Protective effects of peel and seed extracts of Citrus aurantium on glutamate-induced cytotoxicity in PC12 cell line

A b s t r a c t Oxidative stress and apoptosis contribute to neuronal degeneration in many neurodegenerative diseases such as Alzheimer's disease. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) and is considered responsible for the pathogenesis of many neurological disorders. Reactive oxygen species (ROS) production is thought to be involved in glutamate-induced apoptosis process. In this study, the neuroprotective effects of Citrus aurantium in the glutamate-induced rat's adrenal pheochromocytoma cell line (PC12 cells) were investigated. The cell viability and apoptotic cell death were measured using MTT and propidium iodine (PI)

Protective effect of Rheum turkestanicum root against mercuric chloride-induced hepatorenal toxicity in rats

Objective: The present study was designed to investigate the protective effects of hydroalcoholic extract of Rheum turkestanicum against HgCl2 hepatorenal toxicity in rats. Materials and Methods: Animals were randomly divided into five groups (n= 6 in each group) and received HgCl2 and plant’s extract, intraperitoneally. Group1 received saline (1 mL/kg/day), group 2 received extract (200 mg/kg/day), group 3 was treated with HgCl2 (5 mg/kg/day,) and groups 4 and 5 received the extract (100 and 200 mg/kg/day, respectively), 1 hr before HgCl2 administration. All injections last for 3 days. Blood samples and specimens of the liver and kidney were collected 24 hr after the last injection. Results: Data showed that HgCl2 significantly increases liver malondialdehyde (MDA) level, reduces total sulfhydryl content and increases serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, compared to control group. The histopathological changes such as inflammatory cells infiltration was observed in HgCl2-treated group while plant’s extract partially improved histological changes. The extract (100 and 200 mg/kg/day) improved the liver functions as reflected by significant reductions in AST and ALT levels in serum, MDA decreased and the content of total sulfhydryl elevated. Also, the extract improved necrosis and atrophy of the kidney induced byHgCl2. Pretreatment with the extract reduced creatinine and urea in serum, and glucose and protein concentrations in urine, compared to HgCl2- treated group (group III). The extract significantly reversed HgCl2-induced depletion in thiol content and elevation in MDA content. Conclusion: Therefore, oxidative stress may play an important role in HgCl2-induced hepatorenal injury and R. turkestanicum extract may be regarded as a useful to protect the kidney and liver against HgCl2-induced oxidative damage

Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats

Introduction: Oxidative stress is a major instigator of various cardiovascular diseases, including myocardial infarction (MI). Despite available drugs, there is still an increased need to look for alternative therapies or identify new bioactive compounds. Sanguisorba minor (S. minor) is a native herb characterized by its potent antioxidant activity. This study was designed to evaluate the effect of S. minor against isoprenaline-induced MI.Methods: Rats were treated with the hydro-ethanolic extract of the aerial parts of S. minor at doses of 100 or 300 mg/kg orally for 9 days. Isoprenaline was injected subcutaneously at the dose of 85 mg/kg on days 8 and 9. Then, the activities of various cardiac injury markers including cardiac troponin (cTnT), lactate dehydrogenase (LDH), creatinine kinase muscle brain (CK-MB), creatinine phosphokinase (CPK), and antioxidant enzymes in serum were determined. Malondialdehyde (MDA) and thiol content were measured in cardiac tissue, and histopathological analysis was conducted.Results: Our results show that isoprenaline increased the serum levels of cTnT, LDH, CK-MB, and CPK (p < 0.001) and elevated MDA levels (p < 0.001) in cardiac tissue. Isoprenaline also reduced superoxide dismutase (SOD), catalase, and thiol content (p < 0.001). Importantly, the extract abolished isoprenaline-induced MI by elevating SOD and catalase (p < 0.001), reducing levels of MDA, and diminishing levels of cTnT, LDH, CK-MB, and CPK cardiac markers (p < 0.001). Histopathological studies of the cardiac tissue showed isoprenaline-induced injury that was significantly attenuated by the extract.Conclusion: Our results suggest that S. minor could abrogate isoprenaline-induced cardiac toxicity due to its ability to mitigate oxidative stress

Protective effect of Rheum turkestanikum root against doxorubicin-induced toxicity in H9c2 cells

Abstract Doxorubicin is a chemotherapy drug but its clinical using is limited because of its cardiotoxicity. Reactive oxygen species play an important role in the pathological process. The aim of this study is to evaluate the protective effect of Rheum turkestanicum Janisch., Polygonaceae, against doxorubicin-induced apoptosis and death in H9c2 cells. The cells were incubated with different concentrations of R. turkestanicum extract and N-acetylcysteine as positive control for 2 h, followed by incubation with 5 µM doxorubicin for 24 h. Cell viability and apoptotic induction were determined by using MTT and PI assays, respectively. The level of reactive oxygen species and lipid peroxidation was measured by fluorimetric methods. Doxorubicin significantly decreased cell viability which was accompanied by an increase in ROS production and lipid peroxidation. Pretreatment with R. turkestanicum increased the viability of cardiomyocytes and could decrease lipid peroxidation and reactive oxygen species generation. Also, R. turkestanicum attenuated apoptotic induction. N-acetylcysteine at 100 µM reduced the levels of reactive oxygen species and lipid peroxidation. But, treating H9c2 cells with N-acetylcysteine did little to protect H9c2 cells from doxorubicin-induced cell death. R. turkestanicum exerts protective effect against oxidative stress-induced cardiomyocytes damage. Our findings showed that R. turkestanicum could exert the cardioprotective effects against doxorubicin-induced toxicity partly by anti-apoptotic activity. Also, N-acetylcysteine prevented oxidative stress via reduction of reactive oxygen species and lipid peroxidation. N-acetylcysteine induced less protective effects than R. turkestanicum extract against doxorubicin-induced cytotoxicity

Protective effects of peel and seed extracts of Citrus aurantium on glutamate-induced cytotoxicity in PC12 cell line

Oxidative stress and apoptosis contribute to neuronal degeneration in many neurodegenerative diseases such as Alzheimer’s disease. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) and is considered responsible for the pathogenesis of many neurological disorders. Reactive oxygen species (ROS) production is thought to be involved in glutamate-induced apoptosis process. In this study, the neuroprotective effects of Citrus aurantium in the glutamate-induced rat’s adrenal pheochromocytoma cell line (PC12 cells) were investigated. The cell viability and apoptotic cell death were measured using MTT and propidium iodine (PI)-staining methods, respectively. In addition, intracellular ROS and malondialdehyde (MDA) levels were determined by fluorometric methods. The results showed that glutamate cytotoxicity in PC12 cells was accompanied by an increment of MDA content, ROS generation, and apoptotic induction. However, pretreatment with peel and seed extracts of C. aurantium significantly reduced MDA content, ROS generation, and apoptotic cells. All these findings indicated that C. aurantium protected PC12 cells against glutamate-induced apoptosis by inhibiting ROS production. Therefore, the present study supports that C. aurantium extracts possess neuroprotective effects against glutamate-induced toxicity in PC12 cell line. The protective effect of C. aurantium might be attributed to its antioxidant properties

Protective potential of naringenin and its nanoformulations in redox mechanisms of injury and disease

Increasing evidence suggests that elevated intracellular levels of reactive oxygen species (ROS) play a significant role in the pathogenesis of many diseases. Increased intracellular levels of ROS can lead to the oxidation of lipids, DNA, and proteins, contributing to cellular damage. Hence, the maintenance of redox hemostasis is essential. Naringenin (NAR) is a flavonoid included in the flavanones subcategory. Various pharmacological actions have been ascribable to this phytochemical composition, including antioxidant, anti-inflammatory, antibacterial, antiviral, antitumor, antiadipogenic, neuro-, and cardio-protective activities. This review focused on the underlying mechanism responsible for the antioxidative stress properties of NAR and its' nanoformulations. Several lines of in vitro and in vivo investigations suggest the effects of NAR and its nanoformulation on their target cells via modulating signaling pathways. These nanoformulations include nanoemulsion, nanocarriers, solid lipid nanoparticles (SLN), and nanomicelle. This review also highlights several beneficial health effects of NAR nanoformulations on human diseases including brain disorders, cancer, rheumatoid arthritis, and small intestine injuries. Employing nanoformulation can improve the pharmacokinetic properties of NAR and consequently efficiency by reducing its limitations, such as low bioavailability. The protective effects of NAR and its’ nanoformulations against oxidative stress may be linked to the modulation of Nrf2-heme oxygenase-1, NO/cGMP/potassium channel, COX-2, NF-κB, AMPK/SIRT3, PI3K/Akt/mTOR, BDNF, NOX, and LOX-1 pathways. Understanding the mechanism behind the protective effects of NAR can facilitate drug development for the treatment of oxidative stress-related disorders

Effects of standardized extract of Ferula gummosa root on glutamate-induced neurotoxicity

Glutamate is one of the major excitatory neurotransmitters in the central nervous system. Increasing glutamate leads to neurodegenerative disease. Nowadays, plant medicine plays a role in the treatment of some disorders. In this research, we investigated the neuroprotective effect of Ferula gummosa root extract against glutamate-induced oxidative stress in the rat adrenal pheochromocytoma (PC12) and mouse neuroblastoma (N2a) cell lines. The cells were pretreated with extract for 2 h and then exposed to glutamate for 24 h. After 24 h the level of malondialdehyde (MDA), reactive oxygen species (ROS), and apoptotic cells were determined in both cell lines. Glutamate increased lipid peroxidation, ROS, and apoptotic cells in both cell lines. The extract significantly increased the cell viability and decreased the ROS generation under glutamate-induced oxidative stress in these cells. Also, the extract decreased the MDA level and apoptotic cells. The results showed that Ferula gummosa root may have a protective effect on glutamate-induced toxicity, suggesting that the extract protects neuronal cells from glutamate-induced oxidative stress

Punica granatum peel supplementation attenuates cognitive deficits and brain injury in rat by targeting the Nrf2-HO-1 pathway

The critical role of nutrition to prevent neurodegenerative disorders is well documented. Punica granatum fruit is identified as a highly nutritional food for alleviating various ailments. The ameliorating properties of P. granatum peel on memory dysfunction and the possible roles of oxidative stress, acetylcholinesterase (AchE), and nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway in the scopolamine-treated rats were assessed. The hydroethanolic extract was standardized using high-performance liquid chromatography (HPLC). The animal groups were as follows: Control, scopolamine (2 mg/kg), and treatment groups (the extract at doses of 200–800 mg/kg). The behavioral performance was evaluated using the Morris water maze (MWM) and passive avoidance equipment. Various biochemical parameters were then measured. Rats received the extract properly found on the platform location, indicated by a shorter traveling time and distance during 5 days of learning MWM. Moreover, the extract increased the delay and light time, while decreasing dark time and the frequency of entries to the dark in the passive avoidance test. The extract also exerted a significant increase in superoxide dismutase activity and thiol content, while decreasing AchE activity and lipid peroxidation in the brain of scopolamine-injured rats. Our results demonstrated the neuroprotective effects of P. granatum peel in minimizing scopolamine injury possibly through targeting the Nrf2-HO-1 pathway

Evaluation of the immune-modulatory, anti-oxidant, proliferative, and anti-apoptotic effects of nano-silymarin on mesenchymal stem cells isolated from multiple sclerosis patients' adipose tissue sources

Silymarin (SL) has a long history of use for the treatment of a variety of diseases, but several limitations, such as poor bioavailability and negligible solubility, have restricted its successful translation in a clinical setting. However, the nano-micelle delivery system is a highly reproducible method which capable of improving poor-water solubility and bioavailability of free-SL. Mesenchymal stem cells (MSCs) are multipotent cells proficient in tissue renewal and regeneration. MSCs have similar properties to SL including immunomodulatory, antioxidant, and neuroprotective effects. Here, we show that nano-SL (1 and 2.5) increased AD-MSCs proliferation and protected from apoptosis. Our findings indicated that the levels of anti-inflammatory agents including IL-10, IL-4, FOXp3 and TGF-B mRNA expression were significantly upregulated in nano-SL-treated MSCs along with downregulated mRNA expression of pro-inflammatory cytokines (IL-6, IL-17). We identified that nano-SL elevated the T-regulatory (Treg) population (1 and 2.5 µM) and superoxide dismutase activity (2.5 µM) while decreasing nitrite oxide content. Conclusively, combinatorial therapy by nano-SL and MSCs may be useful for MS patients who are receiving MSCs for treatment