scholarly journals Antidiarrheal Effect of Zornia brasiliensis Vogel (Leguminosae) on Mice Involves Adrenergic Pathway Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Filipe R. M. B. Oliveira ◽  
Sarah R. D. Ferreira ◽  
Giulyane T. Aires-Moreno ◽  
Anne D. S. Silva ◽  
Yuri M. Nascimento ◽  
...  
Keyword(s):  
Castor Oil ◽  
Ethanolic Extract ◽  
Intestinal Transit ◽  
Dependent Manner ◽  
Fluid Accumulation ◽  
Aerial Parts ◽  
Pathway Activation ◽  
Defecation Frequency ◽  
Adrenergic Systems ◽  
Underlying Mechanisms

Several secondary metabolites have been isolated from Zornia brasiliensis (Leguminosae), mainly flavonoids. These compounds are known for many pharmacological actions, such as antispasmodic and antidiarrheal. Therefore, we evaluated the antidiarrheal effect of the ethanolic extract obtained from Zornia brasiliensis aerial parts (ZB-EtOHAP), as well as its underlying mechanisms. Castor-oil-induced diarrhea, fluid accumulation, and intestinal transit (normal and castor oil induced) were performed to assess the antidiarrheal, antisecretory, and antipropulsive activities of the extract. The involvement of opioid and adrenergic pathways was also investigated. ZB-EtOHAP inhibited, in a dose-dependent manner, both total defecation frequency and the number of watery stools. The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the marker in the small intestine. Investigation of the involvement of opioid and adrenergic systems showed that the pharmacological potency of the extract did not change in the presence of naloxone, but it was reduced in the presence of yohimbine. The data indicate that Zornia brasiliensis has an antidiarrheal effect due to inhibition of the intestinal motility through adrenergic pathway activation.

scholarly journals Antidiarrheal Activity of Ethanolic Extract of Melochia corchorifolia L. and Glochidion thomsonii in Experimental Animal Models

2019 ◽  
Vol 22 (2) ◽  
pp. 192-199
Author(s):  
Nusrat Jahan ◽  
Jannatul Ferdousi ◽  
Md Jahir Alam ◽  
Tasmina Rahman ◽  
Mizanur Rahman ◽  
...  
Keyword(s):  
Castor Oil ◽  
Folk Medicine ◽  
Public Health Problem ◽  
Ethanolic Extract ◽  
Pharmaceutical Journal ◽  
Fluid Accumulation ◽  
Standard Drug ◽  
Whole Plant ◽  
Dose Dependent ◽  
Gi Motility

Diarrhoea is a public health problem in developing countries. It is therefore important to identify plants with antidiarrhoeal activity. Melochia corchorifolia and Glochidion thomsonii have been used in folk medicine to alleviate several diseases. The present study was performed to investigate the anti-diarrheal properties of ethanolic extract of M. corchorifolia whole plant and G. thomsonii bark. Anti-diarrheal potential was evaluated using castor oil and MgSO4 induced diarrhea, GI motility test as well as castor oil induced enteropooling assay in mice. Extracts were used at 250 and 500 mg/kg per orally. Loperamide (10 mg/kg p.o) was used as standard drug. The ethanolic crude extracts exhibited statistically significant and dose-dependent (250 and 500 mg/kg) anti-diarrheal effect against the total number of episodes of defecation as well as diarrheal feces. In animals pretreated with MC and GT extract showed 42.53% (p<0.05) and 53.13% (p<0.001) protection at a dose of 250 mg/kg and 89.40% (p<0.001)and 57.47% (p<0.001) protection at 500 mg/kg against castor oil induced diarrhea. The MC extract at 500 mg/kg exhibited significant (p<0.05) inhibition of diarrhea (51.04%) in MgSO4 induced diarrhea. In BaSO4 induced GI motility test both the extracts inhibited GI motility and GT at 500 mg/kg dose 38.77% which was highly significant (p<0.01). In the Castor oil induced enteropooling assay MC 250 and 500 mg/kg and GT 250 and 500 mg/kg reduced the intestinal fluid accumulation by 27.42% and 48.39% (p<0.01) and 38.71% (p<0.05) and 51.61% (p<0.01), respectively. The results suggested that both the extracts possessed significant antidiarrhoeal properties which was comparable with standard drug, loperamide and further studies are required to evaluate these effects and the potential of the plant. Bangladesh Pharmaceutical Journal 22(2): 192-199, 2019

scholarly journals Anticonvulsant Effects of Aerial Parts of Verbena officinalis Extract in Mice: Involvement of Benzodiazepine and Opioid Receptors

2017 ◽  
Vol 22 (4) ◽  
pp. 632-636 ◽  
Author(s):  
Amir Rashidian ◽  
Fatemeh Kazemi ◽  
Saeed Mehrzadi ◽  
Ahmad Reza Dehpour ◽  
Shahram Ejtemai Mehr ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Hind Limb ◽  
Ethanolic Extract ◽  
Maximal Electroshock ◽  
Dependent Manner ◽  
Reference Drug ◽  
Mes Test ◽  
Aerial Parts ◽  
Tonic Extension ◽  
Dose Dependent

To evaluate the anticonvulsant activity of the aerial parts of Verbena officinalis used traditionally by local Iranians for the treatment of convulsion. The anticonvulsant activity of the extract was assessed in pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizures in mice. Diazepam was used as reference drug. In addition, for investigating the mechanism of V officinalis in PTZ model, flumazenil and naloxone were injected before V officinalis. The extract showed no toxicity and significantly increased the period taken before the onset and decreased the duration of the seizures induced by PTZ. In the MES test, V officinalis displayed significant reduction in hind limb tonic extension duration in a dose-dependent manner. The results propose that V officinalis ethanolic extract has anticonvulsant activity against seizure. It seems that these effects may be related to potentiating of GABAergic system. Moreover, this study supports the use of this plant by local Iranians in order to treat convulsion.

EVALUATION OF ANTI-DIARRHOEAL ACTIVITY OF PUNICA GRANATUM STEM BARK

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (09) ◽  
pp. 34-40
Author(s):  
N Khan ◽  
◽  
S Hugar ◽  
V Patil ◽  
H.M Nanjappaiah ◽  
...  
Keyword(s):  
Castor Oil ◽  
Ethanolic Extract ◽  
Punica Granatum ◽  
Stem Bark ◽  
Fluid Accumulation ◽  
Fecal Matter ◽  
Hydroalcoholic Extract ◽  
Experimental Animal Models ◽  
Pharmacologically Active ◽  
Dose Dependent

Evaluation of anti-diarrhoeal effect of Punica granatum stem bark ethanolic extract was carried out on various experimental animal models of diarrhea. Different paragons used were castor oil induced diarrhoea, magnesium sulphate induced diarrhoea, castor oil induced enteropooling and gastrointestinal motility test. The various parameters recorded were onset of diarrhoea, mean number of fecal drops, mean weight of fecal matter, mean weight of small intestine, volume of fluid accumulation in the intestine and mean distance travelled by charcoal meal in the intestine. The test extract demonstrated dose dependent significant anti-diarrhoeal effect. The results of this investigation revealed that, 70% hydroalcoholic extract of Punica granatum stem bark contains pharmacologically active substance(s) with anti-diarrhoeal efficacy.

scholarly journals Phytochemistry and effects of Ethanol Leaf Extract of Meytenus senengalensis (Lam) on Castor-oil Induced Diarrhoea in Albino Rats

2020 ◽  
Vol 17 (1) ◽  
pp. 1-6
Author(s):  
Kyari Abba Sanda ◽  
Umar Kyari Sandabe ◽  
Ibrahim Bulama ◽  
Mohammed ‎Babakura ◽  
Hanna Madziga ◽  
...  
Keyword(s):  
Castor Oil ◽  
Cardiac Glycosides ◽  
Leaf Extract ◽  
Significant Inhibition ◽  
Intestinal Transit ◽  
Saline Control ◽  
Albino Rats ◽  
Phytochemical Analysis ◽  
Intestinal Fluid ◽  
Fluid Accumulation

Abstract Meytenus senengalensis (Lam). Ethanol leaf extract was investigated for its phytochemical contents as well as anti-diarrhoea effects. The ethanol leaf extract which is normally used in folkloric medicine was subjected to qualitative phytochemical screening. Graded doses of the extract (200, 400 and 800 mg per kg) were administered orally to the three groups of rats (n = 5) before induction of diarrhoea with castor oil. Another two groups of animals were treated with normal saline (control) and loperamide, a conventional anti-diarrhoea drug respectively. Gastro-intestinal transit of charcoal meal and gastro-intestinal enteropooling with the same graded doses of the ethanol leaf extract were used for comparison. The extract produced a significant inhibition of the castor oil induced diarrhoea. The gastro-intestinal transit of charcoal meal was also reduced by the various graded doses of the extract used in this study. However, the intestinal fluid accumulation was only slightly reduced by 400 mg/kg dose of the extract. The phytochemical analysis of the ethanol leaf extract revealed the presence of secondary metabolites such as   carbohydrates, cardenolides, cardiac glycosides, flavonoids, saponins, tannins and terpenoids. The findings suggest that, the ethanol leaf extract of M. senengalensis possesses antidiarrhoeal effect, which could be related to inhibition of gastro-intestinal motility and secretion.  

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells

2020 ◽  
Vol 20 (4) ◽  
pp. 307-317
Author(s):  
Yuan Yang ◽  
Jin Huang ◽  
Jianzhong Li ◽  
Huansheng Yang ◽  
Yulong Yin
Keyword(s):  
Cell Viability ◽  
P38 Mapk ◽  
Butyric Acid ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Mrna Level ◽  
Dependent Manner ◽  
M Phase ◽  
High Concentrations ◽  
Underlying Mechanisms

Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated. Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes. Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.

scholarly journals Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Zhimin Zhang ◽  
Congying Wei ◽  
Yanfen Zhou ◽  
Tao Yan ◽  
Zhengqiang Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Homologous Protein ◽  
Intracellular Ros ◽  
Underlying Mechanisms ◽  
Umbilical Vein Endothelial Cells

Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3. Prolonged Hcy treatment also upregulated glucose-regulated protein 78 (GRP78), activated protein kinase RNA-like ER kinase (PERK), and induced the expression of C/EBP homologous protein (CHOP) and the phosphorylation of NF-κb. The inhibition of NOX4 decreased the production of ROS and alleviated the Hcy-induced HUVEC apoptosis and ER stress. Blocking the PERK pathway partly alleviated Hcy-induced HUVEC apoptosis and the activation of NF-κb. Taken together, our results suggest that Hcy-induced mitochondrial dysfunction crucially modulated apoptosis and contributed to the activation of ER stress in HUVEC. The excessive activation of the PERK pathway partly contributed to Hcy-induced HUVEC apoptosis and the phosphorylation of NF-κb.

scholarly journals HMGB1 orchestrates STING-mediated senescence via TRIM30α modulation in cancer cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Je-Jung Lee ◽  
In Ho Park ◽  
Man Sup Kwak ◽  
Woo Joong Rhee ◽  
Songhee H. Kim ◽  
...  
Keyword(s):  
High Mobility ◽  
Dependent Manner ◽  
Signal Transducer ◽  
Therapeutic Concept ◽  
Doxorubicin Treatment ◽  
Tripartite Motif ◽  
Anticancer Mechanism ◽  
Tripartite Motif Protein ◽  
Underlying Mechanisms ◽  
Novel Therapeutic

AbstractAlthough cellular senescence has emerged as a novel therapeutic concept in cancer, its underlying mechanisms remain unclear. High mobility group box 1 (HMGB1) and stimulator of interferon genes (STING) are involved in senescence. However, their interactions in senescence have not been reported. Therefore, in this study, we investigated the relationships between HMGB1 and STING in senescence in cancer and other cells. In mouse melanoma cells and several other cell lines, doxorubicin treatment induced senescence in an HMGB1-dependent manner. These responses were mediated by STING, and this function of STING was negatively regulated by the E3 ligase tripartite motif protein 30α (TRIM30α). We also found that HMGB1 bound to the TRIM30α promoter and then suppressed its expression by inhibiting its transcription, which enhanced STING-induced senescence. This mechanism was further mediated by signal transducer and activator of transcription 6 (STAT6) and p21. Overall, our findings demonstrated that HMGB1 orchestrated STING-STAT6-p21-mediated senescence by regulating TRIM30α as an alternative anticancer mechanism.

scholarly journals The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1025
Author(s):  
Ahmed Alalaiwe ◽  
Jia-You Fang ◽  
Hsien-Ju Lee ◽  
Chun-Hui Chiu ◽  
Ching-Yun Hsu
Keyword(s):  
Molecular Docking ◽  
Fatty Acid Synthase ◽  
Structural Similarity ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

Abstract P204: Epithelial Sodium Channel Stimulation by Glucose

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Parijat S Joy ◽  
Peter M. Snyder
Keyword(s):  
Diabetes Mellitus ◽  
Cell Surface ◽  
Collecting Duct ◽  
Short Circuit ◽  
Primary Cultures ◽  
Endocytic Pathway ◽  
Sodium Absorption ◽  
Dependent Manner ◽  
Elevated Glucose ◽  
Underlying Mechanisms

There is a link between diabetes mellitus and hypertension, but the underlying mechanisms are poorly understood. The epithelial Na + channel ENaC plays an important role in blood pressure control; ENaC mutations cause Liddle’s syndrome, an inherited form of hypertension. Previous work suggests that ENaC abundance is increased in diabetes mellitus, but the underlying mechanisms are unclear. Here we tested the effect of glucose on ENaC regulation. In Ussing chamber experiments using mouse kidney collecting duct cells (mCCD) and primary cultures of human lung epithelia, elevated glucose increased ENaC-mediated short-circuit current by 2-3 times in a dose-dependent manner from 100mg/dl to 400mg/dl of glucose. This was caused by an increase in ENaC abundance at the cell surface. We hypothesized that hyperglycemia might enhance ENaC cell surface abundance by altering activity of Nedd4-2, an E3 ubiquitin-protein ligase that binds to PY motifs within ENaC. Consistent with this hypothesis, we found that mutation of the PY motifs abolished ENaC stimulation by elevated glucose. Moreover, using a biotinylation assay, we found that elevated glucose (300 mg/dl) slowed ENaC endocytosis and reduced its degradation in the endocytic pathway. These changes in trafficking are explained by our finding that glucose reduced ENaC binding to Nedd4-2, and hence, reduced ENaC ubiquitination. O-GlcNAcylation plays a role in insulin signaling and glucose toxicity due to increased O-GlcNAcylation of target proteins. To test a role for O-GlcNAcylation in ENaC stimulation by glucose, we used 6-Diazo-5-oxo-l-norleucine (DON) to inhibit O-GlcNAcylation. DON abolished ENaC stimulation by elevated glucose. Using anti-O-GlcNAc antibody, we found that Nedd4-2 is a substrate for O-GlcNAcylation, and this modification was increased by elevated glucose. DON also reversed the reduction in binding of Nedd4-2 to ENaC at high glucose levels. Together, our data suggest a model in which hyperglycemia stimulates ENaC through O-GlcNAcylation of Nedd4-2, increasing ENaC abundance at cell surface thus increasing epithelial sodium absorption.

Sign in / Sign up

Export Citation Format

Share Document