scholarly journals Inhibitory Effect of Ocimum gratissimum Leaf Extract on Postprandial Increase of Blood Glucose

2019 ◽  
Vol 14 (10) ◽  
pp. 1934578X1988372
Author(s):  
Hiroaki Shimada ◽  
Chiaki Kuma ◽  
Taichi Iseri ◽  
Shin-ichi Matsumura ◽  
Atsushi Kawase ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Transporter ◽  
Inhibitory Effect ◽  
Glucose Absorption ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ocimum Gratissimum ◽  
Inhibitory Potential ◽  
Hyperglycemic Effect

The tea of Ocimum gratissimum (OG) leaves has been commonly consumed by people living in Ishigaki Island, Okinawa prefecture, Japan, and is considered to be effective for improving diabetes mellitus. In this study, we aimed to clarify the inhibitory potential of OG leaves extract (OG-ext) on gastrointestinal glucose absorption and to provide theoretical evidence for the anti-hyperglycemic effect of OG-ext. The increase of blood glucose after oral administration of α-starch and glucose in mice was suppressed by co-administration of OG-ext. An in vitro enzymatic assay suggested that amylase and maltase were inhibited weakly by the addition of OG-ext. In Caco-2 cells, a human intestinal epithelial model, the sodium-dependent glucose transporter (SGLT) 1-mediated uptake of fluorescence glucose analog was inhibited significantly by the addition of OG-ext in a concentration-dependent manner. These results indicate that the inhibitory effect on SGLT1 is one of the mechanisms of the anti-hyperglycemic effect of the tea of OG leaves.

Thrombin activatable fibrinolysis inhibitor (TAFI) affects fibrinolysis in a plasminogen activator concentration-dependent manner

2004 ◽  
Vol 91 (03) ◽  
pp. 473-479 ◽  
Author(s):  
Ana Guimarães ◽  
Dingeman Rijken
Keyword(s):  
Plasminogen Activator ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Retardation Factor ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasma Clot ◽  
Concentration Dependent Manner ◽  
Plasmin Inhibitor

SummaryTAFIa was shown to attenuate fibrinolysis. In our in vitro study, we investigated how the inhibitory effect of TAFIa depended on the type and concentration of the plasminogen activator (PA). We measured PA-mediated lysis times of plasma clots under conditions of maximal TAFI activation by thrombin-thrombomodulin in the absence and presence of potato carboxypeptidase inhibitor. Seven different PAs were compared comprising both tPA-related (tPA, TNK-tPA, DSPA), bacterial PA-related (staphylokinase and APSAC) and urokinase-related (tcu-PA and k2tu-PA) PAs. The lysis times and the retardation factor were plotted against the PA concentration. The retardation factor plots were bell-shaped. At low PA concentrations, the retardation factor was low, probably due to the limited stability of TAFIa. At intermediate PA concentrations the retardation factor was maximal (3-6 depending on the PA), with TNK-tPA, APSAC and DSPA exhibiting the strongest effect. At high PA concentrations, the retardation factor was again low, possibly due to inactivation of TAFIa by plasmin or to a complete conversion of glu-plasminogen into lys-plasminogen. Using individual plasmas with a reduced plasmin inhibitor activity (plasmin inhibitor Enschede) the bell-shaped curve of the retardation factor shifted towards lower tPA and DSPA concentrations, but the height did not decrease. In conclusion, TAFIa delays the lysis of plasma clots mediated by all the plasminogen activators tested. This delay is dependent on the type and concentration of the plasminogen activator, but not on the fibrin specificity of the plasminogen activator. Furthermore, plasmin inhibitor does not play a significant role in the inhibition of plasma clot lysis by TAFI.

scholarly journals Quercetin Is a Flavonoid Breast Cancer Resistance Protein Inhibitor with an Impact on the Oral Pharmacokinetics of Sulfasalazine in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 397
Author(s):  
Yoo-Kyung Song ◽  
Jin-Ha Yoon ◽  
Jong Kyu Woo ◽  
Ju-Hee Kang ◽  
Kyeong-Ryoon Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cancer Resistance ◽  
Concentration Dependent Manner ◽  
Resistance Protein

The potential inhibitory effect of quercetin, a major plant flavonol, on breast cancer resistance protein (BCRP) activity was investigated in this study. The presence of quercetin significantly increased the cellular accumulation and associated cytotoxicity of the BCRP substrate mitoxantrone in human cervical cancer cells (HeLa cells) in a concentration-dependent manner. The transcellular efflux of prazosin, a stereotypical BCRP substrate, was also significantly reduced in the presence of quercetin in a bidirectional transport assay using human BCRP-overexpressing cells; further kinetic analysis revealed IC50 and Ki values of 4.22 and 3.91 μM, respectively. Moreover, pretreatment with 10 mg/kg quercetin in rats led to a 1.8-fold and 1.5-fold increase in the AUC8h (i.e., 44.5 ± 11.8 min∙μg/mL vs. 25.7 ± 9.98 min∙μg/mL, p < 0.05) and Cmax (i.e., 179 ± 23.0 ng/mL vs. 122 ± 23.2 ng/mL, p < 0.05) of orally administered sulfasalazine, respectively. Collectively, these results provide evidence that quercetin acts as an in vivo as well as in vitro inhibitor of BCRP. Considering the high dietary intake of quercetin as well as its consumption as a dietary supplement, issuing a caution regarding its food–drug interactions should be considered.

Stimulation of renin secretion by ethacrynic acid is independent of Na(+)-K(+)-2Cl- cotransport

1990 ◽  
Vol 259 (4) ◽  
pp. F539-F544 ◽  
Author(s):  
C. S. Park ◽  
P. S. Doh ◽  
R. E. Carraway ◽  
G. G. Chung ◽  
J. C. Fray ◽  
...  
Keyword(s):  
Loop Diuretic ◽  
Ethacrynic Acid ◽  
Inhibitory Effect ◽  
Renin Secretion ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Specific Membrane ◽  
Cortical Slices ◽  
Stimulation Of

This study investigated the cellular mechanism of stimulation of renin secretion by the loop diuretic ethacrynic acid (EA) in rabbit renal cortical slices. The diuretic rapidly stimulated renin secretion reversibly and in a concentration-dependent manner. The stimulation was independent of the presence of Na+, Cl-, Ca2+, or other loop diuretics (furosemide and bumetanide) in the incubation media, suggesting that the stimulation in vitro was not dependent on the inhibitory effect of the diuretic on Na(+)-K(+)-2Cl-cotransport. The findings do not support the macula densa hypothesis. The stimulation by the diuretic was prevented and reversed by thiols such as cysteine and dithiothreitol, which also prevented and reversed the stimulation of renin secretion by the nondiuretic sulfhydryl reagent P-chloromercuriphenyl-sulfonate (PCMPS). These results suggest that EA stimulates renin secretion in vitro via reversible chemical reactions with specific membrane sulfhydryl groups that may have no functional role in the Na(+)-K(+)-2Cl- cotransport.

The Inhibitory Effect of Herbal Medicine -Dai Kenchu To (DKT)- on the Colonic Motility in Rats In Vitro

2001 ◽  
Vol 29 (01) ◽  
pp. 111-118 ◽  
Author(s):  
Mohammad Alhakam Tulimat ◽  
Tadashi Ishiguchi ◽  
Susumu Kurosawa ◽  
Takashi Nakamura ◽  
Toku Takahashi
Keyword(s):  
Herbal Medicine ◽  
Colonic Motility ◽  
Distal Colon ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Ginseng Root ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Beneficial Effects

Dai-Kenchu-To (DKT) is a herbal medicine and is currently used as the treatment of paralytic ileus in Japan. We investigated the mechanism of beneficial effects of DKT in vitro. DKT-extract powder (DKT-EP; 30–300 μg/ml) caused a significant inhibition on carbachol (CCH; 10-6)-induced contraction in a concentration dependent manner of the rat distal colon. DKT-EP (100 μg/ml) consists of 20 μg/ml of Zanthoxylum Fruit, 30 μg/ml of Ginseng Root and 50 μg/ml of Ginger Rhizome. Although each of them had no effect on CCH-induced muscle contraction, the combination of three ingredients caused a significant inhibition on CCH-induced contraction.

scholarly journals Myostatin regulates glucose uptake in BeWo cells

2007 ◽  
Vol 293 (5) ◽  
pp. E1296-E1302 ◽  
Author(s):  
Nisha Antony ◽  
John J. Bass ◽  
Christopher D. McMahon ◽  
Murray D. Mitchell
Keyword(s):  
Glucose Uptake ◽  
Cell Lines ◽  
Transforming Growth Factor ◽  
Muscle Growth ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Bewo Cells ◽  
Placental Cells

Myostatin is a member of the transforming growth factor (TGF)-β superfamily, known for its ability to inhibit muscle growth. It can also regulate metabolism and glucose uptake in a number of tissues. To determine the mechanism of myostatin's effect on glucose uptake, we evaluated its actions using choriocarcinoma cell lines that are widely used as models for placental cells. Protein and mRNA were determined using immunoblotting and RT-PCR/PCR, respectively. Glucose uptake was assessed by uptake of radiolabeled deoxyglucose in vitro. All choriocarcinoma cell lines tested i.e., BeWo, JEG, and Jar, are used as models of placental cells, and all expressed myostatin protein and mRNA. Treatment of BeWo cells with myostatin resulted in inhibition of glucose uptake in a concentration-dependent manner ( P < 0.01). At all concentrations tested, follistatin, a functional inhibitor of myostatin, completely blocked the inhibitory effect of myostatin (40 nM) on glucose uptake by BeWo cells (0.4 nM, P < 0.05). Follistatin treatment alone also increased glucose uptake (0.4 and 4 nM, P < 0.001; 40 nM, P < 0.05). Because BeWo cells proliferated and greater cell densities were achieved, glucose uptake declined irrespective of treatment. Myostatin treatment of BeWo cells did not alter the levels of myostatin receptor, ActRII A/B proteins. The levels of glucose transport proteins also remained unaltered in BeWo cells with myostatin treatment. This study has shown that myostatin specifically inhibits glucose uptake into BeWo cells, suggesting that locally produced myostatin may control glucose metabolism within the placenta.

scholarly journals In vitro inhibition of topoisomerase IIα by reduced glutathione.

2011 ◽  
Vol 58 (2) ◽  
Author(s):  
Zahid M Delwar ◽  
Marina Fernanda Vita ◽  
Åke Siden ◽  
Mabel Cruz ◽  
Juan Sebastian Yakisich
Keyword(s):  
Redox Balance ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Topoisomerase Iiα ◽  
Physiological Concentration ◽  
Concentration Dependent Manner ◽  
Disulfide Exchange ◽  
Intracellular Redox

In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances. In this study, the inhibitory effect of physiological concentration of GSH and GSSG on topoisomerase IIα activity in vitro was investigated. GSH (0-10 mM) inhibited topoisomerase IIα in a concentration-dependent manner while GSSG (1-100 µM) had no significant effect. These findings suggest that the GSH/GSSG system could have a potential in vivo role in regulating topoisomerase IIα activity.

scholarly journals Novel Roles of Chloroquine and Hydroxychloroquine in Graves’ Orbitopathy Therapy by Targeting Orbital Fibroblasts

2020 ◽  
Vol 105 (6) ◽  
pp. 1906-1917 ◽  
Author(s):  
Yan Guo ◽  
Hai Li ◽  
Xueying Chen ◽  
Huasheng Yang ◽  
Hongyu Guan ◽  
...  
Keyword(s):  
Western Blot ◽  
Real Time ◽  
Fluorescent Protein ◽  
Inhibitory Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Graves Orbitopathy ◽  
Orbital Fibroblasts

Abstract Context Graves’ orbitopathy (GO) causes infiltrative exophthalmos by inducing excessive proliferation, adipogenesis, and glycosaminoglycan production in orbital fibroblasts (OFs). Interference with OF autophagy is a potential therapy for proptosis. Objectives Here, we aimed to evaluate the effects of chloroquine (CQ) and hydroxychloroquine (HCQ), the autophagy inhibitors commonly used in clinical practice, on OFs. Design/Setting/Participants OFs isolated from patients with GO (GO-OFs) or control individuals (non-GO-OFs) were cultured in proliferation medium (PM) or subjected to differentiation medium. OFs were treated with CQ or HCQ (0, 0.5, 2, and 10 μM), and subsequently examined in vitro. Main Outcome Measures CCK-8, EdU incorporation, and flow cytometry assays were used to assess cellular viability. Adipogenesis was assessed with Western blot analysis, real-time polymerase chain reaction (PCR) , and Oil Red O staining. Hyaluronan production was determined by real-time PCR and enzyme-linked immunosorbent assay. Autophagy flux was detected through red fluorescent protein (RFP)-green fluorescent protein (GFP)-LC3 fluorescence staining and Western blot analyses. Results CQ/HCQ halted proliferation and adipogenesis in GO-OFs in a concentration-dependent manner through blockage of autophagy, phenotypes that were not detected in non-GO-OFs. The inhibitory effect of CQ/HCQ on hyaluronan secretion of GO-OFs was also concentration dependent, mediated by downregulation of hyaluronan synthase 2 rather than hyaluronidases. Moreover, CQ (10 μM) induced GO-OF apoptosis without aggravating oxidative stress. Conclusions The antimalarials CQ/HCQ affect proliferation, adipogenesis, and hyaluronan generation in GO-OFs by inhibiting autophagy, providing evidence that they can be used to treat GO as autophagy inhibitors.

In vitro myometrial inhibition by the partitioned aqueous fraction of Anthocleista djalonensis leaves

2010 ◽  
Vol 88 (9) ◽  
pp. 880-887
Author(s):  
Enitome Evi Bafor ◽  
Lucky Osaro Okunrobo
Keyword(s):  
Uterine Contraction ◽  
Calcium Influx ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Response Curves ◽  
Concentration Dependent Manner ◽  
Aqueous Fraction ◽  
Uterine Contractions ◽  
Β Adrenergic Receptors

This study investigated the effect on the uterus of the aqueous fraction of the partitioned methanol crude extract of the leaves of Anthocleista djalonensis (AD) and the possible mechanism of AD activity. AD inhibited the concentration–response curves induced by oxytocin and CaCl2 on the rat uterus in vitro and significantly reduced the EC50 in a concentration-dependent manner (p < 0.05). A similar effect was observed with salbutamol and verapamil on the concentration–response curves obtained for oxytocin and CaCl2. The inhibitory effect of AD was not attenuated in the presence of propranolol. AD, salbutamol, and verapamil also produced a concentration-dependent relaxation on K+-induced sustained uterine contraction. In Ca2+-free medium, AD and salbutamol similarly inhibited oxytocin-induced contraction, but verapamil failed to produce this effect. The present results suggest that AD, being a mixture of phytochemicals, probably exerts inhibitory activity on in vitro uterine contractions of the nonpregnant, diethylstilboestrol-treated rat by multiple mechanisms that do not involve interaction with β-adrenergic receptors and do not solely depend on inhibition of calcium influx.

G protein-coupled estrogen receptor 1 mediates relaxation of coronary arteries via cAMP/PKA-dependent activation of MLCP

2014 ◽  
Vol 307 (4) ◽  
pp. E398-E407 ◽  
Author(s):  
Xuan Yu ◽  
Fen Li ◽  
Enno Klussmann ◽  
John N. Stallone ◽  
Guichun Han
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Ischemia Reperfusion ◽  
Inhibitory Effect ◽  
Regulatory Subunit ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rhoa Activity ◽  
Vascular Regulation

Activation of GPER exerts a protective effect in hypertension and ischemia-reperfusion models and relaxes arteries in vitro. However, our understanding of the mechanisms of GPER-mediated vascular regulation is far from complete. In the current study, we tested the hypothesis that GPER-induced relaxation of porcine coronary arteries is mediated via cAMP/PKA signaling. Our findings revealed that vascular relaxation to the selective GPER agonist G-1 (0.3–3 μM) was associated with increased cAMP production in a concentration-dependent manner. Furthermore, inhibition of adenylyl cyclase (AC) with SQ-22536 (100 μM) or of PKA activity with either Rp-8-CPT-cAMPS (5 μM) or PKI (5 μM) attenuated G-1-induced relaxation of coronary arteries preconstricted with PGF2α (1 μM). G-1 also increased PKA activity in cultured coronary artery smooth muscle cells (SMCs). To determine downstream signals of the cAMP/PKA cascade, we measured RhoA activity in cultured human and porcine coronary SMCs and myosin-light chain phosphatase (MLCP) activity in these artery rings by immunoblot analysis of phosphorylation of myosin-targeting subunit protein-1 (p-MYPT-1; the MLCP regulatory subunit). G-1 decreased PGF2α-induced p-MYPT-1, whereas Rp-8-CPT-cAMPS prevented this inhibitory effect of G-1. Similarly, G-1 inhibited PGF2α-induced phosphorylation of MLC in coronary SMCs, and this inhibitory effect was also reversed by Rp-8-CPT-cAMPS. RhoA activity was downregulated by G-1, whereas G36 (GPER antagonist) restored RhoA activity. Finally, FMP-API-1 (100 μM), an inhibitor of the interaction between PKA and A-kinase anchoring proteins (AKAPs), attenuated the effect of G-1 on coronary artery relaxation and p-MYPT-1. These findings demonstrate that localized cAMP/PKA signaling is involved in GPER-mediated coronary vasodilation by activating MLCP via inhibition of RhoA pathway.

scholarly journals Antivenom Effects of 1,2,3-Triazoles againstBothrops jararacaandLachesis mutaSnakes

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Thaisa F. S. Domingos ◽  
Laura de A. Moura ◽  
Carla Carvalho ◽  
Vinícius R. Campos ◽  
Alessandro K. Jordão ◽  
...  
Keyword(s):  
Biological Effects ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Snake Venoms ◽  
Concentration Dependent Manner ◽  
Biological Assays ◽  
Snake Bites ◽  
Lachesis Muta

Snake venoms are complex mixtures of proteins of both enzymes and nonenzymes, which are responsible for producing several biological effects. Human envenomation by snake bites particularly those of the viperid family induces a complex pathophysiological picture characterized by spectacular changes in hemostasis and frequently hemorrhage is also seen. The present work reports the ability of six of a series of 1,2,3-triazole derivatives to inhibit some pharmacological effects caused by the venoms ofBothrops jararacaandLachesis muta.In vitroassays showed that these compounds were impaired in a concentration-dependent manner, the fibrinogen or plasma clotting, hemolysis, and proteolysis produced by both venoms. Moreover, these compounds inhibited biological effectsin vivoas well. Mice treated with these compounds were fully protected from hemorrhagic lesions caused by such venoms. But, only theB. jararacaedema-inducing activity was neutralized by the triazoles. So the inhibitory effect of triazoles derivatives against somein vitroandin vivobiological assays of snake venoms points to promising aspects that may indicate them as molecular models to improve the production of effective antivenom or to complement antivenom neutralization, especially the local pathological effects, which are partially neutralized by antivenoms.

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