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.

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.

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.

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.

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.

Soluble epoxide hydrolase inhibitors from Docynia indica (Wall.) Decne.

Nine bioactive compounds, including one new dihydroisocoumarin glycoside, 3S-thunberginol C 6-O-ß-D-glucopyranoside (1a/1b), were isolated by chromatographic separation from the fruits of the Vietnamese medicinal plant Docynia indica (Wall.) Decne. 3S-thunberginol C 6-O-ß-D-glucopyranoside was determined as a mixture of boat-like conformers based on NMR evidence and density functional theory (DFT) calculations. The in vitro inhibition of soluble epoxide hydrolase (sEH) by the isolated compounds was comparable to that of AUDA (positive control), yielding IC50 values ranging from 10.0 ± 0.6 to 88.4 ± 0.2 µM. Among isolated compounds, 3-methoxy-4-hydroxy-benzoic acid (7) and 2',6'-dihydroxy 3',4'-dimethoxychalcone (9) were identified as a potent inhibitor of sEH, with IC50 values of 19.3 ± 2.2 and 10.0 ± 0.6 mM, respectively. These results suggest that the fruits of D. indica may be useful as daily supplements for the prevention of cardiovascular and other sEH-related diseases.[Figure: see text].

Design, synthesis, structure, in vitro cytotoxic activity evaluation and docking studies on target enzyme GSK-3ß of new indirubin-3'-oxime derivatives.

The addition of chalcone and amine components into indirubin-3'-oxime resulted in 15 new derivatives with high yields. Structures of new derivatives were also elucidated through 1D, 2D-NMR and HR-MS(ESI) spectra and X-ray crystallography. All designed compounds were screened for cytotoxic activity against four human cancer cell lines (HepG2, LU-1, SW480 and HL-60) and one human normal kidney cell line (HEK-293). Compound 6f exhibited the most marked cytotoxicity meanwhile cytotoxicity of compounds 6e, 6h and 6l was more profound toward cancer cell lines than toward normal cell. These new derivatives were further analyzed via molecular docking studies on GSK-3ß enzyme. Docking analysis shows that most of the derivatives exhibited potential inhibition activity against GSK-3ß with characteristic interacting residues in the binding site. The fast pulling of ligand scheme was then employed to refine the binding affinity and mechanism between ligands and GSK-3ß enzyme. The computational results are expected to contribute to predicting enzyme target of the trial inhibitors and their possible interaction, from which the design of new cytotoxic agents could be created in the future.

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.

Serine protease inhibitors and activators from Dalbergia tonkinensis species.

The vulnerable plant Dalbergia tonkinensis Prain is a rare species in Vietnam. In the course of our studies on biologically active plants, we performed serine protease enzyme screenings. The results suggest that at concentrations of 25-250 ng/mL, methanol extracts of leaf and root, root ethanol extract and its dichloromethane fraction, and heartwood water decoction extract can serve as useful sources to stimulate trypsin enzyme activity. In addition, water decoction extracts of leaf and stem bark may explain unknown ethno-pharmacology due to the high inhibitory effects in enzyme assays using trypsin, chymotrypsin, and elastase. Among 23 isolated compounds and two semi-synthetic derivatives tested, quercetin (17) inhibits the activities of trypsin and chymotrypsin with IC50 9.7 µM. Flavonoids categorized as flavanone, isoflavanone, flavone, isoflavone, pretocarpan, aurone, and neoflavanone demonstrated variable activities. Several substitutions are closely correlated with protease actions, including hydroxylation at C-3 and C-3' in flavone and C-5 and C-3' in isoflavone, hydroxylation at C-3, C-5 and C-3', carboxylation at C-6 and C-8, and 7-substitution in flavanone; 7-substitution and methoxylation at C-3' in isoflavanone; and lactone ring opening in neoflavanone. In the assessment of casein cleavage, at a dose of 25 ng/mL, leaf water decoction extract demonstrates an inhibitory effect on casein cleavage by trypsin, whereas ethanol and methanol extracts of the root caused activation.

Successful intralipid-emulsion treatment of local anesthetic systemic toxicity following ultrasound-guided brachial plexus block: case report.

BACKGROUND: Local anesthetic systemic toxicity (LAST) is a life-threatening complication that may follow application of LAs through various routes. Despite increasing usage of LA techniques in a large number of health-care settings, contemporary awareness of LAST and understanding of its management are inadequate. CASE PRESENTATION: We report two cases who suffered LAST following brachial plexus block for surgery on the upper extremity. The first patient received an ultrasound-guided supraclavicular block with 300 mg lidocaine (6 mg/kg) and 50 mg ropivacaine (1 mg/kg) in 25 mL without epinephrine, and the second patient received an ultrasound guided interscalene block with 200 mg lidocaine (4.5 mg/kg) and 45 mg ropivacaine (1 mg/kg) supplemented with epinephrine 1:200,000. Both patients presented with symptoms of central nervous and respiratory system depression, the first roughly 10 minutes after injection, and the second immediately after withdrawal of the needle. In both cases, thorough recovery was obtained using lipid-emulsion therapy. CONCLUSION: The complication of LAST following ultrasound-guided brachial plexus block could be treated successfully applying the American Society of Regional Anesthesia and Pain Medicineprotocol of intravenous administration of lipid emulsion.

Preemptive analgesia after lumbar spine surgery by pregabalin and celecoxib: a prospective study.

OBJECTIVE: To evaluate the preemptive analgesic effect of combination pregabalin with celecoxib for lumbar spine surgery. METHODS: A prospective, randomized study was conducted among 60 lumbar spine surgery patients and divided into two groups. Postoperative pain relief was achieved with intravenous patient-controlled analgesia with morphine. The preemptive analgesia group received oral pregabalin (150 mg) and celecoxib (200 mg) 2 hrs before surgery, and the control group received a placebo. Pain was assessed by visual analogue scale (VAS). Side effects and morphine consumption were monitored until 48 hrs after surgery. RESULTS: VAS score at rest and during movement was statistically significantly lower in the preemptive analgesia group at most time points (p<0.05). Morphine consumption was significantly lower in the preemptive analgesia group compared with control group in the 24 first hours (29.03±4.38 mg vs 24.43±4.94) and 48 hrs (52.23±9.57 mg vs 44.20±10.21 mg), p<0.05. Hemodynamics, respiratory rate, and SpO2 were similar for both groups. The sedation score was only statistically significant at H8 time point. The incidence of nausea/vomiting in the preemptive group did not statistically differ from the control group. CONCLUSION: Preoperative administration of pregabalin combined with celecoxib had a good preemptive analgesia effect and reduced intravenous morphine consumption after lumbar spine surgery. Side effects were mild and transient.

Patient-controlled paravertebral analgesia for video-assisted thoracoscopic surgery lobectomy.

BACKGROUND: Paravertebral block has been proven to be an efficient method to provide post-thoracotomy pain management. This study aimed to compare patient-controlled paravertebral analgesia (PCPA) and intravenous patient-controlled analgesia (IVPCA) in terms of analgesic efficiency, respiratory function, and adverse effects after video-assisted thoracoscopic surgery (VATS) lobectomy. PATIENTS AND METHODS: The prospective randomized trial study was carried out on 60 patients who underwent VATS lobectomy (randomly allocated 30 patients in each group). In the PCPA group, an initial dose of 0.3 mL/kg of 0.125% bupivacaine with fentanyl 2 µg/mL was administered, followed by a 3 mL/h continuous infusion with patient-controlled analgesia (2 mL bolus, 10-minute lockout interval, 25 mL/4 h limit). In the IVPCA group with morphine 1 mg/mL solution, an infusion device was programmed to deliver a 1.0 mL demand bolus with no basal infusion rate, with a 10-minute lockout interval and a maximum of 20 mL/4 h period. Postoperative pain was assessed by visual analog scale at rest and on coughing. Arterial blood gas and spirometry were monitored and recorded for the first 3 postoperative days. Side effects to include were also recorded. RESULTS: The PCPA group had statistically significant lower pain scores (P<0.0001) at rest at all times. Lower pain scores on coughing were statistically significant in PCPA group in the first 4 hours. Postoperative spirometry showed that both the groups had comparable recovery trajectories for their pulmonary function. Arterial blood gas analysis showed pH and PaCO2 were in a normal range in both the groups. The incidence of headache was higher in the IVPCA group (13.3% vs 0%; P=0.038). CONCLUSION: PCPA effectively managed pain after VATS lobectomy, with lower pain scores, similar respiratory function, and fewer side effects than standard IVPCA treatment.

In silico screening of anthraquinones from Prismatomeris memecyloides as novel phosphodiesterase type-5 inhibitors (PDE-5Is) / Cribado virtual de antraquinonas procedentes de Prismatomeris memecyloides como inhibidores noveles de fosfodiesterasa tipo 5 (PDE-5Is)

Objective: Prismatomeris memecyloides Craib (Rubiaceae) is a medicinal plant traditionally used by ethnic minorities in Vietnam for the treatment of erectile dysfunction (ED). The aim of this study was to investigate the chemical compositions and screen in silico its possible inhibitory effect against PDE-5 which reduced cyclic guanosine-3′,5′-monophosphate (cGMP) levels and indirectly caused the male ED. Methods: Separation of natural compounds were carried out on chromatographic column with silica gel or reversed phase materials, eluting with different solvent gradients. The structures of all isolated compounds were elucidated on the basis of spectroscopic data (HR-MS, 1D/2D-NMR). Docking simulation study of compound (1-7) was performed by using flexible side chains protocol based on Iterated Local Search Global Optimizer Algorithm of AutoDock/Vina v.1.1.2. Pharmacokinetic parameters and toxicity prediction were also calculated by appropriate softwares. Results: From the methanol extract of roots of P. memecyloides collected in Vietnam, seven compounds including four anthraquinone/one anthraquinone glycoside namely damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3), rubiadin-3-methyl ether (4), and 1-O-methylrubiadin 3-O-primeveroside (5) along with two iridoid glucosides, asperulosidic acid (6) and aitchisonide A (7) were isolated. The molecular modeling results showed that 5 anthraquinone compounds possess the lowest binding energies to PDE-5. The anthraquinone glucoside 1-O-methylrubiadin 3-O-primeveroside (5) potentially inhibited PDE-5 similarly to commercial PDE-5Is sildenafil (SLD) and tadalafil (TLD). Calculated pharmacokinetic results like pIC50,pred; miLogP, TPSA, enzyme inhibitory of anthraquinone glucoside (5) were similar and even higher to those of the commercial PDE-5 inhibitors. Especially the predictive toxicity of 1-O-methylrubiadin 3-O-primeveroside (5) was even lower than those of SLD and TLD. Conclusion: This is the first study to find a scientific-based evidence for the ethnic use of P. memecyloides as medicinal plant for the treatment of ED. The result indicates that the anthraquinones (damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3) and rubiadin-3-methyl ether (4)), especially anthraquinone glycoside (1-O-methylrubiadin 3-O-primeveroside (5)) are compounds of potential novel drug class for the ED treatment

Objetivo: Prismatomeris memecyloides Craib (Rubiaceae) es una planta medicinal utilizada tradicionalmente por las minorías étnicas en Vietnam para el tratamiento de la disfunción eréctil (DE). El objetivo de este estudio fue investigar sus composiciones químicas y realizar un cribado virtual de su posible efecto inhibitorio frente a PDE-5 con niveles reducidos de guanosín-3′,5′-monofosfato cíclico (cGMP) y la causa indirecta de la DE en los varones. Métodos: Se realizó la separación de los componentes naturales en una columna cromatográfica con gel de silicio o materiales de cambio de fase, diluyéndolos con diferentes gradientes de disolventes. Se dilucidaron las estructuras de los componentes aislados sobre la base de los datos espectroscópicos (HR-MS, 1D/2D-NMR). Se realizó el estudio de simulación de acoplamiento del componente (1-7) utilizando el protocolo de cadenas laterales flexibles basado en el algoritmo «Iterated Local Search Global Optimizer» de los parámetros farmacocinéticos AutoDock Vina v.1.1.2., calculándose asímismo la predicción de toxicidad mediante los softwares adecuados. Resultados: A partir de los extractos de metanol de las raíces de P. memecyloides recolectadas en Vietnam se aislaron 7 componentes, incluyendo 4 antraquinonas/un glucósido antraquinona denominado damnacantal (1), lucidín-ω-metil éter (2), 3-metilalizarín (3), rubiadín-3-metil éter (4) y 1-O-metilrubiadín 3-O-primeverosida (5) junto con 2 glucósidos iridoides, ácido asperulosídico (6) andaitquisonida A (7). Los resultados de modelación molecular reflejaron que 5 componentes de antraquinona poseen las menores energías de ligamiento a PDE-5. El glucósido antraquinona 1-O-metilrubiadín 3-O-primeverosida (5) inhibió potencialmente PDE-5 de manera similar a las PDE-5Is comerciales sildenafil (SLD) y tadalafil (TLD). Los resultados farmacocinéticos calculados como pIC50, pred, miLogP, TPSA, enzima inhibidora de antraquinona glucósido, 1-O-metilrubiadín 3-O-primoverosida (5), fueron similares e incluso más altos que los de los inhibidores comerciales de PDE-5. Especialmente, la toxicidad predictiva de (5) fue incluso menor que la de SLD y TLD. Conclusión: Este es el primer estudio que encuentra una evidencia con base científica para el uso étnico de Prismatormeris memecyloides como planta medicinal para el tratamiento de la DE. El resultado indica que las antraquinonas (damnacantal (1), lucidín-ω-metil éter (2), 3-metilalizarín (3) y rubiadín-3-metil éter (4)), y en especial el glucósido antraquinona (1-O-metilrubiadín 3-O-primeverosida (5)) son componentes de clase farmacológica novel potencial para el tratamiento de la DE

In silico screening of anthraquinones from Prismatomeris memecyloides as novel phosphodiesterase type-5 inhibitors (PDE-5Is).

OBJECTIVE: Prismatomeris memecyloides Craib (Rubiaceae) is a medicinal plant traditionally used by ethnic minorities in Vietnam for the treatment of erectile dysfunction (ED). The aim of this study was to investigate the chemical compositions and screen in silico its possible inhibitory effect against PDE-5 which reduced cyclic guanosine-3',5'-monophosphate (cGMP) levels and indirectly caused the male ED. METHODS: Separation of natural compounds were carried out on chromatographic column with silica gel or reversed phase materials, eluting with different solvent gradients. The structures of all isolated compounds were elucidated on the basis of spectroscopic data (HR-MS, 1D/2D-NMR). Docking simulation study of compound (1-7) was performed by using flexible side chains protocol based on Iterated Local Search Global Optimizer Algorithm of AutoDock/Vina v.1.1.2. Pharmacokinetic parameters and toxicity prediction were also calculated by appropriate softwares. RESULTS: From the methanol extract of roots of P. memecyloides collected in Vietnam, seven compounds including four anthraquinone/one anthraquinone glycoside namely damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3), rubiadin-3-methyl ether (4), and 1-O-methylrubiadin 3-O-primeveroside (5) along with two iridoid glucosides, asperulosidic acid (6) and aitchisonide A (7) were isolated. The molecular modeling results showed that 5 anthraquinone compounds possess the lowest binding energies to PDE-5. The anthraquinone glucoside 1-O-methylrubiadin 3-O-primeveroside (5) potentially inhibited PDE-5 similarly to commercial PDE-5Is sildenafil (SLD) and tadalafil (TLD). Calculated pharmacokinetic results like pIC50,pred; miLogP, TPSA, enzyme inhibitory of anthraquinone glucoside (5) were similar and even higher to those of the commercial PDE-5 inhibitors. Especially the predictive toxicity of 1-O-methylrubiadin 3-O-primeveroside (5) was even lower than those of SLD and TLD. CONCLUSION: This is the first study to find a scientific-based evidence for the ethnic use of P. memecyloides as medicinal plant for the treatment of ED. The result indicates that the anthraquinones (damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3) and rubiadin-3-methyl ether (4)), especially anthraquinone glycoside (1-O-methylrubiadin 3-O-primeveroside (5)) are compounds of potential novel drug class for the ED treatment.

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.

Anti-HIV diphyllin glycosides from Justicia gendarussa.

In a search for new anti-HIV active leads from over several thousands of plant extracts, we have identified a potent plant lead. The active plant is determined as Justicia gendarussa (Acanthaceae), a medicinal plant that has been used for the treatment of injury, arthritis and rheumatism in Asia including China. Our bioassay-guided fractionation of the methanol extract of the stems and barks of the plant led to the isolation of two anti-HIV compounds, justiprocumins A and B. The compounds are identified as new arylnaphthalide lignans (ANL) glycosides. We further determined that the ANL glycosides are the chemical constituents that contribute to the anti-HIV activity of this plant. Justiprocumin B displayed potent activity against a broad spectrum of HIV strains with IC50 values in the range of 15-21 nM (AZT, IC50 77-95 nM). The compound also displayed potent inhibitory activity against the NRTI (nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-11617-1) of the analogue (AZT) as well as the NNRTI (non-nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-1N119) of the analogue (nevaripine).

Changes in knowledge, attitude and involvement of fathers in supporting exclusive breastfeeding: a community-based intervention study in a rural area of Vietnam.

OBJECTIVES: To test the hypotheses of positive changes of fathers' knowledge, attitude and involvement in supporting exclusive breastfeeding (EBF) after receiving breastfeeding education materials and counseling services. METHODS: A quasi-experimental, pre-test-post-test, non-equivalent control group design was used. At baseline, 251 and 241 pregnant women and their husbands were enrolled into the intervention and control groups, respectively. The 1-year intervention targeting fathers included mass media, game show-style community events, group and individual counseling at health facilities and home visits. RESULTS: Compared to fathers in the control group, fathers in the intervention group had higher BF knowledge scores and higher attitude scores reflecting more positive attitudes toward early initiation of BF and 6 months EBF. Fathers in the intervention group were also more likely to report active involvement in supporting mothers to practice EBF during antenatal and postpartum periods. CONCLUSIONS: The community-based education model should be maintained and considered for conducting further test in wider application to mobilize fathers in supporting EBF.

Inhibitory Components from Glycosmis stenocarpa on Pepper Mild Mottle Virus.

The goal of this study was to identify a source of natural plant compounds with inhibitory activity against pepper mild mottle virus (PMMoV). We showed, using a half-leaf assay, that murrayafoline-A (1) and isomahanine (2) isolated from the aerial parts of Glycosmis stenocarpa have inhibitory activity against PMMoV through curative, inactivation, and protection effects. Using a leaf-disk assay, we confirmed that 2 inhibited virus replication in Nicotiana benthamiana. Using electron microscopy, we found that a mixture of the virus with 2 resulted in damage to the rod-shaped virus.