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Introduction: Since there is very little information about the relationship between platelet parameters and vitamin D concentration in patients with COVID-19, the aim of this study is to investigate the relationship between serum vitamin D level and platelet parameters in patients with COVID-19 and to compare these parameters in patients with COVID-19 without vitamin D deficiency and, subsequently, the prognostic value of these parameters in cases of vitamin D deficiency., Methods: Seven hundred and forty-three patients diagnosed with COVID-19 were enrolled in this study. Patients were divided into two groups: those with and without vitamin D deficiency. The associations between platelet indices and vitamin D levels were analyzed by Pearson's correlation analysis and a one-way ANOVA test., Results: Platelet count and mean platelet volume (MPV) were significantly higher in the patients with vitamin D deficiency than in the patients without vitamin D deficiency. There was a significant negative correlation between platelet count and MPV with vitamin D levels in patients with vitamin D deficiency (r = -0.835, P = 0.001 & r = -0.324, P = 0.042, respectively). Vitamin D levels in COVID-19 patients can determine the platelet count and MPV of the patients., Discussion: The aforementioned results imply that maintaining an elevated concentration of vitamin D in COVID-19 patients is important because it is associated with a decrease in MPV, which in turn reduces susceptibility to diseases such as coronary artery disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Talebzadeh, Ghaffari, Ghaffari, Yazdanpanah, Yousefi Goltappeh, Eslami and Ghasemi.)

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe neurological defects. Evidence is mounting that immune function is crucial in neuroinflammatory illnesses like MS. Through its impact on systemic immunological reactions, the large microbial population known as the gut microbiota has been linked to both human health and disease. The gut-brain axis (GBA) therefore encompasses neurological, immunological, and hormonal pathways, and microbiota can have a number of effects on the immune system, influencing MS. Recent research revealed a bidirectional relationship between metabolites originating from the gut microbiota, namely short-chain fatty acids (SCFAs). Intestinal epithelial cells are influenced by SCFAs, which also boosts the secretion of -Defensins and regenerating islet-derived III (REGIII) proteins. These proteins reduce intestinal pathogens, induce T-reg differentiation, and modulate immune responses by reducing IL-1 and IL-6 expression and increasing IL-10. Nutrition and psychological stress are two of the most significant elements that can directly and indirectly change the microbiota compositions along with other environmental influencing factors. An important regulator of intestinal physiology in the gut-brain-microbiota axis is butyrate, a well-known SCFA. Intestinal dysbiosis, altered intestinal barrier function, behavioral abnormalities, and activation of the hypothalamic-pituitary-adrenal (HPA) axis are all brought on by exposure. Probiotics, bacterial metabolite supplementation, fecal matter transplantation, defined microbial communities, and dietary intervention are some methods for modifying the composition of the gut microbiota that may be used to affect disease-related immune dysfunction and serve as the foundation for a new class of therapeutics., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Coronary artery disease (CAD) is a leading cause of death around the world. Micro-ribonucleic acid (miRNA) can be involved in forming of atherosclerotic plaques, inflammation, cholesterol metabolism, and other mechanisms involved in CAD development. This study aimed to evaluate the expression level of miR-22, miR-30c, miR-145, and miR-519d and their possible association with inflammatory markers among patients with CAD., Methods: The expression level of miR-22, miR-30c, miR-145, miR-519d, interleukin 6 (IL-6), and transforming growth factor beta (TGF-β) was determined in peripheral blood mononuclear cells (PBMCs) from 46 patients with CAD and 39 healthy controls using real-time quantitative polymerase chain reaction (qPCR) assay., Results: 53.8% (n = 21) and 52.2% (n = 24) of controls and cases were men, respectively; the mean age was 59.8 ± 7.4 and 57.0 ± 9.8 years, respectively. The miRNA expression pattern of each group showed significantly different expression profiles. In the CAD patients group, miR-22, miR-30c, and miR-145 were down-regulated compared to the control group. On the opposite, miR-519d was up-regulated in patients with CAD compared to the control group. Our results also showed that the expression levels of IL-6 and TGF-β were up-regulated among patients with CAD compared to the control group. In addition, the expression of miR-145 and miR-519d had a significantly negative and positive correlation with TGF-β and IL-6, respectively., Conclusion: The change in expression levels of miR-22, miR-30c, miR-145, and miR-519d in PBMCs of patients with CAD could be considered as a potential biomarker for CAD., (© 2022 Isfahan Cardiovascular Research Center & Isfahan University of Medical Sciences.)

Background: Glioblastoma multiforme is the most invasive and lethal form of brain cancer with unclear etiology. Our study aimed to investigate the molecular prevalence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in patients with glioblastoma multiforme (GBM)., Methods: This case-control study was conducted on 42 FFPE brain tumor samples from GBM patients and 42 brain autopsies from subjects without neurological disorders. The presence of EBV and HCMV DNA was determined, using PCR and nested-PCR assays, respectively., Results: HCMV DNA was detected in 3 out of 42 (7.1%) of GBM samples and was absent from the control group (p = 0.07). Importantly, EBV DNA was detected in 9 out of 42 (21.4%) brain tissue specimens of GBM subjects, but again in none of the control group (p = 0.001)., Conclusion: Our findings indicate that infection with EBV is associated with GBM.

The rapid spread of coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2, poses a huge demand for immediate diagnosis. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) of nasopharyngeal (NP) and oropharyngeal (OP) swabs have been used to confirm the clinical diagnosis. To avoid the risk of viral-exposure of laboratory workers, thermal inactivation is currently recommended but has unknown effects on the accuracy of the rRT-PCR results. Thirty-six NP/OP specimens were collected from COVID-19 patients and subjected to thermal inactivation (60°C for 30 min) or the RNA extraction processes to activate the form. Here, our data showed that the concentration of extracted-RNA increases upon thermal inactivation compared to the active form (p = .028).  Significantly higher levels of RNA copy number were obtained in inactivated compared to the active samples for both N and ORF1ab genes (p = .009, p = .032, respectively). Thermal inactivation elevated concentration and copy number of extracted-RNA, possibly through viral-capsid degradation and/or nucleoprotein denaturation., (© 2020 Wiley Periodicals LLC.)

While limited investigations have been reported on CTC elimination and its profits, recently, some new works were reported on detection followed by the destruction of CTCs. Limitations and complications of CTC capturing procedures have highly reduced the chance of selective destruction of CTCs in the bloodstream in the therapeutic guidelines of the patients. Here, we selectively deactivated the invasive function of CTCs during their circulation in the bloodstream by exposing the whole blood to pure positive electrostatic charge stimulation (PPECS). Our treatment suppressed pulmonary metastasis and extended the survival of the mice had been intravenously injected by electrostatically deactivated 4T1 breast cancer CTCs. Moreover, the number of cancerous lung nodules was drastically reduced in the mice injected by treated CTCs in comparison with the non-treated cohort. Evaluating the side effect of the PPECS on the blood components revealed no major effect on the functional properties of the white blood cells, and just a negligible fraction (∼10%) was damaged during this process. This approach does not need any capturing or targeting of CTCs from the blood as it is focused on perturbing the electrical function of negatively-charged tumor cells after being exposed to positive electrostatic charges. Taken together, continuous in-vivo deactivation of CTCs by PPECS with no requirement to complicated capturing protocols may improve the survival of cancer patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The emergence of drug-resistant strains of herpes simplex virus type 1 (HSV-1) has been increasingly reported. Therefore, attempts to discover new antiviral agents in particular from natural compounds are required. In this study, we evaluated the possible inhibitory effects of hydroalcoholic extract of Sambucus ebulus ( S. ebulus ) against HSV-1. Methods: S. ebulus extract was produced by maceration method. MTT assay was used to evaluate the cytotoxicity effects of the S. ebulus extract; also, antiviral effects were measured both by test TCID50 and quantitative real-time PCR methods. To study the inhibitory impact of S. ebulus extract on the expression of HSV-1 antigens, indirect immunofluorescence assay (IFA) was also performed. All analyses were performed using the GraphPad Prism software v. 7.0. Results: In the postexposure assay of HSV-1 with S. ebulus extract at the highest nontoxic concentration (75 μg/mL), S. ebulus extract led to 2.6 log10 TCID50 reduction in infectious virus titer. At the highest nontoxic concentration, the S. ebulus extract led to inhibition rates of 91.2%, based on the quantitative real-time PCR assay results (p<0.001). Also, in the immunofluorescence assay, a significant reduction was observed in fluorescence emission intensity in HSV-1-infected cell treated with S. ebulus extract compared to the control group. Conclusion: S. ebulus extract is a novel and effective natural compound in reducing HSV-1 titer and future studies should be conducted to discover the complete mechanism of antiviral effect of this natural compound., (© 2021 Iran University of Medical Sciences.)

Background and Objectives: The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in breast cancer pathology is not well understood. Our study aimed to investigate the association of HCMV and EBV infections with breast cancer and distinguish the types of positive EBV and LMP-1 samples in Iranian patients., Methods: Seventy-two formalin-fixed paraffin-embedded (FFPE) breast cancer tissues were analyzed between December 2014 and April 2016. Samples were analyzed for HCMV and EBV using nested-PCR and conventional PCR assays, respectively. Statistical analysis was performed using SPSS software version 18., Results: Overall, HCMV and EBV genomes were detected in 6.9% and 16.7% of FFPE breast cancer tissues, respectively. Clinical factors were not statistically associated with the presence of HCMV and EBV., Conclusion: In this study, we reported EBV and LMP-1 typing in breast carcinoma cases for the first time in Iran. Our findings indicate that HCMV and EBV infections are not associated with the development of breast cancer.

Background: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are important public health issues., Objective: This study aimed to assess the association between microRNAs expression leveland immunological and viral markers in HIV, HCV, and HIV/HCV co-infected patients., Methods: The expression level of miR-29, miR-149, miR-199, miR-let7, miR-223, miR-155, miR-122, and miR-150 was evaluated in 20 HIV, 20 HCV, 20 co-infected patients, and 20 healthy controls using real-time PCR assay. HIV and HCVviral loads were measuredby real-time PCR, and also, CD4+ T-lymphocyte count was measuredby the PIMA CD4 analyzer., Results: The miRNA expression pattern in each mentioned group showed significantly different expression profiles, but some miRNA species were shared between the groups. MiR-122 and miR-155 were upregulated, while miR-29 and miR-223 were downregulated in three patients groups compared to healthy controls. A significant positive correlation was observed between the expression of miR-122 and HIV/HCV loads. But, miR-29 and let-7 were negatively correlated with HIV load, and miR-149 and let-7 were negatively correlated with HCV load. Also, miR-155 was positively correlated with HCV load. MiR-122 and miR-199 were negative while others were positively correlated with CD4+ T cell count., Conclusion: These miRNAs are probably involved in the clinical progression and pathogenesis of HIV and HCV infections. Therefore, determining and manipulating these miRNAs can lead to opening a new gate to control these important infections., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019-nCoV). So far, there are no specific treatments for patients with coronavirus disease-19 (COVID-19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID-19. Cathepsin L is required for entry of the 2019-nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin-converting-enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID-19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019-nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS-CoV disease and can be useful for patients of COVID-19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS-CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS-CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID-19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids., (© 2020 Wiley Periodicals LLC.)

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc , promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1 , more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P  = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC., Competing Interests: Competing interestsAll the authors have stated to have no conflict of interest for declaration., (© The Author(s) 2020.)

Background: Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus., Methods: The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed., Results: Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6 and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control., Conclusions: Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.

Despite the numerous publications regarding the role of Epstein-Barr virus (EBV) in breast cancer development, the topic has still remained controversial. The aim of the meta-analysis was to estimate the overall prevalence of EBV in the breast cancer population, and to investigate the association between EBV and breast cancer risk. The overall prevalence of EBV was calculated 26.37% (95% CI: 22-31%) from the 44 included studies. Meta-analysis of 30 case-control studies showed that the pooled association between EBV and risk of breast cancer is odds ratio 4.74 (95% CI: 2.92-7.69; Z = 6.30; p < 0.0001). Our analyses indicate a strong statistical relationship between EBV infection and risk of breast cancer, suggesting a potential role of EBV infection in the development of breast cancer.

Background: Some studies implicate rotavirus infection as a trigger for the development of type 1 diabetes mellitus (T1DM) in children, however findings are controversial., Objectives: We investigated the link between rotavirus infection and autoantibodies against islet antigens and T1DM in children., Methods: Serum samples from 80 new-onset diabetic and 80 nondiabetic children were screened for anti-rotavirus IgG, anti-GAD65 and anti-IA-2 autoantibodies using ELISA kits., Results: Positivity percentages of anti-rotavirus IgG detection in diabetic and nondiabetic children were 51.3% and 35.0%, respectively (p = 0.03). The mean anti-GAD65 and anti-IA-2 antibody titers in anti-rotavirus IgG positive samples were statistically higher than that the anti-rotavirus IgG negative samples. A positive correlation was found between anti-rotavirus IgG and anti-GAD65 antibody levels (p = 0.004; r = 0.22)., Conclusions: Our findings support the hypothesis that rotovirus infection may induce T1DM in children.

Background: Different outcomes of parvovirus B19 (B19V) infection in immunocompromised patients, including HIV1-infected persons, may be life-threatening. Considering the hematologic disorders associated with B19V infection, this study aimed to investigate the prevalence of B19V infection among HIV1-infected individuals in Iran. Methods: Serum samples from 100 HIV1-infected patients were analyzed for B19 viral DNA using real-time PCR assay. COBAS TaqMan HIV-1 test was performed for quantitative measurements of HIV-1 RNA in the patients' sera. Results: Real-time PCR analysis revealed that 10 out of 100 cases (10%) were positive for B19V infection. Across various age groups, the B19V infection was more prevalent among patients within the age range of 21-40 years. Higher prevalence of B19V infection was observed among HIV1-infected patients with a viral load of higher than 400 copies/mL. Conclusion: Despite limitations, this study may set the stage for further evaluations with larger sample sizes to elucidate the potential role of B19V in hematologic disorders, which may result in exacerbation of the disease in HIV1-infected patients. Moreover, as it has been shown that B19V infection can be treated using intravenous immunoglobulin (IVIG) therapy, available treatments may help improve the quality of life in HIV-infected persons.

Background: Colorectal cancer (CRC) is widespread across the world. While conventional anticancer treatments can help the affected patients, cells of vital organs such as the kidney, lungs, bladder and nervous system may suffer from side effects of chemotherapeutic drugs, so that it is necessary to search for alternatives. From ancient times, attention has focused on medicinal plants and natural products. In the current work, Camellia sinensis, whose leaves are used to produce green tea was evaluated for anticancer effects in cell culture. Materials and Methods: A hydroalcoholic extract of Camellia sinensis young leaves was prepared by percolation and compared with Cisplatin as a known anticancer drug for effects on two cell lines: Caco-2, colon carcinoma cells, and mouse normal fibroblasts (L929). Cytotoxicity of 50, 100, 200, 400 and 800 μg/ml of Camellia sinensis extract was evaluated by MTT assay and aquaporin 5 (AQP5), detected as a biomarker for surviving cells using immunofluorescence microscopy. Results: MTT assays with hydroalcoholic extract of Camellia sinensis showed considerable inhibition of growth of Caco-2 cells, significant at 800 μg/ml (P<0.05), with little effect on L929 cells. Levels of aquaporin 5 protein decreased in Caco-2 cell culture following green tea extract treatment. Conclusion: According to the results of the current study, Camellia sinensis is a medicinal plant with potent anticancer influence which might be specific., (Creative Commons Attribution License)

Background: Human parvovirus B19 was known as one of the possible cause of mild respiratory tract diseases in previous studies. However, there are some reports of acute obstructive respiratory disease and severe pneumonia. The purpose of current study was to assess the prevalence and clinical features of parvovirus B19 in respiratory infection. Methods: This study was conducted on 156 patients diagnosed with respiratory infection at the Iran University of Medical Sciencesaffiliated hospitals. After extraction of viral DNA from swab samples, detection of parvovirus B19 was performed by real-time PCR assay. Results: In 156 patient's samples, parvovirus B19 was found in 8 (5.1 %) cases including 5 males (5.9%) and 3 females (4.1%). The most common clinical symptoms were wheezing (100%), tachypnea (100%), fever (75%) and rhinorrhea/pharyngitis (75%). Conclusion: This is the first attempt to assess the prevalence of parvovirus B19 infection in Iranian patients with respiratory infection. The low frequency of parvovirus B19 detected in our study does not support the role of this virus in the development of respiratory infection. However, further studies are needed to better evaluate the etiological role of parvovirus B19 in respiratory infection.

Background: The etiology and molecular mechanisms involved in the development of breast cancer still remain poorly understood. Some epidemiological studies have shown an association between human papillomavirus (HPV) and breast cancer. However, the findings are controversial., Objective: Our study was aimed to investigate the presence of HPV DNA in breast carcinomas of Iranian women., Methods: In total, 72 samples of formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer collected between December 2014 and April 2016 were examined. HPV DNA detection was performed by nested-PCR assay. Next, positive samples were subjected to genotyping by the CLART HPV2 microarray system. All statistical analysis was carried out using SPSS v.18.0., Results: HPV DNA was detected in 4/72 (5.55%) samples. Clinical factors were not statistically associated with HPV presence. However, CLART HPV2 microarray assay failed to determine the genotype of any positive samples., Conclusion: The low frequency of HPV detected in our study does not support an association between breast carcinoma and HPV infection. However, it is possible that HPV may be responsible for breast carcinogenesis only in small percentage of all breast cancer.

Background: Human parvovirus B19 (B19V) is one of the smallest DNA viruses and shows great resistance to most disinfectants. Therefore, it is one of the common contaminant pathogens present in blood and plasma products. Parvovirus 4 (PARV4) is a newly identified parvovirus, which is also prevalent in parenteral transmission. In this study, we aimed to evaluate the prevalence of B19V and PARV4 DNA among patients with hemophilia in Birjand County in eastern Iran., Methods: This was a cross-sectional epidemiological study comprising nearly all people with hemophilia in this region. Whole blood samples were taken after patient registration and sent for plasma isolation. After nucleic acid extraction, B19V was detected with real-time polymerase chain reaction, PARV4 DNA was then detected using sensitive semi-nested PCR., Results: In total, there were 86 patients with hemophilia, with mean age 28.5±1.5 years. Of these, 90.7% were men and 9.3% women; 84.9% had hemophilia A and 7.0% had hemophilia B. We found 11 patients (12.8%) were positive for B19V DNA and 8 were positive (9.3%) for PARV4 DNA. The prevalence of B19V was higher in middle-aged groups rather than younger people, whereas PARV4 infection was more common in younger patients ( P <0.05)., Conclusion: There was a high prevalence of B19V and PARV4 infection in this high-risk group of patients with hemophilia. Due to the clinical significance of the B19 virus, imposing more precautionary measures for serum and blood products is recommended., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Aims: Oxidative stress plays a key role in several ailments including neurodegenerative conditions. The aim of the study was to demonstrate the effect of rosmarinic acid (RA) in preventing oxidative stress related death of neuronal cell lines., Main Methods: In the present study, we demonstrated direct neuroprotective effect of RA using H2O2-induced oxidative challenge in N2A mouse neuroblastoma cells. The mechanism of neutralization of H2O2-induced toxicity by RA was evaluated using MTT, lactate dehydrogenase, mitochondrial membrane potential (MMP), intracellular ROS, and comet assays. Up-regulation of brain neuronal markers at molecular level was performed by RT-PCR., Key Findings: Results presented in the paper indicate that H2O2-induced cytotoxicity in N2A cells was suppressed by treatment with RA. Moreover, RA is very effective in attenuating the disruption of lactate dehydrogenase, mitochondrial membrane potential and intracellular ROS. Pretreatment with RA significantly prevents genotoxicity (3.7-fold, p<0.01) and promotes the up-regulation of tyrosine hydroxylase (TH) (4.5-fold, p<0.01), and brain-derived neurotrophic factor (BDNF) genes (5.4-fold, p<0.01) against H2O2-induced cytotoxicity in N2A cells., Significance: Our results revealed that N2A cells are suitable cellular models to evaluate neuroprotective effects of RA, and suggest that RA may potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Solanum xanthocarpum Schard. and Wendl. (Solanaceae) has been used in traditional Indian medicines for its antioxidant, anti-inflammatory, and antiasthmatic properties., Objective: The present study demonstrates the antioxidant and hepatoprotective effects of S. xanthocarpum. On the basis of in vitro antioxidant properties, the active fraction from column chromatography of the methanol extract of S. xanthocarpum leaves (SXAF) was chosen as the potent fraction and used for hepatoprotective studies in rats., Materials and Methods: The antioxidant activity was evaluated by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reducing power assays. Rats were pre-treated with 100 and 200 mg/kg b.w. of SXAF for 14 d with a single dose of CCl4 in the last day. Hepatoprotective properties were determined by serum biochemical enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), antioxidant enzymes (SOD, CAT, GSH, and GST), and histopathology studies., Results: SXAF exhibited significant antioxidant activity in scavenging free radicals with IC50 values of 11.72 µg (DPPH) and 17.99 µg (ABTS). Rats pre-treated with SXAF demonstrated significantly reduced levels of serum LDH (1.7-fold), ALP (1.6-fold), and AST (1.8-fold). Similarly, multiple dose SXAF administration at 200 mg/kg b.w. demonstrated significantly enhanced levels of SOD (1.78 ± 0.13), CAT (34.63 ± 1.98), GST (231.64 ± 14.28), and GSH (8.23 ± 0.48) in liver homogenates. Histopathological examination showed lowered liver damage in SXAF-treated groups., Discussion and Conclusion: These results demonstrate that SXAF possesses potent antioxidant properties as well as hepatoprotective effects against CCl4-induced hepatotoxicity.

The present study was carried out to investigate the antioxidant and neuroprotective effects of Hyptis suaveolens methanol extract (HSME) using various in vitro systems. The total phenol and flavonoids contents of the HSME were quantified by colorimetric methods. The HSME extract exhibited potent antioxidant activity as determined by 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, 2,2-diphenyl-1-picrylhydrazyl, and ferric reducing antioxidant power assays. The neuroprotective activity of HSME was determined on mouse N2A neuroblastoma cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase, intracellular ROS assays, and upregulation of brain neuronal markers at genetic level. The N2A cells were pretreated with different concentrations (0.5, 1, 1.5, and 2 mg/ml) of the extract and then exposed to H2O2 to induce oxidative stress and neurotoxicity. The survival of the cells treated with different concentrations of HSME and H2O2 increased as compared to cells exposed only to H2O2 (47.3 %) (p < 0.05). The HSME also dose-dependently reduced LDH leakage and intracellular ROS production (p < 0.05). Pretreatment with HSME promotes the upregulation of tyrosine hydroxylase (2.41-fold, p < 0.05), and brain-derived neurotrophic factor genes (2.15-fold, p < 0.05) against H2O2-induced cytotoxicity in N2A cells. Moreover, the HSME showed antioxidant activity and decreased neurotoxicity. These observations suggest that HSME have marked antioxidant and neuroprotective activities.

Ethnopharmacological Relevance: Preparations of Orthosiphon diffusus (Benth.) have been used by folk medicinal practitioners in the Western Ghats of India for treating inflammation, hepatitis and jaundice for many years and their effectiveness is widely acclaimed among the tribal communities., Aim of the Study: To evaluate the mechanisms behind the antioxidant and hepatoprotective potential of Orthosiphon diffusus methanol active fraction (MAF) using in vivo (rat) and in vitro (cell culture) models., Materials and Methods: Neutralization of CCl4-induced hepatotoxicity by MAF was evaluated in rats. Towards this, serum levels of hepatic injury markers (lactate dehydrogenase and alkaline phosphatase), antioxidant enzymes in the liver homogenates, and histological examination were performed. In in vitro studies, mechanisms of neutralization of H2O2-induced toxicity by MAF using MTT, Comet assay and up-regulation of antioxidant enzymes at genetic level (RT-PCR) was performed in HepG2 cells., Results: Rats pre-treated with Orthosiphon diffusus MAF demonstrated significantly reduced levels of serum LDH (1.3-fold, p<0.05) and ALP (1.6-fold, p<0.05). Similarly, multiple dose MAF administration demonstrated significantly enhanced levels (p<0.05) of antioxidant enzymes in the liver homogenates. Histological analysis revealed complete neutralization of CCl4-induced liver injury by the extract. The in vitro studies demonstrated that, pre-treatment of MAF effectively prevented H2O2-induced oxidative stress, genotoxicity and significantly enhanced (~6-fold, p<0.01) expression of genes for antioxidant enzymes., Conclusions: Orthosiphon diffusus MAF demonstrated significant hepatoprotection against CCl4-induced hepatotoxicity by antioxidant mechanisms comparable to silymarin. H2O2-induced oxidative stress was completely neutralized by MAF through enhanced expression of genes for antioxidant enzymes. Therefore, this study validates the use of Orthosiphon diffusus by folk medicinal practitioners in India. Further, MAF of Orthosiphon diffusus can serve as a strong candidate for the development of herbal hepatoprotective agents., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate capacity of Hyptis suaveolens (H. suaveolens) methanol extract as an antioxidant to protect against carbon tetrachloride (CCl(4))-induced oxidative stress, hepatotoxicity in Albino Wistar rats and cytoprotective effect of hydrogen peroxide (H(2)O(2)) induced cell death in HepG(2) cell line., Methods: Two different doses of methanol extract of H. suaveolens were evaluated for the hepatoprotective activity against carbon tetrachloride (CCl(4)) induced hepatotoxicity in rats. Animals in Group I: served as control, group II: H. suaveolens (100 mL/kg b.w), group III: H. suaveolens (50 mL/kg b.w) + CCl(4) (1 mg/kg), group IV: H. suaveolens (100 mL/kg b.w) + CCl(4) (1 mL/kg) and group V: CCl(4) (1 mL/kg). Histopathologic changes of liver were also evaluated. Cytotoxicity was also determined by 3, (4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay., Results: Oral sigle dose treatment of CCl(4) produced a marked elevation in the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH). Histopathological analysis of the liver of CCl(4)-induced rats revealed marked liver cell necrosis with inflammatory collections that were conformed to increase in the levels of SOD, GSH, GST, GR and LPO. Treatment with H(2)O(2) significantly induced death of HepG(2) cell. Pretreatment with H. suaveolens methanol extract inhibited or attenuated H(2)O(2) induced cytotoxicity., Conclusions: This study shows that H. suaveolens methanol extract can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats and protect the cells against H(2)O(2)-induced oxidative damage in HepG(2) cells. The hepatoprotective and cytoprotective effects might be correlated with its antioxidant and free radical scavenger effects., (Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)