Exploring the therapeutic effects of sulforaphane: an in-depth review on endoplasmic reticulum stress modulation across different disease contexts.

The endoplasmic reticulum (ER) is an intracellular organelle that contributes to the folding of proteins and calcium homeostasis. Numerous elements can disrupt its function, leading to the accumulation of proteins that are unfolded or misfolded in the lumen of the ER, a condition that is known as ER stress. This phenomenon can trigger cell death through the activation of apoptosis and inflammation. Glucoraphanin (GRA) is the predominant glucosinolate found in cruciferous vegetables. Various mechanical and biochemical processes activate the enzyme myrosinase, leading to the hydrolysis of glucoraphanin into the bioactive compound sulforaphane. Sulforaphane is an organosulfur compound that belongs to the isothiocyanate group. It possesses a wide range of activities and has shown remarkable potential as an anti-inflammatory, antioxidant, antitumor, and anti-angiogenic substance. Additionally, sulforaphane is resistant to oxidation, has been demonstrated to have low toxicity, and is considered well-tolerable in individuals. These properties make it a valuable natural dietary supplement for research purposes. Sulforaphane has been demonstrated as a potential candidate drug molecule for managing a range of diseases, primarily because of its potent antioxidant, anti-inflammatory, and anti-apoptotic properties, which can be mediated by modulation of ER stress pathways. This review seeks to cover a wealth of data supporting the broad range of protective functions of sulforaphane, improving various diseases, such as cardiovascular, central nervous system, liver, eye, and reproductive diseases, as well as diabetes, cancer, gastroenteritis, and osteoarthritis, through the amelioration of ER stress in both in vivo and in vitro studies.

Thymoquinone attenuates olanzapine-induced metabolic disorders in rats.

BACKGROUND: Olanzapine (OLZ) is an atypical antipsychotic agent for psychotic disorders. Evidence has shown that OLZ is related to metabolic side effects, including obesity, hypertension, and insulin resistance. Thymoquinone (TQ) is the principal bioactive component of Nigella sativa. Several studies have been conducted to investigate the effectiveness of TQ in alleviating metabolic abnormalities. In the current research work, the protective effects of TQ on metabolic disorders induced by OLZ and possible underlying mechanisms were investigated. METHODS AND RESULTS: Wistar rats were exposed to TQ alone (10 mg/kg), OLZ (5 mg/kg), or OLZ plus TQ (2.5, 5, or 10 mg/kg) given daily by intraperitoneal injection. After the treatment, variations in body weight, food intake, systolic blood pressure, serum leptin, biochemical factors, liver malondialdehyde (MDA), and glutathione (GSH) content were evaluated. Protein expression of AMPK in the liver was also measured by a western blotting test. OLZ increased body weight, food intake, MDA levels, and blood pressure. OLZ also elevated glucose, triglyceride, low-density lipoprotein cholesterol, and leptin serum levels. It decreased GSH. In the western blot, decreased AMPK protein level was obtained. These changes were attenuated by TQ co-administration. CONCLUSIONS: The present study demonstrates the effectiveness of TQ on OLZ-induced metabolic abnormalities related to its antioxidant activity and regulation of glucose homeostasis and lipid metabolism.

Survival of the hospitalized patients with COVID-19 receiving atorvastatin: A randomized clinical trial.

As statins decrease the progression of sepsis and its related mortality, this study aimed to evaluate the effect of atorvastatin on survival and symptom improvement in hospitalized patients with COVID-19. This randomized controlled trial was performed on 156 hospitalized patients with COVID-19 in Bojnourd city in 2021. Patients were randomly divided into comparison (standard therapy: hydroxychloroquine + Kaletra®) and intervention groups (atorvastatin 20 mg, SD, plus standard therapy). The main outcomes were the rate of symptom improvement, duration of hospitalization, need for intubation, and mortality rate. In this study, seven patients died, two patients (2.6%) in the comparison group and five (6.6%) in the intervention group. The mean hospitalization days (p = 0.001), the pulse rate (p = 0.004), and the frequency of hospitalization in the ICU ward (18.4% vs. 1.3%) were longer and greater in the intervention group. The remission probability in the comparison group was greater (p = 0.0001). The median hospitalization days in the intervention group was longer (p < 0.001) and remission in the comparison group occurred 1.71 times sooner (hazard ratio = 1.70, 95% confidence interval = 1.22-2.38, p = 0.002). Totally, adding atorvastatin to the standard regime in this study increased hospitalization days and imposed negative effects on symptom improvement in hospitalized patients with COVID-19.

In Vivo and In Vitro Protective Effects of Rosmarinic Acid against Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) is an anticancer medicine that may trigger cardiomyopathy. Rosmarinic acid (RA) has shown antioxidant, anti-inflammatory, and anticancer effects. This investigation assessed the cardioprotective effect of RA on DOX-induced-toxicity in both in vivo and in vitro experiments. Male rats were randomized on 7 groups: (1) control, (2) DOX (2 mg/kg, per 48 h, 12d, i.p), (3) RA (40 mg/kg, 12d, i.p.), (4-6) RA (10, 20, 40 mg/kg, 16d, i.p.)+ DOX, (7) Vitamin E (200 mg/kg, per 48 h, 16d, i.p.) + DOX and then indices of cardiac function were estimated. Also, DOX and rosmarinic acid effects were examined on MCF7 cells (breast cancer cells line) to clarify that both cardiotoxicity and anticancer effects were analyzed. DOX increased heart to body weight ratio, RRI, QA, STI, QRS duration and voltage, attenuated HR, blood pressure, Max dP/dt, Min dP/dt, LVDP, enhanced MDA, declined GSH amount, and caused fibrosis and necrosis in cardiac tissue. Administration of RA ameliorated the toxic effects of DOX. In vitro studies showed that RA did not affect the cytotoxic effect of DOX. RA as an antioxidant, anti-inflammatory, and cardioprotective compound could be a promising compound to help minimize DOX-induced cardiotoxicity.

Dexamethasone and ketorolac compare with ketorolac alone in acute renal colic: A randomized clinical trial.

BACKGROUND: Multidrug pain control can be beneficial in relieving pain and limiting narcotic use in renal colic. The purpose of this study was to evaluate the effects of adding dexamethasone to ketorolac on pain control in acute renal colic. METHODS: One hundred twenty patients with renal colic were randomized into comparison and intervention groups to investigate the effect of 8 mg of dexamethasone with 30 mg ketorolac administered immediately after the patient's admission. The primary outcome was pain intensity based on the visual analog scale (VAS), which was assessed at the baseline and after 30 and 60 min of drugs treatment. Also, grade of vomiting and narcotic or antiemetic requirement were measured at the baseline and after the 60-min intervention. RESULTS: A total of 120 patients were included in the final analysis, with 60 patients (50%) randomized to the comparison group (just ketorolac) and 60 (50%) randomized to the intervention group (ketorolac + dexamethasone). There were no significant demographic differences between groups (P > 0.05 for all). Differences in VAS scores were significantly lower in the intervention group after 30 min of drug administration (P = 0.009, compared with the control). However, there was not a significant difference in the median VAS score between groups at the baseline and end of the study (P > 0.05). At the end of the study, the percent of patients who need to narcotics (35% vs. 58%, P = 0.01) and/or antiemetic (12% vs. 28%, P = 0.022) were significantly lower in the intervention group compared with the controls. CONCLUSIONS: In comparison with the patients who just received ketorolac, adding dexamethasone provided improved pain control after 30 min of therapy. Furthermore, it decreased opioid requirements and decreased an antiemetic need at the end of the study. Dexamethasone should be considered an important multimodal adjunct for controlling pain and nausea in renal colic.

Cardioprotective effects of alpha-mangostin on doxorubicin-induced cardiotoxicity in rats.

The main adverse effect of doxorubicin is cardiotoxicity. Oxidative stress and apoptosis induction have been suggested as mechanisms involved in its cardiotoxicity. In this study, cardioprotective effects of alpha-mangostin against doxorubicin-induced cardiotoxicity have been investigated in rats. Forty-two rats were divided as follows: Control, doxorubicin (2 mg/kg every 48 hr), alpha-mangostin (200 mg/kg), alpha-mangostin (50, 100, 200 mg/kg) + doxorubicin (2 mg/kg every 48 hr), and vitamin E (200 IU/kg) + doxorubicin (2 mg/kg every 48 hr). Alpha-mangostin was administered by gavage for 19 days, while doxorubicin (12 days) and vitamin E (19 days) were injected intraperitoneally. Doxorubicin decreased heart rate, increased electrocardiogram signal components duration and reduced systolic and diastolic arterial blood pressure, and caused histological damage in the heart of rats. Doxorubicin decreased heart weight and heart/body weight ratio, as well as elevated creatine phosphokinase isoenzyme and lactate dehydrogenase. Doxorubicin increased malondialdehyde, inflammatory biomarkers, and caspases 3 and 9 and decreased reduced glutathione content in heart tissue but co-administration of alpha-mangostin (100 mg/kg) restored all doxorubicin toxic effects. Results show that alpha-mangostin has protective effects against doxorubicin-induced cardiotoxicity by antioxidant, antiinflammatory, and antiapoptotic effects that may ameliorate doxorubicin cardiotoxicity in human chemotherapy without reduction in its anticancer effect.

Evaluation of green tea extract and epigallocatechin gallate effects on bisphenol A-induced vascular toxicity in isolated rat aorta and cytotoxicity in human umbilical vein endothelial cells.

This study was designed to assess bisphenol A (BPA)-induced vascular toxicity, the effectiveness of green tea extract and epigallocatechin gallate (EGCG) against BPA toxicity, and possible underlying mechanisms. In isolated rat aorta, contractile and relaxant responses as well as malondialdehyde levels were evaluated. Cell viability and effects on the protein levels of apoptotic (bax, bcl2, and caspase-3), autophagic (LC3), and cell adhesion molecules were calculated using the MTT method and western blotting in human umbilical vein endothelial cells (HUVECs). BPA increased aorta MDA levels (p < .0001) and decreased vascular responses to KCl [20 and 40 mM (p < .0001), 80 mM (p < .001)], phenylephrine [10-8 , 10-6 , and 10-5 M (p < .001), 10-7 and 10-4 M (p < .0001)], and acetylcholine [10-6 M (p < .01), 10-5 and 10-4 M (p < .0001)]. In HUVECs, BPA enhanced the levels of LC3A/B, bax/bcl2 ratio, cleaved caspase-3, and vascular cell adhesion molecule-1. Green tea extract, EGCG, and vitamin E co-treatment with BPA diminished the toxic effects of BPA. These findings provide evidence that green tea extract and EGCG possess beneficial effects in preventing BPA-induced vascular toxicity through increasing the antioxidant activities and the regulation of signaling pathways.

Carnosic acid prevented olanzapine-induced metabolic disorders through AMPK activation.

Olanzapine, an atypical antipsychotic medication, has been associated with weight gain and metabolic toxicity, especially in long term usage. Carnosic acid (CA), a major constituent of rosemary extract, has been shown to improve metabolic abnormalities. In this experiment, the effect of CA on olanzapine-induced obesity and metabolic toxicity has been evaluated. Female Wistar rats were divided into six groups. (1) control; (2) olanzapine (5 mg/kg/day, IP); (3, 4 and 5) olanzapine (5 mg/kg/day, IP) plus CA (5, 10 and 20 mg/kg/day, gavage) and (6) CA (20 mg/kg/day, gavage). Bodyweight and food intake were measured during the study. After 14 days, mean systolic blood pressure (MSBP), glycemia, serum lipid profile, the serum concentration of leptin, insulin, AMPK, P-AMPK, and P-ACC liver protein levels were evaluated. The mean weight in the group received olanzapine increased by 4.8 g at the end of the study. The average food intake was increased by olanzapine. Olanzapine increased triglyceride, fasting blood glucose (FBG), and leptin levels. It increased MSBP and down-regulated P-AMPK/AMPK ratio and P-ACC protein levels. CA (three doses) decreased body weight gain and reduced average food intake at 10 and 20 mg/kg. CA especially at the highest dose decreased the changes in lipid profile, FBG, leptin level, and MSBP. P-AMPK/AMPK and P-ACC protein levels were increased by carnosic acid. In conclusion, the activation of AMPK by CA can be proposed as a key mechanism against olanzapine-induced metabolic toxicity where the activation of AMPK increases fat consumption and regulates glucose hemostasis in the liver.

The Use of Nanomaterials in Tissue Engineering for Cartilage Regeneration; Current Approaches and Future Perspectives.

The repair and regeneration of articular cartilage represent important challenges for orthopedic investigators and surgeons worldwide due to its avascular, aneural structure, cellular arrangement, and dense extracellular structure. Although abundant efforts have been paid to provide tissue-engineered grafts, the use of therapeutically cell-based options for repairing cartilage remains unsolved in the clinic. Merging a clinical perspective with recent progress in nanotechnology can be helpful for developing efficient cartilage replacements. Nanomaterials, < 100 nm structural elements, can control different properties of materials by collecting them at nanometric sizes. The integration of nanomaterials holds promise in developing scaffolds that better simulate the extracellular matrix (ECM) environment of cartilage to enhance the interaction of scaffold with the cells and improve the functionality of the engineered-tissue construct. This technology not only can be used for the healing of focal defects but can also be used for extensive osteoarthritic degenerative alterations in the joint. In this review paper, we will emphasize the recent investigations of articular cartilage repair/regeneration via biomaterials. Also, the application of novel technologies and materials is discussed.

Vitis vinifera (grape) seed extract and resveratrol alleviate bisphenol-A-induced metabolic syndrome: Biochemical and molecular evidences.

The mechanisms of bisphenol-A (BPA)-induced metabolic syndrome as well as the protective role of grape seed extract (GSE) and resveratrol were investigated. Rats were treated with BPA (0 and 35 mg·kg-1 ·day-1 , gavage) plus resveratrol (25, 50, and 100 mg·kg-1 ·day-1 , i.p.) or GSE (3, 6, 12 mg·kg-1 ·day-1 , i.p.) or vitamin E (200 IU/kg/every other day, i.p.). After 2 months, mean systolic blood pressure, serum lipid profile, glycaemia, and fat index were examined. By enzyme-linked immunosorbent assay, the serum concentrations of insulin, leptin, adiponectin, and paraoxonase 1, and by real-time polymerase chain reaction as well as western blotting, key liver elements in cholesterol hemostasis (LDLR, CYP7A1, ABCG5 and 8) and insulin signaling (p-Akt/Akt and p-PI3K/PI3K) were measured. BPA increased mean systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol and reduced paraoxonase1 and the hepatic expression of both ABCG5 and ABCG8. It increased the body fat index, leptin, adiponectin, insulin, and glycaemia level and decreased the hepatic protein expression of p-Akt/Akt and p-PI3K/PI3k. GSE, resveratrol, or vitamin E coadministration along with BPA restored the detrimental effects of BPA in some levels. Herein, the predisposing effects of BPA-induced metabolic syndrome were restored by GSE and resveratrol, linked to the regulation of insulin signaling, ABCG8 expression, and their antioxidant properties.

Toxicological effects of Camellia sinensis (green tea): A review.

Many scientific articles proved that green tea (GT), Camellia sinensis, has a great potential to manage central nervous system, cardiovascular, and metabolic diseases and treat cancer and inflammatory disorders. However, it is important to consider that "natural" is not always "safe." Some relevant articles reported side effects of GT, detrimental effects on health. The aim of this study is to provide a classified report about the toxicity of GT and its main constituents in acute, subacute, subchronic, and chronic states. Furthermore, it discusses on the cytotoxicity, genotoxicity, mutagenicity, carcinogenicity, and developmental toxicity of GT and its main constituents. The most important side effects have been reported hepatotoxicity and gastrointestinal disorders specially while consumed on an empty stomach. GT and its main components are not major teratogen, mutagen, or carcinogen substances. However, there is limited data in using them during pregnancy, and they should be used with caution in pregnancy, breast-feeding, and susceptible people. Because GT and its main components have a wide variety of drug interactions, consideration should be taken in coadministration of them with narrow therapeutic indexed drugs. Furthermore, they evoke selective cytotoxicity on cancerous cells that could engage them as an adjuvant substance in cancer therapy.

Bisphenol A vascular toxicity: Protective effect of Vitis vinifera (grape) seed extract and resveratrol.

The underlying mechanism of Bisphenol A (BPA)-induced vascular toxicity and the protective role of grape seed extract (GSE) and resveratrol were investigated in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of GSE and resveratrol. Then, BPA was added to the cells and cell viability and effects on the protein level of cell adhesion molecules were measured through MTT and western blotting. Animals were randomly divided into control, GSE (3 and 12 mg·kg-1 ·day-1 ip), resveratrol (100 mg·kg-1 ·day-1 ip), BPA (35 mg·kg-1 ·day-1 , gavage), BPA plus GSE (3, 6, and 12 mg·kg-1 ·day-1 ip), BPA plus resveratrol (25, 50, and 100 mg·kg-1 ·day-1 ip), and BPA plus vitamin E (200 IU/kg per every other day ip). After 2 months, contractile and relaxant responses were evaluated on the isolated aorta. BPA increased the level of aorta malondialdehyde (p < 0.001) and decreased vascular responses to KCl (p < 0.01), phenylephrine (p < 0.001), and acetylcholine (p < 0.01). In HUVECs, BPA (IC50 : 220 µM) increased protein level of vascular cell adhesion molecule (p < 0.05) and cleaved capase3 (p < 0.001). GSE, resveratrol, and vitamin E cotreatment restored toxic effects of BPA in some levels. BPA vascular toxicity was attributed to lipid peroxidation and endothelial dysfunction. The protective role of GSE and resveratrol against BPA-endothelial dysfunction could be attributed to their potent antioxidant properties.

Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review.

Licorice (Glycyrrhiza glabra) has been considered as an herbal drug since ancient time. Nowadays, it is a well-known spice that possesses worth pharmacological effects. However, some relevant articles have revealed negative impacts of licorice in health. By considering the great wishes in using herbal medicine, it is important to show adverse effects of herbal medicine in health. At present, there are misunderstandings toward the safety of herbal medicines. Herein, we gathered scientific research projects on the toxicity effects of licorice and glycyrrhizin to highlight their safety. In this regards, we categorized our findings about the toxicity effects of licorice and glycyrrhizin in acute, sub-acute, sub-chronic, and chronic states. Besides, we discussed on the cytotoxicity, genotoxicity, mutagenicity, and carcinogenicity of licorice and glycyrrhizin as well as their developmental toxicity. This review disclosed that G. glabra and glycyrrhizin salts are moderately toxic. They need to be used with caution during pregnancy. G. glabra and glycyrrhizin possess selective cytotoxic effects on cancerous cells. The most important side effects of licorice and glycyrrhizin are hypertension and hypokalemic-induced secondary disorders. Licorice side effects are increased by hypokalemia, prolonged gastrointestinal transient time, decreased type 2 11-beta-hydroxysteroid dehydrogenase activities, hypertension, anorexia nervosa, old age, and female sex. Copyright © 2017 John Wiley & Sons, Ltd.

Protective effects of Panax ginseng as a medical food against chemical toxic agents: molecular and cellular mechanisms.

Humans are exposed to different types of toxic agents, which may directly induce organ malfunction or indirectly alter gene expression, leading to carcinogenic and teratogenic effects, and eventually death. Ginseng (Panax ginseng) is the most valuable of all medicinal herbs. Nevertheless, specific data on the antidotal mechanisms of this golden herb are currently unavailable. Based on the findings of in vitro, in vivo, and clinical studies, this review focused on the probable protective mechanisms of ginseng and its major components, such as protopanaxadiols, protopanaxatriols, and pentacyclic ginsenosides against various chemical toxic agents. Relevant articles from 2000 to 2023 were gathered from PubMed/Medline, Scopus, and Google Scholar. This literature review shows that P. ginseng and its main components have protective and antidotal effects against the deteriorative effects of pesticides, pharmaceutical agents, including acetaminophen, doxorubicin, isoproterenol, cyclosporine A, tacrolimus, and gentamicin, ethanol, and some chemical agents. These improvements occur through multi-functional mechanisms. They exhibit antioxidant activity, induce anti-inflammatory action, and block intrinsic and extrinsic apoptotic pathways. However, relevant clinical trials are necessary to validate the mentioned effects and translate the knowledge from basic science to human benefit, fulfilling the fundamental goal of all toxicologists.

Carnosic acid mitigates doxorubicin-induced cardiac toxicity: Evidence from animal and cell model investigations.

Objectives: Utilization of doxorubicin (DOX) as a chemotherapy medication is limited due to its cardiotoxic effects. Carnosic acid exerts antioxidant, anti-inflammatory, besides cytoprotective effects. The objective of this study was to investigate the ability of carnosic acid to protect rat hearts and the MCF7 cell line against cardiotoxicity induced by DOX. Materials and Methods: The study involved the classification of male Wistar rats into seven groups: 1) Control 2) DOX (2 mg/kg, every 48h, IP, 12d), 3-5) Carnosic acid (10, 20, 40 mg/kg/day, IP, 16d)+ DOX, 6) Vitamin E (200 mg/kg, every 48h, IP, 16d)+ DOX 7) Carnosic acid (40 mg/kg/day, IP, 16d). Finally, cardiac histopathological alterations, ECG factors, carotid blood pressure, left ventricular function, heart-to-body weight ratio, oxidative (MDA, GSH), inflammatory (IL-1ß, TNF-α), plus apoptosis (caspase 3, 8, 9, Bcl-2, Bax) markers were evaluated. DOX toxicity and carnosic acid ameliorative effect were evaluated on MCF7 cells using the MTT assay. Results: DOX augmented the QRS duration, QA, RRI, STI, and heart-to-body weight ratio, and reduced HR, LVDP, Min dP/dt, Max dP/dt, blood pressure, boosted MDA, TNF-α, IL1-ß, caspase 3,8,9, Bax/Bcl-2 ratio, decreased GSH content, caused fibrosis, necrosis, and cytoplasmic vacuolization in cardiac tissue but carnosic acid administration reduced the toxic effects of DOX. The cytotoxic effects of DOX were not affected by carnosic acid at concentrations of 5 and 10 µM. Conclusion: Carnosic acid as an anti-inflammatory and antioxidant substance is effective in reducing DOX-induced damage by enhancing antioxidant defense and modifying inflammatory signal pathway activity and can be used as an adjunct in treating DOX cardiotoxicity.

Protective effects and therapeutic applications of ellagic acid against natural and synthetic toxicants: A review article.

Traditional herbal drugs are widely used for the treatment of various diseases. Ellagic acid (EA) as an herbal polyphenol metabolite exists in many medicinal plants. EA has an important role against natural and chemical toxicities due to its antioxidant and anti-inflammatory properties. For this review, several search engines or databases such as PubMed, Scopus, the Web of Science, and Google Scholar were used, and the most relevant published papers till February 2022 were included. The protective effects of EA against natural and chemical compounds are mediated through molecular mechanisms including scavenging of free radicals, modulation of proinflammatory cytokine synthesis, and reduction of lipid peroxidation. These properties make EA a highly fascinating compound that may contribute to different aspects of health; whereas, more studies are needed, especially on the pharmacokinetic profile of EA. In this review, we selected articles that include the protective effect of EA against several synthetic and natural toxins such as aflatoxin, lipopolysaccharide, acrylamide, and rotenone.

Evaluating the possible role of mitochondrial ATP-sensitive potassium channels in the cardioprotective effects of morin in the isolated rat heart.

AIMS: During heart ischemia, the lack of oxygen in the myocardial cells causes pH and ion disturbances and cell death through opening mitochondrial permeability transition pores (mPTP). Considering the inhibitory effects of mitochondrial ATP-dependent potassium channels (mt-KATP) on these pores and anti-ischemic effects of morin, we hypothesized that it may exert its positive effects via activating mt-KATP as well as its anti-oxidative effects. MAIN METHODS: Isolated rat hearts were perfused by Krebs-Henseleit solution enriched with the morin (0.25, 0.5 and 1 mg/L) or 5-hydroxydecanoate (5-HD, a mt-KATP blocker;100 µM) or both as needed 5 min before starting regional ischemia till the first 10 min of the reperfusion period. The reperfusion was developed with Krebs-Henseleit solution 60 or 120 min respectively for biochemical evaluations (lactate dehydrogenase and malondialdehyde level) or the assessment of myocardial infarct size. During the experiments, hemodynamic functions were recorded and cardiac arrhythmias were determined. KEY FINDINGS: Our findings demonstrated that morin reduced the infarct size. Also, morin perfusion could remarkably prevent the malondialdehyde over-production during ischemia. Total ventricular ectopic beats had the same significant changes as the malondialdehyde level, in both ischemia and reperfusion phases. Morin could also relatively improve the ischemia-induced hemodynamic dysfunction. All mentioned protective effects of morin were reversed by concomitant perfusion of 5-HD. SIGNIFICANCE: Morin has protective effects against ischemic hearts through anti-oxidative effects. It also suggests a link between the cardioprotective effects of morin and mt-KATP. However, additional studies are required to prove this preliminary hypothesis.

Erratum: Correction of Title.

[This corrects the article DOI: 10.15171/apb.2018.012.].

An overview of glucagon-like peptide-1 receptor agonists for the treatment of metabolic syndrome: A drug repositioning.

Metabolic syndrome (MetS) is a clustering of several cardiovascular risk factors that include: obesity, dyslipidemia, hypertension and high blood glucose, and often requires multidrug pharmacological interventions. The management of MetS therefore requires high healthcare cost, and can result in poor drug treatment compliance. Hence drug therapies that have pleiotropic beneficial effects may be of value. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are the newest anti-diabetic drugs that mimic incretin effects in the body. They appear to be safe and well tolerable. Herein, the pharmacology of GLP-1RAs, their side effects, drug interactions and their effects in MetS is assessed. We conducted a Google Scholar, PubMed, Scopus, and Web of Science search since 2010 to identify publications related to the use of GLP-1RAs in treating component features of the MetS. Keywords used for the search were: GLP-1 receptor agonist, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, MetS, obesity, triglyceride, cholesterol, lipid, hypercholesterolemia hyperlipidemia, atherosclerosis, hypertension, blood pressure, hyperglycemia, hypoglycemia and blood glucose. According to the gathered data, GLP-1RAs appear safe and well tolerated. Pre-clinical and clinical studies have evaluated the lipid-lowering, anti-atherosclerotic, anti-hypertensive and anti-diabetic effects of this class of drugs. Some these effects are related to a reduction in food-seeking behavior, an increase in atrial natriuretic peptide level and hence vascular relaxation and natriuresis, and an increase of pancreas ß-cell mass and protection against glucotoxicity. Collectively, this review indicates that there may be some value in GLP-1RAs repositioning to manage MetS risk factors beyond their anti-diabetic effects.