Abstract
Objective The paper studied the effects of Rhynchophylline on the leptin-mediated JAK2/STAT3 pathway in hypothalamus. Using the leptin / leptin receptor and leptin-mediated JAK2/STAT3 pathway as an entry point, the research evaluated the effect of the hypotensive drug, and clarified the preliminary mechanism, expecting to provide new therapeutic ideas for essentially improving obese hypertension, balancing the body's neuro-endocrine function, and preventing the occurrence of cardiovascular diseases. Methods: A model of obese hypertensive rats was established, and the serum lipids, Lep, AngII, NPY and NO contents in each group of rats were measured. Immunohistochemical staining was used to observe the distribution of leptin receptor (LepR) and angiotensin II type 1 receptor (AT1R) in hypothalamus and aorta of rats. Western Blot method was employed to detect JAK2, STAT3, SOCS3, LepR and AT1R protein expressions in the hypothalamus of rats. After the third ventricle injection of AG490, Western blot was applied to detect the expressions of various proteins. Results: Rhynchophylline can significantly reduce AngII, Lep, and NPY levels in serum circulation. Immunohistochemistry showed that the hypothalamus and aorta AT1R distribution was significantly reduced, the hypothalamic LepR distribution increased, and the aortic LepR distribution decreased. The expressions of JAK2, LepR, and STAT3 proteins in the hypothalamus increased significantly, and the expressions of SOCS3 and AT1R proteins significantly decreased. After injection of AG490 in the third ventricle of Rhynchophylline rats, the expressions of JAK2 and STAT3 in the hypothalamus decreased significantly, while the SOCS3expression increased remarkably. Conclusion: Rhynchophylline can reduce blood lipid, as well as serum AngII, Lep, and NPY levels, increase serum NO levels in obese hypertension rats. Rhynchophylline can effectively inhibit the expression of SOCS3 by activating the JAK2/STAT3 pathway in the hypothalamus. Therefore, it is speculated that the JAK2/STAT3 signaling pathway is the main pathway through which Rhynchophylline plays a role in improving selective leptin resistance and reducing blood pressure and weight.
Highlights
Obese hypertension, known as obesity-related hypertension, refers to a disease in which obesity and hypertension coexist
Leptin secreted by adipose tissue plays an indispensable role in regulating appetite and energy metabolism
The weight and blood pressure which exceeded the average of the control group by 25% were used as the criterion for the successful establishment of the “obese hypertension rat model” [3], and rats that met the criteria were selected for the model group
Summary
Known as obesity-related hypertension, refers to a disease in which obesity and hypertension coexist. As an independent risk factor for essential hypertension, obesity features a strong synergistic effect with hypertension. The nature of obesity is a food/energy imbalance (DeMarco et al, 2014). Leptin secreted by adipose tissue plays an indispensable role in regulating appetite and energy metabolism. After binding to specific transport proteins, leptin crosses the blood-brain barrier and binds to long leptin receptors in the ventral medial, lateral, and arcuate nucleus of the hypothalamus, transferring the energy storage of adipose tissue to the hypothalamus. The hypothalamus regulates feeding behavior, energy metabolism, water balance, and weight changes through the feeding and satiety center, and regulates changes in blood pressure through the hypothalamus-adrenocortical axis (HPA), sympathetic-adrenal medulla system (SAM), and hypothalamus-pituitary-thyroid Axis (HPT) (Simonds et al, 2014; Fellmann et al, 2013)
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