ABSTRACT
A novel pair of Z/E isomeric compounds with unprecedented carbon skeleton were isolated from an aqueous extract of Aspongopus chinensis Dallas by macroporous resin, silica gel, and semi-preparative high performance liquid chromatography (HPLC). Their structures were identified by nuclear magnetic resonance (NMR), Infrared spectroscopy (IR), Mass spectroscopy (MS) and other spectroscopic methods as (Z)-3-(but-1″-en-1″-yl)-1-(2ʹ-hydroxyethyl)-4-propylpyridin-1-ium, namely aspongopyridine A, and (E)-3-(but-1″-en-1″-yl)-1-(2ʹ-hydroxyethyl)-4-propylpyridin-1-ium, namely aspongopyridine B, respectively. Besides, the anti-inflammatory, anti-tumor, acetylcholinesterase inhibition and butyrylcholinesterase inhibition activities of the compounds 1 and 2 were evaluated. The results showed that compounds 1 and 2 have no anti-inflammatory, anti-tumor, and butyrylcholinesterase inhibition activities instead of weak acetylcholinesterase inhibition activity.
ABSTRACT
OBJECTIVE Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol is a com?pound isolated from Magnolia officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. METHODS ① Male SD rats (220 g) were randomly divided into 5 groups (n=10): the normoxia group, the hypoxia group, the hypoxia plus Magnolol (10 and 20 mg·kg-1·d-1) group, and the vehicle group. Rats in the normoxia group were kept in a normoxia environment for 4 weeks, while rats in the hypoxia group were kept in a hypoxic chamber (10％ O2). The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg-1 (ip) once a day for 4 weeks. At the end of 4 weeks, the heart function was assessed by Doppler echocardiography, and then the rats were anesthetized with sodium pentobarbital (30 mg·kg-1, ip). The RVSP was measured by the right heart catheterization method. The heart tissues were collected and dissected to calculate the index of RV remodeling (RV/LV+IVS, RV/tibial length, or RV/body weight). Part of the RV samples was fixed with 4％paraformaldehyde for morphological analysis, while other samples were frozen at-80℃for molecular studies (measurements of ANP, BNP,α-SMA, and col?lagen Ⅰ/Ⅲ mRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels). ② To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis, H9c2 or cardiac fibroblasts were divided into 7 groups: the control group, cells were cultured under normal conditions; the hypoxia group, cells were cultured under hypoxic condition (3％ O2);the hypoxia plus magnolol 10 mg·kg-1 group, magnolol10μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg-1 group, magnolol 20μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group, TG-101348 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group, JSI-124 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group, an equal volume of vehicle (DMSO) was added to the culture medium before the hypoxia treatment. At the end of the experiments, the cells were collected for morphological and molecular analysis. RESULTS In vivo, male Sprang-Daley rats were exposed to 10％ O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of RV remodeling index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3％ O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagenⅠ, collagenⅢandα-SMA). Administration of mag?nolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.
ABSTRACT
Antithrombus is one of the effective methods to prevent and treat cardiovascular diseases. Based on the theory of traditional Chinese medicine,the author's previous research and relevant literature,it was found that the alkaloids in Houttuynia cordata has potential antithrombotic effect. However,the pharmacological substance basis and antithrombotic mechanism of H. cordata have not been clarified. In this study,molecular docking was used for virtual screening of antithrombotic alkaloids from H. cordata. Seventy alkaloids selected from H. cordata were screened in the docking ligand data-base with teen thrombosis targets with known crystal structures as the receptors. In addition,the small-molecule approved or to be approved drugs of targets from Drug Bank database were set as a positive reference with minimum score(S value) of each target's approved or to be approved drugs as threshold. The Dock module in Molecular Operating Environment(Version 2016) software was applied to screen the potential active compounds which their scores(S value) were lower than the minimum score of reference. At last the mechanism of antithrombotic effect was preliminarily revealed by compared the main active sites of the test alkaloids with original ligands and references. This study provided some useful information to development of antithrombus drugs.
Subject(s)
Alkaloids , Pharmacology , Fibrinolytic Agents , Pharmacology , Houttuynia , Chemistry , Molecular Docking Simulation , Phytochemicals , PharmacologyABSTRACT
Sixteen lignanoids were isolated from an aqueous extract of the commonly used Chinese traditional medicine Dangshen, the dried roots of Codonopsis pilosula, by using a combination of various chromatographic techniques, including silica gel, macroporous adsorbent resin, MCI resin, sephadex LH-20, and reversed phase semi-preparative HPLC. On the basis of spectral data analysis, their structures were elucidated and identified as (-)-(7R, 7'R, 8R, 8'S)-4, 4'-dihydroxy-3, 3', 5, 5', 7-pentamethoxy-2, 7'-cyclolignane (1), (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranosyl-(1"'→2")-β-D-glucopyranoside (2), (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol (3), (+)-(7S, 8R)-dehydrodiconiferyl alcohol (4), (+)-balanophonin (5), (+)-demethoxypinoresinol (6), (+)-pinoresinol (7), (+)-epipinoresinol (8), (-)-syringaresinol (9), (-)-medioresinol (10), (-)-lariciresinol (11), (-)-secoisolariciresinol (12), (-)-ent-isolariciresinol (13), (+)-(7S, 8S)-3-methoxy-3', 7-expoxy-8, 4'-neolignan-4, 9, 9'-triol (14), (+)-(7S, 8R)-3', 4-dihydroxy-3-methoxy-8, 4'-neolignan (15), and (-)-(7R, 8R)-3', 4-dihydroxy-3-methoxy-8, 4'-neolignan (16). All these compounds were isolated from C. pilosula for the first time, while compound 1 is a new natural product of 2, 7'-cyclolignan and 2 is a new 4', 7-epoxy-8, 3'-neolignan diglucoside. Compound 12 showed activity against Fe2+-cysteine induced rat liver microsomal lipid peroxidation with an inhibition ratio of (63.4±8.3)% at 1×10-5 mol·L-1.
ABSTRACT
Eighteen compounds were isolated by a combination of various chromatographic techniques including column chromatography over macroporous resin, MCI gel, silica gel, and sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by spectroscopic data analysis as adinoside A (1), stryspinoside (2), benzyl alcohol beta-glucopyranoside (3), benzyl 2-o-beta-D-glucopyranosyl-2,6-dihydroxybenzoate (4) , gentisic acid 2-O-beta-D-glucopyranoside (5), eugenyl beta-D-glucopyranoside (6) , eugenyl-P-xylopyranosyl-(1-->6)-beta-glucopyranoside (7), (-)-lyoniresinol 9-O-fP-D-glucopyranoside (8) , (+)-lyoniresinol 9-O-beta-D-glucopyranoside (9) , apigenin-7-O-L-rhamnopyranoside (10), luteolin-3 '-O-L-rhamnoside (11) , ursolic acid (12) , beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate (13), abscisic acid (14), guanosine (15), 5-methyluracil (16), trans-cinnamic acid (17), and 4-hydroxybenzaldehyde(18). These compounds were obtained from this plant for the first time.
Subject(s)
Benzaldehydes , Flowers , Chemistry , Gentisates , Glucosides , Hydroxybenzoates , Lonicera , Chemistry , Luteolin , Thymine , TriterpenesABSTRACT
Objective To analyze the effect of endoscopic ultrasonography guided interstitial iodine 125 seed implantation in treatment of unresectable pancreatic cancer and migration of implanted seeds. Methods A total of 17 patients with unresectale pancreatic cancer underwent endoscopic ultrasono- graphy guided interstitial iodine seeds implantation.The therapeutic plan system was used to calculate the number of implanted seeds before procedure.The patients were followed-up monthly and tumor alteration and migration number or loss of implanted seeds were investigated by abdominal plain film.Results Io- dine 125 seeds were successfully implanted in all patients under endoscopic ultrasonography. Before treatment,the median size of tumor was 5.4cm(ranged from 3.7 to 9.0cm)and the number of implan- ted seeds was 27,with median 14(ranged from 7 to 24)once for 2 times.The mean radioactivity per seed was(0.6894?0.016)mCi.The patients were follow-up of 2 to 14 months(mean 4.8 months). Three months after implantation,partial relief was observed in 5 patients(29.4%),no change in 7 patients(41.2%)and progressing in 5 patients(29.4%).The implanted seeds migrated into spleen in 1 case, into liver in 1 case and into bowel in 3 cases.The seeds loss was found in 4 patients.Conclusions Endoscopic uhrasonography guided interstitial implantation of iodine 125 seeds in treatment of advanced pancreatic cancer may significantly inhibit tumor growth,and attention must be paied on the complications of seeds migration or loss,which will impair the nearby organs because of its radioactivity.