New Dibenzocyclooctadiene Lignans and Phenolics from Kadsura heteroclite with Anti-Inflammatory Activity.

A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3-16) by using multiple chromatographic techniques. New compounds (1 and 2) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14 µM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 µM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 µM) toward TNF-α production, respectively.

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.

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.

Synthesis of Multifunctional Eu(III) Complex Doped Fe3O4/Au Nanocomposite for Dual Photo-Magnetic Hyperthermia and Fluorescence Bioimaging.

In this paper, the luminescent complex Eu(3-thenoyltrifluoroacetonate)3 was integrated with Fe3O4 and gold (Au) nanoparticles to form a multifunctional nanocomposite, Fe3O4/Au/Eu(TTA)3 (FOASET NC), for dual magnetic-photothermal therapy and biomedical imaging. Upon functionalization with amine-NH2, the FOASET NC exhibits a small size of 60-70 nm and strong, sharp emission at λmax = 614 nm, enhanced by surface plasmon resonance (SPR) of Au nanoparticles that provided an effective label for HT29 colorectal cancer cells by fluorescence microscopy imaging. In addition, a hyperthermia temperature (42-46 °C) was completely achieved by using these FOASET NCs in an aqueous solution with three heating modes for (i) Magnetic therapy (MT), (ii) Photothermal therapy (PT), and (iii) Dual magnetic-photothermal therapy (MPT). The heating efficiency was improved in the dual magnetic-photothermal heating mode.

Laparoscopic Surgery for Intestinal Obstruction Caused by an Internal Paracecal Hernia.

Paracecal hernia is rarely associated with ischemia and has seldom been reported in the few published studies in the review literature. We present a case of incarcerated paracecal hernia with intestinal obstruction that was effectively treated with laparoscopic intervention. A 64-year-old woman who had not previously undergone any intestinal surgery arrived complaining of abdominal pain and vomiting at our hospital. Abdominal computed tomography suggested intestinal obstruction. A laparoscopic emergency procedure demonstrated an incarcerated small bowel loop in the paracecal region. The confined small bowel was removed from the paracecal area. On the fourth postoperative day, the patient was discharged. This case is unusual because the patient presented with small bowel strangulation, leading to intestinal obstruction. Laparoscopic surgery is beneficial for diagnosing internal hernias and curing small-bowel obstructions caused by paracecal hernias.

A ruptured pancreatic pseudocyst causes acute peritonitis with clinical characteristics of a gastrointestinal tract perforation.

Intraperitoneal air in pancreatic pseudocysts is a rare complication that can jeopardize hemodynamic stability and requires emergency surgery. A 61-year-old man was admitted to our hospital after abdominal pain, vomiting and diarrhea. Computed tomography showed a hollow visceral perforation with intraperitoneal air and two pseudocysts close to the pancreas. The patient was transferred to the emergency operating room with symptoms of septic shock. We histopathologically diagnosed a ruptured pancreatic pseudocyst combined with an intracystic haemorrhage. We resected a portion of the pseudocyst wall using surface electrocautery inside the lumen, cholecystectomy and peritoneal toilet and maintained adequate external drainage. The patient was discharged on postoperative Day 12. The patient achieved relapse-free survival for 12 months postoperatively. Ruptured pancreatic pseudocysts with extraluminal gas are dangerous if effective medical interventions are not performed. Emergency surgery should be completed as soon as possible to drain the pancreatic cyst and cleanse the abdomen.

Cytotoxic and nitric oxide inhibitory activities of triterpenoids from Lycopodium clavatum L.

Using combined chromatographic separation techniques, three new triterpenoids named lycomclavatols A-C (1-3), a new natural product, methyl lycernuate-A (4), as well as seven known compounds (5-11), were isolated from the methanol extract of the whole plants of Lycopodium clavatum. Their chemical structures were established based on 1 D/2D NMR and HR-ESI-MS spectroscopic analyses. Among the isolates, compound 1 exhibited inhibitory activity on NO production in LPS-stimulated BV2 cells (IC50 = 36.0 µM). In addition, 1 was cytotoxic against both HepG2 and A549 cancer cell lines, with IC50 values of 40.7 and 87.0 µM, respectively. Compounds 10 and 11 showed cytotoxicity on only HepG2 and A549 cells, with IC50 values of 91.2 and 57.6 µM, respectively. Our results contribute to understanding more the secondary metabolites produced by L. clavatum and provide a scientific rationale for further investigations of anti-inflammatory and anticancer effects for this valuable medicinal plant.

Chemical constituents from Lycopodiella cernua and their anti-inflammatory and cytotoxic activities.

Phytochemical investigation of the whole plants of Lycopodiella cernua resulted in the isolation and identification of three new compounds (1-3), namely lycocernuaside E (1), lycernuic ketone F (2), and lycernuic B (3) and 12 known ones (4-15). Their chemical structures were established based on 1 D/2D NMR spectroscopic and HR-ESI-MS data analyses. Compounds 5, 12, and 13 displayed NO inhibitory effects in LPS-stimulated BV2 cells, with IC50 values of 21.2 ± 1.1, 28.5 ± 1.4, and 21.9 ± 1.1 µM, respectively. In addition, cytotoxic activity of the isolated compounds against MCF7 (breast carcinoma), HepG2 (hepatocarcinoma), and SK-Mel2 (melanoma) cancer cell lines were also reported.

Synthesis and In Vitro Testing of YVO4:Eu3+@silica-NH-GDA-IgG Bio-Nano Complexes for Labelling MCF-7 Breast Cancer Cells.

We present a visual tool and facile method to detect MCF-7 breast cancer cells by using YVO4:Eu3+@silica-NH-GDA-IgG bio-nanocomplexes. To obtain these complexes, YVO4:Eu3+ nanoparticles with a uniform size of 10-25 nm have been prepared firstly by the hydrothermal process, followed by surface functionalization to be bio-compatible and conjugated with cancer cells. The YVO4:Eu3+@silica-NH-GDA-IgG nanoparticles exhibited an enhanced red emission at 618 nm under an excitation wavelength of 355 nm and were strongly coupled with MCF-7 breast cancer cells via biological conjugation. These bio-nanocomplexes showed a superior sensitiveness for MCF-7 cancer cell labelling with a detection percentage as high as 82%, while no HEK-293A healthy cells were probed under the same conditions of in vitro experiments. In addition, the detection percentage of MCF-7 breast cancer cells increased significantly via the functionalization and conjugation of YVO4:Eu3+ nanoparticles. The experimental results demonstrated that the YVO4:Eu3+@silica-NH-GDA-IgG bio-nanocomplexes can be used as a promising labelling agent for biomedical imaging and diagnostics.

Chemical Constituents from the Leaves of Pachyrhizus erosus Collected in Vietnam.

A phytochemical investigation of methanol extract from leaves of Pachyrhizus erosus (L.) Urban, a leguminous shrub distributed in Vietnam and other tropical and subtropical countries led to the isolation of a new prenylated chalcone, erosusone (1) and a new megastigmane glycoside epimer, 3-episedumoside F1 (9), together with thirteen known compounds including flavonoids (2-6), a 3-benzoxepine lactone (7), a pyridine-4,5-diol derivative (8), megastigmanes and megastigmane glycosides (10-15). Their structures were elucidated by means of high resolution-electrospray ionization (HR-ESI)-MS, one dimensional (1D) and two-dimensional NMR (2D-NMR) spectroscopy as well as comparison with the data reported in the literature. The cytotoxic effects on LU-1 (lung carcinoma), HepG2 (hepatocellular carcinoma), and MCF7 (breast carcinoma) cell lines were assessed. Prenylated chalcones 1-2 and isoflavone 3 exhibited cytotoxicity against all tested cell lines with IC50 values ranging from 22.04 to 45.03 µM.

Efficacy of laparoscopic-assisted pancreaticoduodenectomy in Vietnamese patients with periampullary of Vater malignancies: A single-institution prospective study.

INTRODUCTION: Minimally invasive pancreaticoduodenectomy is a technically complex technique, that is being used to treat periampullary malignancy. We provide our experience with laparoscopic-assisted pancreaticoduodenectomy (LAPD) with statistics on the outcomes of periampullary cancer patients. MATERIAL AND METHOD: Thirty patients underwent surgery between June 1, 2016 and May 30, 2020, with 21 undergoing classical PD and 9 undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). Prospectively gathered data on surgical outcomes and long-term oncological results are given. RESULTS: The median operative time was 277.5 min (range, 258.7-330 min), and the median intraoperative estimated blood loss was 319.5 mL (range, 241.2-425 mL). The rate of conversion to OPD, surgical reintervention, and mortality was 20%, 13.3%, and 10% respectively. Cumulative surgery-related morbidity was 33.4%, including bleeding (n = 4), severe POPF (n = 4), biliary fistula (n = 1), DGE (n = 2), and intestinal obstruction (n = 1). Pathologic diagnoses were AoV cancer (n = 23), distal CBD cancer (n = 4), PDAC (n = 2), and AoV NET (n = 1). The mean survival time of the LAPD group was 29.9 months. The long-term survival time of the N0 group was 36.8 months, which was significantly longer than that of the N1 group. The long-term survival times of stages I-B, II-A, and II-B were 36.9, 26.5, and 15.7 months, respectively (p = 0.016). CONCLUSION: LAPD has a high rate of conversion to OPD, morbidity, and mortality. However, LPD is feasible technique for highly selected patients. Lymph node metastasis and stage of disease are the risk factors for long-term survival.

Outcomes of surgical management of peptic ulcer perforation using the falciform ligament: A cross-sectional study at a single centre in Vietnam.

INTRODUCTION: Peptic ulcer perforation (PUP) is one of the most common critical surgical emergencies. The omentum flap is commonly used to cover a PUP. However, the omentum cannot be used in cases of severe peritonitis or previous surgical removal. This is the first study conducted in Vietnam that was designed to analyse the outcomes of patients with PUPs who were treated using the falciform ligament. METHOD: In this study, we retrospectively identified 40 consecutive patients who were treated for PUP at a single high-volume centre in Vietnam from February 2018 to February 2021. Peptic ulcer perforation was measured during diagnostic evaluation based on preoperative imaging, such as X-ray, and CT scan. Patients who had malignancy, laparoscopic surgery, omentopexy and nonoperative treatment were excluded from this research. RESULTS: Forty patients were included; the mean age of the patients was 66.3 years (range 33-99 years), and some patients had comorbid disease (57.5%), hypertension (30%), diabetes (10%), cirrhosis (7.5%), and chronic renal failure (7.5%). The PUPs were located in the duodenum (80%), or the pyloric (15%) and prepyloric (5%) regions. The procedures used to treat the patients included duodenostomy (32.5%), gastrojejunostomy (37.5%), and antrum resection (2.5%). The average operative time was 88.6 min (45-180 min), hospital stay was 9.6 days (2-35 days), and oral intake was started at 4.1 days (3-8 days); additionally, the 30-day mortality (17.5%) and incidences of pneumonia (25%), multiorgan failure (15%), acute liver failure (5%), wound infection (7.5%), and ulcer peptic fistula (0%) were assessed. Univariate tests showed that an ASA ≥ III and comorbidities, such as pulmonary complications, liver failure and multiorgan failure, were associated with mortality. The multivariate test showed that multiorgan failure was the only factor related to mortality. CONCLUSION: The falciform ligament can be efficiently used for the closure of a PUP. Although there were no instances of complication with a reperforated peptic ulcer, the mortality rate was slightly highly related to severe comorbidities and postoperative multiorgan failure.

Pancreaticoduodenectomy for hepatic portal lymph node metastasis after hepatic resection for hepatocellular carcinoma: A clinical case report.

INTRODUCTION: In 2018, Hepatocellular carcinoma (HCC) was predicted to be the sixth most commonly diagnosed cancer. Extra-hepatic metastasis due to HCC is a poor prognostic factor, depending on the stage of the disease. PRESENTATION OF CASE: We report a case of a 52-years old male who had undergone Segment 5 (S5) hepatectomy for HCC of 4.7 × 2 cm. Transcatheter arterial chemoembolization (TACE) four times postoperatively was performed based on a preoperative diagnosis of a recurrent tumour at the S1. After 2 years, the solitary tumour (7.5 × 2.5 × 3.5 cm) is located behind the right lobe of the liver and the head of the pancreas. The tumour was abnormally supplied with blood from the superior mesenteric artery (SMA) and the gastroduodenal artery (GDA). The patient was underwent pancreaticoduodenectomy (PD) to remove a large tumour. Postoperative pathology and immunohistochemical staining showed metastatic HCC. There was no tumour recurrence after 6 months. DISCUSSION: The organs in the body that liver cancer cells most often spread to are the lungs (44%), the portal vein (35%), the hepatobiliary ganglion (27%), and a small number of cases of bone, eye socket, bronchus metastases. Otherwise, recurrence of lymph nodes (LNs) after hepatectomy for HCC is very rare. CONCLUSIONS: HCC can metastasize to the hepatic pedicle LN after hepatectomy and maybe confused with recurrent liver tumours in the S1. Indications for PD are feasible for solitary metastatic at peri-pancreas. Pathology incorporating immunohistochemistry can determine the origin of metastases.

Sesquiterpenoids from Saussurea costus.

Sixteen sesquiterpenoids (1 - 16), including two new compounds namely saussucostusosides A and B (1 and 2), were isolated from the roots of Saussurea costus by various chromatographic separations. Their structures were elucidated by 1 D and 2 D NMR and HR-QTOF-MS experiments. Among isolated compounds, costunlide (6), 3ß-[4-hydroxymethacryloyloxy]-8α-hydroxycostunolide (10) and 11ß,13-dihydrozaluzanin C (16) exhibited potent inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 7.08 ± 0.34, 2.40 ± 0.06 and 5.55 ± 0.24 µM, respectively.

Chemical constituents of Vietnamese mangrove Hibiscus tiliaceus with antioxidant and alpha-glucosidase inhibitory activity.

Using various chromatographic techniques, a total of 15 compounds, including one novel megastigmane named tiliaceic acid A (1) and 14 known compounds, were isolated from the traditional medicinal Vietnamese mangrove Hibiscus tiliaceus. Their structures were confirmed based on spectroscopic experiments including, UV, 1 D- and 2 D-NMR, HR-ESI-MS, and ECD analysis. The antioxidant and α-glucosidase inhibitory activities of the isolated compounds from H. tiliaceus were evaluated for the first time. Compound 2 showed strong α-glucosidase inhibitory activity with an IC50 of 77.78 ± 1.00 µM compared with the positive control acarbose at 105.71 ± 2.29 µM.

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.

Diterpenoids and Flavonoids from Andrographis paniculata.

Chemical investigation of the aerial parts of Andrographis paniculata resulted in isolation of nine compounds, including a new ent-labdane diterpenoid, andrographic acid methyl ester (1), a new chalcone glucoside, pashanone glucoside (5), and seven known metabolites, andrograpanin (2), andrographolide (3), andropanolide (4), andrographidine A (6), andrographidine F (7), 6-epi-8-O-acetyl-harpagide (8), and curvifloruside F (9). Their chemical structures were elucidated based on comprehensive analyses of the spectroscopic data, including NMR and MS. Among the isolated compounds, andropanolide exerted cytotoxicity toward LNCaP, HepG2, KB, MCF7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 31.8 to 45.9 µM. In addition, andropanolide significantly inhibited the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with an IC50 value of 13.4 µM.

Anti-inflammatory secondary metabolites from the stems of Millettia dielsiana Harms ex Diels.

A phytochemical investigation for the constituents of the stems of Millettia dielsiana Harms ex Diels resulted in the isolation of a new isoflavone glycoside, mildiside A (1), and 14 known compounds (2-15). Their chemical structures were determined using a combination of IR, NMR, MS, and optical rotation analysis, as well as comparison with the literature data. The ethanolic (EtOH) extract and several isolated compounds exert the inflammatory effect of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells.

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.