Folate receptor alpha autoantibodies in the serum of patients with relapsing-remitting multiple sclerosis (RRMS).

OBJECTIVE: Multiple sclerosis (MS) is a potentially progressive, autoimmune neurologic disorder of the central nervous system (CNS), resulting from an autoimmune attack on central nervous system white matter. Folate deficiencies are linked to DNA instability and breakdown of phospholipid membranes and thus might affect myelin integrity. Folic acid exerts its effects through its receptors (FRs). Folate receptor alpha autoantibodies (FRAA) can block folate transport to the brain. Due to important role of folate in the pathogenesis of MS, in this project we aimed to study FRAA serum levels in patients with relapsing remitting multiple sclerosis (RRMS). METHODS: Fifty-four patients with RRMS and 58 healthy individuals were enrolled in this study. Serum samples were collected from all participants and folate receptor alpha autoantibody (FRAA) serum concentration was measured by Enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that FRAA serum levels in patients with RRMS is 67.20 ± 19.79 ng/ml as compared to controls which was 37.32 ± 13.26 ng/ml. Significant increase in folate receptor autoantibody serum concentration was seen in patients with RRMS when compared to control group (P = 0.007). The results showed that a high concentration of folate receptor autoantibody is associated with RRMS. We have also found that 85.18% (46/54) of patients with RRMS were positive for serum FRAA, whereas the prevalence in controls was only 46.55% (27/58). CONCLUSIONS: It is concluded that serum FRAA are more prevalent in RRMS patients than controls. The findings also suggest that FRAA might be involved in the pathophysiology of RRMS.

Evaluation of anti-oxidant and antimelanogenic effects of the essential oil and extracts of Rosa × damascena in B16F10 murine melanoma cell line.

Objectives: Rosa × damascena Herrm. belonging to the Rosaceae family has demonstrated anti-inflammatory and anti-oxidant effects previously. Excessive production of free radicals and activation of tyrosinase enzyme caused by UV induces excessive concentration of melanin pigment and skin spots in the long term. Therefore, finding natural sources with anti-oxidant and antityrosinase effects helps to regulate the melanogenesis process. In the current research, we investigated the antimelanogenic, anti-oxidant, and anti-tyrosinase effects of its essential oil, methanol extract (MeOH), and different fractions including n-hexane, dichloromethane (CH2Cl2), n-butanol (BuOH), ethyl acetate (EtOAc), and H2O of R. × damascena in B16F10 cell line. Materials and Methods: For this purpose, impacts of extracts and essential oil of R. × damascena were investigated on cell viability, cellular tyrosinase, melanin content, mushroom tyrosinase, reactive oxygen species (ROS) production, as well as the amount of tyrosinase protein in the B16F10 murine melanoma cell line. Results: Essential oil, MeOH, and different fractions of R. × damascena were not cytotoxic on B16F10 cells. However, they had significant reducing effects on mushroom tyrosinase activity, melanin content, and ROS production. Also, there is a significant decrease in tyrosinase protein levels at 200 µg/ml but not at other concentrations. Conclusion: Therefore, the essential oil, MeOH, and different fractions of R. × damascena had promising antimelanogenic activity via repression of mushroom tyrosinase activity and ROS production.

Effects of sesame (Sesamum indicum L.) and bioactive compounds (sesamin and sesamolin) on inflammation and atherosclerosis: A review.

Inflammation, oxidative stress, obesity, infection, hyperlipidemia, hypertension, and diabetes are the main causes of atherosclerosis, which in the long term lead to hardening of the arteries. In the current study, we reviewed recent findings of the mechanism of sesame and its active compounds of sesamin and sesamolin regulates on atherosclerosis. Sesame can decrease the lipid peroxidation and affect the enzymes, which control the balance of oxidative status in the body. Besides modulating the inflammatory cytokines, sesame regulates the main mediators of the signaling pathways in the process of inflammation, such as prostaglandin E2 (PGE2), nuclear factor kappa light-chain enhancer of activated B cells (NF-kB) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Sesame decreases the growth of different pathogens. It fights against obesity and helps to reduce weight, body mass index (BMI), waist circumference, and lipid count of serum and liver. In addition to lowering fasting blood sugar (FBS), it decreases the hemoglobin A1c (HbA1c) and glucose levels and improves insulin function. With high content of linoleic acid, α-linolenic acid, and total polyunsaturated fatty acid (PUFA), sesame efficiently controls the blood plasma lipids and changes the lipid profile. In the case of hypertension, it maintains the health of endothelium through multiple mechanisms and conserves the response of the arteries to vasodilation. PUFA in sesame suppresses blood clotting and fibrinogen activity. All the mentioned properties combat atherosclerosis and hardening of blood vessels, which are detailed in the present review for sesame.

Protective effects of Lavandula stoechas L. methanol extract against 6-OHDA-induced apoptosis in PC12 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder associated with oxidative stress-induced neuronal damage and death. In European and Persian Traditional Medicine, aerial parts (leaves, stems, and flowers) of Lavandula stoechas L. have been widely used for treating neurodegenerative disorders including PD. AIM OF THE STUDY: Herein, the protective effects of L. stoechas methanol extract were investigated on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and oxidative damage in PC12 cells. MATERIALS AND METHODS: The cells were pretreated with a standardized L. stoechas methanol extract (2.5-20 µg/mL) for 24 h and exposed to 6-OHDA (200 µM) thereafter. The cell viability percentage was determined by AlamarBlue test. Intracellular reactive oxygen species (ROS) production was determined by a fluorimetric method using 2',7'-dichlorodihydrofluorescein diacetate and cellular apoptosis was assessed by the fluorescent probe propidium iodide test. Finally, the expression of proteins involved in apoptosis pathway (Phospho SAPK/JNK, SAPK/JNK, p44/42 MAPK (ERK1/2) and Poly ADP ribose polymerase (PARP)) was measured via Western blot analysis. RESULTS: Treatment of PC12 cells with 6-OHDA could significantly increase cytotoxicity, ROS level, and cell apoptosis. Pretreatment of PC12 cells with the extract could significantly decrease 6-OHDA cytotoxicity, ROS production, (2.5 and 5 µg/mL) and cell apoptosis (5 µg/mL). Western blot analysis showed that 6-OHDA exposure could increase the expression of proteins involved in apoptosis signaling, while pretreatment with L. stoechas (5 µg/mL) reduced apoptotic proteins. CONCLUSIONS: The present study demonstrated that L. stoechas, which has been traditionally used in Persian Medicine for treating CNS diseases, is a valuable source of active compounds with neuroprotective, anti-oxidant, and anti-apoptotic activity.

Crocin Protects Against Beta-Amyloid Peptide-Induced Apoptosis in PC12 Cells Via the PI3 K Pathway.

BACKGROUND: Crocin is a known compound with the antioxidant and anti-inflammatory properties which may help to reduce the progression of neurological disorders. In this study, we aimed to investigate the protective effects of crocin on beta-amyloid peptide Aß (1-40) and hydrogen peroxide (H2O2) induced neurotoxicity in PC12 cells. METHODS: PC12 cells were pretreated with crocin and donepezil (5 and 10 µM) for 2 h and then treated with Aß (1-40) (25 µM) for 24 h. In parallel, after pretreatment with crocin (5 and 10 µM) and donepezil (5 and 10 µM) for 24 h, cells were treated with H2O2 (800 µM) for 4 h. Finally, the cell viability and intracellular reactive oxygen species (ROS) generation were evaluated using Alamar- Blue® and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. The western blot test was done to compare the protein level of phospho SAPK/JNK, SAPK/JNK, PI3 Kinase P85, Phospho-PI3 Kinase P85, caspase-3 and cytochrome c) cyt c). RESULTS: Crocin and donepezil could significantly decrease the Aß toxicity and ROS level. While treatment with Aß increased Cyt c release from mitochondria to cytosol, cleaved form of caspase-3 (17 kDa) and activated form of SAPK/JNK p44/4 decreased the activated form of PI3 Kinase P85 protein, indicating that crocin could significantly block the apoptosis initiated with Aß. CONCLUSION: According to the results, crocin could be a promising candidate for further evaluations against the development of Alzheimer's disease through mitogen-activated protein kinases (MAPK) and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling (PI3 K/AKT) pathways.

Biological effects of red beetroot and betalains: A review.

Over the past few years, the use of natural substances as protective or therapeutic agents has gained much attention worldwide. Recent modern studies have shown a variety of health benefits for red beetroot and its active compounds betalains (also betanin) such as antioxidative, anti-inflammation, anticancer, blood pressure and lipid lowering, also antidiabetic and anti-obesity effects. Betanin, the main component of the red beetroot, is a betalain glycosidic pigment, which is used as a food additive. This review summarizes findings in the literature and shows the therapeutic potential of red beetroot and its active compounds (betalains) as promising alternatives for supplemental therapies in multiple diseases.

Vitamin K2 protects PC12 cells against Aß (1-42) and H2O2-induced apoptosis via p38 MAP kinase pathway.

Alzheimer's is an age-related disease with a hallmark of progressive loss of memory formation followed by a damage in the brain function due to the neural degeneration and extracellular beta-amyloid (Aß) plaques accumulation. This study examines the protective effects of vitamin K2 on toxicity induced by (Aß) (1-42) and H2O2 in PC12 cells as an appropriate model of Alzheimer's cell damage. PC12 cells pretreated with vitamin K2 (5-200 µM) for 4, 24 and 48 h, and exposed to either Aß (25 µM) for 48 h or H2O2 (150 µM) for 24 h. Then the protective, antioxidant and anti-apoptotic effects of vitamin K2 in PC12 cells were investigated. Vitamin K2 pretreatment (5-200 µM) significantly decreased the Aß (1-42) and H2O2 cytotoxicity. In addition, vitamin K2 could attenuate reactive oxygen species (ROS) level after exposure of cells to H2O2 for 24 h and Aß (1-42) for 48 h. Cell apoptosis significantly increased following application of Aß (1-42) (25 µM) and H2O2 (150 µM) compared to control. However, flow cytometry histograms of PI-stained cells after pretreatment with vitamin K2 (20 and 50 µM) showed significantly reduced apoptosis. Vitamin K2 increased the amount of glutathione after exposure of cells to H2O2 for 24 h and Aß (1-42) for 48 h. Western blot analysis of PC12 cells showed that 25 µM Aß (1-42) and 150 µM H2O2 treatment could increase Bax, PARP cleavage, Phospho-p38 MAPK. Moreover, the activated form of caspase 3 proteins led to the reduction in the Bcl-2. Real-time PCR of PC12 cells showed that 150 µM H2O2 treatment increased the ratio of Bax/Bcl-2 while vitamin K2 (20 and 50 µM) reduced the rate. According to these findings, it seems that vitamin K2 possess anti-apoptotic and antioxidant effects and suggests that vitamin K2 may be a valuable protective candidate against the progression of Alzheimer's disease via inactivating p38 MAP kinase pathway.

Betanin Attenuates Oxidative Stress Induced by 6-OHDA in PC12 Cells via SAPK/JNK and PI3 K Pathways.

Parkinson's disease is a neurodegenerative disorder which accompanied with cognitive decline, chorei form moves and behavioral difficulties. Oxidative stress which promote the apoptotic cell death are responsible for neurodegeneration in Parkinson. The purpose of this study is to evaluate the protective effects of betanin against toxicity and oxidative damage induced by 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Parkinson's cell damage. PC12 cells pretreated with betanin (1-200 µM) for 24 h, and exposed to either 6-OHDA (100 µM) or H2O2 (150 µM) for 24 h. Cell survival and intracellular reactive oxygen species (ROS) production analyzed by resazurin and DCF-DA assay. The anti-apoptotic effects of betanin in PC12 cells were studied using flow cytometry of PI stained cells. Also, western blot analysis of survivin, Cyt c, Phospho SAPK/JNK, SAPK/JNK, Phospho-PI3 kinase P85, PI3 kinase P85 was performed for detection of apoptosis. Betanin (1-200 µM) significantly decreased the 6-OHDA and H2O2 cytotoxicity also attenuated the ROS level. Cell apoptosis significantly increased after 6-OHDA (100 µM) treatment, compared to the control. However, pretreatment with betanin (20 and 50 µM), protected against apoptosis. Western blot analysis of PC12 cells showed that 100 µM 6-OHDA could increase the proteins involved in apoptosis signaling and betanin (20 and 50 µM), could decrease the apoptosis. The results show that betanin has antioxidant and anti-apoptotic effects and may have the ability to prevent or delay the progress of neural death in Parkinson's disease.

Safranal protects against beta-amyloid peptide-induced cell toxicity in PC12 cells via MAPK and PI3 K pathways.

Alzheimer's disease is a type of cerebrovascular problem with progressive mental disabilities for the patient. This study aimed to investigate the protective effect of safranal on toxicity and oxidative damage induced by beta-amyloid (Aß) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Alzheimer's cell damage. PC12 cells pretreated with saffron extract (2.5-40 µg/ml), essential oil (2.5-40 µg/ml), safranal (2.5-5-40 µM) and donepezil (5, 10 and 20 µM) for 120 min. Then exposed to either Aß (25 µM) for 48 h or H2O2 (150 µM) for 24 h. In the end, the cell survival and intracellular reactive oxygen species (ROS) production analyzed. The anti-apoptotic effects of safranal in PC12 cells were studied using flow cytometry after PI staining. Also, western blot analysis of Cyt c, survivin, p44/42 MAPK (ERK1/2), Phospho-p44/42 MAPK (ERK1/2), PI3 Kinase P85, Phospho-PI3 Kinase P85, phospho SAPK/JNK, SAPK/JNK and caspase 3 performed for detection of apoptosis. Safranal (2.5 and 5 µM) and donepezil (10 and 20 µM) significantly decreased the Aß toxicity. The ROS significantly attenuated when cells pretreated with essential oil, saffron extract, safranal, and donepezil. Cell apoptosis significantly increased after treatment with Aß (25-35) (25 µM) compared to control. However, after pretreatment with safranal (2.5 µM) apoptosis was significantly reduced. Western blot analysis of PC12 cells showed that 25 µM Aß (25-35) could increase proteins involved in apoptosis signaling and pretreatment with safranal (2.5 µM) could decrease the apoptosis. According to the results, safranal showed anti-apoptotic and antioxidant effects and may exert promising potential for the prevention of Alzheimer's disease.

Anxiolytic-like effect of hydroalcoholic extract of ripe pistachio hulls in adult female Wistar rats and its possible mechanisms.

The present study was designed to study the preventive effect of hydroalcoholic extract of ripe pistachio hulls (RPH) in the elevated plus maze model of anxiety. One hundred twenty female wistar rats in their estrous cycle were divided into 15 groups of 8 each and received various concentrations of hydroalcoholic extract of RPH except the control groups. Elevated plus maze was used to measure the level of anxiety. Percentage of time spent in the open arms (%OAT), percentage of the number of entries into the open arms (%OAE), locomotor activity, and time spent in the closed arms (CAT), and the number of entries in to the closed arms (CAE) were measured and compared. Dose-response experiments showed that only 10 mg/kg dose of RPH extract significantly increased %OAT (P < 0.001) and %OAE (P < 0.05) compared to the control group, indicating anti-anxiety effects of the extract. Also, pentylenetetrazol and an estrogen receptor antagonist (ERA) tamoxifen could block anti-anxiety effects of the extract (P < 0.001). It was also noticed that tamoxifen was able to significantly reduce locomotor activity. As the RPH extract showed a preventive effect in experimental model of anxiety, it might be concomitantly administered with other anxiolytic medications.