Atherosclerosis is a pathological condition of the accumulation of fat in the arteries, leading to cardiovascular disorders. Atherosclerosis management remains a challenge and conventional medicines are used for the management of the company has several limitations. This study evaluated the effects of tabersonine protection against atherosclerosis and rated the molecular mechanisms of action.Atherosclerosis induced by feeding the apolipoprotein E (ApoE) -deficient mice a high-fat diet. Mice treated with 20 or 40 mg / kg intraperitoneally tabersonine for 12 weeks of the study. Atherosclerosis markers and nitric oxide are measured in the serum of ApoE-deficient mice. Inflammatory mediators and markers of oxidative stress were assessed using enzyme-linked immunosorbent assay tests.
Western blotting, reverse transcriptase quantitative polymerase chain reaction and immunohistochemistry analyzes were performed to determine the expression of proteins in tissue.The tabersonine-treatment group aorta had improved lipid profile and liver function improved, compared with the group treated ApoE. tabersonine treatment resulted in decreased levels of nitric oxide, cytokines, and oxidative stress, compared with ApoE.
Change expression levels of protein inhibitor activated Stat3 (PIAS3), signal transducer and activator of transcription-3 (STAT-3), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα) in ApoE mice -deficient tabersonine are helped by treatment. In addition, cAMP-response-element-binding (CREB) expression increased in aortic tissue tabersonine treatment group, compared with ApoE group.These results suggest tabersonine which ameliorates expression of Stat3 by activating CREB protein in atherosclerotic ApoE-deficient mice.
Activation of CREB Protein With Tabersonine Attenuates STAT3 During Atherosclerosis in Apolipoprotein E-Deficient Mice.
Dimethyl fumarate relieve nitroglycerin (NTG) -induced migraine in rats.
Oxidative stress and inflammatory pathways involved in migraine and endogenous antioxidant defense system have a role in hyperalgesia in migraine prevention. In this study, we aimed to evaluate the role of the molecules of the most pharmacologically effective between the ester of fumaric acid (FAEs), fumaric dimethyl, nuclear factor E2-related factor 2 / response element antioxidants (NRF-2 / ARE) pathway-mediated, in regulating hypersensitivity in a mouse model of nitroglycerin (NTG) -induced migraine.Mice administered orally with DMF at a dose of 10, 30, and 100 mg / kg, 5 minutes after intraperitoneal injection of NTG.
We did histological and molecular analysis throughout the brain and behavioral tests after 4 hours with NTG-induced migraine. The expression of nuclear factor kappa-light-chain-enhancer activated B cells (NF-кB) subunit p65, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), nitric oxide synthase (iNOS), cyclooxygenase 2 (COX- 2), NRF-2, manganese superoxide dismutase (Mn-SOD), and heme oxygenase – 1 (HO-1) was detected by Western blot.
The tail of the film, hot plate, orofacial formalin, and photophobia tests used to evaluate migraine-like pain and light sensitivity associated with migraine. In addition, we evaluated the NRF-2-dependent mechanism in vitro stimulation of the trigeminal ganglia cells extracted by dietilenatriamina / nitric oxide (DETA / NO), nitric oxide (NO) donor. Cells pre-treated with DMF and antagonists of NRF-2, trigonelline (TR) 2 hours before treatment DETA / NO stimulation.DMF particularly reducing histological damage as shown by cresyl violet staining; Also, set both NF-kB and NRF-2 pathway, DMF treatment reduce the severity of inflammation and boost protective antioxidant action
