Neuroprotective effect of a novel Chinese herbal decoction on cultured neurons and cerebral ischemic rats.

BACKGROUND: Historically, traditional Chinese medicine has been widely used to treat stroke. Based on the theory of Chinese medicine and the modern pharmacological knowledge of herbal medicines, we have designed a neuroprotective formula called Post-Stroke Rehabilitation (PSR), comprising seven herbs - Astragalus membranaceus (Fisch.) Bunge, Salvia miltiorrhiza Bunge, Paeonia lactiflora Pall., Cassia obtusifolia L., Ligusticum chuanxiong Hort., Angelica sinensis (Oliv.) Diels, and Glycyrrhiza uralensis Fisch. We aim to examine the neuroprotective activity of PSR in vitro and in vivo, and to explore the underlying molecular mechanisms, to better understand its therapeutic effect and to further optimize its efficacy. METHODS: PSR extract or vehicle was applied to primary rat neurons to examine their survival effects against N-methyl-D-aspartate (NMDA)-elicited excitotoxicity. Whole-cell patch-clamp recording was conducted to examine the NMDA-induced current in the presence of PSR. ERK- and CREB-activation were revealed by western blot analysis. Furthermore, PSR was tested for CRE promoter activation in neurons transfected with a luciferase reporter. The protective effect of PSR was then studied in the rat middle cerebral artery occlusion (MCAO) model. MCAO rats were either treated with PSR extract or vehicle, and their neurobehavioral deficit and cerebral infarct were evaluated. Statistical differences were analyzed by ANOVA or t-test. RESULTS: PSR prominently reduced the death of cultured neurons caused by NMDA excitotoxicity in a dose-dependent manner, indicating its neuroprotective property. Furthermore, PSR significantly reduced NMDA-evoked current reversibly and activated phosphorylation of ERK and CREB with distinct time courses, with the latter's kinetics slower. PSR also triggered CRE-promoter activity as revealed by the increased expression of luciferase reporter in transfected neurons. PSR effectively reduced cerebral infarct and deficit in neurological behavior in MCAO rats when PSR decoction was administered starting either 6 days before or 6 h after onset of ischemia. CONCLUSIONS: PSR is neuroprotective both in vitro and in vivo - it protects cultured neurons against NMDA excitotoxicity, and effectively reduces ischemic injury and neurobehavioral deficit in MCAO rats in both the pre- and post-treatment regimens. The underlying neuroprotective mechanisms may involve inhibition of NMDA receptor current and activation of ERK and CREB. This study provides important preclinical data necessary for the further development of PSR for stroke treatment.

A novel antioxidant isobenzofuranone derivative from fungus Cephalosporium sp.AL031.

Bioassay-guided fractionation of metabolites from the fungus Cephalosporium sp.AL031 isolated from Sinarundinaria nitida led to the discovery of a new isobenzofuranone derivative, 4,6-dihydroxy-5-methoxy-7-methylphthalide (1), together with three known compounds: 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (2), 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (3) and 4,5,6-trihydroxy-7-methylphthalide (4). The structure of the new compound 1 was determined based on MS, 1D and 2D NMR spectral data. Compounds 1-4 showed potent antioxidant activity with EC50 values of 10, 7, 22 and 5 µM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging assay.

A novel 18-norclerodane diterpenoid from the roots of Tinospora sagittata var. yunnanensis.

A novel 18-nor-clerodane diterpenoid named sagitone (1) was isolated from the 95% ethanol extract of dry roots of Tinospora sagittata var. yunnanensis together with the five known diterpenoids columbin (2), palmatoside C (3), fibleucin (4), tinophylloloside (5) and epitinophylloloside (6). The structure of the new compound 1 was determined based on MS, IR, 1D and 2D NMR spectral data. The compounds 1-6 did not show significant cytotoxic activity against cancer cell lines K562 and HL-60.

Improving the solubility of ampelopsin by solid dispersions and inclusion complexes.

The aim of this study was to increase the solubility of ampelopsin (AMP) in water by two systems: solid dispersions with polyethylene glycol 6000 (PEG 6000) or polyvinylpyrrolidone K-30 (PVP K30) and inclusion complexes with beta-cyclodextrin (BCD) and hydroxypropyl-beta-cyclodextrin (HPBCD). The interaction of AMP with the hydrophilic polymers was evaluated by differential scanning calorimetry (DSC), Fourier transformation-infrared spectroscopy (FTIR), scanning electron microscopy (SEM). The results from DSC, FTIR and SEC analyses of solid dispersions and inclusion complexes showed that AMP might exist as an amorphous state or as a solid solution. On the other hand, the SEM images of the physical mixtures revealed that to some extent the drug was present in a crystalline form. The influence of various factors (pH, temperature, type of polymer, ration of the drug to polymer) on the solubility and dissolution rate of the drug were also evaluated. The solubility and dissolution rates of AMP were significantly increased by solid dispersions and cyclodextrin complexes as well as their physical mixtures. The improvement of solubility using polymers was in the following order: HPBCD approximately BCD>PVP K30>PEG 6000.

[Studies on the chemical constituents from the aerial parts of Breynia fruticosa].

OBJECTIVE: To investigate the chemical constituents from the aerial parts of Breynia fruticosa. METHOD: Various chromatographic techniques were employed for isolation and purification of the constituents. The structures were elucidated by chemical evidence and spectral methods. RESULT: Seven compounds were obtained and identified by spectroscopic methods and compared with authentic samples as aviculin [(+)-isolariciresinol-9'-rhamno-pyranoside], friedelan-3beta-ol, friedelin, arborinone, isoarborinol, 5-hydroxy-7,8,4'-trimethoxy flavone, 2,4-dihydroxy-6-methoxy-3-methyl-acetophenone. CONCLUSION: All compounds were firstly isolated from B. genus, furthermore, aviculin was isolated from Euphorbiaceae for the first time.

Acutissimanide, a new lignan with antioxidant activity isolated from the bark of Quercus acutissima Carruth.

Acutissimanide (1), a new lignin, together with 11 known polyphenols (2-12) were isolated from the bark of the deciduous oak tree, Quercus acutissima Carruth. The structure of compound 1 was determined using multidimensional (1)H and (13)C NMR and mass spectroscopy. The antioxidant properties of compounds 1-12 were investigated using a 1,1-diphenyl-2-picryhydrazyl radical-scavenging assay with compounds 6-11 displaying significant antioxidant activity (EC50 values of 5.2-23.7 µM). Our findings suggest the extracts of Q. acutissima Carruth are a potential source of natural antioxidant additives for use in the food and other allied industries.

A novel lignan glycoside with antioxidant activity from Tinospora sagittata var. yunnanensis.

A novel lignan glysocide, namely sagitiside A (1), together with two known ones, (+)-lyoniresinol-2α-O-ß-D-glucopyranoside (2) and (+)-5'-methoxyisolariciresinol 3α-O-ß-D-glucopyranoside (3), was isolated from the 95% ethanol extract of dry roots of Tinospora sagittata var. yunnanensis. The structure of the new compound (1) was determined based on MS, 1D and 2D NMR spectral data. Compounds 1-3 showed antioxidant activity with EC(50) values 55, 75 and 80 µM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging assay.

A new carotenoid glycoside from Rehmannia glutinosa.

A new carotenoid glycoside, namely neo-rehmannioside (1), together with five known compounds, 6-O-seco-hydroxyaeginetoyl ajugol (2), oxyrehmaionoside B (3), ajugol (4), geniposidic acid (5) and geniposide (6) was isolated from the 95% ethanol extract of dry roots of Rehmannia glutinosa. The structure of the new compound (1) was determined based on MS, IR, 1-D and 2-D NMR spectral data.

Resveratrol/phloroglucinol glycosides from the roots of Lysidice rhodostegia.

Two new phloroglucinol glycosides, lysidisides C (1) and D (2), together with two new resveratrol glycosides, lysidisides E (3) and F (4), were isolated from the n-BuOH extract of the roots of Lysidice rhodostegia. The structures were elucidated on the basis of spectroscopic and chemical evidence. The antioxidant activity of the isolates was also investigated

Two novel phloroglucinol derivatives from Euphorbia ebracteolata hayata.

Two new phloroglucinol derivatives, named ebracteolatain A and ebracteolatain B, along with three known phloroglucinol derivatives were isolated from Euphorbia ebracteolata Hayata., and their structures were elucidated as 3,3'-diacetyl-2,4'-dimethoxy-2',4,6,6'-tetrahydroxy-5'-methyl diphenylmethane (1) and 1-[3,5-bis-(3-acetyl-2,6-dihydroxy-4-methoxy-benzyl)-2,4,6-trihydroxy-phenyl]-ethanone (2) on the basis of spectroscopic techniques and chemical methods.

Yuexiandajisu D, a novel 18-nor-rosane-type dimeric diterpenoid from Euphorbia ebracteolata Hayata.

Yuexiandajisu D, a novel 18-nor-rosane-type dimeric diterpenoid, was isolated from the roots of Euphorbia ebracteolata Hayata. Its structure was elucidated as 6,3':7,2'-diepoxy-di-2,3-dihydroxy-18-nor-ros-1(10),2,4,15-tetraene by spectroscopic techniques (HSQC, HMBC, DQF-COSY, TOCSY, NOESY) and chemical methods. Yuexiandajisu D showed moderate cytotoxic activity against cancer cell lines on HCT-8 and Bel-7402, with IC50 values of 2.66 and 3.76 microM, respectively.

Five new cytotoxic triterpenoid saponins from the roots of Symplocos chinensis.

Five new triterpenoid saponins, named symplocososides G-K, were isolated from the roots of Symplocos chinensis. Their structures were elucidated by spectral and chemical methods as symplocososide G, 3beta-O-{[beta- D-glucopyranosyl(1-->2)][alpha-L-arabinofuranosyl(1-->4)]-beta-D-(3-O-acetyl)-glucuronopyranosyl}-21beta- O-[(2 Z)-3,7-dimethyl-2,6-octadienoyl]-22 alpha-O-(2-methylbutanoyl)-R1-barrigenol, symplocososide H, 3beta-O-{[beta-D-glucopyranosyl(1-->2)][alpha-L-arabinofuranosyl(1-->4)]- beta-D-(3-O-acetyl)-glucuronopyranosyl}-21beta-O-[(2E)3,7-dimethyl-2,6-octadienoyl]-22alpha-O-(2-methylbutanoyl)-R1-barrigenol, symplocososide I, 3beta-O-{[beta-D-glucopyranosyl(1-->2)][ alpha-L-arabinofuranosyl(1-->4)]-beta-D-(3- O-acetyl-6-O-methyl)-glucuronopyranosyl}-21beta-O-[(2 Z)3,7-dimethyl-2,6-octadienoyl]-22alpha-O-(2-methylbutanoyl)-R1-barrigenol, symplocososide J, 3 beta-O-{[ beta-D-glucopyranosyl(1-->2)][alpha-L-arabinofuranosyl(1-->4)]-beta-D-(3- O-acetyl)-glucuronopyranosyl}-21beta-O-[(2 Z)3,7-dimethyl-2,6-octadienoyl]-22alpha-O-benzoyl-R1-barrigenol, and symplocososide K, 3beta-O-{[beta-D-glucopyranosyl (1-->2)][alpha-L-arabinofuranosyl(1-->4)]- beta-D-(3-O-acetyl-6-O-methyl)-glucuronopyranosyl}-21beta-O-[(2Z)3,7-dimethyl-2,6-octadienoyl]-22alpha-O-benzoyl-R1-barrigenol. Symplocososides G-K showed significant cytotoxicity against cancer cell lines KB, HCT-8, Bel-7402, BGC-823 and A549 with IC50 values ranging from 0.82 microM to 5.09 microM, except for symplocososide I against cancer cell lines KB, BGC-823, A549 and symplocososide K against cancer cell line BGC-823 with IC50 values >10.00 microM.

Iridoid glycosides and grayanane diterpenoids from the roots of Craibiodendron henryi.

Four new iridoid glycosides, 10-O-trans-p-coumaroylscandoside (1), 10-O-cis-p-coumaroylscandoside (2), 10-O-trans-p-coumaroyldesacetyl asperulosidic acid (3), and 10-O-cis-p-coumaroyldesacetyl asperulosidic acid (4), and two new grayanane diterpenoids, 14beta-O-(2S,3S-nilyl)-2alpha,3beta,5beta,6beta,16alpha-pentahydroxygrayanane (5) and 14beta-O-(2S,3S-nilyl)-2alpha,3beta,5beta,6beta,16alpha-pentahydroxygrayan-10(20)-ene (6), have been isolated from Craibiodendron henryi. The structures of these compounds were determined by chemical and spectroscopic methods including 1H-1H COSY, HMQC, HMBC, and NOESY experiments. Antioxidant activities and vasodilator effects of these compounds were assessed.