A new cyclic peptide from the fibrous root of Pseudostellaria heterophylla.

A new cyclic peptide, Pseudostellarin K (1), together with thirteen known compounds, including two cyclic peptides (2 and 3), one ß-carboline alkaloid (4), two amides (5 and 6), three phenylpropanoids (7-9) and other compounds (10-14), were isolated from the fibrous root of Pseudostellaria heterophylla. Their structures were elucidated by extensive spectroscopic analysis. Compounds 1, 4-6, 10 were isolated from the genus pseudostellaria for the first time. All compounds were evaluated for cytotoxic activities against MCF-7, A549, HCT-116 and SGC-7901 cell lines by MTT assay. Unfortunately, all these compounds displayed weak cytotoxic activities.

Xianglian Pill ameliorates antibiotic-associated diarrhea by restoring intestinal microbiota and attenuating mucosal damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP), a traditional Chinese pharmaceutical preparation for the treatment of gastrointestinal disease, possessing anti-inflammatory, anti-microbial and analgesic activities, may represent a promising candidate for the treatment of antibiotic-associated diarrhea (AAD). AIM OF THE STUDY: This study aimed to unravel the underlying mechanism of XLP on the amelioration of AAD. MATERIALS AND METHODS: AAD was induced by intragastric administration of a mixture of cefuroxime and levofoxacin (300 mg/kg. bw + 200 mg/kg. bw) for five consecutive days. Then AAD mice were treated with XLP at the dose of 500, 1000 and 2000 mg/kg. bw, respectively for 5 days. The physical manifestations, diarrhea status were monitored during the drug delivery. Histopathology of colon, intestinal microbiota, inflammatory cytokines, tight junction protein and short chain fat acids (SCFAs) were determined. RESULTS: Mice received cefuroxime and levofoxacin for 5 days developed medium to severe diarrhea. XLP treatment, however, mitigated the diarrhea status. Further evaluation revealed that XLP promoted the recovery of mucosa, maintained the integrity of tight junction, attenuated the inflammatory disorders, restored intestinal microbiota and increased SCFAs level in feces. CONCLUSION: XLP ameliorates AAD by restoring intestinal microbiota and attenuating mucosal damage.

Inulin as carriers for renal targeting delivery of ferulic acid.

Inulin (IN), as a classic diagnostic for determination of glomerular filtration rate, reached high concentration in kidney. Introducing drug into IN derivatives may be a new method to target kidney for drug delivery. To test the hypothesis, ferulic acid (FeA) was conjugated into IN by ester bond and amide bond (ethylenediamine as spacer), respectively, and the two FeA-IN conjugations, inulin ferulate (IN-FeA) and inulin ethylenediamine ferulate (IN-EDA-FeA) were obtained. NMR spectrum was involved to characterize the conjugations. The FeA in vitro release profiles were tested in mice plasma and renal homogenate. Finally, the biodistribution test was performed to evaluate their renal-targeting ability. Both IN-FeA and IN-EDA-FeA showed a higher release rate of FeA in renal homogenate than in mouse plasma suggesting the conjugates are relatively stable in plasma and more likely FeA release in kidney. The renal area under the curve (AUC) for IN-FeA and IN-EDA-FeA were 539.6 ± 107.9 and 558.5 ± 131.6 µg h/mL, respectively, which were 4.47 and 4.62 times of 120.8 ± 18.1 µg h/mL for free FeA. Meanwhile, significant smaller FeA accumulation in other organs was observed. These data indicated that IN-FeA and IN-EDA-FeA effectively targeted kidney for FeA delivery.

Recent Advances in the Catalytic Asymmetric Reactions of Oxaziridines.

Oxaziridines have emerged as powerful and elegant oxygen- and nitrogen-transfer agents for a broad array of nucleophiles, due to the remarkably high and tunable reactivities. However, the asymmetric catalysis involving oxaziridines is still in its infancy. Herein, this review aims to examine recent advances in the catalytic asymmetric transformations of oxaziridines, including oxidation, amination, cycloaddition and deracemization.

Recent advances in N-heterocyclic carbene catalyzed achiral synthesis.

N-Heterocyclic carbenes (NHCs) have emerged as powerful and elegant organocatalysts in a variety of newly developed and unprecedented enantioselective transformations due to their unique umpolung capacity. As a supplement to conventional enantioselective organocatalysis, NHC-induced non-asymmetric catalysis has gradually attracted much interest in recent years. Herein, this review aims to reveal the recent developments in NHC-promoted non-asymmetric umpolung transformations resulting in the expeditious construction of versatile achiral natural heterocycles, carbocycles and acylated products.

Expeditious assembly of fused dihydropyranones via N-heterocyclic carbene-catalyzed tandem Michael addition/lactonization.

A convergent and efficient NHC-catalyzed enantioselective tandem Michael addition/lactonization sequence of ynals with 1,2-dione as the dual-nucleophile is disclosed. This straightforward strategy expeditiously assembles the synthetically and pharmaceutically valuable optically active fused dihydropyranones in good to high yields (70-88%) and with excellent enantioselectivities (92-99% ee).

Saponin rich fractions from Polygonatum odoratum (Mill.) Druce with more potential hypoglycemic effects.

AIMS: The root of Polygonatum odoratum (YuZhu), also a medicinal food has long been used for the treatment of diabetes. The objective of the study was to characterize the anti-diabetic active fractions or compounds in this herb. MATERIALS AND METHODS: Fractions with a different polarity were prepared by solvent extraction and macroporous absorptive resin (D101) column and their anti-diabetic potentials were evaluated by glucose uptake in HepG2 cells and STZ-induced diabetic rats. In addition, α-glycosidase inhibitory activities of active fractions were measured in vitro and chemical compositions including saponin, total flavonoids and total sugar in the fractions were determined. RESULTS: The n-buthanol fraction, a saponin-rich fraction obtained by partitioning the ethanol extract with n-buthanol after petroleum ether and acetic ether showed the highest anti-diabetic potential in glucose uptake in HepG2 cells followed by acetic ether fraction which was rich in flavonoids. Further fractionation the saponin-rich fraction using macroporous resin column (D101), polysaccharide, flavonoid and saponin rich fractions were obtained by elution with water, 40% and 60% ethanol, respectively and their anti-diabetic potentials proved by glucose uptake test in HepG2 cells and STZ-induced diabetic rats were in the order of saponin rich fraction>flavonoid rich fraction>polysaccharide rich fraction. Long-term therapy test (60d) in severe diabetic rats indicated that saponin-rich fraction significantly ameliorated clinical symptoms of diabetes including the elevated blood glucose, body weight loss as well as the increased food and water intake while flavonoid-rich fraction was more potential than saponin-rich fraction to increase superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) level in rat plasma. Additionally, saponin-rich fraction and flavonoid-rich fraction showed α-glycosidase inhibitory activity with IC(50) value of 2.05±0.32 and 3.92±0.65mg/ml, respectively. CONCLUSION: The results suggested that saponin in this herb was more important than flavonoid in exhibiting anti-diabetic activity and flavonoid contributed more to anti-oxidant activity in vivo.

Separation of two constituents from purple sweet potato by combination of silica gel column and high-speed counter-current chromatography.

It is known that the choice of solvent system for high speed counter-current chromatography separation is of utmost importance. In this study, a simple and rapid thin layer chromatograph coupling with fluorometric (TLC-F) method has been used to determine the partition coefficient of target compounds in HSCCC solvent system. Two components, 6,7-dimethoxycoumarin and 5-hydroxymethyl-2-furfural were successfully separated from purple sweet potato extracts by successive sample injection for the first time, using n-hexane-ethyl acetate-methanol-water (1:2:1:1, v/v/v/v) as the solvent system. Additionally, statistical analysis showed that there was no significant difference in partition coefficient obtained by the TLC-F method and by HPLC, which demonstrated the usefulness of TLC-F method.

Synthesis and antimicrobial activity of 8-alkylberberine derivatives with a long aliphatic chain.

The compounds 8-ethyl- (2), 8-butyl- (3), 8-hexyl- (4), 8-octyl- (5), 8-decyl- (6) and 8-dodecylberberine chloride (7) were synthesized and tested for their antimicrobial activity in vitro to evaluate structure-activity relationships. Substitution of the alkyl groups at C-8 led to significant changes in the antimicrobial activity. All compounds were more potent against the tested microorganisms than berberine (1), especially against Gram-positive bacteria. The antimicrobial activity increased as the length of aliphatic chain was elongated and then decreased gradually when the alkyl chain exceeded eight carbon atoms. 8-octylberberine (5) displayed the highest antimicrobial activity of all compounds. The toxicity of compounds 2 - 7 was stronger than that of 1. However, upon elongating the aliphatic chain, the toxicity decreased gradually.

Size of the aliphatic chain of sodium houttuyfonate analogs determines their affinity for renin and angiotensin I converting enzyme.

Sodium houttuyfonate analogs (SHAs), CH(3)-(CH(2))(n)-CO-CH(2)-CH(OH)SO(3)Na, (n=6-14) were synthesized and their molecular interactions with renin and angiotensin I converting enzyme (ACE) studied using fluorescence quenching techniques. Unlike renin, inhibition of ACE activity was not directly proportional to the aliphatic chain length of SHAs. Ability of SHAs to inhibit enzyme activities and quench protein fluorescence was greater with renin than with ACE. The presence of an ACE substrate (angiotensin I) did not reduce quenching ability of SHAs, suggesting that enzyme-inhibitor interactions did not involve the active site or the substrate was displaced by inhibitor molecules. The results showed that renin is a more sensitive target than ACE for the potential antihypertensive ability of SHAs.

Hypoglycemic and hypocholesterolemic effects of Coptis chinensis franch inflorescence.

Hypocholesterolemic and hypoglycemic activities of Coptis chinensis franch inflorescence (Coptis inflorescence) were studied using animal models. Serum total and LDL cholesterol of rats fed a diet containing 1% cholesterol and 0.5% cholic acid increased, as compared with those of rats fed a normal diet. The level of total and LDL cholesterol were reduced markedly in a dose dependent manner, in rats given Coptis inflorescence extract orally at doses of 0.25, 0.5 g/kg.day for 4 weeks. In diabetic rats induced by alloxan, Coptis inflorescence extract showed a significant (p < 0.05) blood sugar lowering activity at all experimented doses (0.125, 0.25 and 0.5 g/kg.day). The highest reduction of blood sugar was about 58% when the rats were given Coptis inflorescence extract orally at a dose of 0.5 g/kg.day for 3 weeks. The 100 g dried water extract of Coptis inflorescence contained 8.11 g total alkaloid, 3.34 g berberin, 1.08 g palmatine and 0.66 g jatrorrhizine, which had long been identified as active compounds in Coptis chinensis franch root (Coptis root). Thus, the results suggest that Coptis inflorescence would be effective in the prevention and management of coronary artery disease by lowering serum cholesterol and blood sugar.

Kinetics of renin inhibition by sodium houttuyfonate analogs.

A series of chemical analogs of sodium houttuynin, the major constituent in the volatile oil of the perennial plant Houttuynia cordata Thunb, were studied for in vitro inhibition of renin activity. At a reaction concentration of 0.196 mg/ml, each of the sodium houttuynin analogs (SHAs), viz., hexanoyl acetal sodium sulfite (SHA-C6), octanoyl acetal sodium sulfite (SHA-C8), decanoyl acetal sodium sulfite (SHA-C10), dodecanoyl acetal sodium sulfite (SHA-C12) and tetradecanoyl acetal sodium sulfite (SHA-C14), inhibited renin activity up to 34.37%, 44.03%, 79.33%, 83.04%, and 93.19% respectively. The IC50 values (the concentration of SHA that is required to reduce renin activity by 50%) of the most potent analogs were 273, 195, and 44 microM for SHA-C10, SHA-C12, and SHA-C14 respectively. Kinetic studies with SHA-14 indicated a linear mixed-type of enzyme inhibition with a Ki value of 45.35 microM. It was concluded that the SHAs constitute potentially useful ingredients for the formulation of antihypertensive products.

Restriction of the in vitro formation of angiotensin II by leucinyl-arginyl-tryptophan, a novel peptide with potent angiotensin I-converting enzyme inhibitory activity.

Leucinyl-arginyl-tryptophan (LRW) is a new peptide inhibitor of the angiotensin converting enzyme (ACE) that was previously predicted through quantitative structure-activity relationship modeling. LRW inhibited ACE activity in a competitive manner with a higher K(m) value in the presence of the peptide, and the in vitro formation of angiotensin II by ACE was significantly reduced in the presence of LRW up to 60 min of incubation time.