Inhibitory Effect of Persimmon Tannin on Pancreatic Lipase and the Underlying Mechanism in Vitro

2018 ◽  
Vol 66 (24) ◽  
pp. 6013-6021 ◽  
Author(s):  
Wei Zhu ◽  
Yangyang Jia ◽  
Jinming Peng ◽  
Chun-mei Li
Keyword(s):  
Pancreatic Lipase ◽  
Underlying Mechanism ◽  
Inhibitory Effect

IMB-BZ as an Inhibitor Targeting ESX-1 Secretion System to Control Mycobacterial Infection

2021 ◽  
Author(s):  
Pingping Jia ◽  
Yi Zhang ◽  
Jian Xu ◽  
Mei Zhu ◽  
Shize Peng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterial Infection ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Dependent Manner ◽  
High Potency ◽  
Resistance Development

Abstract Background Resistance to anti-tuberculosis (TB) drug is a major issue in TB control, and demands the discovery of new drugs targeting virulence factor ESX-1. Methods We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacterium and reducing bacterial virulence. We further investigated the probability of inducing drug-resistance and the underlying mechanism using M-PFC. Results A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1-dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10-EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drug, and exhibit high potency against chronic mycobacterial infection. Conclusion Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.

IN VITRO STUDIES OF SOME EDIBLE SPICES ON PANCREATIC LIPASE INHIBITORY ACTIVITY

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 62-68
Author(s):  
S Mhatre ◽  
◽  
A. Bhagit ◽  
R. P Yadav
Keyword(s):  
Pancreatic Lipase ◽  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Syzygium Aromaticum ◽  
High Potency ◽  
Good Source ◽  
Zanthoxylum Armatum ◽  
Methanolic Extracts ◽  
Cinnamomum Tamala

Pancreatic lipase inhibitory effect of some edible spices in light of percent inhibition, efficacy, reversibility/ irreversibility and effect of pH on inhibition is presented here. Lipase inhibitory activities of methanolic extracts of eighteen spices were evaluated. Extracts of Zanthoxylum armatum, Cinnamomum tamala, Syzygium aromaticum and Myristica fragrans were considered to be of high potency in synthetic substrate assay. Only Syzygium aromaticum showed high potency in natural substrate based lipase assay. Zanthoxylum armatum extract displayed lowest IC50 of 9.0 μg/mL. On dialysis, all extracts lost their lipase inhibitory activity indicating reversible nature of inhibition. pH significantly affected the performance of spice extracts during inhibition of pancreatic lipase. Most of the extracts lost their pancreatic lipase inhibitory activity at pH 3.0 with the exception of Brassica nigra and Cinnamomum tamala. Results showed spice are good source of pancreatic lipase inhibitor and its potential as drug for obesity can be explored by addressing various issues.

scholarly journals IN VITRO ANTI-OBESITY EFFECT OF MACROLICHENS HETERODERMIA LEUCOMELOS AND RAMALINA CELASTRI BY PANCREATIC LIPASE INHIBITORY ASSAY

2017 ◽  
Vol 9 (5) ◽  
pp. 137
Author(s):  
Rashmi Shivanna ◽  
Hengameh Parizadeh ◽  
Rajkumar H. Garampalli
Keyword(s):  
Ethyl Acetate ◽  
Pancreatic Lipase ◽  
Methanol Extract ◽  
Well Being ◽  
Inhibitory Effect ◽  
Potential Effect ◽  
Protective Role ◽  
Treatment Of Obesity ◽  
Molecular Sequencing

Objective: Obesity is a chronic disorder caused by an imbalance between energy intake and expenditure in which excessive fat will be deposited in adipose tissue and poses a risk to the health and well-being of humans. Agents which inhibit pancreatic lipase play an important role in the treatment of obesity. The aim of this study was to assess the potential effect of macro lichens Heterodermia leucomelos (L.) Poelt a foliose lichen and Ramalina celastri (Sprengel) Krog and Swinscow a fruticose lichen in the treatment of obesity.Methods: In vitro anti-obesity inhibitory effect of macro lichens were evaluated by using chicken pancreatic lipase activity. Lipase was extracted from the chicken pancreas. Different concentrations from 5-25 mg/ml of methanol and ethyl acetate extracts of lichens Heterodermia leucomelos and Ramalina celastri was incubated with pancreas lipase.Results: With the increase in the concentration of extracts the higher inhibition of the enzyme was observed. Solvent methanol showed good activity compared to ethyl acetate. Percentage of inhibition ranged from 19.7-69.8 and 20.0-86.6 % in the methanol extract of Heterodermia leucomelos and Ramalina celastri respectively. Comparatively lichen Ramalina celastri in methanol extract showed maximum inhibition of 86.6 %, whereas ethyl acetate showed an inhibition of 63.0% at 25 mg/ml against enzyme lipase.Conclusion: In the present study, the inhibitory activity of lichen indicates its protective role in treating obesity. Molecular sequencing of this lichen helps in future to determine the various metabolic pathways that are responsible for the production of novel compounds.

scholarly journals CDK7 Inhibitor THZ1 Induces the Cell Apoptosis of B-Cell Acute Lymphocytic Leukemia by Perturbing Cellular Metabolism

2021 ◽  
Vol 11 ◽  
Author(s):  
Tuersunayi Abudureheman ◽  
Jing Xia ◽  
Ming-Hao Li ◽  
Hang Zhou ◽  
Wei-Wei Zheng ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Apoptosis ◽  
Acute Lymphocytic Leukemia ◽  
Cellular Metabolism ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Lymphocytic Leukemia ◽  
High Concentration ◽  
P53 Expression

B-cell acute lymphocytic leukemia (B-ALL) is a malignant blood cancer that develops in children and adults and leads to high mortality. THZ1, a covalent cyclin-dependent kinase 7 (CDK7) inhibitor, shows anti-tumor effects in various cancers by inhibiting cell proliferation and inducing apoptosis. However, whether THZ1 has an inhibitory effect on B-ALL cells and the underlying mechanism remains obscure. In this study, we showed that THZ1 arrested the cell cycle of B-ALL cells in vitro in a low concentration, while inducing the apoptosis of B-ALL cells in vitro in a high concentration by activating the apoptotic pathways. In addition, RNA-SEQ results revealed that THZ1 disrupted the cellular metabolic pathways of B-ALL cells. Moreover, THZ1 suppressed the cellular metabolism and blocked the production of cellular metabolic intermediates in B-ALL cells. Mechanistically, THZ1 inhibited the cellular metabolism of B-ALL by downregulating the expression of c-MYC-mediated metabolic enzymes. However, THZ1 treatment enhanced cell apoptosis in over-expressed c-MYC B-ALL cells, which was involved in the upregulation of p53 expression. Collectively, our data demonstrated that CDK7 inhibitor THZ1 induced the apoptosis of B-ALL cells by perturbing c-MYC-mediated cellular metabolism, thereby providing a novel treatment option for B-ALL.

scholarly journals Brusatol Inhibits Proliferation and Invasion of Glioblastoma by Down-Regulating the Expression of ECM1

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhang’an Dai ◽  
Lin Cai ◽  
Yingyu Chen ◽  
Silu Wang ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Herbal Extract ◽  
Extracellular Matrix Protein ◽  
Glioblastoma Cells ◽  
Primary Glioblastoma ◽  
Proliferation And Invasion

Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

scholarly journals Inhibitory Effects of Prunella vulgaris L. Extract on 11β-HSD1 in Human Skin Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Kyung-Baeg Roh ◽  
Deokhoon Park ◽  
Eunsun Jung
Keyword(s):  
Biological Activities ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Herbaceous Plant ◽  
Prunella Vulgaris ◽  
Beneficial Effects ◽  
Skin Cells ◽  
Promising Therapeutic Target ◽  
And Function

Glucocorticoids are a risk factor for age-induced skin structure and function defects, and the glucocorticoid-activating enzyme, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), represents a promising therapeutic target. Prunella vulgaris L. (PV) is a perennial and an edible herbaceous plant normally cultivated in Asia and Europe. A recent study demonstrated a broad range of biological activities of PV including immune modulatory, antiviral, antiallergic, anti-inflammatory, antioxidant, and antidiabetic. However, little is known about the inhibitory effect of PV on 11β-HSD1. In this study, we investigated the inhibitory effect of Prunella vulgaris L. extract (PVE) and the underlying mechanism of 11β-HSD11 inhibition. Consistent with these results, cortisol levels were also reduced by PVE in vitro. The cortisone-induced translocation of glucocorticoids receptor (GR) was also attenuated. In addition, PVE inhibited a cortisone-mediated decrease in collagen content in skin. Collectively, these results suggest the beneficial effects of PVE in maintaining skin integrity.

Abstract 198: Angiotensin II Inhibits Cardiac Angiogenesis via the Cooperation of p53 and Jagged 1

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Aili Guan ◽  
Hui Gong ◽  
Yong Ye ◽  
Jianguo Jia ◽  
Guoping Zhang ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Ang Ii ◽  
Capillary Formation ◽  
Angiogenic Effect ◽  
Endothelial Growth Factor

It is well established that angiotension II (Ang II) is an important regulator in vascular homeostasis. Under certain conditions, Ang II could exert anti-angiogenic effects in cardiovascular system. However, the potential mechanism is unclear. P53 has been reported to suppress angiogenesis by promoting hypoxia-inducible factor-1 (Hif-1α) degradation. This study was conducted to determine the contribution of P53 and the underlying mechanism to the anti-angiogenic effect of Ang II. Angiogenesis was determined by tube formation from the cardiac microvascular endothelial cells (ECs). Microvessel density and cardiac function were analyzed in mice subjected to Ang II infusion (200 ng/kg/min ) or vehicle for 2 weeks. Ang II (1μM) greatly inhibited tube formation and stimulated phosphorylation and upregulation of P53 in cultured cardiac ECs. P53 inhibitor, pifithrin-α (PFT-α,3.0mg/kg), significantly reversed the inhibitory effect of Ang II on tube formation. Vascular endothelial growth factor (VEGF ) and Hif-1α has been reported as important pro-angiogenetic factors. The present study indicated that Ang II decreased VEGF concentration in cultured medium and downregulated Hif-1α expression in cultured ECs. Interestingly, Ang II also stimulated the upregulation of Jagged 1, a ligand of Notch, but it didn't affect the Delta-like 4 (Dll 4) , another ligand of Notch, expression in cardiac ECs. However, PFT-α partly abolished these effects of Ang II. These results were consistent with the study in vivo. Further research revealed that siRNA-Jagged 1 transfection in cultured ECs dramatically abolished the phosphorylation of P53 and the downregulation of Hif-1α induced by Ang II. Additionally, Ang II- induced inhibitory effect on capillary formation was blocked by siRNA-Jagged 1 transfection in cultured cardiac ECs. In conclusion, Ang II promoted the phosphorylation and upregulation of P53, and increased Jagged 1 expression, the upregulation of Jagged 1 in turn stimulated the phosphorylation of P53, which resulted in the downregulation of Hif-1α and VEGF, then induced the inhibitory effects of Ang II on capillary formation. The present data suggest that Ang II exerts anti-angiogenesis via the cooperation of P53 and Jagged 1 in vitro and in vivo.

scholarly journals In-Vitro Inhibition of Human Lipase PS by Polyphenols From Kiwi Fruit

2014 ◽  
Vol 3 (4) ◽  
pp. 71 ◽  
Author(s):  
Eidenberger Thomas ◽  
Selg Manuel ◽  
Fuerst Sigrid ◽  
Krennhuber Klaus
Keyword(s):  
Pancreatic Lipase ◽  
Higher Plants ◽  
Inhibitory Effect ◽  
Enzyme Inactivation ◽  
Kiwi Fruit ◽  
Beneficial Effects ◽  
Wide Range ◽  
Vegetables And Fruits ◽  
Lipase Inhibition

<p>Polyphenols are widely distributed in higher plants. It is well recognized that they are responsible for many beneficial effects observed in humans after ingestion of vegetables and fruits. Kiwis (<em>Actinidia chinensis</em>) are an increasingly popular fruit in Europe and contain a wide range of polyphenols.</p> <p>Different preparations from kiwi fruits were compared for the content of soluble and condensed polyphenols and tested <em>in-vitro</em> for inhibition of human pancreatic lipase. It is shown that human pancreatic lipase is substantially inhibited by kiwi polyphenols as long as the proportion of condensed polyphenols remains intact. Lipase inhibition is negligible when condensed polyphenols are hydrolysed by acidic treatment. It was also demonstrated that Kiwi polyphenols do not precipitate proteins as described for the tannin class of condensed polyphenols. Hence, the inhibitory effect of condensed Kiwi polyphenols is not considered to be related to unspecific enzyme inactivation by a tannin-like effect.</p>

Comparative effects of piperine and simvastatin in fat accumulation and antioxidative status in high fat-induced hyperlipidemic rats

2016 ◽  
Vol 94 (12) ◽  
pp. 1344-1348 ◽  
Author(s):  
Sakara Tunsophon ◽  
Krongkarn Chootip
Keyword(s):  
Pancreatic Lipase ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Liver Cholesterol ◽  
High Fat ◽  
Serum Aminotransferase ◽  
Fat Accumulation ◽  
Antioxidative Status ◽  
Beneficial Effects

The present study investigated the comparative effects of piperine (PIP) — the active ingredient of black and long peppers — and simvastatin (SIM) on hepatic steatosis in hyperlipidemic rats. Male Wistar rats were fed a cholesterol mixture daily by intragastric gavage for 8 weeks. Piperine was given by oral gavage 8 h after cholesterol feeding. The animals were divided into 4 groups: control, high fat (HF), high fat plus 40 mg PIP/kg, and high fat plus 2 mg SIM/kg. At the end of the treatment, liver cholesterol, triglyceride, thiobaribituric reacting substances, superoxide dismutase (SOD), serum aminotransferase (AST), and alanine transferase (ALT) were measured. The result demonstrated that PIP and SIM significantly reduced the accumulation of cholesterol, triglyceride, and lipid peroxidation in the liver, while elevation of SOD was observed. The activities of AST and ALT significantly decreased in PIP when compared with the HF group. Our in vitro study of pancreatic lipase also showed the inhibitory effect of PIP higher than 30% at 5 mmol/L. These results demonstrate that PIP has beneficial effects in the treatment and (or) prevention of fat accumulation in the liver and that this mechanism is due to the inhibition of pancreatic lipase and the improvement of oxidative status.

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