In Vitro and in Silico Study of New Biscoumarin Glycosides from Paramignya trimera against Angiotensin-Converting Enzyme 2 (ACE-2) for Preventing SARS-CoV-2 Infection.

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Anti-Alzheimer's Activity of Polyphenolic Stilbene-Rich Acetone Fraction of the Oil-Removed Seeds of Passiflora edulis: in Vivo and in Silico Studies.

The stilbene-rich acetone fraction in high yield (6.6 %, PEAS) of Passiflora edulis Sims was prepared and evaluated for neuroprotective activity in murine Alzheimer's disease model induced by aluminum chloride and D-galactose. The phytochemical and HPLC-DAD-MS analysis of the polyphenolic stilbene-rich acetone fraction showed that it contained different stilbenes including trans-piceatannol, scirpusins A-B and cassigarol E. The total phenolic content (TPC) of PEAS was 413.87±1.71 mg GAE eqv/g. The neuroprotective activity of PEAS is typically presented in the Morris water maze-reference Spatial Memory test, where the Alzheimer's mice treated at 100 mg/kg (Alz-ED1) and 200 mg/kg (Alz-ED2) spent less than 47 % and 66 % of the time, respectively, than the Alzheimer's model mice (Alz). Two simple stilbenes, trans-piceatannol and trans-resveratrol, showed selectively inhibitory activity in silico against acetylcholinesterase (AChE). Two stilbene dimers, cassigarol E and scirpusin A, exhibited low nanomolar inhibitory potential against AChE and butyrylcholinesterase (BChE), significantly lower than those of the positive control, donepezil and tacrine. These findings suggest that the stilbenes from P. edulis seeds, particularly the stilbene dimers, warrant further investigation as potential neuroprotective candidates in the prevention of cognitive deficits associated with Alzheimer's disease.

Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators.

Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting KCa1.1 and CaV1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Dalbergia tonkinensis Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba2+ currents through CaV1.2 channels (IBa1.2) were blocked in a concentration-dependent manner by sativanone, 3'-O-methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7-O-[ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside], ambocin, butin, and biochanin A increased IKCa1.1. In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, Dalbergia tonkinensis is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs.

Vasorelaxing Activity of R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol from Dalbergia tonkinensis: Involvement of Smooth Muscle CaV1.2 Channels.

Dalbergia species heartwood, widely used in traditional medicine to treat various cardiovascular diseases, might represent a rich source of vasoactive agents. In Vietnam, Dalbergia tonkinensis is an endemic tree. Therefore, the aim of the present work was to investigate the vascular activity of R-(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol isolated from the heartwood of D. tonkinensis and to provide circular dichroism features of its R absolute configuration. The vascular effects of R-(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol were assessed on the in vitro mechanical activity of rat aorta rings, under isometric conditions, and on whole-cell Ba2+ currents through CaV1.2 channels (IBa1.2) recorded in single, rat tail main artery myocytes by means of the patch-clamp technique. R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol showed concentration-dependent, vasorelaxant activity on both endothelium-deprived and endothelium intact rings precontracted with the α 1 receptor agonist phenylephrine. Neither the NO (nitric oxide) synthase inhibitor Nω-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin affected its spasmolytic activity. R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol-induced vasorelaxation was antagonized by (S)-(-)-Bay K 8644 and unaffected by tetraethylammonium plus glibenclamide. In patch-clamp experiments, R-(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol inhibited IBa1.2 in a concentration-dependent manner and significantly decreased the time constant of current inactivation. R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol likely stabilized the channel in its closed state, as suggested by molecular modelling and docking simulation to the CaV1.2 channel α 1c subunit. In conclusion, D. tonkinensis species may represent a source of agents potentially useful for the development of novel antihypertensive drugs.

New Records of Potent In-Vitro Antidiabetic Properties of Dalbergia tonkinensis Heartwood and the Bioactivity-Guided Isolation of Active Compounds.

Alpha-glucosidase inhibitory activity has been commonly used for the evaluation of antidiabetic property in vitro. The aim of this study is to investigate and characterize Dalbergia tonkinensis as a potential source of antidiabetic compounds. The screening of the active parts used, such as trunk bark, heartwood, and the leaves of Dalbergia tonkinensis indicated that all these extracted parts used with methanol demonstrated potent α-glucosidase inhibitory activity. The in vitro antidiabetic property of Dalbergia tonkinensis was notably recorded for the first time and showed activity (EC50 = 0.17⁻0.78 mg/mL) comparable to those of reported potent herbal extracts (EC50 = 0.25⁻4.0 mg/mL) and higher activity than that of acarbose, a commercial antidiabetic drug (EC50 = 1.21 mg/mL). The stability tests revealed that the heartwood of Dalbergia tonkinensis extract (HDT) possesses high pH stability with relative activity in the range of 80⁻98%. Further bioassay-guided purification led to the isolation of 2 active compounds identified as sativanone and formononetin from the ethyl acetate fraction and water fraction of HDT, respectively. These α-glucosidase inhibitors (aGIs) show promising inhibition against various types of α-glucosidases. Remarkably, these inhibitors were determined as new mammalian aGIs, showing good effect on rat α-glucosidase. The results suggest that Dalbergia tonkinensis is a potent source of aGIs and suggest promise in being developed as functional food with antidiabetic efficacy. The results of this study also enrich our knowledge concerning current biological activity and constituents of Dalbergia tonkinensis species.

Inhibition of soluble epoxide hydrolase activity by compounds isolated from the aerial parts of Glycosmis stenocarpa.

The aim of this study is to search for soluble epoxide hydrolase (sEH) inhibitors from natural plants, bioassay-guided fractionation of lipophilic n-hexane and chloroform layers of an extract of the aerial parts of Glycosmis stenocarpa led to the isolation of 12 compounds (1-12) including murrayafoline-A (1), isomahanine (2), bisisomahanine (3), saropeptate (4), (24 S)-ergost-4-en-3,6-dione (5), stigmasta-4-en-3,6-dion (6), stigmast-4-en-3-one (7), ß-sitosterol (8), 24-methylpollinastanol (9), trans-phytol (10), neosarmentol III (11) and (+)-epiloliolide (12). Their structures were elucidated on the basis of spectroscopic data. Among them, neosarmentol III (11) was isolated from nature for the first time. All the isolated compounds were evaluated for their inhibitory activity against sEH. Among isolated carbazole-type compounds, isomahanine (2) and bisisomahanine (3) were identified as a potent inhibitor of sEH, with IC50 values of 22.5 ± 1.7 and 7.7 ± 1.2 µM, respectively. Moreover, the inhibitory action of 2 and 3 represented mixed-type enzyme inhibition.

Morinlongosides A-C, Two New Naphthalene Glycoside and a New Iridoid Glycoside from the Roots of Morinda longissima.

Two new naphthalene glycosides, morinlongosides A and B (1, 2) and a new iridoid glycoside, morinlongoside C (3), together with four known ones, geniposidic acid (4), (3R)-3-O-[ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranosyl]-l-octen-3-ol (5), lucidin-3-O-ß-primeveroside (6), and morindone-6-O-ß-gentiobioside (7), were isolated from the roots of Morinda longissima Y. Z. RUAN. The structures of all isolated compounds (1-7) were elucidated on the basis of spectroscopic data (high resolution (HR)-MS, one and two dimensional (1/2D)-NMR).

Sensitization of cardiac Ca²âº release sites by protein kinase C signaling: evidence from action of murrayafoline A.

In the present study, we explored the effects of a plant alkaloid compound, 1-methoxy-3-methylcarbazole (murrayafoline A, Mu-A), on focal and global Ca(2+) signaling, and the underlying cellular mechanisms. Rapid two-dimensional confocal Ca(2+) imaging and image analysis were used to measure Ca(2+) signals in rat ventricular myocytes. Application of Mu-A (10-100 µM) significantly enhanced the magnitude and rate of Ca(2+) release on depolarization with no change in Ca(2+) transient decay. Focal Ca(2+) release events (Ca(2+) sparks) occurred more often, and their duration and size were greater after the application of Mu-A. In addition, sarcoplasmic reticulum (SR) Ca(2+) loading and fractional release were increased by exposure to Mu-A. All these effects reached steady state within 2-3 min after Mu-A application. The higher occurrence of Ca(2+) sparks in the presence of Mu-A was resistant to SR Ca(2+) clamping, removal of extracellular Ca(2+) and Na(+), and blockade of either protein kinase A, Ca(2+)/calmodulin-dependent protein kinase II, phospholipase C, or inositol 1,4,5-trisphosphate receptors, but it was abolished by the inhibition of protein kinase C (PKC). SR Ca(2+) clamping prevented the Mu-A-induced Ca(2+) spark prolongation and enlargement. The Mu-A-induced enhancement of Ca(2+) transients was also eliminated by PKC blockade. Mu-A enhanced PKC activity in vitro. These results suggest that Mu-A may increase spark occurrence via its direct enhancement of PKC activity and subsequent sensitization of ryanodine receptor clusters and that this mechanism, as well as increased SR Ca(2+) loading, may partly explain larger and more rapid global Ca(2+) releases in the presence of Mu-A during depolarization.

Chemical constituents of Miliusa balansae leaves and inhibition of nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells.

Methanolic extract of Miliusa balansae Finet et Gagnep exerts an anti-inflammatory effect via inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Three new megastigmane glycosides, milbasides A-C (1-3), together with fifteen known compounds (4-18), were isolated from the active fraction. Their chemical structures were elucidated using extensive spectroscopic analyses, including 1D and 2D NMR, HR ESI MS, and CD analysis, as well as comparison with previously reported data. Compounds 1-3, 11 and 14 (20.0 µM) showed potent inhibitory activities with inhibition values of 98.5 ± 1.6%, 90.9 ± 7.8%, 84.8 ± 3.5%, 91.5 ± 8.7%, and 91.8 ± 2.7%, respectively. Our results suggest that megastigmane glycosides from M. balansae leaves may be used to treat inflammatory diseases.

In vitro vasoactivity of zerumbone from Zingiber zerumbet.

The sesquiterpene zerumbone, isolated from the rhizome of Zingiber zerumbet Sm., besides its widespread use as a food flavouring and appetiser, is also recommended in traditional medicine for the treatment of several ailments. It has attracted great attention recently for its effective chemopreventive and therapeutic effects observed in various models of cancer. To assess the zerumbone safety profile, a pharmacology study designed to flag any potential adverse effect on vasculature was performed. Zerumbone was tested for vasorelaxing activity on rat aorta rings and for L-type Ba(2+) current blocking activity on single myocytes isolated from the rat-tail artery. The spasmolytic effect of zerumbone was more marked on rings stimulated with 60 mM than with 30 mM K(+) (IC50 values of 16 µM and 102 µM, respectively). In the presence of 60 mM K(+), zerumbone concentration-dependently inhibited the contraction induced by the cumulative additions of Ca(2+), this inhibition being inversely related to the Ca(2+) concentration. Phenylephrine-induced contraction was inhibited by the drug, though less efficiently and independently of the presence of an intact endothelium, without affecting Ca(2+) release from the intracellular stores. Zerumbone inhibited the L-type Ba(2+) current (estimated IC50 value of 458.7 µM) and accelerated the kinetics of current decay. In conclusion, zerumbone showed an overall weak in vitro vasodilating activity, partly attributable to the blocking of the L-type Ca(2+) channel, which does not seem to represent, however, a serious threat to its widespread use.

Paratrimerins A and B, Two New Dimeric Monoterpene-Linked Coumarin Glycosides from the Roots and Stems of Paramignya trimera.

Two new dimeric monoterpene-linked coumarin glucosides, paratrimerins A (1) and B (2), and three known coumarins, 6-(6-hydroxy-3,7-dimethylocta-2,7-dienyl)-7-hydroxycoumarin (3), ostruthin (4), and ninhvanin (5), were isolated from the roots and stems of Paramignya trimera (OLIV.) GUILL. collected in Khanh Hoa province, Vietnam. Compound 1 comprises two 7-O-ß-D-glucopyranoside coumarins linked at positions 6,6' via a 1,3,4,4-tetrasubstituted cyclohexene containing a monoterpene bridge, whereas compound 2 is a ß-D-apiofuranosyl(1→6)-ß-D-glucopyranosyl derivative of 1. The chemical structures of these compounds were determined by one dimensional (1D) and 2D-NMR and high resolution-electrospray ionization (HR-ESI)-MS spectroscopy.

Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells.

The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [(3)H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

A new phenylpropanoid and an alkylglycoside from Piper retrofractum leaves with their antioxidant and α-glucosidase inhibitory activity.

Two new compounds, piperoside (1) and isoheptanol 2(S)-O-ß-D-xylopyranosyl (1→6)-O-ß-D-glucopyranoside (11), along with 10 known compounds 3,4-dihydroxyallylbenzene (2), 1,2-di-O-ß-D-glucopyranosyl-4-allylbenzene (3), tachioside (4), benzyl-O-ß-D-glucopyranoside (5), icariside F2 (6), dihydrovomifoliol-3'-O-ß-D-glucopyranoside (7), isopropyl O-ß-D-glucopyranoside (8), isopropyl primeveroside (9), n-butyl O-ß-D-glucopyranoside (10), isoheptanol 2(S)-O-ß-D-apiofuranosyl-(1→6)-O-ß-D-glucopyranoside (12), were isolated from the leaves of Piper retrofractum. Their structures were determined from 1D-NMR, 2D-NMR, and HR-ESI-MS spectral, a modified Mosher's method, and comparisons with previous reports. All of the isolated compounds showed modest α-glucosidase inhibitory (4.60±1.74% to 11.97±3.30%) and antioxidant activities under the tested conditions.

Vascular L-type Ca²âº channel blocking activity of sulfur-containing indole alkaloids from Glycosmis petelotii.

In the search for novel natural compounds endowed with potential antihypertensive activity, a new sulfur-containing indole alkaloid, N-demethylglypetelotine (2), and its known analogue glypetelotine (1), were isolated from the leaves of Glycosmis petelotii. Their structures were established on the basis of spectroscopic evidence. The two alkaloids were assessed for vasorelaxing activity on rat aorta rings and for L-type Ba(2+) current [I(Ba(L))] blocking activity on single myocytes isolated from rat tail artery. Both glypetelotine and N-demethylglypetelotine inhibited phenylephrine-induced contraction with IC50 values of 20 and 50 µM, respectively. The presence of endothelium did not modify their spasmolytic effect. Neither glypetelotine nor N-demethylglypetelotine affected Ca(2+) release from the sarcoplasmic reticulum induced by phenylephrine. The spasmolytic effect of glypetelotine increased with membrane depolarization. In the presence of 60 mM K(+), both compounds inhibited, in a concentration-dependent manner, the contraction induced by cumulative addition of Ca(2+), this inhibition being inversely related to Ca(2+) concentration. Glypetelotine and, less efficiently N-demethylglypetelotine, inhibited I(Ba(L)), the former compound also affecting I(Ba(L)) kinetics. In conclusion, glypetelotine is a novel vasorelaxing agent which antagonizes L-type Ca(2+) channels.

Bioactive compounds from Vitex leptobotrys.

A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (3), two known dehydroflavones, tsugafolin (4) and alpinetin (5), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known carotenoid metabolites, vomifoliol, dihydrovomifoliol, dehydrovomifoliol, loliolide, and isololiolide, were isolated from the leaves and twigs of Vitex leptobotrys through bioassay-guided fractionation. The chalcone (3) was found to inhibit HIV-1 replication by 77% at 15.9 µM, and the two dehydroflavones (4 and 5) showed weak anti-HIV activity with IC50 values of 118 and 130 µM, respectively, while being devoid of cytotoxicity at 150 µM. A chlorophyll-enriched fraction of V. leptobotrys, containing pheophorbide a, was found to inhibit the replication of HIV-1 by 80% at a concentration of 10 µg/mL. Compounds 1 and 3 were further selected to be evaluated against 21 viral targets available at NIAID (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA).

Vasorelaxing activity of two coumarins from Murraya paniculata leaves.

In the search for novel chemical scaffolds leading to potential antihypertensive agents, the methanol extract of Murraya paniculata leaves was assessed for its effects on isolated rat aorta rings. The vasorelaxing effect of the chloroform fraction of the methanol plant extract was the most potent for its vasorelaxing activity on rat aorta rings contracted by 60 mM K(+) (K60). Two coumarins were isolated from the chloroform fraction: the novel kimcuongin (1) and the known murracarpin (2). Their structures were determined from spectroscopic evidences including (1)H- and (13)C-NMR, correlation spectroscopy (COSY), nuclear Overhauser effect spectroscopy (NOESY), heteronuclear multiple bond correlation (HMBC), heteronuclear single quantum correlation (HSQC), and high resolution mass spectrometry (HR-MS). Kimcuongin and, to a lesser extent, murracarpin, showed vasorelaxing activity with IC50 values of 37.7 µM and 139.3 µM, respectively. The coumarins kimcuongin and murracarpin may thus represent a novel class of vasodilators of natural source.

Laparoscopic treatment for median arcuate ligament syndrome in children: A case report.

In median arcuate ligament syndrome (MALS), the median arcuate ligament compresses the celiac trunk and surrounding nerves leading to chronic functional abdominal pain and vague gastrointestinal symptoms. MALS can be effectively treated by dividing the arcuate ligament through open surgery or laparoscopy. This is a rare vascular condition and mostly encountered in adult patients. We hereby report a case of a pediatric patient diagnosed with MALS and treated successfully by laparoscopic approach. An 11-year-old girl presented with severe abdominal cramps for 3 months, accompanied by nonbilious vomiting. Computed tomography (CT) angiography demonstrated clear images of celiac trunk compression suggesting MALS. Laparoscopic surgery to cut the ligament and decompress the celiac artery was performed. The patient was discharged on day 7 postoperative with no recurrence of symptoms after 12 months of follow-up. This report suggested the diagnostic value of CT scan, and the safety and the feasibility of laparoscopic surgical techniques to treat MALS in children.

Acetylcholinesterase inhibitory activities of some flavonoids from the root bark of Pinus krempfii Lecomte: in vitro and in silico study.

From the root bark of Pinus krempfii Lecomte, four flavonoids were isolated and evaluated for their inhibitory activities against AChE and BChE enzymes in vitro and in silico. Tectochrysin (1) was found to inhibit AChE with an IC50 value of 33.69 ± 2.80 µM. The docking study results also showed agreement with the in vitro test results. All four compounds also showed the best binding affinity for the AChE enzyme, characterised by binding energy (ΔG) values as low as -8.1 to -9.3 kcal/mol, in which, the compound tectochrysin had the best binding affinity for the AChE protein with a ΔG value of -9.329 kcal/mol. Tectochrysin (1) was also bound to the amino acid Phe295 of AChE with a bond length of 2.8 Å, similar to the control dihydrotanshinone-I. Galangin (2) also showed its in vitro inhibitory activity against BChE with an IC50 value of 82.21 ± 2.70 µM. In silico, it also had the best binding energy value of -9.072 kcal/mol with BChE and formed hydrogen bonds with the His438 (2.85 Å) residues of BChE like the positive control (tacrine). The steered molecular dynamics (SMD) simulation results of these two complexes revealed a mechanistic insight that the protein-ligand complexes showed stable trajectories throughout the 20 and 150 ns simulations. Moreover, the drug likeliness suggested that both flavonoids (1 and 2) were expected to be drug-like and have an LD50 toxicity level of 5. This study has contributed new results for drug discovery and the development of substances with neuroprotective effects, especially for the treatment of Alzheimer's disease.Communicated by Ramaswamy H. Sarma.

Giant coronary artery fistula: A case report.

Coronary artery fistulas (CAFs) are abnormal connections of coronary arteries where venous circuits bypass the normal capillaries in the myocardium. CAFs are rare, and most patients are asymptomatic. However, CAFs are the most common coronary artery anomalies affecting coronary hemodynamics. While most CAFs are asymptomatic in young patients, symptoms and complications become more frequent with increasing age. CAFs are characterized by variable clinical manifestations based on their size, origin, and drainage site. We describe a 35-year-old woman presenting with the shortness of breath after walking. Despite attempting medical treatment, the patient continued to experience dyspnea, fatigue, fainting the and chest pain episodes. After admission, cardiac imaging was immediately performed and recorded symptomatic CAFs. Percutaneous transcatheter closure treatment was indicated. The patient was discharged with clinical recovery. The treatment of symptomatic CAFs often requires the clear cardiac imaging and endovascular approach to achieve the best clinical results.

A Complicated Case Report of Coronary Artery Fistula.

Background: Coronary artery fistulas (CAFs), also, known as coronary arteriovenous malformation, are aberrant connections between coronary arteries and other structures, such as other artery branches or heart chambers. CAFs are infrequent and asymptomatic in young patients, but symptoms and complications become more frequent with age. CAFs can affect hemodynamic parameters and lead to complications, such as myocardial ischemia, heart failure, arrhythmia, and infective endocarditis. Objective: The aim of this article was to present a typical CAF case with severe symptoms who underwent successful embolization to resolve their symptoms. Case presentation: A 50-year-old Vietnamese male visited our cardiac outpatient clinic (S.I.S General Hospital, Can Tho, Vietnam) because of exertional dyspnea and chest pain. Signs of congestive heart failure and abnormal murmur were not presented on chest auscultation. Diagnostic digital subtraction angiography was performed to determine the detailed angioarchitecture of the CAF, revealing a fistulous connection between the left anterior descending artery (LAD) and the LV chamber through an aneurysm. In addition, the RCA measured 7 mm in diameter with a fistula (16 × 9 mm) draining into an aneurysm and then terminating into the LV chamber. The patient had an RCA aneurysm with a fistula into the LV. It was treated successfully by closing the fistula with a vascular plug. Access to the fistula was complex and difficult because of complications due to the CAF. After the procedure, the patient had no chest pain or shortness of breath and was discharged after three days. After six months, he was taking dual antiplatelet therapy and antihypertensive medications and felt better. We performed contrast computed tomography (CT) to examine the fistula after a year, which showed the successful closure of the fistula without any relevant alteration in the coronary artery. Conclusion: CAF closure is indicated if patients have symptoms or secondary complications, and percutaneous closure is a safe and effective method to manage CAF. A CAF is rare and does not have specific symptoms, making it difficult to diagnose. Most patients are asymptomatic and have serious recent complications. Currently, the percutaneous transcatheter method is popular because it is noninvasive and successful in most patients.