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International Journal of Pharmacology
eISSN: 1812-5700
pISSN: 1811-7775

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Research Article
Zein Coated Zinc Oxide Nanoparticles: Fabrication and Antimicrobial Evaluation as Dental Aid
Ghada Hussein Naguib, Faten Ebraheem Al-Hazmi, Mallesh Kurakula, Ayman Abdulaziz Al-dharrab, Khaled Mohamed Hosny, Hala Mohammed Alkhalidi, Mohamed Tharwat Hamed, Ali HabibAllah Hassan, Ameen M Al-mohammadi, Abeer Mohamed Alnowaiser and David Henry Pashley
Background and Objective: Bacterial strains resistance to conventional antibiotics has gained the attention of researchers to frame a materialistic approach and to identify an agent from physical source rather than biological. Zinc oxide (ZnO) has proven antimicrobial competence but had not explored as dental aid due to its solubility and agglomeration issues. This study aimed to utilize a newer technique to formulate ZnO nanoparticles and to refurbish with zein coating in order to optimize the desired pharmacological activity. Materials and Methods: Zein based ZnO nanoparticles were synthesized using hydrothermal technique at two different pH 1.24 and 11, respectively. Both zein coated and uncoated nanoparticles were characterized for particle size, surface charge, morphology, crystallinity and even metal oxide compatibility studies. In vitro dissolution studies were performed in order to determine the effect of zein over the solubility and release of ZnO nanoparticles. Antimicrobial assay for the zein coated ZnO nanoparticles were performed on Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis and Candida albicans using both Kirby-bauer and direct kill tests. Results: The uncoated ZnO nanoparticles were in 25 nm size but aggregate, tend to increase up to 280 nm after 1 h aqueous dispersion, oppositely zein coated were 40 nm with no aggregation. Scanning electron microscopy indicated agglomerate of uncoated ZnO nanoparticles while as distinct nanospheres when zein coated. Uncoated and zein coated nanoparticles exhibited a surface charge of 28 and -24 mV at pH 1.24 and -18 and -20 mV at pH 11, respectively. X-ray crystallography indicated crystalline nature and Fourier-transform infrared spectra with no possible interaction or formation of new product. Interestingly, at pH 1.4, zein coated ZnO nanoparticles release was just 20% at 12 h in comparison to uncoated indicating prolonged release. Conclusion: The synthesized zein coated ZnO nanoparticles were found to be highly crystalline with enhanced solubility and better compatibilities. Among the four microbial strains tested, zein coated ZnO nanoparticles exhibited higher pharmacological activity against C. albicans strains in comparison to the uncoated. These experimental outcomes can indicate the potential of ZnO nanoparticles in formulating an antimicrobial dental aid.
Research Article
Spectral Properties of the Interaction Between Hesperidin of Tangerine Peel’s Active Ingredient with Protein
Tianhu Wang, Yuxia Sun, Tianyu Chen and Yue Hu
Background and Objective: Tangerine peel has high medical value due to its physiological active including volatile components, flavonoids, alkaloids etc. In this paper, the aim of this work was to study the spectral properties of tangerine peel and the binding interaction between hesperidin of its effective components and bovine serum albumin (BSA). Methodology: The fluorescence spectroscopy was used with the different excitation wavelength under simulative physiological conditions. The dynamic quenching mechanism could be described by the Stern-Volmer equation. The binding parameters between hesperidin and BSA was calculated by double logarithmic equation. Results: The results show the fluorescence peak of tangerine peel is about 448 nm and there a certain red shift occur with the increase of the excitation. The investigation of between BSA and hesperidin show that hesperidin could intact with BSA and the hesperidin-BSA complex was formed. The binding constants between hesperidin and BSA are 3.26, 2.71 and 1.98×104 mol–1 L at 298, 305 and 310 K, respectively, indicating the binding capacity of hesperidin to BSA was weakened with the increasing temperature. Conclusion: It is concluded that, the peak wavelength of tangerine peel is about 448 nm, the hesperidin could interact with BSA, the fluorescence quenching of BSA caused by hesperidin is a static quenching.
Research Article
In vivo Pharmacodynamics Studies of Acacia tortilis Found in Kingdom of Saudi Arabia on Cardiovascular System of Rats
Abdulhalim S. Serafi, Aisha Azmat, Muhammad Ahmed, Mohammed Bafail and Zahir Hussain
Background and Objectives: Herbal medicines are recommended as remedy for different cardiac diseases. Acacia possessing significant pharmacological activities, widely found in KSA. The effect of Acacia tortilis leaves decoction (ATLD) on cardiac hemodynamics was evaluated in rats. Methods: Different hemodynamic parameters (systolic, diastolic, mean arterial blood pressure and heart rate) were recorded in normotensive rats before and after the intravenous administration of ATLD. Results: The different doses showed a dose dependent significant hypotensive effect. However the highest dose (30 mg kg–1) showed maximum activity and lowered the systolic pressure (17.4±2.95%), diastolic blood pressure (15.2±1.8%) and mean arterial blood pressure (17.1±2.4%). Intravenous administration of ATLD also showed a dose-dependent reduction in heart rate (p<0.001). Conclusion:The hypotensive and bradycardia might had been due to presence of N,N Dimethyltryptamine in extract that reduced the blood pressure and heart rate. Thus, the authors conclude that the ATLD possesses potent hypotensive activity and sought to be useful for anti hypertensive drug development and worth much merit to be investigated.
Research Article
Licorice (Glycyrrhizza glabra) Extract Prevents Production of Th2 Cytokines and Free Radicals Induced by Ova Albumin in Mice
Hala AbdEl-Rahman Hassan Khattab, Umama Allam Abdel-Dayem, Hanan AbdulSalam Jambi, Aymn Tallat Abba, Morooj Talal Ahmead Abdul-Jawad and Nagla Abd El-Aziz Fouad El-Shitany
Background and Objective: Previous studies demonstrated that licorice (Glycyrrhiza glabra) inhibits airway hyperresponsiveness, inflammation and remodeling in murine models of asthma. However, licorice use is faced with many side effects including, increased adrenal hydrocortisone secretion and hypertension which are dose-dependent. This study aimed to test the effect of three different doses of licorice extract on, lung pathology, bronchoalveolar lavage oxidative stress markers, plasma immunoglobulin E (IgE) and Th2 cell cytokine in a model of ovalbumin (OVA)-induced bronchial asthma. Methodology: Mice were sensitized with 10 mg OVA on days 0 and 14. On days 21, 22 and 23, mice were challenged with 1% OVA solution. Six groups of mice were used in this study: 1-normal saline (S), 2-OVA-sensitized and challenged (OVA), 3- OVA+montelukast (M), 4-OVA+10 mg kg–1 licorice (L10), 5-OVA+20 mg kg–1 licorice (L20) and 6-OVA+40 mg kg–1 licorice extract (L40). Results: The results revealed that the lowest dose of licorice (10 mg kg–1 ) protected against OVA-induced lung inflammation and mucus secretion. It also, reduced interleukin (IL)-5, IL-13 and IgE. Moreover, it significantly reduced the raised malondialdehyde (MDA) and nitric oxide (NO) and restored superoxide dismutase (SOD) and catalase (CAT) activity. Conclusion: The results of this study offered clear evidence for the antioxidant and anti-inflammatory effects of licorice in a murine model of bronchial asthma. The lowest dose of licorice is the most effective and as the dose increase the antioxidant and anti-inflammatory action decrease. This provides an advantage as licorice has many side effects which appears with the high doses.
Research Article
Induction of Beta-amyloid Protein by Sevoflurane Is Associated with Cognitive Impairment During Anesthesia in Aged Rats
Junbao Liu, Wei Zhang, Ying Tao and Long-Yun Li
Background and Objective: Sevoflurane is known to be associated with cognitive impairment during anesthesia in Alzheimer's Disease (AD) patients. However, the molecular mechanism underlying the pathogenesis caused by sevoflurane-induced anesthesia is not properly understood. The present investigation was an attempt to understand the molecular mechanism of sevoflurane anesthesia in causing cognitive decline in AD patients using aged rats as the model organism. Materials and Methods: In this study, aged rats (n = 60) were categorized into six different groups (CON, SLF-0, SLF-2, SLF-4, SLF-6 and SLF-8) having a population size of 10 rats in each group. The Control (CON groups were given 40% O2 for 2 h) and the SLF groups were placed under anesthesia with 2.2% sevoflurane and 30% O2 for 60 min. The rats in each of the SLF groups were analyzed for the exposure. The MWM (Morris water maze) test was assessed for assessing the cognitive function of the aged rats and the expression level of APP (Amyloid Precursor Protein), BACE-1 (β-site APP Cleavage Enzyme-1) and Aβ42 (Beta-amyloid-42) oligomers were analyzed compared to the CON group. Results: The study observed that the protein expression levels of APP mRNA were increased because of sevoflurane-induced anesthesia thereby promoting the overproduction of Aβ42 oligomers and depletion of APP protein. Interestingly, the expression of BACE-1 was not affected. Moreover, the SLF groups showed an increase in the escape latency and impaired memory. Conclusion: The study suggested that sevoflurane-induced anesthesia contributed to the cognitive decline in aged rats due to had increased expression of APP mRNA and oligomerization of Aβ42 peptide.
Research Article
Evaluation of Anticoagulant and Antithrombotic Activities of Berberine: A Focus on the Ameliorative Effect on Blood Hypercoagulation
Can Wang, Yan-Bin Wu, Ai-Ping Wang, Jian-Dong Jiang and Wei-Jia Kong
Background and Objective: Thrombosis and related diseases are the leading causes of mortality and disability worldwide. This study aimed to investigate the anticoagulant and antithrombotic activities of natural product berberine (BBR) using in vitro and in vivo models. Materials and Methods: In in vitro experiments, BBR was used to treat venous blood or plasma isolated from rabbits, with heparin sodium (HS) as a positive control. In the animal experiments, BBR was orally administered to Wistar rats fed with a regular diet or a high-fat diet (HFD) for 2 or 4 weeks, respectively. After experiments, whole blood clotting time (CT), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB) and the activities of a series of coagulation factors and anti-thrombin-III (AT-III) were determined. In the HFD-feeding experiment, metabolic parameters such as blood lipids and glucose were assayed. In parallel experiments, the effect of BBR on inferior vena cava thrombus formation was determined by ligation. Results: The BBR significantly prolonged CT and APTT/PT/TT but decreased FIB both in vitro and in vivo. In addition, BBR significantly increased the activity of AT-III and suppressed the activities of coagulation factors participating in the intrinsic, common and extrinsic coagulation pathways. These BBR-induced changes resulted in a significant inhibition in thrombus formation in the inferior vena cava. In response to HFD-feeding, the rats developed a hypercoagulable state, as indicated by the shortening of CT and APTT/PT/TT, an increase in FIB, overactivation of coagulation factors and the deterioration of thrombosis. After treatment, BBR improved the metabolic parameters of the rats and effectively prevented the HFD-induced blood hypercoagulation. Conclusion: The BBR has anticoagulant activity, which is responsible for its anti-thrombotic effect. The BBR may be suitable for the intervention of hypercoagulability and thrombosis when it is used to treat metabolic diseases.
Research Article
Ethyl Acetate Fraction Activities of Myrmecodia tuberosa Jack. in Anemic Mice
Yufri Aldi, Dian Fadilla, Rahmi Yosmar, Agus Sri Banowo, Afriwardi and Aditya Alqamal Alianta
Background and Objective: Ethyl acetate fraction of Myrmecodia tuberosa Jack. increases phagocyte activity of macrophage and lymphocyte proliferation and also prevents cutaneous anaphylactic reactions. Based on that, this present research aim to investigate the effect of an acetate fraction from Myrmecodia tuberosa Jack. on numbers of erythrocyte, reticulocyte, hemoglobin content and hematocrit in mice. Materials and Methods: The research was conducted over 3 months and consisted of a positive control group and 3 groups treated with Myrmecodia tuberosa Jack. ethyl acetate fractions at 3 dosing levels. Anemia was induced in the mice using chloramphenicol 130 mg kg–1 b.wt., for 14 days then for next 14 days daily oral doses of 40 mg kg–1 b.wt., 63.2 mg kg–1 b.wt., or 100 mg kg–1 b.wt., of Myrmecodia tuberosa Jack. ethyl acetate fraction were administered to each group. Blood samples were taken on day 0, 14, 21 and 28 for analysis. Statistical analysis was conducted using two-way ANOVA then Duncan Multiple Range Test (DMRT). Results: About 40-63.2 mg kg–1 b.wt. doses of Myrmecodia tuberosa Jack. ethyl acetate fraction significantly increased the erythrocyte, reticulocyte and hemoglobin count and hematocrit from the 14th day (p<0.01). Conclusion: Ethyl acetate fraction of Myrmecodia tuberosa Jack. could have potential as an anemia treatment.
Research Article
Hepato-Protective Effect of Ginsenosides from the Fruits of Panax ginseng Against Acetaminophen-Induced Liver Damage in Mice
Ge Yang, Zi Wang, Shen Ren, Xiao-tong Yan, Xing-yue Xu, Jun-nan Hu, Yan Zhang and Wei Li
Background and Objective: Acetaminophen (APAP)-induced hepatotoxicity is a severe public health problem in western countries. Current treatment methods for poisoning are limited and novel therapeutic strategies are needed. The aim of the present study was to investigate the protective effect of ginsenosides from the fruits of Panax ginseng (GFG)against APAP-induced liver injury in mice and its potential molecular mechanisms of action. Materials and Methods: In this study, mice were orally administered with 150 or 300 mg kg–1 of GFG for 7 consecutive days, followed by a single injection of APAP (250 mg kg–1). Severe liver injury was observed after 24 h APAP injection and the protective effect of GFG was assessed. Results: The results showed that pre-treatment with GFG reduced the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Moreover, GFG showed anti-oxidant activities characterized by reducing hepatic MDA contents and increasing hepatic SOD and GSH levels, accompanied by inhibiting expression level of 4-HNE. Likewise, GFG decreased APAP-induced the expression of cytochrome P450 E1 (CYP2E1). Pre-treatment with GFG significantly inhibited pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), Bax, Bcl-2 and cyclooxygenase-2 (COX-2) levels expression of which contributed to ameliorating APAP caused hepatotoxicity. Furthermore, liver histopathological observation provided further evidence that GFG pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration. Conclusion: The present study clearly showed that GFG exerted a protective effect against APAP-induced hepatotoxicity due to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.
Research Article
The Influence of L-carnitine on Aspartame Toxicity in Kidney of Male Rats
Rasha A. Al-Eisa, Reham Z. Hamza, Amir E. Mehana and Nahla S. El-Shenawy
Background and Objective: Aspartame (ASP) one of the famous artificial sweeteners used as substitution of the sugar in foods and beverages. The study was aimed to investigate the oxidative responses and histopathological changes induced by ASP on the kidney of rats and the ameliorative role of L-carnitine (LC) to prevent the toxicity. Materials and Methods: Rats were split into six groups (n = 8) as follow: control, ASP (low dose, LD) (75 mg kg–1), ASP (high dose, HD) (150 mg kg–1), 10 mg kg–1 of LC, ASP-LD+LC and ASP-HD+LC, all groups treated for successive 30 days. Results: The ASP marked decreased the renal levels of reduced glutathione (GSH), activities of antioxidant enzyme markers and increased lipid peroxidation levels. DNA damage was significantly increased in ASP-LD and ASP-HD groups as compared to control animals. The LC prevented the ASP-induced kidney damage as specified by ameliorating all the above-mentioned parameters. Histopathological changes were parallel with the biochemical alternation in ASP groups. Conclusion: The renal toxicity induced by ASP in rats could be improved by LC through different protective mechanisms.
Research Article
Ameliorative Effect of Mesenchymal Stem Cells-derived Exosomes on Diethylnitrosamine-induced Liver Injury in Albino Rats
Faisal Abdelrahman Alzahrani, Saleh Alkarim and Islam Mohamed Saadeldin
Background and Objective: Regenerative medicine through stem cells holds a great promise and potential therapeutics to regenerate the damaged tissue. Exosomes through their complex cargo of proteins and genetic materials can potentiate treatment of damaged tissues and circumvents some of the concerns and limitations in using viable replicating stem cell. The therapeutic effect of bone marrow mesenchymal stem cells (BM-MSC)-derived exosomes on diethylnitrosamine-induced liver injury was explored in the present study. Materials and Methods: The MSCs were isolated from rats’ bone marrow and characterized by flow cytometry. Exosomes were isolated from MSCs through gradient ultracentrifugation and identified by transmission electron microscopy. Liver was injured with a single intraperitoneal injection of 100 mg kg–1 diethylnitrosamine in 1 mL PBS. BM-MSCs-exosomes were intravenously injected in liver-injured rats. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and albumin were measured. Liver homogenate levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and malondialdehyde (MDA) were measured. Cellular changes have been investigated through histopathological examination and relative quantitative polymerase chain reaction (qPCR) of Bax, Bcl2, Tgfβ1, Tnfa, Cox2 and NFkB transcripts. Data were analyzed by one-way ANOVA followed by Tukey's Honestly Significant Difference test. Significance was considered at p<0.05. Results: MSCs-exosomes significantly reduced serum levels of liver enzymes ALT, AST and ALP, as compared to liver-injured rats. Exosomes also significantly improved the antioxidant enzymatic activities of SOD, CAT, GPx and decreased MDA in liver tissues. In addition to restoration of the deteriorated hepatic histology, exosomes also inhibited expression of the apoptotic gene, Bax and the tissue transforming gene, Tgfβ, whereas they induced the expression of the anti-apoptotic gene, Bcl2 and liver regeneration-related genes, TNFa, NFkB, Cox2. Conclusion: These results suggest ameliorative effect for exosomes on liver injury through induction of liver cells regeneration and inhibition of oxidative stress, apoptosis and epithelial-to mesenchymal transition (EMT) marker, which may be helpful to understand the mechanism of liver diseases and highlight new therapeutic strategies for these diseases.
Research Article
Effect of Rutin on Cisplatin-induced Small Intestine (Jejunum) Damage in Rats
Ismail Topal, Ulas Emre Akbulut, Orhan Cimen, Abdulselim Kolkiran, Selcuk Akturan, Ferda Keskin Cimen, Murat Cankaya, Arif Onur Eden, Zeynep Suleyman and Asli Ozbek Bilgin
Background and Objective: Cisplatin is an antineoplastic, platinum derivative used in the treatment of various cancers. Mucositis is a notable side effect of cisplatin treatment. Rutin (vitamin P1) is a drug with antioxidant, anticancer, antidiabetic and antimicrobial properties. The aim of this study was to biochemically, histopathologically and immunohistochemically investigate the effect of rutin on cisplatin-induced mucositis of the small intestine (jejunum) in rats. Materials and Methods: Twenty four rats were divided into four groups with six animals in each group: healthy group (HG), cisplatin-only group (CCG), 50 mg kg–1 of rutin plus cisplatin group (RG-50) and 100 mg kg–1 of rutin plus cisplatin group (RG-100). Rutin or distilled water were administered via an oral gavage. One hour after the administration of rutin or distilled water, the CCG, RG-50 and RG-100 were intraperitoneally injected with 5 mg kg–1 of cisplatin once every 2 for 8 days. At the end of this period, all the animals were sacrificed using a high-dose anesthetic and their small intestines (jejunum) were removed for biochemical and histopathological procedures. Differences between the groups were analyzed using a one-way analysis of variance, followed by Dunnett’s multiple comparisons test. Results: The levels of oxidants increased in all the cisplatin-treated groups, whereas those of antioxidants decreased. Rutin administered at a dose of 100 but not 50 mg kg–1 reduced oxidant levels and increased antioxidant levels to those of healthy tissues. Histopathologically, tissue damage was observed in jejunal tissue of the rats administered only cisplatin, whereas treatment with 100 mg kg–1 of rutin prevented cisplatin-induced histopathological damage. In the group administered 50 mg kg–1 of rutin, jejunal tissue showed a near-normal appearance, except for mildly dilated congested blood vessels. As shown immunohistochemically, rutin prevented cisplatin-induced jejunal damage more effectively when administered at a dose of 100 mg kg–1 than 50 mg kg–1. Conclusion: Rutin may be useful in the prevention of cisplatin-induced jejunal mucositis.
Research Article
Cardioprotective Efficiency of Tangeretin Against Heart Failure Induced by Isoproterenol in Rats
Huizhi Lu, Yun Tan, Luyu Yang, Hui Dong, Youxia Liao, Song Cao and Shouzhi Fu
Background and Objective: Heart failure or myocardial infarction (MI) is one of the deadliest condition which claims many lives globally. This pre-clinical animal study was intended to investigate the beneficial role of Tangeretin (TAN) against isoproterenol (ISO) induced heart failure in a rat model. Materials and Methods: Forty healthy male rats were randomly separated into four group with 10 rats in each. Saline treat rats are considered as a control group, whereas ISO (85 mg kg–1, i.p) induced rats (2 consecutive days) are considered as ISO group. The TAN (100 mg kg–1 via o.p) pretreated rats for 28 days followed by induction of ISO will be considered as SAB-B+ISO group, only TAN (100 mg kg–1, o.p) received rats for 28 days are considered as TAN group. Results: A pronounced increase in the levels of various hemodynamic parameters and the activities of antioxidants were observed in TAN pre-treated rats as compared to ISO-induced rats. However, the levels of infarct size, lipid peroxidation product like MDA, inflammatory markers, apoptotic markers are significantly decreased upon treatment with TAN for 28 days. Furthermore, TAN administration markedly reverted the histomorphological changes (cardiac tissue) caused by ISO induction. Conclusion: Taking together, that 28 days of pre-treatment with TAN significantly preserved cardiac function by suppressing oxidative stress, inflammation, apoptosis in ISO-induced heart failure (myocardial infarction) model and hence it can be recommended to treat myocardial infarction/heart failure with conventional (standard) cardio protective agents.
Research Article
Effects of Long-term Treatment of Linagliptin on Glycemic Control in Japanese Patients with Type 2 Diabetes
Masataka Kusunoki, Yukie Natsume, Hideyo Tsutsui, Tetsuro Miyata, Kazuhiko Tsutsumi and Yoshiharu Oshida
Background and Objective: Dipeptidyl peptidase-4 (DPP-4) inhibitors contribute to glycemic control in diabetes patients. However, each DPP-4 inhibitor differs in effects on glycemic control when treated for longterm. In this study, the effects of a long-term treated with linagliptin on glycemic control and serum lipids were investigated. Materials and Methods: Linagliptin (5 mg day–1) was administered to 25 type 2 diabetes patients for 18 months and assessed for its effects on hemoglobin A1c (HbA1c) and serum lipids. The two-side paired t-test and Dunett’s post hoc test were used. Results: Three months after the start of linagliptin treatment, the HbA1c of the 13 patients was significantly lowered (p<0.01) and its effect continued for 18 months. In addition, serum total cholesterol and LDL cholesterol of the patients was also improved. On the other hand, HbA1c significantly increased in the12 patients from 6 months of linagliptin treatment (p<0.05) and linagliptin had no effect on the serum lipids. It was found that the HbA1c in patients whose HbA1c decreased with linagliptin was significantly high before treatment compared to the patients whose HbA1c increased after treatment(p<0.01). Furthermore, the effects of linagliptin treatment on HbA1c was correlated with baseline HbA1c levels before treatment. Conclusion: About 18 month treatment with linagliptin significantly improved the glycemic control and serum lipids of diabetic patients with high HbA1c before treatment, whereas those parameters may not be improved in patients with low HbA1c.
Research Article
Astragaloside IV Attenuates Trinitrobenzene Sulphonic Acid (TNBS)-Induced Colitis via Improving Mucosal Barrier Function: Role of Goblet Cells
Kai-hong Zang, Hong-yan Qin, Hai-Jing Duan, Qing-lin Ma and Yuan Ren
Background and Objective: Astragaloside IV, the main bioactive ingredient of Radix Astragali showed anti-inflammation and would healing effect in practice. This study aimed to investigate the therapeutic effect of astragaloside IV (AS-IV) on experimental colitis as well as its role in mucosal healing and barrier function. Materials and Methods: TNBS-induced colitis rats were orally treated with AS-IV at the dose of 10, 20 and 40 mg kg–1 per day for 8 consecutive days. After drug treatment, histological damage score and myeloperoxidase activity of the colon tissue were detected, mucosal barrier function was evaluated by measuring the serum level of D-lactate and diamine oxidase and colonic goblet cells and the mRNA expression of Mucin were also evaluated by immuno-histochemistry and RT-PCR, respectively. The proteins and genes in Wnt and Notch signaling were further investigated by Western blot and RT-PCR to identify the effect of AS-IV on the differentiation of goblet cells. Results: Histological scores, myeloperoxidase activity and serum level of D-lactate and diamine oxidase in colitis rats were significantly increased, while mRNA expression of Muc-2 and Muc-3 were significantly decreased. AS-IV administration significantly reduced histological scores, myeloperoxidase activity and the level of D-lactate and diamine oxidase in colitis rats and the expression of Muc-2 and Muc-3 were markedly increased. Moreover, the protein expression in Wnt signaling, i.e., Lrp5, Lrp6 and β-catenin, in the colon of colitis rats was significantly elevated, but the genes expression in Notch signaling, i.e., Rath1, Gfi1 and Klf4, in colitis rats were markedly decreased, and these alteration of Wnt and Notch signaling in colitis rats were markedly reversed by AS-IV administration. Conclusion: AS-IV attenuates colon inflammation in colitis rats via improving mucosal barrier function, the regulatory effect on the proliferation and differentiation of goblet cells may contribute to the therapeutic role of AS-IV in colitis.
Research Article
Effectiveness of Osthole on Uric Acid Crystal-induced Acute Gouty Arthritis Through the Inhibition of NLRP3 Inflammasome
Ming Yang, Gaopeng Teng, Guangjian Li, Tao Huang and Renguo Xu
Background and Objective: Inflammation is a key factor in the pathogenesis of arthritis. In the present study, investigated the potential of osthole, a major natural product, to treat monosodium urate crystal (MSU) induced acute gouty arthritis in rats and explore the mechanisms underlying osthole mediated immunomodulation. Materials and Methods: Rats were oral administrated with osthole at 24 h prior to 3 mg MSU injection, the volume and width of swelling ankle were recorded to evaluate the protection of osthole in vivo. LPS+MSU in Raw 264.7 cells was utilized to assess the effects of osthole on NLRP3 inflammasome in vitro. Results: Osthole could alleviate MSU-induced arthritis through inhibiting the generation of inflammatory factors and NLRP3 inflammasome activation in vivo. Pretreatment with osthole significantly suppressed MSU or LPS induced NF-κB signal along with the transcription of inflammatory factors. In addition, osthole decreased MSU induced oxidative stress and lysosomal damage. Current findings illustrated that osthole significantly suppressed NLRP3 inflammasome in synovial tissue and macrophage cells. The potential mechanism may be based on the attenuation of NF-κB mediated first signal and oxidative stress and lysosome mediated second signal in NLRP3 inflammasome activation. Conclusion: Osthole might be a promising therapeutic agent for alleviating gouty arthritis through inhibiting NLRP3 inflammasome.
Research Article
Ameliorative Potential of Lagenaria sicereria Extract as Anti-Anxiety Drug in Various Models of Anxiety in Rats
Shuyuan Wang, Shujing Wu, Souravh Bais and Ruihua Hou
Background and Objective: Anxiety is an emotional state with imbalance of neurotransmitters like Gamma Amino Butyric Acid, serotonin and leads to feeling of discomfort, concern or fears to define or undefined objects/situation. The aim of present study was to evaluate the potential effect of Lagenaria sicereria extracts in various models of anxiety in rats. Materials and Methods: Three well established models (Elevated Plus maze, Light Dark and social interaction in rats) were selected for evaluation of anxiety in rats. The protocol was designed by giving drugs for seven days and various behavioral parameters like Time spent in the open and closed arm, No. of entries in each arm, Latency, Time spent in light and dark compartment, No. of crossings, Immobility, Sniffing, Crawling and Aggressive behaviors were evaluated on 1st, 3rd and 7th day of study. The rats were treated at two doses (250 and 500 mg kg–1, p.o.) of methanolic extract of Lagenaria sicereria (MELS) leaf. The dose selections were based on acute toxicity study in mice. The standard drug, Fluoxetine (10 mg kg–1, p.o.) were also given to compare its beneficial effects in anxiety. At the end of an experiment, all animals were subjected to dissection and serotonin and GABA levels were determined in brain tissues. Results: MELS was found to possess a therapeutic effect against anxiety disorder. The Rats treated with 500 mg kg–1, p.o. showed significant changes in behavioral and mobility in all three models during experiment. Conclusion: From the present findings, it was concluded that MELS extracts poss significant anxiolytic effects in rats and its due to modulation of GABA and serotonin level in brain tissues of rats.
Review Article
Anti-aging Effects of Ginseng and Ginsenosides on the Nervous System
Min Lai, Hui-juan Zhang, Fei Wang, Ya-lan Shao, Mei-wen Yang, Fen-fang Hong and Shu-long Yang
Senescence is the comprehensive manifestation of human body deterioration induced by various environmental factors. Ginsenosides are the main anti-aging ingredients of ginseng. Ginsenoside Rg1 protects the nervous system from aging by promoting human intelligence, inhibiting the release of LDH and MDA and decreasing intracellular calcium overload. Loss of memory and learning ability resulting from aging can be resisted by ginsenoside Rg1, Rb1 and Rg2. Ginsenoside are effective in inhibiting neuronal cell apoptosis and promoting proliferation of these cells. These molecules also inhibit the aging process regulated by the Rb and p53-dependent pathways and exert their function against Alzheimer's disease. In addition, experimental results from animals demonstrated that ginseng saponins protected the brain cortex and regulated TrkB mRNA expression in the hippocampus. This paper reviewed all recent developments in the study of the anti-aging effects of ginseng and its ginsenosides on neural systems to provide a theoretical basis for the clinical application of these molecules in the prophylaxis and treatment of diseases related to the neural system aging.
Short Communication
Foot-shock Stimulation Decreases the Inhibitory Action of ATP on Contractility and End-plate Current of Frog Sartorius Muscle
Ayrat Usmanovich Ziganshin, Rafis Rustemovich Kamaliev, Azat Iskhakovich Gabdrakhmanov, Adel Evgenyevich Khairullin and Sergey Nikolaevich Grishin
Background and Objective: Inhibitory action of ATP on contractions of frog isolated sartorius muscle was shown earlier, while hydrocortisol prevented that effect of ATP. The aim of this study was to investigate whether ATP also inhibits the contractility of sartorius muscle on stress-induced animals. Materials and Methods: The influence of ATP on contractions and end-plate current (EPC) of sartorius muscles isolated from frogs exposed to electric foot-shock stimulation (EFSS) was analyzed. Results: In the muscles of frogs exposed to EFSS, the inhibitory effect of ATP on contractions was significantly decreased and on EPC was abolished. The level of cortisol was much higher in the blood obtained from EFSS animals comparing with control ones. Conclusion: The EFSS has inhibitory action on the effect of ATP on the frog sartorius muscle and that could be due to increase of cortisol blood level.

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