IntRoductIonHypertension (HTN) is a significant risk factor for various cardiovascular disorders; stroke and millions of people worldwide suffer from the disease resulting in significant morbidity, mortality, and financial burden globally. [1][2][3] In 90%-95% of cases, the high blood pressure is due to nonspecific lifestyle and genetic factors. [4,5] Myocardial ischemia develops when the coronary blood supply to the myocardium is reduced either in terms of absolute flow rate (low-flow or no-flow ischemia) or relative to increased tissue demand (demand ischemia). [6] While reperfusion is necessary for tissue survival and it is worth noting that reperfusion itself can also cause tissue damage termed as reperfusion injury. [7] Reperfusion injury results in myocyte damage through myocardial stunning, microvascular and endothelial injury, and irreversible cell damage or necrosis termed lethal ischemia-reperfusion (I/R) injury. [8] This usually occurs in cardiomyocytes that not only have been severely injured by ischemia but also may develop in reversibly injured myocytes. [9] Ischemic preconditioning (IPC) is defined as Aim: To investigate the myocardial preconditioning potential of hedgehog activator smoothened (SMO) receptor agonist purmorphamine (PUR) against ischemia-reperfusion (I/R) injury in deoxycortisone acetate (DOCA) salt-induced hypertensive rat heart. Methods: Hypertension in rats was produced by surgical removal of the kidney and DOCA salt administration for 6 weeks. Isolated rat heart was subjected to 30 min ischemia followed by 120 min of I/R. The heart was subjected to pharmacological preconditioning with the hedgehog (Hh) activator PUR (1 µM), PUR (2 µM), and atractyloside (4 µM), an mPTP opener, in the last episode of reperfusion before I/R. Elevated blood pressure was evaluated through tail-cuff method. Myocardial infarction was assessed in terms of the increase in lactate dehydrogenase, creatinine kinase-muscle/brain, and infarct size through triphenyltetrazolium chloride staining. Further, there were a decrease in the release of nitrite and coronary flow rate. Immunohistochemistry was performed for the assessment of tumor necrosis factor-α level in cardiac tissue. Results: Pharmacological preconditioning with PUR significantly attenuated I/R-induced myocardial infarction. However, atractyloside limits the ameliorative preconditioning potential of PUR and confirmed the role of Hh pathway in ischemic preconditioning. Conclusion: It may be concluded that the Hh activator PUR (SMO receptor agonist) prevents I/R injury in DOCA salt-induced hypertensive rat heart.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra. The pathogenesis of PD, including oxidative stress, mitochondrial dysfunction, neuroin ammation, and neurotransmitter dysregulation. L-theanine is an amino acid found in green tea and has antioxidant, anti-in ammatory, and neuroprotective effects with a high BBB permeability.Therefore, the current study was designed to investigate the possible neuroprotective effect of L-theanine in lipopolysaccharide (LPS) induced motor de cits and striatal neurotoxicity in a rat model of PD. LPS was infused at a dose of 5 µg/5 µl PBS, stereotaxically into SNpc of rats. Treatment with L-theanine at (50 and 100 mg/kg; po), and Sinemet (36 mg/kg; po) was given from day 7 to 21 in of LPS injected rat.On a weekly basis all behavioral parameters were assessed, and animals were sacri ced on day 22. The striatum tissue of brain was isolated for biochemicals (Nitrite, GSH, catalase, SOD, mitochondrial complexes I and IV), neuroin ammatory markers (IL-1β, TNF-α, and IL-6), and neurotransmitters (serotonin, dopamine, norepinephrine, GABA, and glutamate) estimations. Results revealed that Ltheanine dose-dependently and signi cantly reversed motor de cits, assessed through locomotor and rotarod activity. Moreover, L-theanine attenuated biochemical markers, reduced oxidative stress, and neurotransmitters dysbalance in the brain. L-theanine treatment at 100 mg/kg; po substantially reduced these pathogenic events by increasing mitochondrial activity, restoring neurotransmitter levels, and inhibiting neuroin ammation. Moreover, data suggest that the positive effects of L-theanine on motor coordination may be mediated by the suppression of nuclear factor-κB (NF-κB) induced by LPS.
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra. The pathogenesis of PD, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and neurotransmitter dysregulation. L-theanine is an amino acid found in green tea and has antioxidant, anti-inflammatory, and neuroprotective effects with a high BBB permeability. Therefore, the current study was designed to investigate the possible neuroprotective effect of L-theanine in lipopolysaccharide (LPS) induced motor deficits and striatal neurotoxicity in a rat model of PD. LPS was infused at a dose of 5 µg/5 µl PBS, stereotaxically into SNpc of rats. Treatment with L-theanine at (50 and 100 mg/kg; po), and Sinemet (36 mg/kg; po) was given from day 7 to 21 in of LPS injected rat. On a weekly basis all behavioral parameters were assessed, and animals were sacrificed on day 22. The striatum tissue of brain was isolated for biochemicals (Nitrite, GSH, catalase, SOD, mitochondrial complexes I and IV), neuroinflammatory markers (IL-1β, TNF-α, and IL-6), and neurotransmitters (serotonin, dopamine, norepinephrine, GABA, and glutamate) estimations. Results revealed that L-theanine dose-dependently and significantly reversed motor deficits, assessed through locomotor and rotarod activity. Moreover, L-theanine attenuated biochemical markers, reduced oxidative stress, and neurotransmitters dysbalance in the brain. L-theanine treatment at 100 mg/kg; po substantially reduced these pathogenic events by increasing mitochondrial activity, restoring neurotransmitter levels, and inhibiting neuroinflammation. Moreover, data suggest that the positive effects of L-theanine on motor coordination may be mediated by the suppression of nuclear factor-κB (NF-κB) induced by LPS.
Background: Hedgehog pathway plays a crucial role in the neovascularisation and angiogenesis during the embryonic stage in humans. Three genes of hedgehog protein isolated from humans are Sonic hedgehog, Desert hedgehog and Indian hedgehog gene. Two G-protein coupled receptors identified in the sonic hedgehog pathway served as patched receptor and smoothened receptor. Materials and Methods: Particularly, sonic hedgehog gene plays a versatile role in cellular homeostasis and can be a novel therapeutic target in the prevention of cardiovascular disorders. Further various sonic hedgehog modulators have been reported working as futuristic drug molecules in the modulation of cardiovascular dysfunctions. Results: However, there was limited literature availability that has summarized the possible mechanism of targeting Sonic hedgehog signaling pathway. Conclusion: Thus, the present review is aimed at exploring the role of targeting sonic hedgehog protein signaling and modulators as well as to enlighten that how targeting sonic hedgehog protein involves in the amelioration of atherosclerosis, ischemic heart diseases, vascular endothelial dysfunction, heart failure and congenital heart diseases.
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