The Protective Effects of Taurine, a Non-essential Amino Acid, Against Metals Toxicities: A Review Article.

Taurine is a non-proteinogenic amino acid derived from cysteine. It is involved in several phenomena such as the regulation of growth and differentiation, osmoregulation, neurohormonal modulation, and lipid metabolism. Taurine is important because of its high levels in several tissues such as the central nervous system (CNS), heart, skeletal muscles, retinal membranes, and platelets. In this report, we present the functional properties of taurine indicating that it has potential effects on various metal toxicities. Therefore, a comprehensive literature review was performed using the Scopus, PubMed, and Web of Science databases. According to the search keywords, 61 articles were included in the study. The results indicate that taurine protects tissues against metal toxicity through enhancement of enzymatic and non-enzymatic antioxidant capacity, modulation of oxidative stress, anti-inflammatory and anti-apoptotic effects, involvement in different molecular pathways, and interference with the activity of various enzymes. Taken together, taurine is a natural supplement that presents antitoxic effects against many types of compounds, especially metals, suggesting public consumption of this amino acid as a prophylactic agent against the incidence of metal toxicity.

Preventive and therapeutic effects of azithromycin on acrylamide-induced neurotoxicity in rats.

BACKGROUND: Acrylamide (ACR) can induce neurotoxicity through different pathways, including oxidative stress and apoptosis. Azithromycin is well-known for its antioxidant and anti-apoptotic properties. OBJECTIVE: To evaluate the potential neuroprotective effect of azithromycin in an in vivo model of ACR-induced neurotoxicity, by investigating its impact on oxidative stress and apoptosis pathways. METHODS: Male rats were divided into eleven groups at random (n = 6). 1:control (vehicle), 2:ACR (50 mg/kg, 11 days, I.P.), 3-7:ACR+ azithromycin (3.1, 6.25, 12.5, 25, 50 mg/kg, 11 days, I.P.), 8-9:ACR+ azithromycin (3.1, 6.25 mg/kg, from day 3-11), 10: ACR+ vitamin E (200 mg/kg, every other day, I.P.), 11. Azithromycin (50 mg/kg). Following the treatment period, a gait score examination was performed, and malondialdehyde (MDA), glutathione (GSH), Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and caspase-3 levels in the cerebral cortex were measured. RESULTS: Gait abnormality, a drop in GSH, and an increase in lipid peroxidation, Bax/Bcl-2 ratio, and caspase-3 levels were all significantly triggered by ACR in the cerebral cortex versus the control group. Azithromycin 3.1 and 6.25 mg/kg with ACR and azithromycin 6.25 mg/kg with ACR from day 3-11 ameliorated movement disorders caused by ACR. Azithromycin in all doses and both protocols along with ACR decreased the MDA level. Azithromycin (3.1, 6.25 mg/kg) along with ACR in both protocols increased the level of GSH, reduced the Bax/Bcl-2 ratio and caspase-3 amounts in the brain tissue versus the ACR group. CONCLUSIONS: Administration of azithromycin had both preventive and therapeutic effects on ACR-induced neurotoxicity through its antioxidant and antiapoptotic properties.

Pharmacological effects of Safranal: An updated review.

Safranal (a monoterpene aldehyde) is the major volatile component of saffron which is responsible for the saffron unique odor. Several studies have shown the pharmacological activities of safranal including anti-oxidant, anti-inflammatory, cardioprotective, neuroprotective, nephroprotective, gastrointestinal protective, etc. This study was designed to review the pharmacological and medical effects of safranal and up-to-date previous knowledge. Moreover, some patents related to the pharmacological effects of safranal were gathered. Therefore, electronic databases including Web of Sciences, Scopus, and Pubmed for pharmacological effects and US patent, Patentscope, and Google Patent for patents were comprehensively searched by related English keywords from 2010 to June 2022. According to our review, most of the studies are related to the safranal effects on CNS such as antianxiety, analgesic, anticonvulsant, antiischemic, anti-tremor, memory enhancement and its protective effects on neurodegenerative disorders such as Alzheimer's, Parkinson and Huntington diseases. Other effects of safranal are antiasthmatic, antihypertensive, antiaging, anticataract, etc. Moreover, the protective effects of this agent on metabolic syndrome and diabetic nephropathy have been shown. Different mechanisms including anti-oxidant, anti-inflammatory, muscle relaxation, antiapoptotic, and regulatory effects on the genes and proteins expression related to signaling pathways of oxidative stress, inflammation, apoptosis, proliferation, etc. are involved in safranal pharmacological effects. Some patents for the prevention and/or treatment of different diseases such as liver cancer, sleep disorder, depression, cognitive disorder, obesity and PMS were also included. Based on the documents, safranal is considered a promising therapeutic agent although more clinical studies are needed to verify the beneficial effects of safranal in humans.

Evaluating the effect of alpha-mangostin on neural toxicity induced by acrylamide in rats.

Acrylamide (ACR) is known to be a neurotoxic agent for humans and animals that has many applications in industry. Alpha-mangostin is a natural antioxidant that is extracted from mangosteen. This study aimed to investigate the protective effects of alpha-mangostin against ACR-induced neurotoxicity in rats and PC12 cells. Male Wistar rats were used in this investigation for 11 days, divided into 8 groups: 1. control group (normal saline), 2. ACR (50 mg/kg, i.p.), 3-6. ACR + alpha-mangostin (20, 40, 60 mg/kg, p.o.), 7. ACR + vitamin E (200 mg/kg, i.p., every other day) 8. alpha-mangostin (60 mg/kg, p.o.). On the last day of the study, the behavioral test was performed. The amounts of malondialdehyde (MDA) and glutathione (GSH) were measured. Also, the effects of ACR and alpha-mangostin were assessed by MTT assay on PC12 cells, and the levels of reactive oxygen species (ROS), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 proteins were measured by Western blotting. Receiving ACR caused motor disorders in animals, increased MDA, and decreased GSH levels of the cerebral cortex versus the control group. Alpha-mangostin (60 mg/kg) reduced ACR motility disorders, MDA amounts, and augmented GSH levels. The concurrent administration of vitamin E and ACR reduced gait score, MDA level, and amplified GSH content versus the ACR group. In the in vitro section, alpha-mangostin (1.25 µM, 24 h) increased cell viability, attenuated ROS, Bax/Bcl-2, and cleaved caspase-3 levels versus the ACR group. Alpha-mangostin reduced the toxicity of ACR by inhibiting oxidative stress and apoptosis. Therefore, it could be a promising compound for managing ACR-induced neurotoxicity.

Amifostine inhibits acrylamide-induced hepatotoxicity by inhibiting oxidative stress and apoptosis.

Objectives: Acrylamide (ACR) is a toxic chemical agent that can induce hepatotoxicity through different mechanisms including oxidative stress and apoptosis. Amifostine is an important hepatoprotective and anti-oxidant compound. In this research, the hepatoprotective effect of amifostine on ACR-induced hepatotoxicity in rats has been investigated. Materials and Methods: Male Wistar rats were randomly divided into 7 groups, including: 1. Control group, 2. ACR (50 mg/kg, 11 days, IP), 3-5. ACR+ amifostine (25, 50, 100 mg/kg, 11 days, IP), 6. ACR+ N-acetyl cysteine (NAC) (200 mg/kg, 11 days, IP), and 7. Amifostine (100 mg/kg, 11 days, IP). At the end of the injection period, animals' liver samples were collected to determine the content of glutathione (GSH), malondialdehyde (MDA), and apoptotic proteins (B-cell lymphoma 2 (Bcl2), Bcl-2-associated X protein (Bax), and cleaved caspase-3. Serum samples were also collected to measure alanine transaminase (ALT) and aspartate transaminase (AST) levels. Results: Administration of ACR increased MDA, Bax/Bcl2 ratio, cleaved caspase-3, ALT, and AST levels, and decreased GSH content compared with the control group. The administration of amifostine with ACR decreased MDA, Bax/Bcl2 ratio, cleaved caspase-3, ALT, and AST levels, and increased GSH content compared with the ACR group. Receiving NAC along with ACR reversed the alterations induced by ACR. Conclusion: This study shows that pretreatment with amifostine can reduce ACR-induced toxicity in the liver tissue of rats. Since oxidative stress is one of the most important mechanisms in ACR toxicity, amifostine probably reduces the toxicity of ACR by increasing the anti-oxidant and anti-apoptotic capacity of the hepatic cells.

Therapeutic effects of minocycline on oleic acid-induced acute respiratory distress syndrome (ARDS) in rats.

Acute respiratory distress syndrome (ARDS) is a serious intensive care condition. Despite advances in treatment over the previous few decades, ARDS patients still have high fatality rates. Thus, more research is needed to improve the outcomes for people with ARDS. Minocycline is an antibiotic with antioxidant, anti-inflammatory, and anti-apoptotic effects. In the current investigation, the therapeutic effects of minocycline on oleic acid-induced ARDS were evaluated. Male rats were classified into 6 groups, 1. control (normal saline), 2. oleic acid (100 µL, i.v.), 3-5. oleic acid + minocycline (50, 100, 200 mg/kg, i.p.), and 6. minocycline (200 mg/kg, i.p.) alone. Twenty-four hours after the oleic acid injection, the lung tissue is isolated, weighed, and the middle part of the right lung is immediately placed in the freezer, while the middle part of the left lung is placed in formalin and sent to the laboratory for pathology testing. Then, the amounts of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), cytokines (interleukin-1 beta (IL-1ß), tumor necrosis factor-α (TNF-α)), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), and cleaved caspase-3 were determined in lung tissue. Administration of oleic acid increased emphysema, inflammation, vascular congestion, hemorrhage, MDA amount, Bax/Bcl-2 ratio, cleaved caspase-3, IL-1ß, TNF-α levels, and decreased GSH, SOD, and CAT levels in comparison with the control group. The administration of minocycline could significantly reduce pathological and biochemical alterations induced by oleic acid. Minocycline has a therapeutic effect on oleic acid-induced ARDS through antioxidant, anti-inflammatory, and anti-apoptotic properties.

Effect of trans-sodium crocetinate on contrast-induced cytotoxicity in HEK-293 cells.

Objectives: Contrast media (CM) are used for diagnostic or therapeutic intervention purposes in medicine. The main adverse reaction after the administration of CM is contrast-induced nephropathy (CIN). This complication is the third cause of renal failure after hospital treatment. The current study is designed to investigate the possible protective effect of trans-sodium crocetinate (TSC), derived from carotenoid crocetin, against sodium amidotrizoate/meglumine amidotrizoate (SAMA) induced cytotoxicity in HEK-293 cells. Materials and Methods: HEK-293 cells were incubated with different concentrations of TSC (1, 2.5, 5, 10, 25, and 50 µM, for 48 hr) and then SAMA (7 mgI/ml, for 24 hr) was added. The cell viability, intracellular ROS, and phosphatidyl serine exposure were detected by MTT assay, DCFH-DA, and annexin V-FITC/PI method, respectively. The P-ERK/ERK ratio, apoptosis (Bax/Bcl-2 ratio and cleaved caspase-3), and autophagy (LC3 II/I ratio and beclin-1) markers in cells were evaluated by the western blot method. Results: The exposure of HEK-293 cells to SAMA reduced viability, increased apoptotic cells, enhanced ROS production, and subsequently decreased P-ERK/ERK ratio. Similarly, SAMA enhanced apoptosis (Bax/Bcl-2 ratio and cleaved caspase-3) and autophagy (LC3 II/I ratio and beclin-1) markers in HEK-293 cells. The pretreatment of cells with TSC before exposure to SAMA significantly attenuated contrast-induced cytotoxicity. TSC reduced intracellular ROS production and activated the phosphorylation of ERK. In addition, TSC decreased the levels of apoptosis and autophagy proteins. Conclusion: The pretreatment of HEK-293 cells with TSC can decrease contrast-induced cytotoxicity through antioxidant effect and modulate ERK, apoptosis, and autophagy pathways.

Protective effects of pomegranate (Punica granatum) and its main components against natural and chemical toxic agents: A comprehensive review.

BACKGROUND: Different chemical toxicants or natural toxins can damage human health through various routes such as air, water, fruits, foods, and vegetables. PURPOSE: Herbal medicines may be safe and selective for the prevention of toxic agents due to their active ingredients and various pharmacological properties. According to the beneficial properties of pomegranate, this paper summarized the protective effects of this plant against toxic substances. STUDY DESIGN: In this review, we focused on the findings of in vivo and in vitro studies of the protective effects of pomegranate (Punica granatum) and its active components including ellagic acid and punicalagin, against natural and chemical toxic agents. METHODS: We collected articles from the following databases or search engines such as Web of Sciences, Google Scholar, Pubmed and Scopus without a time limit until the end of September 2022. RESULTS: P. granatum and its constituents have shown protective effects against natural toxins such as aflatoxins, and endotoxins as well as chemical toxicants for instance arsenic, diazinon, and carbon tetrachloride. The protective effects of these compounds are related to different mechanisms such as the prevention of oxidative stress, and reduction of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2(COX-2) and nuclear factor ĸB (NF-ĸB) as well as the modulation of apoptosis, mitogen-activated protein kinase (MAPK) signaling pathways and improvement of liver or cardiac function via regulation of enzymes. CONCLUSION: In this review, different in vitro and in vivo studies have shown that P. granatum and its active constituents have protective effects against natural and chemical toxic agents via different mechanisms. There are no clinical trials on the protective effects of P. granatum against toxic agents.

Alpha-mangostin Protects PC12 Cells Against Neurotoxicity Induced by Cadmium and Arsenic.

Arsenic and cadmium are nonessential elements that are of importance in public health due to their high toxicity. Contact with these toxic elements, even in very small amounts, can induce various side effects, including neurotoxicity. Oxidative stress and apoptosis are part of the main mechanisms of arsenic- and cadmium-induced toxicity. Alpha-mangostin is the main xanthone derived from mangosteen, Garcinia mangostana, with anti-oxidative properties.In this study, PC12 cells were selected as a nerve cell model, and the protective effects of alpha-mangostin against neurotoxicity induced by arsenic and cadmium were investigated. PC12 cells were exposed to cadmium (5-80 µM) and arsenic (2.5-180 µM) for 24 h. Cytotoxicity, reactive oxygen species (ROS) production, and the protein expression of Bax, Bcl2, and cleaved caspase 3 were determined using MTT assay, fluorimetry, and western blot, respectively.Arsenic (10-180 µM) and cadmium (50-80 µM) significantly reduced cell viability. IC50 values were 10.3 ± 1.09 and 45 ± 4.63 µM, respectively. Significant increases in ROS, Bax/Bcl-2 ratio, and cleaved caspase-3 were observed after arsenic and cadmium exposures. Cell viability increased and ROS production decreased when cells were pretreated with alpha-mangostin for 2 h. Alpha-mangostin reduced the increased level of cleaved caspase-3 induced by cadmium and decreased the elevated level of the Bax/Bcl-2 ratio after arsenic exposure.Alpha-mangostin significantly increased cell viability and reduced oxidative stress caused by cadmium and arsenic in PC12 cells. Moreover, alpha-mangostin reduced cadmium-induced apoptosis through the reduction in the level of cleaved caspase 3. Further studies are required to determine the different mechanisms of alpha-mangostin against neurotoxicity induced by these elements.

Minocycline as a Neuroprotective Agent in Arsenic-Induced Neurotoxicity in PC12 Cells.

Arsenic is a naturally occurring metalloid that exists in water, soil, food, and air. Humans can be exposed to arsenic through occupational, medical, or nutritional routes. Both acute and chronic forms of toxicity with severe outcomes are likely following arsenic exposure. Neurotoxicity is one of the serious manifestations of arsenic toxicity. In our study, the effect of minocycline, a widely used antimicrobial agent with antioxidant aspects and the ability to cross the blood-brain barrier, was evaluated against arsenic-induced neurotoxicity. PC12 cell line was used as the cellular model of this study. Cells were pre-treated with minocycline (50 nM-1 µM) for 2 h, and then incubated for 24 h after adding sodium arsenite (10 µM). The MTT assay and fluorimetry were performed to study cytotoxicity and reactive oxygen species generation, respectively. Finally, Western blotting was done to determine the levels of caspase-8, Bax, Bcl-2, and caspase-3. Once exposed to arsenic, the cell viability was significantly reduced, the intracellular oxidative balance was significantly disrupted, and the levels of proteins caspase-8, Bax/Bcl-2, and caspase-3 were significantly increased. Minocycline not only attenuated arsenic-induced cytotoxicity and reduced oxidative stress, but also led to lower levels of caspase-8, Bax/Bcl-2, and caspase-3 proteins compared with the arsenic-treated cells. Minocycline can significantly protect cells against arsenic-induced neurotoxicity by antioxidant and anti-apoptosis properties via both intrinsic and extrinsic caspase-dependent apoptotic pathways; therefore, at this point, it's worth considering it as a promising agent for the treatment of arsenic toxicity.

Minocycline Protects PC12 Cells Against Cadmium-Induced Neurotoxicity by Modulating Apoptosis.

Cadmium (Cd) is a well-known heavy metal and a neurotoxic agent. Minocycline (Mino) is an anti-microbial agent with a lipophilic structure that crosses the blood-brain barrier and enters the cerebral tissue. In recent studies, Mino has been introduced as an antioxidant and anti-apoptotic chemical compound, and therefore, it was examined as a protective candidate against Cd-induced neurotoxicity. In this study, PC12 cells were exposed to Cd alone, or after being pre-treated with Mino. Initially, the cell viability and oxidative stress were analyzed using the MTT assay and fluorimetry, respectively. Then, Cd-induced apoptosis and Mino anti-apoptotic effect were evaluated in both intrinsic and extrinsic pathways using western blot analysis. Exposing PC12 cells to Cd for 24 h decreased cell viability and increased production of reactive oxygen species in comparison with the control group. Cd (35 µM) also elevated the level of caspase-8, Bax/Bcl-2, and caspase-3 proteins in the cells. Mino pre-treatment for 2 h (100 nM) increased the number of viable cells and decreased the production of reactive oxygen species, and the level of all apoptotic markers in comparison to Cd-treated cells. Considering all the evidence, it appears that Mino holds promising antioxidant and anti-apoptotic activity and can protect cells against Cd-induced oxidative stress and prevent apoptotic cell death.

Interaction of saffron and its constituents with Nrf2 signaling pathway: A review.

Saffron (Crocus sativus) is a natural compound and its constituents such as crocin, crocetin, and safranal have many pharmacological properties such as anti-oxidant, anti-inflammatory, antitumor, antigenotoxic, anti-depressant, hepatoprotective, cardioprotective, and neuroprotective. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays an important role against inflammation, oxidative stress, and carcinogenesis. In the regulation of the Nrf2 signaling pathway, kelch-like ECH-associated protein 1 (keap1) is the most studied pathway. In this review, we gathered various studies and describe the pharmacological effects of saffron and its constituents with their related mechanisms of action, particularly the Nrf2 signaling pathway. In this review, we used search engines or electronic databases including Scopus, Web of Science, and Pubmed, without time limitation. The search keywords contained saffron, "Crocus sativus", crocetin, crocin, safranal, picrocrocin, "nuclear factor erythroid 2-related factor 2", and Nrf2. Saffron and its constituents could have protective properties through various mechanisms particularly the Nrf2/HO-1/Keap1 signaling pathway in different tissues such as the liver, heart, brain, pancreas, lung, joints, colon, etc. The vast majority of studies discussed in this review indicate that saffron and its constituents could induce the Nrf2 signaling pathway leading to its anti-oxidant and therapeutic effects.

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.

Effect of carnosic acid on acrylamide induced neurotoxicity: in vivo and in vitro experiments.

Acrylamide (ACR), one of the most toxic chemical agents in humans and animals has several uses in different industries. Carnosic acid is an important biological antioxidant extracted from rosemary. In this study, the protective effect of carnosic acid on ACR-induced neurotoxicity in rat and PC12 cells has been investigated. Male Wistar rats were randomly divided into eight groups including (1) control group, (2) ACR (50 mg/kg, i.p.), (3-6) ACR plus carnosic acid (5, 10, 20, and 40 mg/kg, i.p.), (7) ACR plus vitamin E (200 mg/kg i.p., every other day), and (8) carnosic acid (40 mg/kg i.p.). After 11 days, behavioral tests were evaluated. Malondialdehyde (MDA), glutathione (GSH) and Bax, Bcl-2, and caspase 3 protein levels in brain tissue were measured. In in vitro study, the protective effects of carnosic acid on ACR toxicity were assessed by MTT assay. ACR caused severe motor impairment compared to control, increased MDA, and decreased GSH level. ACR increased Bax/Bcl-2 ratio and cleaved caspase-3. Carnosic acid (40 mg/kg) significantly recovered locomotor disorders. Additionally, carnosic acid increased GSH content, reduced MDA, and decreased Bax/Bcl-2 ratio, and caspase 3 protein levels. Carnosic acid increased cell viability compared to ACR at concentrations of 2.5-10 µM. Carnosic acid is the most abundant antioxidant compound found in the rosemary leaves. Recently, natural compounds have been suggested as potential treatment interventions for various diseases through their antioxidant properties. In this study, carnosic acid reduced ACR-induced toxicity through inhibition of oxidative stress and apoptosis.

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.

In search of elixir: Pharmacological agents against stem cell senescence.

Stem cell senescence causes different complications. In addition to the aging phenomenon, stem cell senescence has been investigated in various concepts such as cancer, adverse drug effects, and as a limiting factor in cell therapy. This manuscript examines protective medicines and supplements which are capable of hindering stem cell senescence. We searched the databases such as EMBASE, PubMed, and Web of Science with the keywords "stem cell," "progenitor cell," "satellite," "senescence" and excluded the keywords "cancer," "tumor," "malignancy" and "carcinoma" until June 2020. Among these results, we chose 47 relevant studies. Our investigation indicates that most of these studies examined endothelial progenitor cells, hematopoietic stem cells, mesenchymal stem cells, adipose-derived stem cells, and a few others were about less-discussed types of stem cells such as cardiac stem cells, myeloblasts, and induced pluripotent stem cells. From another aspect, 17ß-Estradiol, melatonin, metformin, rapamycin, coenzyme Q10, N-acetyl cysteine, and vitamin C were the most studied agents, while the main protective mechanism was through telomerase activity enhancement or oxidative damage ablation. Although many of these studies are in vitro, they are still worthwhile. Stem cell senescence in the in vitro expansion stage is an essential concern in clinical procedures of cell therapy. Moreover, in vitro studies are the first step for further in vivo and clinical studies. It is noteworthy to mention the fact that these protective agents have been used in the clinical setting for various purposes for a long time. Given that, we only need to examine their systemic anti-senescence effects and effective dosages.

Quercetin and metabolic syndrome: A review.

Metabolic syndrome (MetS) is a complex of diseases that lead to mortality due to the development of cardiovascular problems. Quercetin, as an important flavonoid, has various properties such as decreasing blood pressure, anti-hyperlipidemia, anti-hyperglycemia, anti-oxidant, antiviral, anticancer, anti-inflammatory, anti-microbial, neuroprotective, and cardio-protective effects. In this review article, we collected original articles from different sources such as Google Scholar, Medline, Scopus, and Pubmed, which is related to the effect of quercetin on the improvement of the signs of MetS, including elevated glucose level, hyperlipidemia, obesity, and blood pressure. According to these data, quercetin may also have a role in the management of metabolic disorders via different mechanisms such as increasing adiponectin, decreasing leptin, anti-oxidant activity, reduction of insulin resistance, the elevation of insulin level, and blocking of calcium channel. We have attempted to make some recommendations on the quercetin application in patients. However, it needs to do further clinical trials and more investigations to show the real clinical value of quercetin on metabolic syndrome.

The effects of Allium cepa L. (onion) and its active constituents on metabolic syndrome: A review.

Metabolic syndrome as a clustering disorder includes excess abdominal fat distribution, abnormal insulin and glucose metabolism, disturbed blood lipids, pro-inflammatory state, and hypertension. Regarding to the adverse effects of synthetic medicines, the identification of appropriate healthcare approaches, such as herbal medicines, with fewer side effects is more favorable. Allium cepa L. (onion) is a culinary and medicinal herb belonging to the family of Amaryllidaceae. Flavonoids such as quercetin and kaempferol, alk(en)yl cysteine sulfoxides including S-methyl cysteine sulfoxide and S-propyl cysteine sulfoxide, cycloalliin, thiosulfinates, and sulfides are main compounds existing in the plant. A. cepa and its pharmacologically active constituents display broad-spectrum activities including anti-oxidant, anti-inflammatory, lipid-modifying, anti-obesity, antihypertensive, and antidiabetic effects. Our objective in this review was to find out the role of A. cepa and its bioactive phytochemicals as cardiovascular protective agents in different metabolic syndrome risk factors, including hyperlipidemia, high blood glucose, obesity, and hypertension.

Effects of Nigella sativa oil and thymoquinone against bisphenol A-induced metabolic disorder in rats.

The underlying mechanisms of bisphenol A (BPA)-induced metabolic disorder and the protective impact of Nigella sativa oil (NSO) and thymoquinone (TQ) against BPA-induced metabolic disorder were investigated. Rats were treated as follows: Control, BPA (10 mg/kg), TQ (2 mg/kg), NSO (84 µL/kg), BPA + TQ (0.5, 1, 2 mg/kg), and BPA + NSO (21, 42, 84 µL/kg). BPA was administered by gavage, while, TQ and NSO were injected intraperitoneally (daily, 54 days). The weight, blood pressure, serum parameters [glucose, lipid profile, hepatic enzymes, insulin, interlukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, adiponectin], malondialdehyde (MDA), glutathione (GSH) and insulin signaling pathways [insulin receptor substrate (p-IRS,IRS); kinase (p-Akt,Akt); glycogen synthase kinase (p-GS3K,GS3K)] were measured. BPA increased the blood pressure, MDA, lipid profile, hepatic enzymes, insulin, IL-6, TNF-α, and leptin, and decreased the GSH and phosphorylated forms of IRS, Akt, GS3K but did not alter weight, glucose, IRS, AKT, and GS3K in the liver. Administration of NSO or TQ with BPA reduced the blood pressure, liver level of MDA, lipid profile, hepatic enzymes, insulin, IL-6, TNF-α, leptin, and increased the liver level of GSH and p-IRS, p-AKT, p-GS3K. TQ and NSO are thought to be effective in controlling metabolic disorders induced by BPA.

Investigating the ameliorative effect of alpha-mangostin on development and existing pain in a rat model of neuropathic pain.

Mangosteen fruit has been used for various disorders, including pain. The effects of alpha-mangostin, the main component of mangosteen, on the neuropathic pain caused by chronic constriction injury (CCI) were evaluated in rats. In treatment groups, alpha-mangostin (10, 50, 100 mg/kg/day, i.p.) was administered from Day 0, the day of surgery, for 14 days. The degree of heat hyperalgesia, cold, and mechanical allodynia was assessed on Days 0, 3, 5, 7, 10, and 14. The lumbar spinal cord levels of MDA, GSH, inflammatory markers (TLR-4, TNF-α, MMP2, COX2, IL-1ß, iNOS, and NO), apoptotic markers (Bcl-2, Bax, and caspase-3) were measured by western blot on Days 7 and 14. Rats in the CCI group showed thermal hyperalgesia, cold, and mechanical allodynia on Days 3-14. All concentrations of alpha-mangostin alleviated CCI-induced behavioral alterations. MDA level augmented and GSH level decreased in the CCI group and alpha-mangostin (50, 100 mg/kg) reversed the alterations. An enhancement in the levels of all inflammatory markers, Bax, and caspase-3 was shown on Days 7 and 14, which was controlled by alpha-mangostin (50 mg/kg). The detected antinociceptive effects of alpha-mangostin may be mediated through antioxidant, anti-inflammatory, and antiapoptotic properties.