Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Objective:To compare the cardioprotective efficacy of equimolar doses(50 mM/kg,p.o.)of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats.Methods:Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg.This study included four treatment groups of rats(n=6):the control group(0.5%carboxymethyl cellulose solution-treated),the doxorubicin-treated group(0.5%carboxymethyl cellulose solution along with doxorubicin),the genistein-treated group(50 mM/kg/day;p.o.along with doxorubicin)and phloretin-treated group(50 mM/kg/day;p.o.along with doxorubicin).On the 10th day of dosing,rats were anesthetized for recording ECG,mean arterial pressure,and left ventricular function.Oxidative stress,nitric oxide levels,and inflammatory cytokines were estimated in the cardiac tissue.Cardiac function parameters(creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase)were estimated in the serum samples.Results:Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats.Phloretin administration attenuated doxorubicin-induced alterations in hemodynamic parameters(heart rate,mean arterial blood pressure,and left ventricular function)and suppressed the expression of pro-inflammatory cytokines.The cardiac injury markers like creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase were reduced by both genistein and phloretin.All these effects of phloretin were more prominent than genistein.Conclusions:Phloretin offers cardioprotection that is comparable to genistein,a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity.Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

Aloin attenuates chronic constriction injury-induced neuropathic pain in rats by inhibiting inflammatory cytokines and oxidative stress

Objective:To investigate the effect of aloin against chronic constriction injury(CCI)-induced neuropathic pain in rats.Methods:Rats were randomly divided into 7 groups:GroupⅠ(normal control),GroupⅡ(sham-operated),GroupⅢ(CCI control)and GroupⅣ,Ⅴ,Ⅵ,andⅦ,which underwent CCI surgery and then were administered with aloin(5 mg/kg,p.o.;25 mg/kg,p.o.;125 mg/kg,p.o.)and gabapentin(50 mg/kg,p.o.),respectively for 14 days.Peripheral neuropathy was induced by silk ligatures(4-0)loosely placed around the sciatic nerve.Nociceptive thresholds against mechanical stimuli(Von-Frey filaments)and thermal stimuli(12℃and 40℃)were measured at midplantar paw region ipsilateral to the compressed nerve on day-3,7,11,and 14.The concentration of cytokines including tumor necrosis factor-α(TNF-α),interleukin-6,and interleukin-1βwas estimated at day-7.At day 14,motor nerve conduction velocity was determined under urethane anesthesia(1.25 g/kg).Oxidative stress parameters(malondiadehyde,glutathione,catalase,and superoxide dismutase)were estimated in sciatic nerve homogenates at day 14.Representative nerve samples were processed for histological investigations.Results:Aloin significantly reduced CCI-induced mechanical and thermal allodynia.It also improved motor nerve conduction velocity and decreased oxidative stress in nerve tissues.In addition,it decreased pro-inflammatory cytokine levels and restored the histoarchitecture of compressed sciatic nerve.Conclusions:Aloin mitigates CCI-induced neuropathic pain in rats by inhibiting oxidative stress and pro-inflammatory cytokines in the afflicted sciatic nerve.

Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals

Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.