scholarly journals Phyllanthus reticulatus Prevents Ethanol-Induced Gastric Ulcer via Downregulation of IL-8 and TNF-α Levels

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hafsa Izhar ◽  
Arham Shabbir ◽  
Muhammad Shahzad ◽  
Aisha Mobashar ◽  
Syed Shoaib Ahmed

The current study aimed to determine the protective effect of P. reticulatus on ethanol-induced gastric ulcer. For this purpose, thirty-six Sprague-Dawley rats were divided into six groups. The first group served as normal control, while, in other five groups, absolute ethanol was used to induce gastric ulcer. Group II served as a diseased group, while groups III, IV, and V were treated with methanol extract, ethyl acetate fraction, and n-hexane fraction, respectively, in a dose of 400 mg/kg bodyweight. Group VI was given omeprazole in a dose 20 mg/kg bodyweight. The stomachs were removed, ulcer score was evaluated, and histopathological examination of gastric lumen was conducted. Total acidity and pH values were determined in gastric juice. TNF-α and IL-8 mRNA expressions levels were determined using the reverse transcription real-time PCR method. The data indicated that P. reticulatus protected against gastric ulcer, which was evident by attenuation of ulcer score. The pretreatment with P. reticulatus raised the gastric pH and improved all evaluated histopathological parameters such as ulcer score, erosion score, hemorrhage score, fibrinoid necrosis score, inflammatory infiltrate score, and edema score. P. reticulatus significantly reduced mRNA expression levels of TNF-α and IL-8. In conclusion, P. reticulatus possess antiulcer property which might be attributed to downregulation of TNF-α and IL-8 expression levels.

2021 ◽  
Vol 18 (9) ◽  
pp. 1873-1879
Author(s):  
Xin Jin ◽  
Qiang Liu Liu ◽  
Minyan Dang ◽  
Wenzhi Zhang ◽  
Xia Li

Purpose: To investigate the gastroprotective effect of Alpinia conchigera rhizome in an ulcer rat model. Method: Sprague-Dawley rats were treated with ethanol extract of Alpinia conchigera at doses of 75 and 150 mg/kg body weight. After 28 days, the rats were sacrificed. Ulcer index, total acidity, pH, hemoglobin levels, and hemorrhagic lesions were determined through macroscopic assessment and histopathological examination. The levels of lipid peroxidation (LPO), superoxide dismutase (SOD), and catalase (CAT), and inflammatory markers (TNF-α, IL-1β, and IL-6) were also determined. Results: Alpinia conchigera significantly reduced ulcer index, total acidity, pH and hemoglobin levels (p < 0.05). Results from histology revealed that the extract protected the mucosa from lesions. Moreover, the extract significantly enhanced gastric mucosal activities of SOD and CAT, and decreased LPO levels and plasma concentrations of TNF-α, IL-1β, and IL-6 (p < 0.05). Conclusion: These results validate the traditional claims on the gastroprotective effects of Alpinia conchigera as revealed through its antioxidant and ulcer-healing properties by stimulation of important cellular mechanisms.


Author(s):  
MANOBHARATHI VENGAIMARAN ◽  
KALAIYARASI DHAMODHARAN ◽  
MIRUNALINI SANKARAN

Objective: The central motive of this study is to explore the therapeutic impact of Diosgenin encapsulated Chitosan nanoparticles (DG@CS-NP) on mammary carcinogenesis in female Sprague Dawley rats via modulating hormonal status, cell proliferation, inflammatory responses, and Apoptosis. Methods: 7,12-dimethylbenz(a)anthracene (DMBA) was administered subcutaneously near the mammary gland (25 mg/kg b. wt) to provoke mammary tumor in female Sprague Dawley rats. Following the progress of a tumor, DMBA-induced tumor-bearing rats were medicated orally with 5 mg/kg b. wt of DG@CS-NP. Consequently, the expression of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, Bcl-2, Caspases-3, and p53 in experimental rats were revealed via architectural immunohistochemistry. Further, Diosgenin interactions with these proteins were evidently confirmed by molecular docking analysis. Results: As a result, we noticed diminished levels of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, and Bcl-2 expressions in DG@CS-NP medicated rats as well as with elevated levels of Caspases-3 and p53 expressions. In DMBA rats, the expressions were vice versa. Additionally, molecular docking analyses support these outcomes by highlighting the strong interaction between Diosgenin and breast cancer targets. Conclusion: These reports prove that DG@CS-NP imposes its therapeutic impact by hormonal adjustments, downregulating proteins involved in inflammation and cellular proliferation, and thereby promotes apoptosis by impeding apoptotic inhibitors.


2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Al-Qaraghuli AMS ◽  
Abdel Wahab EMN ◽  
Al-Ani IM ◽  
Faisal GG

Introduction: Xiang Sha Yang Wei Wan (XSYWW) is a Chinese traditional medicine that is used for gastrointestinal disorders, specifically gastric ulcer in many countries of South-East Asia. The aim of the study was to evaluate the potential effects of XSYWW on ethanol-induced gastric ulcer in rats by means of histological Study. On a similar basis of treatment, ranitidine, a conventional medication was used as gold standard. Methods: Fifty five male Sprague-Dawley rats (250-300 gm) were divided into four groups. Group I (ethanol treated group) was the control group and gastric ulcers were induced by administering 100% ethanol (1 ml/200 g). Group II (Pre-treatment group) was divided into two subgroups; they were orally fed with 1.0 gm/kg and 2.0 gm/kg respectively of XSYWW solution. Thirty minutes later they were administered with absolute ethanol as in group I. Group III, was given an oral dose of 2gm/kg of XSYWW solution after one hour of ethanol administration. Group IV was given an oral dose of 200mg/kg ranitidine solution after one hour of ethanol administration. Five rats from groups I, III and IV were sacrificed on day 1, 2 and 3 while the animals of group II were sacrificed one hour after ethanol administration. Results: Histological study of the stomachs from ethanol treated rats showed multiple ulcers of various depths that reached the muscularis and the serosa. Conclusion: Pre or post-treated rats with XSYWW showed that XSYWW has protective effect against ethanol-induced gastric mucosal lesion. However, there was a faster and more complete healing process in the ranitidine treated group when compared to the XSYWW treated subjects.


2020 ◽  
Vol 23 (4) ◽  
pp. 570-579
Author(s):  
Mahboubeh Sheikhan ◽  
◽  
Mohammad Reza Kordi ◽  
Hamid Rajabi ◽  
◽  
...  

Background and Aim: Several microRNAs are involved in regulating muscle mass, which plays an essential role in hypertrophy and atrophy of skeletal muscle, The present study examined the expression of some genes as regulators of muscular atrophy following a period of inertia in rats. Methods & Materials: For this purpose, 18 male Sprague-Dawley rats were divided into three groups (Control, Exercise+inactivity, and Inactivity). The exercise+inactivity group run on the treadmill for 18 weeks and five times per week. The hindlimb of the animal was immobilized for seven days with the casting method. Soleus muscle was extracted and the expression of the genes was measured by the RT-PCR method. Univariate ANOVA and Tukey post hoc test was used to determine the differences (α=0.05). Ethical Considerations: The Ethics Committee of the Tehran University of Medical Sciences Research approved this study (Code: IR.SUMS.REC.1396.S 463). Results: Results showed that immobilization in both Exercise+ inactivity and inactivity groups, compare to the control group, increased expression of miR-1 genes (P<0.10), FOXO3a (P<0.001) and decreased expression of miR-206 (P<0.007) and IGF-1 (P<0.001). This difference was statistically significant. Conclusion: According to the results of this study, it can be said that changes in the expression of RNAs by chromatography cause changes in the expression of muscle regulating genes, and although endurance exercises have protective effects, they cannot prevent these changes.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9138
Author(s):  
Abubakar El-Ishaq ◽  
Mohammed A. Alshawsh ◽  
Kein Seong Mun ◽  
Zamri Chik

Asparagus africanus Lam. is a plant used traditionally to treat different ailments. Currently, scanty information is available on its safety. The aim of this study is to determine the acute toxicity of the methanolic extract on vital organs and its associated biochemical parameters. Fifteen female Sprague-Dawley rats were divided into five groups. Group I served as normal control, groups II, III, IV, and V were orally administered single dose of crude extract dissolved in distilled water at 5 mg/kg BW, 50 mg/kg BW, 300 mg/kg BW and 2,000 mg/kg BW. Rats were observed for 14 days and body weights were recorded. On day 15, the rats were sacrificed and blood samples were collected for biochemical and haematological analyses, while the liver and kidneys were sampled for histopathological examination. Body weight and haematology parameters results showed significance difference (p < 0.05) among means of HGB, RDW, RBC, and MCHC; likewise, (p < 0.001) for WBC and platelet among treated groups. Histopathology result showed that kidneys appeared normal while livers were congested with mildly swollen hepatocytes and occasional binucleation. Focal lobular hepatitis was observed in all treated animals. However, hepatic enzymes were not significantly affected and no histopathological harmful effects were observed in kidney. In conclusion, methanolic extracts of A. africanus are safe up to 2,000 mg/kg BW. The obtained results could be used as a justification for the traditional application of the plant for treatment of various ailments.


2012 ◽  
Vol 302 (1) ◽  
pp. G145-G152 ◽  
Author(s):  
Vairappan Balasubramaniyan ◽  
Gavin Wright ◽  
Vikram Sharma ◽  
Nathan A. Davies ◽  
Yalda Sharifi ◽  
...  

Ammonia is central in the pathogenesis of hepatic encephalopathy, which is associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals. This study aimed to determine whether endothelial NO synthase activity is altered in the brain of cirrhotic animals, whether this is associated with changes in the endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats were studied 4-wk after bile duct ligation (BDL) ( n = 16) or sham operation ( n = 8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF-α, plasma, and brain ADMA were measured using standard techniques. NOS activity was measured radiometrically, and protein expression for NOS enzymes, ADMA, DDAH-1, 4-hydroxynonenol (4HNE), and NADPH oxidase (NOX)-1 were measured by Western blotting. BDL significantly increased arterial ammonia ( P < 0.0001), brain water ( P < 0.05), and brain TNF-α ( P < 0.01). These were reduced significantly by OP treatment. The estimated eNOS component of constitutive NOS activity was significantly lower ( P < 0.05) in BDL rat, and this was significantly attenuated in OP-treated animals. Brain ADMA levels were significantly higher and brain DDAH-1 significantly lower in BDL compared with sham ( P < 0.01) and restored toward normal following treatment with OP. Brain 4HNE and NOX-1 protein expression were significantly increased in BDL rat brain, which were significantly decreased following OP administration. We show a marked abnormality of NO regulation in cirrhotic rat brains, which can be restored by reduction in ammonia concentration using OP.


1991 ◽  
Vol 260 (4) ◽  
pp. G610-G614 ◽  
Author(s):  
K. R. Larsen ◽  
J. G. Moore ◽  
M. T. Dayton

One model of gastric ulcerogenesis implicates a disruption of complementary circadian rhythms between protective and destructive factors. The purpose of this study was to compare circadian rhythms in gastric production of H+ and HCO3- in fasted rats. Sprague-Dawley rats were acclimatized in sound-attenuating, light-proof chambers for 3 wk on a 12:12-h light-dark schedule. Eighteen-hour fasted rats were studied at each of eight sampling times. After anesthesia, the stomachs were cannulated and filled with test solution. Thirty-minute gastric samples were titrated for H+ or assayed for HCO3-. Cosinor analysis of the data showed significant (P less than 0.05) circadian rhythms for both H+ and HCO3-. Peak times were 22:45 HALO (hours after lights on) (4:45 A.M.) for H+ and 05:41 HALO (11:41 A.M.) for HCO3-. These data demonstrate that H+ and HCO3- secretion in the fasting rat gastric lumen follow circadian rhythms with different peak times. Theoretically, this may result in circadian rhythmicity of relative mucosal vulnerability to injury.


2017 ◽  
Vol 1 (S1) ◽  
pp. 60-60
Author(s):  
Andrea Lee Frump ◽  
Margie Albrecht ◽  
Sandra Breuils-Bonnet ◽  
Bakhtiyor Yakubov ◽  
Mary Beth Brown ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Women with pulmonary arterial hypertension (PAH) exhibit superior right ventricular (RV) function and survival compared with men, a phenomenon attributed to poorly understood cardioprotective effects of 17β-estradiol (E2). We hypothesize that E2, through ERα, attenuates PH-induced RV dysfunction by upregulating the pro-contractile and pro-angiogenic peptide apelin. This ERα-mediated increase in apelin is mediated by the myocardial remodeling effector bone morphogenetic protein receptor 2 (BMPR2). METHODS/STUDY POPULATION: ERα, BMPR2, and apelin were measured (western blot) in RVs from patients with PAH-induced RV failure and in RV homogenates from male or female Sprague-Dawley rats with sugen/hypoxia (SuHx) or monocrotaline (MCT)-induced PH. H9c2 rat cardiomyoblasts and cardiac endothelial cells were stressed with TNF-α (10 ng/mL) or staurosporine (50 nM)±E2 (100 nM; 24 h). ERα-, BMPR2-, and apelin-dependence were evaluated by siRNA (5 pM). Downstream apelin target and pro-survival factor ERK1/2 expression was measured (western blot). p<0.05 by ANOVA was considered significant. RESULTS/ANTICIPATED RESULTS: ERα correlated positively with BMPR2 and apelin expression in SuHx-RVs and human RVs. Treatment of SuHx-PH rats with E2 or ERα agonist increased RV BMPR2 and apelin, whereas RV apelin was decreased in E2-treated hypoxic ERα knockout mice (p<0.05), but not in ERβ knockout mice. In H9c2 cells, E2 or ERα agonist attenuated TNF-α- or staurosporine-induced decreases in BMPR2, apelin, and phospho-ERK1/2 (p<0.05 for all endpoints). E2 protection was lost in presence of siRNA directed against ERα, BMPR2, or apelin (p<0.05). ERα was necessary for E2-mediated increases in BMPR2, apelin, and ERK1/2, and BMPR2 was required for the E2-mediated increase in apelin (p<0.05 for siRNA vs. scramble). ERα, BMPR2, and apelin protein was increased in decompensated human RVs but downstream phospho-ERK signaling was disrupted. DISCUSSION/SIGNIFICANCE OF IMPACT: E2, via ERα, increases BMPR2 and apelin in the failing RV and in stressed rat cardiomyoblasts. The E2-mediated increase in apelin is BMPR2-dependent and likely occurs through direct binding of ERα to the BMPR2 promoter. Harnessing this E2-ERα-BMPR2-apelin axis during RV compensation may lead to novel, RV-targeted therapies for PAH patients of either sex.


2003 ◽  
Vol 284 (4) ◽  
pp. R916-R927 ◽  
Author(s):  
Zhi-Hua Zhang ◽  
Shun-Guang Wei ◽  
Joseph Francis ◽  
Robert B. Felder

In pathophysiological conditions, increased blood-borne TNF-α induces a broad range of biological effects, including activation of the hypothalamic-pituitary-adrenal axis and sympathetic drive. In urethane-anesthetized adult Sprague-Dawley rats, we examined the mechanisms by which blood-borne TNF-α activates neurons in paraventricular nucleus (PVN) of hypothalamus and rostral ventrolateral medulla (RVLM), two critical brain regions regulating sympathetic drive in normal and pathophysiological conditions. TNF-α (0.5 μg/kg), administered intravenously or into ipsilateral carotid artery (ICA), activated PVN and RLVM neurons and increased sympathetic nerve activity, arterial pressure, and heart rate. Responses to intravenous TNF-α were not affected by vagotomy but were reduced by mid-collicular decerebration. Responses to ICA TNF-α were substantially reduced by injection of the cyclooxygenase inhibitor ketorolac (150 μg) into lateral ventricle. Injection of PGE2 (50 ng) into lateral ventricle or directly into PVN increased PVN or RVLM activity, respectively, and sympathetic drive, with shorter onset latency than blood-borne TNF-α. These findings suggest that blood-borne cytokines stimulate cardiovascular and renal sympathetic responses via a prostaglandin-dependent mechanism operating at the hypothalamic level.


2020 ◽  
Vol 151 ◽  
pp. 01058
Author(s):  
Siti Aisyah ◽  
Ekowati Handharyani ◽  
Nurliani Bermawie ◽  
Agus Setiyono

The purpose of the research was to study the potency of Murraya koenigii leaves extract to overcome the mammary tumor in Sprague Dawley rat. Thirty-five female rats were divided into seven groups: control (P1), tumor without therapy (P2), methotrexate group (P3), curative groups (P4 and P5) were given extract after the tumor was formed, and preventive groups (P6 and P7) were given extract before the tumor was formed with dose of 300 and 400 mg/kg, respectively. The induction of mammary tumor in rats were carried out using 7,12 dimethylbenz(α) anthracene (DMBA) subcutaneously. Bodyweight and tumor size were measured every week for 4 weeks. At the end of treatment, rats were euthanized and mammary glands were collected for histopathological examination. The result showed tumor size in P2 was significantly higher (p<0.05) than in other groups. On the other hand, tumor size in P4 and P6 were significantly smaller (p<0.05) compared to P5 and P7. Histopathological changes showed PMN cells, 1-3 layers of cuboid epithelial and solid collagen fibers proliferation in P2, while in P3 to P7 showed moderate collagen fibers proliferation. In conclusion, the administration of the extract at a dose of 300 mg/kg can decelerate tumor development in Sprague Dawley rat mammary gland.


Sign in / Sign up

Export Citation Format

Share Document