCR was performed to detect FOXD3AS1, microRNA (miR)1283p and LIM domain kinase 1 (LIMK1) expression levels in CC tissues and cells. Immunohistochemical staining and western blotting were conducted to assess LIMK1 protein expression levels in CC tissues and cells, respectively. Cell Counting Kit8 and BrdU assays were used to determine the role of FOXD3AS1 in regulating cell proliferation. CC cell migration and invasion were assessed by performing Transwell assays. Dualluciferase reporter assays were conducted to verify the binding between miR1283p and FOXD3AS1. FOXD3AS1 expression was significantly increased in CC tissues and cell lines compared with adjacent healthy tissues and normal cervical epithelial cells, respectively. High FOXD3AS1 expression was significantly associated with poor differentiation of tumor tissues, increased tumor size and positive lymph node metastasis. FOXD3AS1 overexpression significantly increased CC cell proliferation, migration and invasion compared with the negative control (NC) group, whereas FOXD3AS1 knockdown resulted in the opposite effects compared with the small interfering RNANC group. Moreover, the results demonstrated that FOXD3AS1 targeted and negatively regulated miR1283p, which indirectly upregulated LIMK1 expression. Therefore, the present study demonstrated that FOXD3AS1 upregulated LIMK1 expression via competitively sponging miR1283p in CC cells, promoting CC progression.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Quinasas Lim/genética , MicroARNs/genética , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Movimiento Celular/genética , Proliferación Celular/genética , Cuello del Útero/patología , Cuello del Útero/cirugía , Femenino , Técnicas de Silenciamiento del Gen , Células HeLa , Humanos , Metástasis Linfática , MicroARNs/metabolismo , Persona de Mediana Edad , ARN Largo no Codificante/genética , Regulación hacia Arriba , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
OBJECTIVE: To observe the effect of Bushen Wenyang Huayu Recipe (BWHR) on hypoxia inducible factor-1α (HIF-1α), proline hydroxylase2 (PHD2), von Hippel Lindau disease (VHL) suppressor gene expressions in endometriosis (EM) rats with Shen yang deficiency blood stasis syndrome (SYDBSS), and to explore the pathogenesis of EM and the mechanism of BWHR for treating EM. METHODS: Totally 50 SD rats were randomly divided into five groups, i.e., the blank control group, the sham-operation group, the model group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 10 in each group. Rats in the blank control group and the sham-operation group were fed routinely. Rats in the rest 3 groups received 30-day "extended refrigerator freezing and ice water immersion" and combined with " autotransplantation" to establish EM rat model with SYDBSS. One Milliliter BWHR at 3.33 g/mL was administered to rats in the CM group by gastrogavage. Gestrinone at the daily dose of 0. 5 mg/kg was administered to rats in the WM group by gastrogavage. Equal volume of normal saline was administered to rats in the model group, the blank control group, and the sham-operation group. The size and morphology of ectopic foci in rats were observed after 4 weeks of medication. Expressions of serum CA125, plasma cyclic adenosine monophosphate (cAMP), and plasma cyclic guanosine monophosphate (cGMP) were detected by radioimmunoassay. Morphological changes of eutopic endometrium and ectopic tissue were observed under the optical microscope by HE staining. Protein expressions and contents of HIF-lα, PHD2, and VHL were detected by immunohistochemical SABC method and Western blot. mRNA expressions of HIF-1α, PHD2, and VHL were detected by RT-PCR. RESULTS: The ectopic foci grew significantly in the model group. Their volumes were obviously contracted after treated by CM and WM. Compared with the blank control group and the sham-operation group, serum CA125 and plasma cGMP obviously increased, cAMP obviously decreased (P < 0.05); expressions and contents of HIF-1α mRNA and protein all decreased (P < 0.05); mRNA and protein expressions and contents of PHD2 and VHL all decreased in the model group (P < 0.05). Compared with model group, levels of CA125 and cGMP obviously decreased; cAMP levels obviously increased, expressions and contents of HIF-1α mRNA and protein all increased, mRNA and protein expressions and contents of PHD2 and VHL all increased in the WM group and the CM group (P < 0.05). Compared with the CM group, PHD2 protein contents were higher in the WM group (P < 0.05). HIF-1α was negatively correlated with PHD2 (r = -0.799, P = 0.00). HIF-1α was negatively correlated with VHL (r = -0. 625, P = 0.003). CONCLUSIONS: BWHR could effectively treat EM. Its mechanism might be associated with reducing contents of HIF-1α, serum CA125, and plasma cGMP, and up-regulating expressions of PHD2, VHL, and cAMP.