فهرست مطالب

Basic Medical Sciences - Volume:22 Issue:10, 2019
  • Volume:22 Issue:10, 2019
  • تاریخ انتشار: 1398/07/09
  • تعداد عناوین: 17
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  • Milad Iranshahi, Behjat Javadi * Pages 1102-1117
    Alzheimer’s disease (AD) is a neurodegenerative disease and the leading cause of dementia worldwide. Epidemiological studies support the important role of diet in prevention and improvement of AD. In Traditional Persian Medicine (TPM), there is multiple dietary guidelines to prevent and alleviate dementia and memory impairment. Pharmacological studies have been shown that most of the TPM-recommended dietary items can improve memory and cognitive decline and possess anti-amyloidogenic, etc. activities. Among them, garlic (Allium sativum) and its compounds, S-allyl-cysteine and diallyl-disulfide, coconut (Cocos nucifera) oil, saffron (Crocus sativus) and crocin and crocetin, honey, fish, lemon balm (Melissa officinalis) and its major compounds rosmarinic acid, raisin and resveratrol, rose flowers (Rosa damascna) and geraniol, ginger (Zingiber officinale) and its 6‐gingerol and 6-shogaol, cumin (Cuminum cyminum) and its main component cuminaldehyde have been found to possess stronger anti-AD activities. Most of these items exhibited antioxidant and AChE inhibitory activities and decreased lipid peroxidation. They also possessed anti-amyloidogenic effects, reduced cerebral plaques and Aβ-species, suppressed cerebral inflammation and alterations in tau protein and inhibited Aβ-induced apoptosis through various mechanisms. Noticeably, there are similarities between TPM anti-AD diet and the typical Mediterranean diet whose beneficial effects on AD have been widely demonstrated. Given the importance of traditional medicine systems in discovering new medicines and nutraceuticals for curing ailments, considering TPM anti-AD dietary recommendations in future research would be helpful.
    Keywords: Alzheimer’s disease, Dementia, Natural products, Saffron, Traditional Persian Medicine
  • Parastoo Rezaee, Tahereh Falsafi, Rouha Kasra * Pages 1118-1124
    Objective(s)
    Treatment of Helicobacter pylori infection by common drugs may be associated with several problems such as antimicrobial resistance to commonly used antibiotics and side effects of employed drugs. Therefore, exploration of non-chemical compounds which are safer than chemical ones is becoming important as an alternative therapy. The purpose of this study was to evaluate the effects of lactic acid bacteria (LAB) against clinical strains of H. pylori.
    Materials and Methods
    Study of antibacterial effects of LAB against H. pylori strains included:  evaluation of LAB effects as well as its cell-free supernatant (CFS) to reduce the number of H. pylori, and to examine the effects of CFS to inhibit the urease activity of H. pylori. The anti-adhesion effect of LAB on adherence of H. pylori to epithelial cell line was also evaluated.
    Results
    Evaluation of the anti H. pylori effect of LAB depended on the strain of H. pylori and Lactobacillus. However, CFS of LAB reduced significantly the growth of all H. pylori strains. Also, urease activity of H. pylori strains was inhibited by CFS of LAB demonstrating that their organic acid may have a role in this inhibition. The significant anti-adhesion effect of LAB on adherence of H. pylori was also observed.
    Conclusion
    Presence of LAB and/or their CFS can reduce the count of H. pylori, inhibit the urease activity of H. pylori, and reduce adhesion of H. pylori to epithelial cell line. This may be important for the impact of H. pylori colonization in the host stomach.
    Keywords: Antibacterial effect, CFS, Epithelial cell line, H. pylori, LAB, Urease activity
  • Behshid Ghadrdoost, Nahid Aboutaleb *, Mojdeh Nakhlestani, Majid Haghjoo, Shahram Samiee, Mahin Nikoguftar Pages 1125-1131
    Objective(s)
    Recent progress in understanding the pathogenesis of premature ventricular contraction (PVC)-induced cardiomyopathy (PIC) has suggested a key role for inflammation. The aim of this study was to evaluate the expression of messenger RNAs (mRNAs) and the protein production of interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-α) and interferon-γ (IFN-γ) and two circulating micro-RNAs related to inflammation and cardiovascular disease; miR-155 and miR-146.
    Materials and Methods
    The study population was comprised 25 patients with PIC and 25 patients with normal left ventricular ejection fraction despite frequent PVCs. TNF-α, IL-6, IL10, and IFN-γ levels were evaluated in peripheral blood mononuclear cells (PBMCs) by flow cytometry and their mRNAs were assessed by real time PCR. We analyzed circulating levels of these cytokines by enzyme linked immunosorbent assay (ELISA). Two circulating micro-RNAs, miR-155 and miR-146a, were also investigated.
    Results
    The flow cytometry findings showed that the median fluorescence intensity (MFI) of antibodies reacted with the IL-6 and TNF-α were higher in PIC group than the control group (P-value<0.001). In ELISA, the levels of IL-6 (P-value <0.001) and TNF-α (P-value <0.001) and in RT-PCR the relative expression levels of IL-6 (P-value <0.001) and TNF-α (P-value <0.001) were significantly higher in the PIC group. The relative expression levels of miR-155 and miR-146a were not significantly different between 2 groups (P-value>0.05).
    Conclusion
    In our patients with PIC, there was an elevation in the expression levels of IL-6 and TNF-α in PBMCs. This finding may provide further insights into the inflammatory pathways involved in PIC.
    Keywords: Cardiomyopathiy, Cytokines, Inflammation, microRNAs, Peripheral blood-mononuclear cells
  • Mengli Shen, Li Wang, Lingyun Kuang, Danhui Liu * Pages 1132-1137
    Objective(s)
    Mitofilin contributes to the maintenance of mitochondrial structure and functions. This study was undertaken to determine the mechanisms underlying its regulation of apoptosis.  
    Materials and Methods
    Mitofilin was knockdowned by specific short hairpin RNA (shRNA) and the stable HeLa cell clone was selected. The autophagy activity were assessed with LC3-II conversion and puncta formation by western blot and fluorescence imaging in starved and normal cultured HeLa cells. Autophagy flux was measured in the presence of NH4Cl. Wortmannin was used to inhibit autophagy. Cell viability and apoptosis were detected with cell counting kit-8 (CCK-8) and fluorescence-activated cell sorting (FACS) assay, respectively.
    Results
    Mitofilin expression was down-regulated in starved HeLa cells. In established mitofilin stable knockdown cell lines, LC3-II conversion and puncta formation were detected, which are both hallmarks of autophagy, under both basal and starvation conditions. Mitofilin down-regulation decreased LC3-II conversion and puncta formation, which indicates that loss of mitofilin function inhibits both basal and starvation-induced autophagy activity. CCK-8 and FACS analysis confirmed mitofilin involvement in the regulation of cell survival since mitofilin down-regulation facilitated starvation-induced apoptosis in HeLa cells.
    Conclusion
    Taken together, mitofilin is a potent regulator of autophagy and it may modulate cell survival through regulation of autophagy.
    Keywords: Apoptosis, Autophagy, HeLa cell, Mitofilin, Starvation
  • Ehsan Karimikia, Javad Behravan, Afshin Zarghi, Morteza Ghandadi, Sina Omid Malayeri, Razieh Ghodsi * Pages 1138-1146
    Objective(s)
    In this study a series of novel colchicine-like β-acetamidoketones was designed and synthesized as potential tubulin inhibitors
    Materials and Methods
    The cytotoxicity of the novel synthesized β-acetamidoketones was assessed against two cancerous cell lines including MCF-7 (human breast cancer cells) and A549 (adenocarcinomic human alveolar basal epithelial cells) employing the MTT test. Tubulin polymerization test was done by using a commercial kit (Tubulin Polymerization Assay Kit).
    Results
    In general, the cytotoxicity activities were highly dependent on the aromatic substitution pattern of phenyl ring at β position of β-acetamidoketones. Based upon, compound 4f possessing the same structural elements of colchicine and chalcone 1, revealed the most cytotoxicity more than the other β-acetamidoketone against the cancerous cell lines and showed moderate antitubulin effect. The tubulin inhibitory effect of 4f, colchicine and chalcone 1 were consistent with their antiproliferative activities. Molecular docking studies of 4f, into the colchicine-binding site of tubulin exhibited possible mode of interaction between this compound and tubulin.
    Conclusion
    The structure activity relationship (SAR) data attained showed that the presence of trimethoxy phenyl attached to carbonyl group of β-acetamidoketones and a methoxy group at para position of the other ring are essential for cytotoxic activity. In general, the cytotoxicity activities were highly dependent on the aromatic substitution pattern of phenyl ring at β position of β-acetamidoketones.
    Keywords: Anticancer activity, Chalcone, Colchicine, Colchicine–like, Molecular docking, Tubulin polymerization, β-acetamidoketones
  • Ali Shivaee, Malihe Talebi, Davood Darban, Sarokhalil *, Behroz Sadeghi Pages 1147-1152
    Objective(s)
    Biofilm formation is one of the most important factors in the development of infections caused by Staphylococcus aureus. In this study, the expression levels of genes responsible for biofilm formation were studied in methicillin sensitive and methicillin resistant S. aureus.
    Materials and Methods
    A total of 100 meticillin-resistant s.aureus (MRSA) and meticillin-sensetive s.aureus (MSSA) isolates were studied. Bacterial biofilm formation was evaluated phenotypically using microtiter plate method. Real-time PCR tests were conducted to determine the expression levels of genes involved in biofilm formation.
    Results
    Quantitative biofilm formation test was repeated three times for each specimen. The prevalence of weak, medium, and strong biofilm producers were 16%, 49%, and 35%, respectively. In MSSA isolates, expression levels of ica genes increased compared to the fnbA, fnbB, clfA and clfB genes. These results were different in MRSA isolates, and ica genes showed a decreased gene expression levels compared to the aforementioned genes.  
    Conclusion
    Considering the results of this study, clf genes probably contribute to the same extent in both MRSA and MSSA isolates, and there is probably no significant difference in the role of these genes in these isolates. In addition, the results of this study indicated that MRSA may not use the conventional route for biofilm formation and may use independent pathways through Polysaccharide intercellular adhesion (PIA).
    Keywords: Biofilm, MRSA, MSSA, PIA, Staphylococcus aureus
  • Yasin KESKİN, Cihan BEDEL *, Nesrin G&Ouml, Kben BECEREN Pages 1153-1157
    Objective(s)
    Pulmonary contusion (PC) is a clinical entity that often accompanies blunt traumas. We aimed to investigate the radiological and histopathological effects of surfactant treatment in an experimental rat model in which lung contusion was formed by blunt thoracic trauma.
    Materials and Methods
    50 female Sprague-Dawley rats were used. Five groups were formed randomly. In groups 2, 4, and 5 lung contusion was made by the drop-weight method after anesthesia. Intratracheal surfactant was administered in the 4th hr in groups 3 and 4 and in the 24th hr in groups 4 and 5. All rats were sacrificed and their lungs removed at 48 hr after contusion. Alveolar edema, congestion, hemorrhage, destruction, leukocyte infiltration, immune staining were examined histopathologically.
    Results
    When the first thoracic CT scans were evaluated, we observed two rats with rib fractures and four rats with pneumothorax. 4 and 48 hr thoracic CT evaluation contusion and atelectasis showed no statistically significant decrease (P>0.05). After sacrifice of group 2, in macroscopic evaluation, there was a heterogeneous contusion and hemorrhagic appearance in the lungs of rats and less hemorrhagic appearance was observed in Groups 4 and 5 than in Group 2. In comparison of Immunohistopathological findings, surfactant treatment showed a statistically significant decrease in leukocyte infiltration scores (P=0.046). Immunohistopathologically, surfactant group had more staining but only statistically significant when compared to groups 4 and sham. (P=0.036).
    Conclusion
    Surfactant treatment may be of significant benefit in lung contusion secondary to blunt chest trauma, and further prospective evidence of its efficacy in such disorders is needed.
    Keywords: Blunt chest trauma, Chest trauma, Contusion, Lung contusion, Rat, Surfactant
  • Nafiseh Pakravan, Fatemeh Kkermanian, Elaheh Mahmoudi * Pages 1158-1165
    Objective(s)
    Zonula occludens proteins (ZO-1 and ZO-2) are important intracellular tight junction (TJ)-associated proteins that link the cell cytoskeleton to the trans-membrane TJ proteins.  Destruction of TJ proteins is called the “leaky gut syndrome” and has been observed in some of the gastrointestinal diseases such as the inflammatory bowel disease (IBD). So, therapeutic approaches aim to restore the expression of TJ proteins and reduce intestinal permeability. Healing effect of Kombucha tea (KT), so-called long-life mushroom, on the gastrointestinal system, particularly its extraordinary healing effects on intestinal ulcers has been purported traditionally and rarely reported scientifically.  This study aimed to investigate the therapeutic effect of filtered KT (fKT) in young and old mice model of colitis.
    Materials and Methods
    Leaky gut was induced in two groups of young and old age using dextran sodium sulfate in drinking water for seven days. Then, fKT was administered to the mice affected by colitis and compared with the age-matched normal and untreated animals with colitis.
    Results
    Survival rate of the fKT-treated young and old animals with colitis increased and weight loss decreased.  Accordingly, digestive disorders characterized by bleeding and diarrhea were improved in fKT-treated mice.  Molecular and histological examination indicated that expression of ZO-1 and ZO-2 was significantly improved in fKT-treated mice.
    Conclusion
    Our results suggest KT as a promising therapeutic candidate to reduce intestinal permeability. Young animals with colitis showed more severe clinical signs and less survival rate than old mice with colitis, but this group responded better to fKT treatment than the old mice.
    Keywords: AGE, Colitis, Kombucha tea, Leaky gut, ZO-1, ZO-2
  • Nastaran Monzavi, Seyed Jalal Zargar *, Nematollah Gheibi, Mehdi Azad, Babak Rahmani Pages 1166-1171
    Objective(s)
    Hepatocellular carcinoma (HCC) is one of the leading fatal neoplasms and the most common primary liver malignancy worldwide. Peptide hormone ANGPTL8 (betatrophin) may act as an important regulator in HCC development through the Wnt/β-catenin pathway. We aimed to evaluate the effects of recombinant ANGPTL8 on Wnt/β-catenin signaling in human liver carcinoma cells (HepG2) and their viability.
    Materials and Methods
    The expression of ANGPTL8 was conducted in the pET-21b-E. coli Bl21 (DE3) system and the produced peptide was purified. HepG2 cells were treated with different concentrations of ANGPTL8 (25, 50, 100, 150, 200, and 250 ng/ml) for 24, 48, and 72 hr. MTT assay was performed to detect the viability of treated cells, and apoptotic induction by ANGPTL8 was measured by flow cytometry assay. Finally, using qRT-PCR the mRNA levels of Wnt signaling modulators WIF-1 and β-catenin were evaluated in treated cells.
    Results
    MTT assay showed that ANGPTL8 inhibits proliferation of HepG2 cells moderately in a time-independent manner. The highest concentration of the ANGPTL8, 250 ng/ml, reduced cell proliferation after 24, 48, and 72 hr similarly about 30%. In the same concentration of ANGPTL8, after 24 hr of treatment flow cytometry assay revealed a mild increase in early and late apoptosis up to 7.7 and 14.3%, respectively. The qRT-PCR showed that in a concentration-dependent and time-independent fashion, the expression of WIF-1 and β-catenin genes respectively increased and decreased significantly (P<0.05).
    Conclusion
    Our findings suggest that ANGPTL8 may act as a moderate suppressor against HCC cell proliferation possibly via affecting Wnt signaling modulators.
    Keywords: ANGPTL8 protein, Beta-catenin, Carcinoma, Hepatocellular, Wnt inhibitory factor 1, Wnt pathway
  • Abdullah Taşkın *, Mehmet Tarakçıoğlu, Hasan Ulusal, Mustafa Örkmez, Seyithan Taysi Pages 1172-1178
    Objective(s)
    The primary cytotoxic effects of anticancer drugs like idarubicin, a chemotherapeutic agent, are not limited to neoplastic cells; they also produce similar effects in normal cells. In this study, we hypothesized that the combination of idarubicin-bromelain could make cancer cells more susceptible to cytotoxicity and genotoxicity.
    Materials and Methods
    To test our hypothesis, the optimal concentrations of idarubicin and bromelain were combined and incubated in the HL-60 cancer cell line and normal human mononuclear leukocytes (PBMC) for 24, 48, and 72 hr. Cytotoxicity and genotoxicity were evaluated by measurement of ATP cell viability test, DNA damage, Caspase-3, Acridine orange/ethidium bromide (AO/EB), and DAPI fluorescent dyes in both cell types.
    Results
    The combination of idarubicin-bromelain significantly reduced cell proliferation in the more potent HL-60 compared to PBMC in all incubation times (P<0.05). DNA damage and Caspase-3 levels (except for 24 hr) were also higher in the HL-60 cell line in comparison with PBMC and were statistically significant (P<0.05). The percentages of apoptotic images obtained by DAPI and AO / EB morphological examination were increased in both cells, depending on the combination dose.
    Conclusion
    Based on these results, it can be concluded that idarubicin combined with bromelain produces more cytotoxic effects in low concentrations in comparison with when it was used per se in the HL-60 cells. Conversely, it was found that this combination in PBMC caused less cytotoxicity and less genotoxicity. Taken together, it can be said that this new combination makes cancer cells more sensitive to conventional therapy.
    Keywords: Apotosis, Bromelain, Cell Survival, DNA damage, Drug Interactions, Idarubicin
  • Monireh, Sadat Mousavi, Alireza Imani, Sogol Meknatkhah, Gholamhossein Riazi * Pages 1179-1185
    Objective(s)
    Association of adolescent emotional stress (ES) with the incidence of cardiovascular disease (CVD) at older age was investigated.
    Materials and Methods
    21 female rats were divided into three groups of 7 each; ES, foot-shock, and control. Chronic ES was induced by exposing the rats to witness foot-shock of their neighboring counterparts in the stress-box system in 5 successive days. 6 weeks after the last stress exposure, M-Mode echocardiographic assessment, qRT-PCR, and western blotting were performed in adult rats to determine the persistent effect of adolescent ES on cardiac performance and gene/protein expression levels of cardiac natriuretic peptide receptor 3 (NPR3) as a biomarker of CVD.
    Results
    Interventricular septum thicknesses in diastole (IVSd) increased from 0.152±0.007 cm to 0.197±0.016 cm (P<0.05), left ventricular posterior wall thickness in diastole (LVPWd) significantly enlarged from 0.169±0.006 cm to 0.288±0.033 cm (P<0.01), left ventricular posterior wall thickness in systole (LVPWs) enlarged from 0.223±0.012 cm to 0.318±0.038 cm (P<0.05), left ventricular mass increased from 1.000±0.024 g to 1.283±0.084 g (P<0.01), and mean heart rate elevated from 229.42±6.57 bpm to 280.29±10.45 bpm (P<0.01). Moreover, ES significantly upregulated the expression levels of cardiac NPR3 gene (P<0.01) and protein (P<0.01).
    Conclusion
    The incidence of adult CVD seemed to be increased under the influence of adolescent ES. Consequently, we suggest that mental healthcare during adolescence would be a critical factor for adult CVD prevention.
    Keywords: Cardiovascular Disease, Emotional stress, Heart rate, M-Mode echocardiography, Natriuretic peptide receptor 3
  • Iman Fatemi, Zahra Hadadianpour, Farangis Fatehi, Ali Shamsizadeh, Jalal Hasanshahi, Mitra Abbasifard, Ayat Kaeidi * Pages 1186-1191
    Objective(s)
     This study investigated the role of locus coeruleus (LC) nucleus TRPV1 receptors (TRPV1r) in the expression and development of morphine physical dependence by intra-LC administration of AMG9810 (selective TRPV1r antagonist) in male Wistar rats.
    Materials and Methods
    For assessing the development of morphine dependence, AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered before each morphine administration for seven continues days (once daily; 6, 16, 26, 36, 46, 56, and 66 mg/kg; sc). Furthermore, for evaluating the expression of morphine dependence, a single dose of AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered to morphine-dependent rats on day 8 of the experiment.
    Results
    Obtained data demonstrated that co-administration of TRPV1r antagonist with morphine reduced the development of morphine withdrawal syndrome somatic signs induced by naloxone. Moreover, single intra-LC administration of TRPV1r antagonist on the final day of the examination period significantly decreased the expression of some signs of morphine withdrawal in rats.
    Conclusion
    The results showed that LC TRPV1r might be participating in the expression and development of morphine dependence.
    Keywords: Acetylsalicylic acid, Antioxidants, Epididymis, Melatonin, Sperm, Testosterone
  • Guo, Guang Wang, Wei Li * Pages 1192-1197
    Objective(s)
    It has been demonstrated that hydrogen sulfide plays a vital role in physiological and pathological processes such as regulating inflammation, oxidative stress, and vessel relaxation. The aim of the study was to explore the effect of hydrogen sulfide on angiogenesis in the ischemic adductor muscles of type 2 diabetic db/db mice and ischemic diabetic wound healing.
    Materials and Methods
    The femoral arteries of diabetic db/db mice were isolated and ligated for preparation of ischemic hind limb model. Round incision was made on ischemic and non-ischemic limbs. The wounds were treated with sodium bisulfide (hydrogen sulfide donor). Real-time PCR and Western blotting were used to measure transcription of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), hypoxia inducible factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) and protein expression of VEGF, VEGF receptor (VEGFR) and PDGF, PDGF receptor (PDGFR), respectively. Angiogenesis and morphological changes in adductor muscles were observed.
    Results
    Hydrogen sulfide significantly increased transcription of VEGF, EGF, PDGF, HIF-1α, eNOS and protein expression of VEGF, PDGF, and phosphorylated VEGFR and PDGFR. Treatment with hydrogen sulfide significantly improved ischemic wound healing and formation of granulation tissue, and increased the number of small vessels in the ischemic adductor muscles.
    Conclusion
    Our data suggested that hydrogen sulfide attenuated injury of ischemic adductor muscle, and promoted the ischemic diabetic wound healing via modulating angiogenesis in type 2 diabetic db/db mice.
    Keywords: Adductor muscle, Angiogenesis, db, db mice, Diabetes, Hydrogen sulfide, Ischemia
  • Sareh Hosseini, Jamshidkhan Chamani, Mohadeseh Sinichi, Amir Mohammad Bonakdar, Zeinolabedin Azad, Najmeh Ahangari, Hamid Reza Rahimi * Pages 1198-1202
    Objective(s)
    Hepatocellular carcinoma (HCC) is one of the most significant health condition around the world. As the only curative therapies, liver transplantation and surgical resection are the clinical treatments of HCC. Due to the systemic toxicity and severe side effects of these treatments, it is vital to establish new therapeutic approaches. The present study aimed to compare cyclin D1 (CCN D1) gene expression in hepatocellular carcinoma cell line (HUH7) when it is treated with nanomicelle curcumin and sorafenib. The purpose was to identify toxicity risk and antioxidant activity of these drugs.
    Materials and Methods
    The toxic dose (IC50) of nanomicelle curcumin and sorafenib were detected after treatment of HUH7 cell lines with different dose of mentioned agents followed by MTT assay. CCN D1 gene expression was evaluated using real-time PCR. Following the Tukey’s multiple comparison tests, statistical analysis is done through Student’s t-test or ANOVA.
    Results
    The expression of the CCN D1 gene was statistically significant (P<0.001) at 289.31, 128 and 152.36 for sorafenib, nanomicelle curcumin and SNC (sorafenib-nanomicelle curcumin) respectively. The finding of this study revealed that, in comparison to sorafenib alone, the treatment of HUH7 with a nanomicelle curcumin IC50 dose, in combination with sorafenib, might down-regulate CCN D1 gene expression.
    Conclusion
    The present research indicates that the treatment of the cell line with only nanomicelle curcumin results in the down-regulation of cyclin D1. To further decrease cyclin D1 expression, the co-delivery of curcumin and sorafenib appears to induce the apoptotic process. As a result, the effect of sorafenib cytotoxicity and CCN D1 gene expression decreases twofold.
    Keywords: Cyclin D1 Gene, Curcumin, Hepatocellular carcinoma, Nanomicelle, Sorafenib
  • Sana Rabiei, Masoud Rezaie, Zahra Abasian, Mohammad Khezri, Mehdi Nikoo, Mahmoud Rafieian, Kopaei *, Maryam Anjomshoaa Pages 1203-1210
    Objective(s)
    Today, consumers are looking for food products providing health benefits in addition to meeting the basic nutritional needs of the body. This study aimed to evaluate the antioxidant and cytotoxic effects of Liza klunzingeri protein hydrolysate both in vivo and in vitro.
    Materials and Methods
    Fish protein hydrolysate (FPH) was prepared using enzymatic hydrolysis with papain. In vitro antioxidant activity was assessed using five different antioxidant assays. The cytotoxic effect on 4T1 cell line was evaluated using the MTT assay. The distribution of the molecular weight of FPH was measured using HPLC. In the in vivo study, CCl4-exposed Wistar rats were orally treated with FPH (150, 300, and 600 mg/kg) or gallic acid (50 mg/kg) for 28 consecutive days.
    Results
    Enzymatic hydrolysis gave hydrolysate rich in low molecular weight peptides (
    Conclusion
    L. klunzingeri protein hydrolysate can be considered as a functional food to alleviate oxidative stress.
    Keywords: Antioxidant activity, Cytotoxicity, Liza klunzingeri, Oxidative stress, Protein hydrolysate
  • Manhong Ye, Mengting XU, Mengmeng Ding, Chao Ji, Jian Ji, Fubiao Ji, Wanhong Wei, Shengmei Yang, Bin Zhou * Pages 1211-1217
    Objective(s)
    The current study investigated the potential hepatoprotective effects of the ethanolic extracts of Chinese propolis (EECP) on ethanol-induced fatty liver in mice.
    Materials and Methods
    C57BL/6J mice were orally gavaged with 50% ethanol alone or co-administrated with EECP at the dose of 0.2 ml/kg bodyweight for eight weeks. The dose for ethanol was 6 ml/kg bodyweight for the first two experimental weeks, and then increased to 8, 10, and 12 ml/kg bodyweight every two experimental weeks. Alterations in the hepatic transcriptome due to concomitant administration of EECP were investigated using RNA-Seq technique.
    Results
    Our results showed that the main EECP-responsive genes were involved in lipid syntheses, which were significantly down-regulated in both female and male mice co-administrated with EECP. In female mice, these differentially expressed genes (DEGs) were mainly associated with fatty acid biosynthesis. While in male mice, these DEGs were mainly involved in the steroid metabolic process and cholesterol biosynthetic process. Despite the sex-associated responses in lipid metabolism, EECP also exerted other beneficial effects in female mice through modulation of the cytokine-cytokine receptor interaction pathway that helped explaining its hepato-protective effectiveness.
    Conclusion
    Our findings indicated that the mechanism regarding the hepato-protective effects of EECP was gender-dependent, which is worthy of further investigation during the development of therapeutic interventions using EECP to reduce the adverse influences of ethanol.
    Keywords: Alcoholic, Chinese propolis, Fatty liver, Inbred C57BL, Lipid metabolism, Mice
  • Dwi Cahyani Ratna Sari, Nur Arfian *, Untung Tranggono, Wiwit Ananda Setyaningsih, Muhammad Mansyur Romi, Emoto Noriaki Pages 1218-1224
    Objective(s)
    Impairment of hippocampus function as a center for memory processing occurs due to stress. Centella asiatica L. (Gotu kola) is known to improve memory, intelligence, and neural protection although the precise mechanism is not well understood. This study aimed to investigate the effects of ethanol extracts of C. asiatica toward MAPK expression as down-stream signaling of brain-derived neurotrophic factor (BDNF).
    Materials and Methods
    We performed a chronic electrical stress model on 20 male Sprague Dawley rats (2 months-old, 180–200 g). Rats were divided into four groups: normal control group (Control) which received distilled water, and three treatment groups receiving oral Gotu kola ethanol extracts in oral doses of 150 mg/kg BW (CeA150), 300 mg/kg BW (CeA300), and 600 mg/kg BW (CeA600) over four weeks. Memory acquisition was assessed with Morris water maze. Hippocampus was harvested, then extracted for protein and RNA analysis. MAPK proteins (p38, ERK1/2, JNK) were measured using Western blot, meanwhile, BDNF and TrkB receptor were analyzed with real-time PCR (RT-PCR).
    Results
    CeA600 group revealed improvement of memory performance as shown by reduction in time and distance parameters compared to control during escape latency test. This finding associated with significant elevation of hippocampal BDNF protein and mRNA level with up-regulation of TrkB mRNA expression in CeA600 group compared to control. Western-blot analysis showed significant up-regulation of ERK1/2 protein level in CeA600 group (P<0.05) compare to control.
    Conclusion
    BDNF signaling through TrkB and ERK1/2 pathway contributes significantly to amelioration of memory performance after C. asiatica treatment in electrical stress model.
    Keywords: BDNF signaling, Chronic electrical stress model, Centella asiatica, ERK1, 2, TrkB