Magic™ Anti-NGF (aa 74-85-113-124) polyclonal antibody

Objective To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor (NGF) and leukemia inhibitory factor (LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction ((sic)(sic)(sic)) on sympathetic remodeling by inhibiting cholinergic transdifferentiation. Methods SS-13(BN) and Dahl salt-sensitive (DS) rats were divided into 3 groups: SS-13(BN) group (control group, n=9), DS group (model group, n=9) and GS group (Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle. After 4 weeks' intragastric administration, rats were executed to detect the relevant indicators. Echocardiography and plasma n-terminal pro-B type natriuretic peptide (NT-proBNP) levels were used to assess cardiac function. Noradrenaline (NA) levels in the plasma and myocardium were detected to evaluate the sympathetic function. NGF and LIF expression were detected in the myocardium by Western blot or quantitative real-time PCR. Double immunofluorescence or Western blot was used to detect tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) and growth associated protein 43 (GAP43) in order to reflect anatomical and functional changes of sympathetic nerves. Results DS group had anatomical and functional deterioration of sympathetic nerves in the decompensation period of heart failure compared with SS-13(BN) group. Compared with the DS group, Guizhi Decoction significantly decreased the expression of LIF mRNA/protein (P < 0.01), increased the expression of NGF (PP < 0.01), enhanced the levels of TH+/GAP43(+) and TH+/CHAT(+) positive nerve fibers (P < 0.01), and improved the protein expression of TH and GAP43 in left ventricle, but had no effect on CHAT (P > 0.05). Guizhi Decoction inhibited inflammatory infiltration and collagen deposition of myocardial injury, increased the content of myocardial NA (P < 0.05), reduced the plasma NA level (P < 0.01), improved cardiac function ( P < 0.01), and improved weight and blood pressure to some extent ( P < 0.05), compared with DS group. Conclusions Guizhi Decoction could inhibit cholinergic transdifferentiation of sympathetic nerves, improve the anatomical and functional denervation of sympathetic nerves, and delay the progression of decompensated heart failure. The mechanism may be associated with the correction of the imbalance of NGF and LIF.

Background Oxidative stress (OS) plays a vital role in the pathogenesis of cognitive disorders. In this study, brain antioxidant defense dysregulation as a consequence of hyperlipidemia, and the efficacy of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and zerumbone (Z) in their modulation are assessed. Methods and results Male Wistar rats are fed control, high-fat (HF), HF + fish oil (HF+F), HF + zerumbone (HF+Z), and HF + fish oil + zerumbone (HF+F+Z) diet for 60 days. Markers of OS, antioxidant enzymes, monoamine oxidase, nuclear factor (erythroid-derived 2)-like 2 (NRF-2), nitric oxide-2 (NOS-2), inter cellular adhesion molecule-1 (ICAM-1), and neurotrophins are measured. Hyperlipidemia increases OS, decreases antioxidant enzyme activity, increases monoamine oxidase activity, increases NOS-2 and ICAM-1 expression, decreases NRF-2 activation, decreases nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels in the brain compared to control. While EPA+DHA and zerumbone significantly (p< 0.05) restores the perturbations induced by hyperlipidemia. Conclusion It is concluded that hyperlipidemia cause OS by decreasing the activity of brain antioxidant enzymes via the downregulation of NRF-2. The reduced brain neurotrophins in hyperlipidemia indicate its potential risk on cognitive attributes. EPA+DHA, together with zerumbone, positively modulates hyperlipidemia induced brain dysfunction thereby offering promising therapeutic strategy.