Adipogenic and lipolytic effects of chronic glucocorticoid exposure

Glucocorticoids have been proposed to be both adipogenic and lipolytic in action within adipose tissue, although it is unknown whether these actions can occur simultaneously. Here we investigate both the in vitro and in vivo effects of corticosterone (Cort) on adipose tissue metabolism. Cort increased 3T3-L1 preadipocyte differentiation in a concentration-dependent manner, but did not increase lipogenesis in adipocytes. Cort increased lipolysis within adipocytes in a concentration-dependent manner (maximum effect at 1–10 μM). Surprisingly, removal of Cort further increased lipolytic rates (∼320% above control, P < 0.05), indicating a residual effect on basal lipolysis. mRNA and protein expression of adipose triglyceride lipase and phosphorylated status of hormone sensitive lipase (Ser563/Ser660) were increased with 48 h of Cort treatment. To test these responses in vivo, Sprague-Dawley rats were subcutaneously implanted with wax pellets with/without Cort (300 mg). After 10 days, adipose depots were removed and cultured ex vivo. Both free fatty acids and glycerol concentrations were elevated in fed and fasting conditions in Cort-treated rats. Despite increased lipolysis, Cort rats had more visceral adiposity than sham rats (10.2 vs. 6.9 g/kg body wt, P < 0.05). Visceral adipocytes from Cort rats were smaller and more numerous than those in sham rats, suggesting that adipogenesis occurred through preadipocyte differentiation rather than adipocyte hypertrophy. Visceral, but not subcutaneous, adipocyte cultures from Cort-treated rats displayed a 1.5-fold increase in basal lipolytic rates compared with sham rats ( P < 0.05). Taken together, our findings demonstrate that chronic glucocorticoid exposure stimulates both lipolysis and adipogenesis in visceral adipose tissue but favors adipogenesis primarily through preadipocyte differentiation.

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4969Enhanced gap junction coupling organised and terminated acute ventricular fibrillation in ex-vivo perfused hearts

European Heart Journal ◽

10.1093/eurheartj/ehz746.0028 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

B S Handa ◽

X Li ◽

C Roney ◽

D Pitcher ◽

R A Chowdhury ◽

...

Keyword(s):

Ventricular Fibrillation ◽

Ex Vivo ◽

Electrical Coupling ◽

Underlying Mechanism ◽

Dominant Frequency ◽

Diffuse Fibrosis ◽

Dependent Manner ◽

Sprague Dawley ◽

Concentration Dependent Manner

Abstract Background The underlying mechanism of ventricular fibrillation (VF) remains unclear. There are both experimental and clinical data to support the existence of rotational drivers (RDs), though other opposing studies suggest that VF is the result of disorganized myocardial activation. Abnormal electrical coupling between cardiomyocytes through gap junctions (GJ) has been considered an important factor in the genesis and maintenance of VF and pre-treatment with GJ couplers, rotigaptide (RTG), has been shown to reduce VF inducibility. Purpose We hypothesized that the degree of GJ coupling determines the underlying mechanism of VF, and that changes in GJ coupling can shift or modify the predominant mechanism of fibrillation along the spectrum between disorganised activity and organised drivers. We proposed that increased organisation of VF is critical to its termination. Methods Thirty Sprague-Dawley rat hearts were explanted, perfused ex-vivo and acute VF was induced with burst pacing and 30μM pinacidil. Optical mapping of transmembrane potential was performed at baseline and the effects of GJ coupling on VF dynamics were studied in an acute VF model by perfusing with increasing concentrations of a GJ uncoupler; carbenoxolone (0–50μM, CBX, n=10) or a GJ coupling-enhancer; RTG (0–80nM, n=10). A chronic diffuse fibrosis model (n=10) was generated with 4 weeks of in-vivo angiotensin infusion (500nm/kg/min). Fibrillation dynamics were quantified using phase analysis, phase singularity (PS) tracking and our novel method of global fibrillation organisation quantification, frequency dominance index (FDI), which is a power ratio of highest amplitude dominant frequency in the frequency spectrum. Results RTG increased average rotations per RD (Baseline: 2.86±0.10 vs 80nM: 5.66±0.43, p<0.001) whilst CBX caused a reduction (Baseline: 3.77±0.39 vs 50μM: 0.26±0.26, p<0.001). Maximum rotations for a RD increased with RTG (5.4±0.45 vs 48.20±12.32, p<0.001) and decreased with CBX (8.0±1.3 vs 0.3±0.3, p<0.001). Proportion of time PSs were detected in VF increased with RTG (0.44±0.06 vs 0.93±0.02, p<0.001) and decreased with CBX (0.61±0.9 vs 0.03±0.02, p<0.001). RTG reduced meander of longest duration RD (20.6±1.68 vs 11.51±0.77 pixels, p<0.001) for PS >5 rotations. FDI increased with RTG (0.53±0.04 vs 0.78±0.3, p<0.001) and decreased with CBX (0.60±0.05 vs 0.17±0.03, p<0.001). In the diffuse fibrosis group, in comparison to baseline RTG 80nM increased FDI (0.35 vs 0.65, p<0.001) and terminated VF in 40% of hearts. Conclusion The degree of GJ coupling is a key determinant of the underlying mechanism of VF. RTG organised fibrillation and stabilised RDs in a concentration-dependent manner whilst CBX disorganised VF. Enhancing GJ coupling with RTG in diseased hearts with fibrosis can terminate VF and may be a potential therapeutic target in acute VF. Acknowledgement/Funding BHF Programme Grant PG/16/17/32069

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Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial V̇o2 during exercise

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00044.2012 ◽

2012 ◽

Vol 303 (1) ◽

pp. R94-R100 ◽

Cited By ~ 13

Author(s):

Robert Boushel ◽

Teresa Fuentes ◽

Ylva Hellsten ◽

Bengt Saltin

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Mitochondrial Respiration ◽

Complex I ◽

Ex Vivo ◽

Knee Extension ◽

Physiological Effect ◽

Dependent Manner ◽

Concentration Dependent Manner

Nitric oxide (NO) and prostaglandins (PG) together play a role in regulating blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome- c oxidase. Indomethacin uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus, inhibition of NO and PG synthesis may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG synthesis blockade (l-NMMA and indomethacin, respectively) on mitochondrial respiration in human muscle following knee extension exercise (KEE). Specifically, this study examined the physiological effect of NO, and the pharmacological effect of indomethacin, on muscle mitochondrial function. Consistent with their mechanism of action, we hypothesized that inhibition of nitric oxide synthase (NOS) and PG synthesis would have opposite effects on muscle mitochondrial respiration. Mitochondrial respiration was measured ex vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KEE in control (CON; n = 8), arterial infusion of NG-monomethyl-l-arginine (l-NMMA; n = 4) and Indo ( n = 4) followed by combined inhibition of NOS and PG synthesis (l-NMMA + Indo, n = 8). ADP-stimulated state 3 respiration (OXPHOS) with substrates for complex I (glutamate, malate) was reduced 50% by Indo. State 3 O2 flux with complex I and II substrates was reduced less with both Indo (20%) and l-NMMA + Indo (15%) compared with CON. The results indicate that indomethacin reduces state 3 mitochondrial respiration primarily at complex I of the respiratory chain, while blockade of NOS by l-NMMA counteracts the inhibition by Indo. This effect on muscle mitochondria, in concert with a reduction of blood flow accounts for in vivo changes in muscle O2 consumption during combined blockade of NOS and PG synthesis.

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Dipeptidyl-Peptidase IV Converts Intact B-Type Natriuretic Peptide into Its des-SerPro Form

Clinical Chemistry ◽

10.1373/clinchem.2005.057638 ◽

2006 ◽

Vol 52 (1) ◽

pp. 82-87 ◽

Cited By ~ 145

Author(s):

Inger Brandt ◽

Anne-Marie Lambeir ◽

Jean-Marie Ketelslegers ◽

Marc Vanderheyden ◽

Simon Scharpé ◽

...

Keyword(s):

Natriuretic Peptide ◽

Ex Vivo ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Amino Terminal ◽

Dpp Iv

Abstract Background: Analysis of plasma B-type natriuretic peptide (BNP) has suggested the in vivo formation of a truncated form, BNP (3–32), also called des-SerPro-BNP. The objectives of this study were to investigate (a) whether BNP and other natriuretic peptides are truncated by dipeptidyl-peptidase IV (DPP IV/CD26; EC 3.4.14.5) and (b) whether this truncation affects the susceptibility to cleavage by neutral endopeptidase (NEP; EC 3.4.24.11). Methods: Human BNP (1–32), A-type natriuretic peptide 1–28 (ANP 1–28), and related peptides were incubated with purified DPP IV and with human plasma. In addition, BNP (1–32), BNP (3–32), and ANP (1–28) were subjected to hydrolysis by NEP. Cleavage products were analyzed by mass spectrometry. Results: BNP (1–32) was cleaved by purified DPP IV with a specificity constant of 0.37 × 106 L · mol−1 · s−1. The DPP IV activity in EDTA-plasma was able to truncate BNP (1–32) ex vivo. Addition of Vildagliptin, a specific DPP IV inhibitor, prevented this truncation in a concentration-dependent manner. Under in vitro circumstances in which ANP was hydrolyzed extensively, BNP (1–32) and BNP (3–32) were very resistant to NEP-mediated cleavage. Conclusions: DPP IV cleaves BNP (1–32) with an efficiency higher than or comparable to several known in vivo substrates of the enzyme. Even after loss of the amino-terminal dipeptide, BNP remains highly resistant to cleavage by NEP.

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Inhibitory Effects of Raw-Extract Centella asiatica (RECA) on Acetylcholinesterase, Inflammations, and Oxidative Stress Activities via In Vitro and In Vivo

Molecules ◽

10.3390/molecules25040892 ◽

2020 ◽

Vol 25 (4) ◽

pp. 892 ◽

Cited By ~ 3

Author(s):

Zetty Zulikha Hafiz ◽

Muhammad ‘Afif Mohd Amin ◽

Richard Muhammad Johari James ◽

Lay Kek Teh ◽

Mohd Zaki Salleh ◽

...

Keyword(s):

Oxidative Stress ◽

Centella Asiatica ◽

Raw 264.7 Cells ◽

Dependent Manner ◽

Sprague Dawley ◽

Concentration Dependent Manner ◽

Sprague Dawley Rats ◽

And Oxidative Stress

Centella asiatica (C. asiatica) is one of the medicinal plants that has been reported to exert comprehensive neuroprotection in vitro and in vivo. In view of this, the present study was performed to investigate the effect of ethanolic extract of C. asiatica, designated as raw-extract of C. asiatica (RECA) in reducing the acetylcholinesterase (AChE), inflammations, and oxidative stress activities via both in vitro (SH-SY5Y and RAW 264.7 cells) and in vivo (Sprague Dawley rats). Quantitative high-performance liquid chromatography analysis reveals that RECA contains a significantly high proportion of glycosides than the aglycones with madecassoside as the highest component, followed by asiaticoside. Treatment of SH-SY5Y cells with RECA significantly reduced the AChE activity in a concentration-dependent manner with an IC50 value of 31.09 ± 10.07 µg/mL. Furthermore, the anti-inflammatory and antioxidant effects of RECA were evaluated by lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. Our results elucidated that treatment with RECA significantly suppressed the level of pro-inflammatory cytokine/mediators and oxidative stress released in a concentration-dependent manner. Interestingly, these patterns of inhibition were consistent as observed in the LPS-induced neuroinflammation Sprague Dawley rats’ model. The highest concentration used in the two models presented the most significant results. Herein, our findings strongly suggest that RECA may offer therapeutic potential for the treatment of Alzheimer’s disease through inhibiting the AChE, inflammation, and oxidative stress activities.

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In Silico, Ex Vivo and In Vivo Studies of Roflumilast as a Potential Antidiarrheal and Antispasmodic agent: Inhibition of the PDE-4 Enzyme and Voltage-gated Ca++ ion Channels

Molecules ◽

10.3390/molecules25041008 ◽

2020 ◽

Vol 25 (4) ◽

pp. 1008 ◽

Cited By ~ 1

Author(s):

Najeeb Ur Rehman ◽

Mohd Nazam Ansari ◽

Abdul Samad

Keyword(s):

In Silico ◽

Ex Vivo ◽

In Silico Analysis ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Dependent Manner ◽

Ca Channels ◽

Response Curves ◽

Concentration Dependent Manner

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated rabbit jejunum tissues. For in silico analysis, the identified PDE protein was docked with roflumilast and papaverine using the Autodock vina program from the PyRx virtual screening tool. Roflumilast protected against diarrhea significantly at 0.5 and 1.5 mg/kg doses, with 40% and 80% protection. Ex vivo findings from jejunum tissues show that roflumilast possesses an antispasmodic effect by inhibiting spontaneous contractions in a concentration-dependent manner. Roflumilast reversed carbachol (CCh, 1 µM)-mediated and potassium (K+, 80 mM)-mediated contractile responses with comparable efficacies but different potencies. The observed potency against K+ was significantly higher in comparison to CCh, similar to verapamil. Experiments were extended to further confirm the inhibitory effect on Ca++ channels. Interestingly, roflumilast deflected Ca++ concentration–response curves (CRCs) to the right with suppression of the maximum peak at both tested doses (0.001-0.003 mg/mL), similar to verapamil. The PDE-inhibitory effect was authenticated when pre-incubation of jejunum tissues with roflumilast (0.03-0.1 mg/mL) produced a leftward deflection of isoprenaline-mediated inhibitory CRCs and increased the tissue level of cAMP, similar to papaverine. This idea was further strengthened by molecular docking studies, where roflumilast exhibited a better binding affinity (-9.4 kcal/mol) with the PDE protein than the standard papaverine (-8.3 kcal/mol). In conclusion, inhibition of Ca++ channels and the PDE-4 enzyme explains the pharmacodynamics of the gut inhibitory effect of roflumilast.

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Mechanism of alpha 2-adrenoceptor agonist-induced diuresis

AJP Renal Physiology ◽

10.1152/ajprenal.1988.255.2.f317 ◽

1988 ◽

Vol 255 (2) ◽

pp. F317-F323 ◽

Cited By ~ 5

Author(s):

M. Gellai ◽

R. M. Edwards

Keyword(s):

Pertussis Toxin ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Dependent Manner ◽

Camp Accumulation ◽

Sprague Dawley ◽

Concentration Dependent Manner ◽

Adrenoceptor Agonist ◽

Collecting Ducts

In vivo and in vitro studies were performed to assess the mechanism of the diuretic effect of B-HT 933, a selective alpha 2-adrenoceptor agonist. In conscious Sprague-Dawley rats whose plasma vasopressin (AVP) levels were increased by infusion of hypertonic NaCl, B-HT 933 had no effect on AVP secretion. In Brattleboro homozygous (DI) rats, the antidiuretic dose response to AVP was shifted to the right by B-HT 933. In addition, a sustained antidiuresis induced in rats by infusion of 10 pg/min AVP was attenuated by B-HT 933 in a concentration-dependent manner. Pretreatment of DI rats with pertussis toxin (2 micrograms/kg iv) 4-5 days before testing abolished the inhibitory effect of B-HT 933 on AVP-induced antidiuresis. In outer medullary collecting ducts of DI rats, norepinephrine and B-HT 933 produced significant inhibition of AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation. In contrast, the selective alpha 1-adrenoceptor agonist cirazoline had no effect on AVP-induced cAMP formation. The inhibitory effect of norepinephrine was antagonized by the selective alpha 2-adrenoceptor antagonist rauwolscine but not by prazosin, a selective alpha 1-antagonist. In outer medullary collecting ducts dissected from the pertussis toxin-treated DI rats used in the in vivo studies, the inhibitory effect of norepinephrine and B-HT 933 on AVP-stimulated cAMP accumulation was abolished. The results indicate that the hydrosmotic action of AVP is inhibited by alpha 2-agonists via a pertussis toxin-sensitive mechanism.

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In VitroandIn VivoAssessments of Cardiovascular Effects with Omadacycline

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00320-16 ◽

2016 ◽

Vol 60 (9) ◽

pp. 5247-5253 ◽

Cited By ~ 10

Author(s):

S. Ken Tanaka ◽

Stephen Villano

Keyword(s):

Ex Vivo ◽

Cardiovascular Effects ◽

Herg Channel ◽

Muscarinic Agonist ◽

Dependent Manner ◽

Binding Studies ◽

Concentration Dependent Manner ◽

Node Activity ◽

Sa Node

ABSTRACTOmadacycline is a first-in-class aminomethylcycline antibiotic with a broad spectrum of activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacterial pathogens. A series of nonclinical studies, including mammalian pharmacologic receptor binding studies, human ether-a-go-go-related gene (hERG) channel binding studies, studies of the effects onex vivosinoatrial (SA) node activity, and studies ofin vivoeffects on cardiovascular function in the cynomolgus monkey, was undertaken to assess the cardiovascular risk potential. Omadacycline was found to bind almost exclusively to the muscarinic subtype 2 acetylcholine receptor (M2), and in the SA node model it antagonized the effect of a pan-muscarinic agonist (carbamylcholine) in a concentration-dependent manner. Omadacycline exhibited no effect on hERG channel activity at 100 μg/ml (179.5 μM), with a 25% inhibitory concentration of 166 μg/ml (298.0 μM). Omadacycline had no effect on QTc in conscious monkeys at doses up to 40 mg/kg of body weight. Overall, omadacycline appears to attenuate the parasympathetic influence on the heart rate but has a low potential to induce cardiac arrhythmia or to have clinically significant cardiovascular toxicity.

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Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

Protein and Peptide Letters ◽

10.2174/0929866526666190327130037 ◽

2019 ◽

Vol 26 (7) ◽

pp. 494-501 ◽

Cited By ~ 5

Author(s):

Sameer Suresh Bhagyawant ◽

Dakshita Tanaji Narvekar ◽

Neha Gupta ◽

Amita Bhadkaria ◽

Ajay Kumar Gautam ◽

...

Keyword(s):

Biological Effects ◽

Exchange Chromatography ◽

Health Concern ◽

Carbohydrate Binding ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Ic50 Values ◽

Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

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Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666201230113018 ◽

2020 ◽

Vol 21 ◽

Author(s):

Hana M. Hammad ◽

Amer Imraish ◽

Maysa Al-Hussaini ◽

Malek Zihlif ◽

Amani A. Harb ◽

...

Keyword(s):

Wound Healing ◽

Rural Communities ◽

Ex Vivo ◽

Ethanol Extract ◽

Aortic Ring ◽

Treated Group ◽

Control Group ◽

Dependent Manner ◽

Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

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Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽

10.3390/nu13010123 ◽

2020 ◽

Vol 13 (1) ◽

pp. 123

Author(s):

Natalia K. Kordulewska ◽

Justyna Topa ◽

Małgorzata Tańska ◽

Anna Cieślińska ◽

Ewa Fiedorowicz ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Reaction ◽

Wide Spectrum ◽

Cell Monolayer ◽

In Vivo Studies ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

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