[Research status of glucagon-like peptide-1 receptor agonists on obstructive sleep apnea].

Obstructive sleep apnea (OSA) is the most common sleep-disordered breathing disease. Continuous positive airway pressure (CPAP) is the gold standard for treatment, but compliance is suboptimal. Therefore, new therapeutic strategies need to be explored. OSA is often associated with multiple comorbidities, particularly type 2 diabetes and obesity. Effective weight loss is known to be crucial in reversing OSA and its associated comorbidities. However, sustained weight loss is difficult to achieve with lifestyle changes alone. Medications that have both hypoglycemic and weight-loss effects are one way to achieve this goal. This article discussed the therapeutic effect of glucagon-like peptide-1 receptor agonists on this disease.

[Clinical characteristics and efficacy analysis of various treatments for spontaneous carotid artery dissection].

Objective: To investigate the clinical features of spontaneous carotid artery dissection (SCAD) and the efficacy of different treatment methods. Methods: The clinical data of 164 patients with SCAD who were treated at the First Affiliated Hospital of Zhengzhou University from June 2018 to January 2023 were retrospectively analyzed. There were 127 males and 37 females, with a mean age of (49.5±11.1) years. They were divided into conservative treatment group (n=100) and surgical treatment group (n=64) according to whether they received surgical treatment. Patients were followed at 3, 6, and 12 months after discharge and annually thereafter through outpatient or inpatient visits. The incidence of cerebral ischemic events, cerebral hemorrhage events, and mortality rates during hospitalization and follow-up periods were analyzed in the two patient groups. To examine correlates of revascularization in SCAD, multifactorial logistic regression analysis was used. Results: Of the 164 patients, 18 patients had bilateral SCAD and a total of 182 carotid arteries were included in the study. Ischemic stroke (85 cases, 51.8%) and transient ischemic attack (31 cases, 18.9%) were the main clinical manifestations in SCAD patients. Hypertension (81 cases, 49.4%) and hyperlipidemia (39 cases, 23.8%) were the main comorbidities in SCAD patients. During hospitalization, 100 patients in the conservative treatment group received medication in 113 carotid arteries, no new cerebral ischemic events or symptomatic intracranial hemorrhage events occurred, and no death occurred. A total of 69 carotid arteries were surgically treated in 64 patients in the surgical treatment group. The success rate was 97.1% (67/69). In the surgical treatment group, the proportion of carotid stenosis degree≥90% was 47.8% (33/69), the proportion of type Ⅱ SCAD was 60.9% (42/69), and the proportion discharged from the hospital to receive antiplatelet therapy was 92.8% (64/69), which were higher than those in the conservative treatment group, which were 25.7% (29/113), 45.1% (51/113), and 73.5% (83/113), respectively (all P<0.05). The follow-up time [M(Q1, Q3)] in the conservative treatment group was 24 (13, 34) months, with an 8% (9/113) rate of ischemic events and a 7.1% (8/113) rate of readmission; in the surgical treatment group, the follow-up time was 24 (11, 38) months, and there were no new ischemic events or deaths. The results of multifactorial logistic regression analysis showed that the degree of true luminal stenosis<90% (OR=2.738, 95%CI: 1.067-7.026, P=0.036) and type Ⅰ dissections (OR=2.656, 95%CI: 1.189-5.935, P=0.017) were the correlates of complete revascularization. Conclusions: Ischemic stroke and transient ischemic attack are the main clinical manifestations in patients with SCAD. Pharmacological antithrombotic therapy remains the method of choice, and endovascular treatment after failure of conservative therapy reduces the risk of recurrent long-term cerebral ischemic events and the re-admission rate of patients.

Noni as an anxiolytic and sedative: a mechanism involving its gamma-aminobutyric acidergic effects.

Noni (Morinda citrifolia) is increasing in worldwide popularity as a food or dietary supplement with versatile health benefits. The aim of this study was to investigate the effects of Noni fruit on anxiety symptoms in vitro. To this end, a competitive GABAa receptor-binding assay was developed. Our preliminary study indicates that the methanol crude extract of Noni fruit showed significant affinity to the gamma-aminobutyric acid A (GABAa) inhibitory neurotransmitter receptors, and displayed 75% binding inhibition of the agonist radioligand [3H] muscimol at a concentration of 100 microg/ml. Further experiments demonstrated that the MeOH extract, and its BuOH and H2O partitions, exhibited IC50 values of 22.8, 27.2, and 17.1 microg/ml, respectively, in the GABAa-binding assay. Experimental results with Noni fruit indicate the presence of competitive ligand(s), which may bind to the GABAa receptor as an agonist, and thus induce its anxiolytic and sedative effects. The study provides an in vitro rationale for one of Noni's versatile and traditional uses. In addition, an HPLC fingerprint profile of the methanolic extract of Noni fruit has been established for quality control purpose.

The first naturally occurring Tie2 kinase inhibitor.

[structure: see text] Bioassay-guided fractionation of the plant Acacia aulacocarpa, guided by a bioassay for Tie2 tyrosine kinase activity, yielded the novel triterpene 3,21-dioxo-olean-18-en-oic acid (1) as the first naturally occurring non-protein inhibitor of Tie2 kinase. The structure of 1 was assigned by analysis of spectral data. In addition to its activity as an inhibitor of Tie2 kinase, compound 1 also shows modest activity against a variety of cultured mammalian cells.

Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.

Analysis of cytotoxicity data of extracts from the National Cancer Institute's Active Repository by the COMPARE protocol was carried out using camptothecin as a reference point. Extracts identified by this process were further characterized by a selective yeast bioassay for inhibitors of topoisomerase I and by a biochemical assay for compounds that stabilize the topoisomerase I-DNA covalent binary complex. Five of the extracts were positive in the yeast bioassay, and eight extracts showed activity on the assay that monitors stabilization of the topoisomerase I-DNA complex. Four of the latter extracts were inactive in the yeast bioassay, and thus would not have been identified as hits without the COMPARE preselection process. One of the extracts, from Pyrenacantha klaineana, was selected for detailed investigation, and fractionation of this extract yielded camptothecin and 9-methoxycamptothecin as the bioactive constituents.

Cytotoxic triterpene acids from the Peruvian medicinal plant Polylepis racemosa.

Cytotoxicity-guided fractionation of the bark and stem extract of Polylepis racemosa led to the identification of ursolic acid, pomolic acid, 3-O-acetylpomolic acid, and 2-oxopomolic acid. Pomolic acid was the most cytotoxic component, and was specific for M-14 melanoma and ME180 cervical carcinoma, with GI50 values of 6.9 and 8.3 micrograms/mL respectively.

Bioactive compounds from Combretum erythrophyllum.

A methanol extract of Combretum erythrophyllum showed inhibitory bioactivities in a yeast-based microtiter assay for DNA-damaging agents. Bioassay-guided fractionation of this extract yielded two known bioactive compounds, combretastatin A-1 and (-)-combretastatin, and two new bioactive glucosides, combretastatin A-1 2'-beta-D-glucoside (1) and combretastatin B-1 2'-beta-D-glucoside (2). The structures of the new compounds were assigned by (1)H and (13)C NMR, DEPT, HMQC, and HMBC spectra.

Isolation and biochemical characterization of a new topoisomerase I inhibitor from Ocotea leucoxylon.

In a continuation of our search for potential tumor inhibitors from plants, we found that a crude extract from Ocotea leucoxylon showed selective activity typical of inhibitors of the enzyme topoisomerase I in a yeast assay for DNA-damaging agents. Using a bioassay-directed fractionation approach, the major bioactive compound was isolated and identified as the known aporphine alkaloid dicentrinone (4); the inactive alkaloid dicentrine (3) was also isolated. Compound 4 showed selective bioactivity against the rad52 repair-deficient yeast strain RS322 (IC(12) 49 microg/mL) and was inactive against the rad52- and topo1-deficient strain RS321 (IC(12) > 2000 microg/mL) and against the repair-proficient strain RJ03 (IC(12) > 2000 microg/mL). Biochemical studies with recombinant human topoisomerase I indicated that dicentrinone (4) is an inhibitor of the human enzyme. Colony formation studies suggest that it is weakly cytotoxic, but that its mechanism of toxicity differs from that of camptothecin and its derivatives.

A new labdane diterpenoid from Renealmia alpinia collected in the Suriname rainforest.

Continuation of a previous study on Renealmia alpinia resulted in the isolation of the new labdane diterpenoid 3, together with two known diterpenoids. The structure of the new diterpenoid was determined by a combination of NMR techniques and HRFABMS.

A new labdane diterpenoid from Renealmia alpinia collected in the Suriname rainforest

Continuation of a previous study on Renealmia alpinia resulted in the isolation of the new labdane diterpenoid 3, together with two known diterpenoids. The structure of the new diterpenoid was determined by a combination of NMR techniques and HRFABMS. (AU)

Bioactive indole alkaloids from the bark of Uncaria guianensis.

Bioassay-guided fractionation of the EtOH extract of the bark of Uncaria guianensis (Aubl.) Gmel (Rubiaceae) using a yeast-based assay for DNA-damaging agents has furnished the two weakly but selectively active indole alkaloids uncarine C (1) and uncarine E (2) as the major bioactive constituents in this assay.

Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity.

In a continuation of our search for potential tumor inhibitors from plants, it was found that the CH2Cl2-MeOH (1:1) extracts from Digitalis purpurea and Penstemon linarioides both showed PKCalpha-inhibitory bioactivity. Bioassay-directed fractionation of the extract from D. purpurea yielded the new, weakly active phenylethanoid glycoside 2-(3-hydroxy-4-methoxy-phenyl)-ethyl-O-(alpha-L-rhamnosyl)-(1-->3) -O- (alpha-L-rhamnosyl)-(1-->6)-4-O-E-feruloyl-beta-D-glucopy ran oside (1) together with the four known compounds calceolarioside A (2), calceolarioside B (3), forsythiaside (4), and plantainoside D (5). The extract from P. linarioides yielded the three known glycosides leucosceptoside A (6), acteoside (7), and poliumoside (8), together with the iridoid plantarenaloside (9). All of the isolated compounds, except compound 9, showed inhibitory activity against PKCalpha with IC50 values (in microM) of 125 (1), 0.6 (2), 4.6 (3), 1.9 (4), 14.8 (5), 19.0 (6), 9.3 (7), and 24.4 (8).

Three new ellagic acid derivatives from the bark of Eschweilera coriacea from the Suriname rainforest.

Bioassay-guided fractionation of Eschweilera coriacea collected in the lowland wet forest of Suriname yielded the new but only weakly active ellagic acid derivative eschweilenol A (1) and the two new but inactive ellagic acid derivatives eschweilenol B (2) and eschweilenol C (3). The four known compounds, sucrose, ellagic acid, 3-O-galloylepigallocatechin, and epigallocatechin, were also isolated. The structures of the three new compounds were determined by spectrometric methods, primarily from the HMQC, HMBC, NOESY, and ROESY NMR techniques, and chemical methods, including methylation and triethylsilylation. The location of a hydroxyl group in one ellagic acid derivative was determined by a new technique involving an NOE correlation of the protons of a triethylsilyl derivative with a proton on a neighboring aromatic ring.

Antioxidant flavonoid glycosides from Daphniphyllum calycinum.

A novel flavonoid diglycoside, 5,6,7,4'-tetrahydroxyflavonol 3-O-rutinoside (1), and a previously known compound, kaempferol 3-O-neohesperidoside (2), were isolated from an ethyl acetate extract of Daphniphyllum calycinum leaves that showed significant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay. The structure of 1 was elucidated by a combination of spectroscopic methods, and compounds 1 and 2 were found to be moderately active as antioxidants in the DPPH assay.

Anti-AIDS agents--XXVI. Structure-activity correlations of gomisin-G-related anti-HIV lignans from Kadsura interior and of related synthetic analogues.

Bioactivity-directed fractionation of an ethanolic extract of the stems of Kadsura interior led to the isolation and identification of 12 known lignans (1-12). Seven of these compounds (1, 6, 8-12) were active as anti-HIV agents. Gomisin-G (11) exhibited the most potent anti-HIV activity with EC50 and therapeutic index (TI) values of 0.006 microgram/mL and 300, respectively. Schisantherin-D (6), kadsuranin (8), and schisandrin-C (10) showed good activity with EC50 values of 0.5, 0.8, and 1.2 micrograms/mL, and TI values of 110, 56, and 33.3, respectively. Ten related synthetic biphenyl compounds, five variously substituted bismethylenedioxy, dimethoxy, and dimethoxycarbonyl isomers (18-22) and five brominated derivatives (23-27) also were evaluated for inhibitory activity against HIV-1 replication in acutely infected H9 cells. The total syntheses of two new isomers (21 and 22) are reported for the first time. The anti-HIV data indicated that the relative position and types of substituents on the phenolic hydroxy groups of either the natural lignans or the synthetic biphenyl compounds rather than the numbers of bromine(s) on the aromatic rings are of primary importance. In the cyclooctane ring of the natural lignans, the position and substitution of hydroxy groups are also important to enhanced anti-HIV activity.

Bioactive labdane diterpenoids from Renealmia alpinia collected in the Suriname rainforest.

The preservation of tropical rainforests is an important goal both for the intrinsic value of their cultural and biological diversity as well as for the well-being of the peoples who make these forests their home. In addition, tropical forests are potential sources of new pharmaceutical products that can only be found by chemical prospecting in Nature's genetically encoded combinatorial library. As part of an effort to integrate biodiversity conservation and drug discovery with economic development, we have initiated a collaborative program to discover potential pharmaceuticals in the rainforest of Suriname. The plant Renealmia alpinia (Zingiberaceae) was selected for investigation based on its ethnomedical use as a febrifuge, but testing in the yeast Sc-7 assay gave a positive response, indicative of cytotoxic activity. Using this bioassay, the two new labdane diterpense, 11-hydroxy-8(17),12(E)-labdadien-15,-16-dial 11,15-hemiacetal (1) and 16-oxo-8(17),12(E)-labdadien-15-oic acid (2), and the known diterpene, 8(17),12(E)-labdadien-15,16-dial (3), have been isolated. Their structures were elucidated by 1D and 2D NMR techniques (DEPT, COSY, HETCOR, HMBC, and NOESY) and IR, UV, and MS spectra, and the absolute stereochemistry of 1 was established by CD spectroscopy and by the formation and NMR analysis of alpha-methoxyphenylacetyl esters. The hemiacetal 1 was cytotoxic to M109 cells, with an IC50 value of 2.6 micrograms/mL.

Two new lignans, interiotherins A and B, as anti-HIV principles from Kadsura interior.

Two new lignans, interiotherins A (1) and B (2), along with two known lignans, angeloylgomisin R (3) and schisantherin D (4), were isolated from Kadsura interior. Their structures and stereochemistries were determined from spectral data. Compounds 1 and 4 inhibit HIV replication with EC50 values of 3.1 and 0.5 micrograms/mL, respectively.

Phenolic and triterpenoid glycosides from Aster batangensis.

A new phenolic glycoside, asterbatanoside A [p-hydroxyacetophenone-4-O-beta-D-xylopyranosyl-(1-->6)-beta-D- glucopyranoside], and two new triterpenoid saponins, asterbatanoside B [2 alpha,3 beta,23-trihydroxyolean-12-en-28-oic acid-28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside] and asterbatanoside C [3-O-beta-D-glucopyranosyl-2 beta,3 beta,23-trihydroxyolean- 12-en-28-oic acid-28-O-beta-D-glucopyranoside] were isolated from the roots of Aster batangensis. Their structures were determined by spectroscopic methods and chemical evidence. The total synthesis of asterbatanoside A is also reported.

Cytotoxicity and NMR spectral assignments of ergolide and bigelovin.

Two potent cytotoxic sesquiterpene lactones, ergolide (1) and bigelovin (2) were isolated from Inula hupehensis I. helianthus-aquatica and their structures and NMR data were assignment unambiguously by using a combination of one-and two-dimensional NMR techniques and computer modeling calculations.

Asteryunnanosides F and G: two new triterpenoid saponins from Aster yunnanensis.

Two new triterpenoid saponins, aster-yunnanosides F and G, were isolated from the roots of Aster-yunnanensis. Their structures were determined as oleanolic acid-28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and 3-O-beta-glucopyranosyloleanolic acid-28-O-beta-D-glucopyranosyl-(1-->6)-[alpha-L-rhamnopyranosyl-(1-->2) ]- beta-D-glucopyranoside by spectral data, especially 2D NMR analysis including COSY, HETCOR, HOHAHA, and ROESY techniques, and chemical transformation.