P831 Anti-inflammatory treatment improves endothelial glycocalyx, peripheral and coronary microcirculatory function and myocardial deformation in inflammatory bowel disease patients

Abstract Funding Acknowledgements Hellenic Society of IBD study (EOMIFNE) Introduction Inflammatory bowel diseases (IBD) alter gastrointestinal physiology and mucosal immunity through a complex inflammatory process. The extensive inflammation leads to significant arterial endothelial dysfunction as well as modification of cardiac structure and function. This study is performed to test the hypothesis that treatment with TNF-a inhibitor or surgical intervention in the IBD population improves cardiovascular function through anti-inflammatory mechanisms. Methods Thirty-seven IBD patients (28 CD and 9 UC, 39 ± 12 years, 62% male) were examined at baseline and 4 months after pharmaceutical (TNF-a inhibitor) (16 patients) or surgical intervention (21 patients). Subjects with a history of established cardiovascular risk factors were excluded. We measured a) carotid-femoral pulse wave velocity (PWV - Complior SP ALAM), central systolic blood pressure (cSBP) and augmentation index (AI), b) flow mediated dilatation (FMD) of the brachial artery), c) perfused boundary region(PBR) of the sublingual arterial microvessels using Sideview Darkfield imaging, d) LV longitudinal strain (GLS), strain rate (GLSR) and (PWV/GLS) as a marker of ventricular-arterial coupling, e) peak LV twisting, peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, f) mitral annulus velocities by tissue doppler imaging (S’ and E’) and mitral inflow velocity (E), g) coronary flow reserve (CFR) by Doppler echocardiography, h) C-reactive protein (CRP), white blood cells (WBC). IBD severity was quantified using Mayo score and Harvey-Bradshaw Index (HBI) for UC and CD respectively, and correlated with the cardiovascular disease markers. Results At baseline, the disease severity score was significantly correlated with markers of diastolic dysfunction (lateral mitral E’ velocity r=-0.352, p < 0.05, UntwVelE r = 0.389, p < 0.05), while the WBC values were negatively associated with lateral mitral E’ velocity: r=-0.5, p < 0.05 and CFRvti (r=-0.332, p = 0.05). Four months after anti-inflammatory treatment, there was a reduction of CRP (15.5 ± 4.7 mg/L vs 5.1 ± 2.1 mg/L, p < 0.05) and WBC values (8.6 ± 0.6 vs 6.6 ± 0.7 x 103, p = 0.06). Moreover, post-treatment, there was a significant reduction of central arterial AI (3.58 ± 4.13 vs 0 ± 4.96, p < 0.05), PBR10-19 (2.47 ± 0.09 vs 2.24 ± 0.08 μm, p < 0.05) and PBR5-25 (2.31 ± 0.08 vs 2.14 ± 0.06 μm, p = 0.05) and increase of FMD (7.6%±0.7 vs 12.2%±1.7, p < 0.05), CFR (2.6 ± 0.1 vs 3.2 ± 0.14, p < 0.05), GLS (-18.7 ± 0.46 vs -20 ± 0.49, p < 0.05) and PWV/GLS (-0,48 ± 0.027 vs -0,42 ± 0.028, p < 0.05). No difference in the examined markers was observed between patients treated with anti-TNFa or surgery (p = NS). Conclusion IBD severity is associated with vascular and diastolic dysfunction. Anti-TNFa inhibition treatment or surgical intervention in IBD lead to improved myocardial deformation, endothelial and coronary microcirculatory function possibly through the reduction of excess inflammatory burden.

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Effects of anti-inflammatory treatment and surgical intervention on endothelial glycocalyx, peripheral and coronary microcirculation and myocardial deformation in inflammatory bowel disease patients

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.423 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

C Triantafyllou ◽

I Ikonomidis ◽

M Nikolaou ◽

G Bamias ◽

J Thymis ◽

...

Keyword(s):

Surgical Intervention ◽

Augmentation Index ◽

White Blood Cells ◽

Mitral Annulus ◽

Myocardial Deformation ◽

Doppler Imaging ◽

Endothelial Glycocalyx ◽

Flow Reserve ◽

Anti Inflammatory ◽

The Difference

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): EOMIFNE (Hellenic Society of IBD study) Introduction IBD alter gastrointestinal physiology and mucosal immunity through a complex inflammatory process which leads to significant arterial endothelial dysfunction and modification of cardiac structure and function. This study is performed to test the hypothesis that treatment with TNF-a inhibitor or surgical intervention improves cardiovascular function through anti-inflammatory mechanisms. Methods 57 IBD patients (45 CD and 12 UC, 40 ± 8 years, 57% male) were examined at baseline and 4 months after pharmaceutical (antiTNF-a) or surgical intervention. Subjects with a history of established cardiovascular risk factors were excluded. We measured a) carotid-femoral pulse wave velocity (PWV - Complior SP ALAM) and augmentation index (AI), b) flow mediated dilatation (FMD) of the brachial artery), c) perfused boundary region (PBR) of the sublingual arterial microvessels, d) LV longitudinal strain (GLS) and (PWV/GLS) as a marker of ventricular-arterial coupling, e) peak LV twisting, peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, f) mitral annulus velocities by tissue doppler imaging (S’ and E’) and mitral inflow velocity (E), g) coronary flow reserve (CFR) by Doppler echocardiography, h) C-reactive protein (CRP), white blood cells (WBC). IBD severity was quantified using Mayo score and Harvey-Bradshaw Index (HBI) for UC and CD respectively. Results At baseline, the disease severity score and the WBC values were significantly correlated with peripheral PWV (r = 0.3, p < 0.05 and r = 0.364, p < 0.05), while central arterial AI was associated with median arterial pressure (r = 0.479, p < 0.05), lateral and septal mitral E’ velocity (r=-0.651, p < 0.05 and r=-0.587, p < 0.05). Four months after treatment, there was a reduction of CRP (13 ± 2.8 mg/L vs 3.9 ± 1.2 mg/L, p < 0.05), CFR (2.5 ± 0.08 vs 3.1 ± 0.11, p < 0.05) and PBR5-25 (2.27 ± 0.06 vs 2.09 ± 0.05 μm, p < 0.05) more significantly in pharmaceutical group (p < 0.05 vs p = 0.23). Moreover, there was an improvement of GLS (-18.6 ± 0.37 vs -20 ± 0.34, p < 0.05), LS-4ch (-18.3 ± 0.47 vs -19.3 ± 0.41, p < 0.05), GcircS (-18.1 ± 0.7 vs -20.1 ± 0.9, p < 0.05) and FMD (7.2%±0.6 vs 11.8%±1.4, p < 0.05). Moreover, there was an overall improvement of PWV/GLS (-0.49 ± 0.02 vs -0.43 ± 0.02, p < 0.05). It was greater after with anti-TNFa therapy compared to surgery (p < 0.05 vs p = 0.1) and particular for the GLS component (p < 0.05 vs p = 0.07). The difference in PBR5-25 was significantly correlated with the difference in GLS (r=-0.403, p < 0.05) and PWV/GLS (r = 0.421, p < 0.05). Conclusion IBD severity is associated with vascular and diastolic dysfunction, with significant improvement after anti-inflammatory treatment. Systemic anti-TNFa inhibition leads to significant improvement in myocardial deformation, endothelial and coronary microcirculatory function compared with local intestinal surgical intervention, possibly through a systemic reduction of excess inflammatory burden.

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Effects of Anti-Inflammatory Treatment and Surgical Intervention on Endothelial Glycocalyx, Peripheral and Coronary Microcirculatory Function and Myocardial Deformation in Inflammatory Bowel Disease Patients: A Two-Arms Two-Stage Clinical Trial

Diagnostics ◽

10.3390/diagnostics11060993 ◽

2021 ◽

Vol 11 (6) ◽

pp. 993

Author(s):

Charilaos Triantafyllou ◽

Maria Nikolaou ◽

Ignatios Ikonomidis ◽

Giorgos Bamias ◽

Dimitrios Kouretas ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Surgical Intervention ◽

Global Longitudinal Strain ◽

White Blood Cells ◽

Reducing Power ◽

Myocardial Deformation ◽

Endothelial Glycocalyx ◽

Flow Reserve ◽

Inflammatory Bowel

Sixty inflammatory bowel disease (IBD) patients (45 Crohn disease and 15 ulcerative colitis, 40 ± 13 years, 53% male) were examined at baseline and 4 months after intervention (surgical (35 patients) or anti-TNFa treatment (25 patients)). IBD severity, using Mayo score, Harvey–Bradshaw Index (HBI) and biomarkers, was correlated with cardiovascular markers. At baseline, the disease severity, the white blood cells (WBC) values and the reducing power (RP) were significantly correlated with the aortic pulse wave velocity (PWV) (r = 0.4, r = 0.44 and r = 0.48, p < 0.05) and the lateral mitral E’ velocity (r = 0.35, p < 0.05 and r = 0.3, p < 0.05). Four months after intervention, there was a reduction of WBC (1962.8/mm3 ± 0.425/mm3, p < 0.001), C-reactive protein (CRP) (8.1 mg/L ± 1.7 mg/L, p < 0.001), malondialdehyde (MDA) (0.81 nmol/mg ± 0.37, p < 0.05) and glycocalyx perfused boundary region (PBR 5-25) (0.24 μm ± 0.05 μm, p < 0.01). Moreover, the brachial flow mediated dilatation (FMD), the coronary flow reserve (CFR) and the left ventricle global longitudinal strain (LV GLS) were significantly improved for both groups (4.5% ± 0.9%, 0.55 ± 0.08, 1.4% ± 0.35%, p < 0.01), while a more significant improvement of PWV/GLS was noticed in the anti-TNFa group. IBD severity is associated with vascular endothelial, cardiac diastolic, and coronary microcirculatory dysfunction. The systemic inflammatory inhibition and the local surgical intervention lead to significant improvement in endothelial function, coronary microcirculation and myocardial deformation.

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Association of endothelial glycocalyx integrity and microvascular perfusion with novel echocardiographic markers and carotid intima-media thickness in patients with psoriasis

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.136 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

P Rafouli-Stergiou ◽

I Ikonomidis ◽

G Makavos ◽

J Thymis ◽

G Pavlidis ◽

...

Keyword(s):

Myocardial Dysfunction ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Microvascular Density ◽

Microvascular Perfusion ◽

Myocardial Deformation ◽

Endothelial Glycocalyx ◽

Media Thickness ◽

Flow Reserve ◽

Glycocalyx Thickness

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Psoriasis has been associated with vascular and myocardial dysfunction through mechanisms of inflammation and oxidative stress. Purpose We aimed to evaluate sublingual microvascular perfusion and glycocalyx barrier properties in psoriasis patients, as well as their correlation with coronary microcirculatory function, markers of myocardial deformation and atherosclerosis (carotid intima-media thickness, IMT). Methods We examined 241 patients with psoriasis and 160 controls, adjusted for age, sex, BMI, smoking, LV mass, heart rate, hyperlipidemia, and office SBP. Perfusion boundary region (PBR), a marker of glycocalyx barrier function, was measured non-invasively in sublingual microvessels with a diameter ranging from 5-25 µm using a dedicated camera (Side field dark imaging, Micrsoscan, Nedelrands). Increased PBR indicates reduced glycocalyx thickness. Indexes of microvascular perfusion, including red blood cell (RBC) filling percentage and functional microvascular density, were also calculated. We measured coronary flow reserve (CFR), carotid IMT and markers of myocardial deformation by speckle tracking imaging utilizing echocardiography [peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw – UtwMVO), at peak (%dpTw – UtwPEF), and the end of early LV diastolic filling (%dpTw – UtwEDF)]. Results Psoriasis patients had higher PBR (PBR5-25: 2.131 ± 0.296 vs. 1.769 ± 0.306; PBR5-9: 1.183 ± 0.150 vs. 1.051 ± 0.132; PBR10-19: 2.318 ± 0.581 vs. 1.993 ± 0.365; PBR20-25: 2.650 ± 0.461 vs. 2.269 ± 0.492, all p < 0.05) and impaired LV twisting-untwisting markers compared to controls (pTw: 14.8 ± 7.8 vs. 13.9 ± 3.5; UtwMVO: 10.3 ± 7.3 vs. 9 ± 4.3; %dpTw – UtwMVO: 31 ± 4.1 vs. 38 ± 7; pTwVel: 105 ± 83 vs. 89 ± 21; pUtwVel: -100 ± 53 vs. -93 ± 31, all p < 0.05). In psoriatic population, levels of PBR5-25 and PBR10-19 were inversely correlated to CFR (r=-0.15 and r=-0.17). The first one was also reversely related to peak LV untwisting at aortic valve closure (r=-0.14). Increased levels of PBR5-9 were associated with reduced untwisting at end of the mitral inflow E wave (UtwEDF, r=-0.13) and reduced percentage difference between peak twisting and untwisting at MVO (%dpTw-UntwMVO) (r=-0.15). Furthermore, decreased RBC filling percentage and perfused microvascular density were related to worse LV longitudinal strain (4-chamber) (r=-0.15), and increased IMT (r=-0.14). Finally, a positive correlation between perfused microvascular density and %dpTw-UntwMVO was observed in patients with psoriasis (r = 0.14). All correlations were statistically significant (p < 0.05). Conclusion Endothelial glycocalyx thickness is reduced in patients with psoriasis and is associated with impaired coronary and myocardial function, and vascular atherosclerosis.

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P4435Effects of interleukin 6 inhibitor tocilizumab on endothelial glycocalyx, vascular and myocardial function compared to prednisolone

European Heart Journal ◽

10.1093/eurheartj/ehz745.0837 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 1

Author(s):

I Ikonomidis ◽

G Pavlidis ◽

P Katsimbri ◽

I Andreadou ◽

H Triantafyllidi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interleukin 6 ◽

Vascular Function ◽

Myocardial Function ◽

Boundary Region ◽

Myocardial Deformation ◽

Endothelial Glycocalyx ◽

Protein Carbonyls ◽

Flow Reserve ◽

Percentage Difference

Abstract Background/Introduction Tocilizumab, a humanised monoclonal antibody against the human interleukin-6 receptor, is used for the treatment of rheumatoid arthritis (RA). Purpose We investigated the effects of tocilizumab on arterial function, LV myocardial deformation and endothelial glycocalyx in RA patients. Methods 80 patients with rheumatoid arthritis were randomized to tocilizumab (n=40) or prednisolone (n=40) for 3 months. At baseline and after 3-month treatment we assessed: a) carotid-femoral pulse wave velocity (PWV-Complior SP ALAM), b) LV longitudinal strain (GLS), systolic (LongSr) and diastolic (LongSrE) strain rate using speckle tracking echocardiography, c) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–25μm) using Sideview Darkfield imaging (Microscan, Glycocheck). Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness, d) flow mediated dilatation (FMD) of the brachial artery after and percentage difference of FMD (FMD%) after hyperemia, e) coronary flow reserve (CFR) of the LAD using Doppler echocardiography, and f) malondialdehyde (MDA), protein carbonyls (PCs) and C-reactive protein (CRP) plasma levels. Results At baseline, all patients had similar disease activity score and markers of vascular and myocardial function. Compared to baseline, all patients had reduced CRP post treatment, while MDA and PCs levels were reduced only after tocilizumab treatment (p<0.05). The percent decrease of MDA was correlated with percent increase of GLS (p<0.001). Compared to baseline, tocilizumab-treated patients reduced PWV (11±3% vs. 10.3±2m/sec) and PBR (2.11±0.2 vs. 1.95±0.18μm) (Figure 1) and increased GLS (−16.1±2.9 vs. −17.6±2.5%), CFR (2.73±0.8 vs. 3.06±1), and FMD% (5.9±2.9 vs. 11.6±3.6) (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients. Figure 1 Conclusions IL-6 inhibition improves endothelial function and oxidative stress resulting to improved vascular function and LV myocardial deformation.

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A Sex-Specific Role of Endothelial Sirtuin 3 on Blood Pressure and Diastolic Dysfunction in Female Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21249744 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9744

Author(s):

Heng Zeng ◽

Xiaochen He ◽

Jian-Xiong Chen

Keyword(s):

Blood Pressure ◽

Diastolic Dysfunction ◽

Diastolic Function ◽

Normal Diet ◽

Specific Role ◽

Sirtuin 3 ◽

Control Female ◽

Female Mice ◽

Flow Reserve

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by a diastolic dysfunction and is highly prevalent in aged women. Our study showed that ablation of endothelial Sirtuin 3 (SIRT3) led to diastolic dysfunction in male mice. However, the sex-specific role of endothelial SIRT3 deficiency on blood pressure and diastolic function in female mice remains to be investigated. Methods and Results: In this study, we demonstrate that the ablation of endothelial SIRT3 in females elevated blood pressure as compared with control female mice. Diastolic function measurement also showed that the isovolumic relaxation time (IVRT) and myocardial performance index (MPI) were significantly increased, whereas the E’ velocity/A’ velocity (E’/A’) ratio was reduced in the endothelial-specific SIRT3 knockout (SIRT3 ECKO) female mice. To further investigate the regulatory role of endothelial SIRT3 on blood pressure and diastolic dysfunction in metabolic stress, SIRT3 ECKO female mice were fed a normal diet and high-fat diet (HFD) for 20 weeks. The knockout of endothelial SIRT3 resulted in an increased blood pressure in female mice fed with an HFD. Intriguingly, SIRT3 ECKO female mice + HFD exhibited impaired coronary flow reserve (CFR) and more severe diastolic dysfunction as evidenced by an elevated IVRT as compared with control female mice + HFD. In addition, female SIRT3 ECKO mice had higher blood pressure and diastolic dysfunction as compared to male SIRT3 ECKO mice. Moreover, female SIRT3 ECKO mice + HFD had an impaired CFR and diastolic dysfunction as compared to male SIRT3 ECKO mice + HFD. Conclusions: These results implicate a sex-specific role of endothelial SIRT3 in regulating blood pressure and diastolic function in mice. Deficiency of endothelial SIRT3 may be responsible for a diastolic dysfunction in aged female.

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The Changing Prognosis of Ulcerative Colitis and Crohn’s Disease by Decades

Crohn's & Colitis 360 ◽

10.1093/crocol/otab008 ◽

2021 ◽

Author(s):

Burton I Korelitz ◽

Judy Schneider

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Medical Therapy ◽

Bowel Disease ◽

Surgical Intervention ◽

Inflammatory Bowel

Abstract We present a bird’s eye view of the prognosis for both ulcerative colitis and Crohn’s disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications and deaths by decades.

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3D ultrasound coronarography: first proof of concept study on isolated beating rat hearts

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.011 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

O Demeulenaere ◽

P Mateo ◽

P Sandoval ◽

O Villemain ◽

M Tanter ◽

...

Keyword(s):

Contrast Agents ◽

Flow Velocity ◽

Coronary Flow ◽

3D Ultrasound ◽

Frame Rate ◽

Doppler Imaging ◽

Coronary Perfusion ◽

Blood Flows ◽

Flow Reserve ◽

Rat Hearts

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Bettencourt Foundation Background/Introduction We demonstrated recently that Ultrafast ultrasound Doppler imaging can image the intramyocardial coronary circulation in beating hearts of large animals and patients [1]. Yet, ultrasound spatial resolution remains limited by wave physics and coronaries smaller than ∼100 µm could not be imaged. Ultrasound Localization Microscopy (ULM) [2] was recently introduced to tackle this issue and exploit the micrometric localization of microbubble contrast agents at ultrafast frame rate in order to image blood flows in micrometer vessels. Purpose The objective of this work was to demonstrate that 3D ultrafast ultrasound with contrast agents can provide the full 3D mapping of the coronary microcirculation with quantitative flow velocity on a beating rat heart. Methods Acquisitions were performed on ex vivo rat hearts (n = 5) with retrograde perfusion (Langendorff model). A flow of a Krebs–Henseleit solution mixed with a diluted microbubbles solution (0.22%) was perfused at controlled pressure into the coronary arteries (between 5 and 15 mL/min). We used a 32 × 32 elements, 8-MHz matrix-array ultrasound transducer connected to a 1024-channel programmable ultrasound scanner. An ultrafast Doppler imaging sequence consisting of 9 plane waves was transmitted at a PRF of 20 kHz during 270 ms and repeated 40 times. After beamforming and SVD clutter filtering, the microbubbles were localized and tracked in 3D. Flow velocity were mapped at baseline and after infusion of Adenosine (10e-5 µMol) at constant coronary perfusion pressure (120 mm Hg). Eventually, the hearts were fixed using formaldehyde perfusion and imaged by µCT after injection of radio opaque agent. Results We successfully imaged the coronary blood flows of entire rat hearts. It revealed the entire vasculature from large main coronaries arteries (cross section up to 1 mm) to small arterioles (smaller than 40 µm). Coronary flow velocities ranged from [1 – 50] cm/s depending on the arteries diameter. Velocity estimates were validated in vitro in tubes of Ø0.58mm and were in good agreement with theoretical values of a Poiseuille’s flow (relative ratio of 10% for maximum velocities). After Adenosine infusion, perfusion flow rates increased 102% ± 50% (p < 0.05) on average. Eventually, anatomy revealed by 3D ultrasound coronarography was in accordance with the anatomy revealed by the µCT. Conclusion(s) We demonstrated the feasibility of 3D ultrasound coronarography on isolated beating rat hearts. This technique has the potential to become a novel imaging tool to investigate the coronary micro-circulation and quantify non-invasively the Coronary Flow Reserve (CFR). Abstract Figure. Ultrasound coronarography

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Preparation, characterization, and in vivo evaluation of anti-inflammatory activities of selenium nanoparticles synthesized by Kluyveromyces lactis GG799

Food & Function ◽

10.1039/d1fo01019k ◽

2021 ◽

Author(s):

Xiao fan Song ◽

Lei Qiao ◽

Shuqi Yan ◽

Yue Chen ◽

Xina Dou ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Kluyveromyces Lactis ◽

Selenium Nanoparticles ◽

Human Diseases ◽

In Vivo Evaluation ◽

Inflammatory Bowel ◽

Anti Inflammatory

Selenium (Se) as an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant...

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The use of tissue Doppler imaging in the assessment of diastolic dysfunction in children with chronic lung diseases

Egyptian Pediatric Association Gazette ◽

10.1186/s43054-020-00027-x ◽

2020 ◽

Vol 68 (1) ◽

Author(s):

Iman H. Draz ◽

Fatma El Zahraa Mostafa ◽

Antoin F. AbdelMassih ◽

Dalia El-Sayed ◽

Rania El-Kaffas

Keyword(s):

Diastolic Dysfunction ◽

Tissue Doppler Imaging ◽

Lung Diseases ◽

Tissue Doppler ◽

Doppler Imaging ◽

Chronic Lung Diseases

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Isoquinolinequinone Derivatives from a Marine Sponge (Haliclona sp.) Regulate Inflammation in In Vitro System of Intestine

Marine Drugs ◽

10.3390/md19020090 ◽

2021 ◽

Vol 19 (2) ◽

pp. 90

Author(s):

Yun Kim ◽

Yeong Ji ◽

Na-Hyun Kim ◽

Nguyen Van Tu ◽

Jung-Rae Rho ◽

...

Keyword(s):

Nitric Oxide ◽

Marine Sponge ◽

Nuclear Translocation ◽

Hydroxyl Group ◽

Subsequent Increase ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Key Functional Groups ◽

Oxide Synthase

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1–8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.

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