Chemical constituents from the rhizome of Polygonum paleaceum and their antifungal activity.

A new compounds neopaleaceolactoside (1), along with nine known compounds phyllocoumarin (2), quercetin (3), quercitrin (4), quercetin-3-methyl ether (5), vincetoxicoside B (6), isoquercitrin (7), kaempferol (8), (-)-epicatechin (9), and chlorogenic acid (10), was isolated from Polygonum paleaceum Wall. Their chemical structures were established based on one-dimensional and two-dimensional nuclear magnetic resonance techniques, mass spectrometry and by comparison with spectroscopic data reported. Some selected compounds were screened for their antifungal activity. Quercetin (3), vincetoxicoside B (6), kaempferol (8), and (-)-epicatechin (9) showed synergistic antifungal activities with the FICI values <0.5. A preliminary structure-activity relationship could be observed that free 3-OH in the structure of flavonoids was important for synergistic antifungal activity.

Trachelogenin, a novel inhibitor of hepatitis C virus entry through CD81.

Although much progress has been made in antiviral agents against hepatitis C virus (HCV) in recent years, novel HCV inhibitors with improved efficacy, optimized treatment duration and more affordable prices are still urgently needed. Here, we report the identification of a natural plant-derived lignan, trachelogenin (TGN), as a potent entry inhibitor of HCV without genotype specificity, and with low cytotoxicity. TGN was extracted and purified from Caulis trachelospermi, a traditional Chinese herb with anti-inflammatory and analgesic effects. A crucial function of TGN was the inhibition of HCV entry during a post-binding step without affecting virus replication, translation, assembly and release. TGN blocked virus infection by interfering with the normal interactions between HCV glycoprotein E2 and the host entry factor CD81, which are key processes for valid virus entry. In addition, TGN diminished HCV cell-to-cell spread and exhibited additional synergistic effects when combined with IFN or telaprevir. In conclusion, this study highlights the effect of a novel HCV entry inhibitor, TGN, which has a target that differs from those of the current antiviral agents. Therefore, TGN is a potential candidate for future cocktail therapies to treat HCV-infected patients.

Constituents from the Roots of Actinidia chinensis and Their Cytochrome P450 Enzyme Inhibitory Activities.

A newly discovered triterpenoid, (2α,3ß)-2,3,23-trihydroxyurs-13(18)-en-28-oic acid (1), along with twelve known compounds (2 - 13), were isolated from the roots of Actinidia chinensis Planch (Actinidiaceae). Their chemical structures were determined by 1D- and 2D-NMR spectra and mass spectrometry (MS). The crude extracts and six main constituents (8 - 13) were tested for cytochrome P450 (CYPs) enzyme inhibitory activity. The results showed that, except for compound 8, compounds 9 - 13 had different inhibitory effects on the cytochrome P450 (CYPs) enzyme, and compound 9 significantly inhibited the catalytic activities of CYP3A4 to < 10% of its control activities.

[Chemical Constituents from Polygonum paleaceum].

Objective: To isolate and identify the chemical constituents from Polygonum paleaceum. Methods: Chemical constituents were isolated and purified by column chromatography on silica gel,Sephadex HL-20 and macroporous resin etc. The chemical structures were identified by MS,NMR and spectral analysis. Results: Ten compounds were isolated and their structures were elucidated as ethyl chlorogenate( 1),methyl chlorogenate( 2), kaempferol-3-O-α-L-rhamnopyranoside( 3), (-)-epicatechin( 4), paleaceolactoside( 5), protocatechuic acid( 6), kaempferol( 7), gallic acid( 8), chlorogenic acid( 9) and isoquercitrin( 10). Conclusion: Compounds 1,3,6,7 and 10 are isolated from this plant for the first time.

Three new compounds from Arnebia euchroma.

A new naphthoquinone dimer, arnebiabinone (1), a new phenolic compound, ethyl 9-(2',5'-dihydroxyphenyl) nonanoate (2), and a new natural product, octyl ferulate (3), were isolated from the EtOH extract of dried roots of Arnebia euchroma (Royle) Johnst. Their structures were elucidated on the basis of chemical reaction and spectral analysis.

[Study on the flavonoids constituents of Trachelospermum jasminoides].

OBJECTIVE: To study the flavonoids constituents of Trachelospemum jasminoides. METHODS: The compounds were separated and purified by column chromatography with silica gel, and identified by IR, MS, NMR and 2D-NMR. RESULTS: Six flavonoids were identified as apigenin (I), apigenin 7-O-beta-glucoside (II), apigenin 7-O-beta-neospheroside (III), luteoloside (IV), narngin (V) 6,8-di-C-glucopyanosylapigenin (VI), respectively. CONCLUSION: Compounds V and VI are isolated from this plant for the first time.

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A.

BACKGROUND: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. OBJECTIVE: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. METHODS: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. RESULTS: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26µM and 1.10µM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. CONCLUSION: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

Alkaloids from Corydalis saxicola and their anti-hepatitis B virus activity.

Eight protoberberine-type alkaloids and two indole alkaloids were isolated from the MeOH extracts of the herb Corydalis saxicola Bunting (Papaveraceae). Their structures were identified as dehydrocavidine (1), dehydroapocavidine (2), dehydroisoapocavidine (3), berberine (4), dehydroisocorypalmine (5), coptisine (6), tetradehydroscoulerine (7), berbinium (8), 1-formyl-5-methoxy-6-methylindoline (9), and 1-formyl-2-hydroxy-5-methoxy-6-methylindoline (10). Compounds 3, 9, and 10 are new alkaloids. All compounds were tested for anti-HBV activity against the 2.2.15 cell line in vitro. Dehydrocavidine (1), dehydroapocavidine (2), and dehydroisoapocavidine (3) exhibited inhibitory activity against HBsAg and HBeAg, but no cytotoxicity against the 2.2.15 cell line.

A new quinazolinedione alkaloid from the fruits of Evodia officinalis.

A new quinazolinedione alkaloid, wuchuyuamide IV (1) was isolated from the fruits of Evodia officinalis.1 showed moderate cytotoxicity against Hela and HT1080 cell lines.

[Aerobic Denitrification and Microbial Community Shift in SBR Bioaugmented with Strains YH01 and YH02].

The enhanced aerobic denitrification capability of the mixed strains YH01+YH02 in utilizing potassium nitrate, and the dynamic changes in the microbial community component during the period of operation, were evaluated. The microbial community in different stages of the SBR was analyzed by using high-throughput sequencing technology after inoculation with YH01+YH02. The results showed that the NO3--N, TN, and COD removal efficiencies increased by 12.1%, 9.2%, and 9.4%, respectively. The relative abundances of the microbes in the microbial community increased at the genus level, and the diversity in the microbial community decreased after enhancement. Principal component analysis and UPGMA analysis revealed that the period of SBR operation was roughly divined into four phases. The relative abundances of Delftia and Acidovorax increased during the period of operation, and YH01+YH02 exhibited excellent compatibility with the SBR ecosystem and played an important part in aerobic denitrification.

A new bisxanthone from Hypericum japonicum.

A new bisxanthone, named jacarelhyperols D (1), was isolated from the whole plant of Hypericum japonicum. Its chemical structure was elucidated as 6-[1',5',6'-trihydroxy-2''-(alpha-hydroxy-alpha-methyl)ethyl-3'',4''-dihydrofuran (2'',3'',3',4') xanthone-3''-oxyl]-1,3,5-trihydroxy-xanthone on the basis of spectroscopic analysis.

[Studies on the separation and purificaton of pumiloside from Nauclea officinalis by macroreticular resin].

OBJECTIVE: To investigate the technological parameters and the process for separation and purification of pumiloside (PML) from Nauclea officinalis Pierrc ex Pitard by macroreticular resin. METHODS: PML was extracted by hot water, and the content of PML was determinated by HPLC method. The static capacity absorption, static elution ratios of five types of resin were studied respectively, and were compared to evaluate their absorption and desorption effect to PML. And then the absorption capacity, elution solution and elution volume of the AB-8 resin were researched to set up the optimum separation process for PML. Finally, PML was recrysallized from MeOH and identified by spectra analysis. RESULTS: The AB-8 resin had the best absorptive and separative properties to PML. The dynamic absorption ratio was 2.44 mg/g. The applicable process was as follows: the water extracted solution of Nauclea officinalis flow through the resin column repeatedly, after being eluted with 6BV of distilled water, the resin column was eluted with 4BV 30% ethanol, the 30% ethanol fraction was combined and the solvent was recovered in vacuum. The precipitation was filtered and recrysallized from MeOH to give pure PML. The yield of PML was 75.1%, and the product purity was up to 99.5%. CONCLUSION: AB-8 resin shows better comprehensive absorption property. It can be used for separation and purification of PML from Nauclea officinalis successfully.

[Study on chemical constituents in rhigome of Ervatamia hainanensis].

OBJECTIVE: To investigate the chemical constituents of the rhizome of Ervatamia hainanensis. METHOD: The solvent extraction and silica column chromatography were used to separate the chemical constituents, and their structures were identified by physico chemical properties and spectra analysis. RESULT: Twelve compounds were isolated and their structures were identified as voacangine (1), ibogaine (2), ibogamine (3), coronaridine (4), 19-heyneanine (5), 19-epi-heyneanine (6), 3-hydroxyl coronaridine (7), coronaridine hydroxyindolenine (8), 3-(2-oxopropyl) coronaridine (9), vobasine (10), alpha-amyrin (11), alpha-amyrin acetate (12). CONCLUSION: Compounds 1, 2, 6, 11 and 12 were first found from this plant.

Monomeric and dimeric ent-kauranoid-type diterpenoids from rabdosia japonica and their cytotoxicity and anti-HBV activities.

Two new ent-kauranoid-type diterpenoids (1 and 2) and one new rare dimer of ent-kauranoids (3) with a cyclobutane ring by a [2+2] cycloaddition, together with nine known diterpenoids (4-12) were obtained from the aerial parts of Rabdosia japonica. Their chemical structures were established by 1D and 2D NMR techniques and mass spectrometry and by comparison with spectroscopic data reported. All ent-kauranoids were test for their cytotoxic effects against A549, HCT116, CCRF-CEM and HL-60 tumor cell lines. Compounds 1, 2, 4, 5, 7, 10 and 12 showed potent and selective cytotoxicity. In addition, some selected ent-kauranoids were test for their anti-HBV activities, and the results showed compound 8 had inhibitory effect on HBsAg with a 59% inhibition ratio at the concentration of 20µg/mL.

Antifungal activities and action mechanisms of compounds from Tribulus terrestris L.

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We used bioassay-guided fractionation to have isolated eight steroid saponins from Tribulus terrestris L., which were identified as hecogenin-3-O-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside (TTS-8), tigogenin-3-O-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside (TTS-9), hecogenin-3-O-beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside (TTS-10), hecogenin-3-O-beta-D-xylopyranosyl (1-->3)-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside (TTS-11), tigogenin-3-O-beta-D-xylopyranosyl (1-->2)-[beta-D-xylopyranosyl (1-->3)]-beta-D-glucopyranosyl (1-->4)-[alpha-L-rhamnopyranosyl (1-->2)]-beta-D-galactopyranoside (TTS-12), 3-O-[beta-D-xylopyranosyl (1-->2)-[beta-D-xylopyranosyl (1-->3)]-beta-D-glucopyranosyl (1-->4)-[alpha-L-rhamnopyranosyl (1-->2)]-beta-D-galactopyranosyl]-26-O-beta-D-glucopyranosyl-22-methoxy-(3beta,5alpha,25R)-furostan-3,26-diol (TTS-13), hecogenin-3-O-beta-D-glucopyranosyl (1-->2)-[beta-D-xylopyranosyl (1-->3)]-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside (TTS-14), tigogenin-3-O-beta-D-glucopyranosyl (1-->2)-[beta-D-xylopyranosyl (1-->3)]-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside (TTS-15). The in vitro antifungal activities of the eight saponins against five yeasts, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Cryptococcus neoformans were studied using microbroth dilution assay. In vivo activity of TTS-12 in a Candida albicans vaginal infection model was studied in particular. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and Cryptococcus neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against Candida albicans (MIC(80) = 10 and 2.3 microg/mL) and Cryptococcus neoformans (MIC(80) = 1.7 and 6.7 microg/mL). Phase contrast microscopy showed that TTS-12 inhibited hyphal formation, an important virulence factor of Candida albicans, and transmission electron microscopy showed that TTS-12 destroyed the cell membrane of Candida albicans. In conclusion, TTS-12 has significant in vitro and in vivo antifungal activity, weakening the virulence of Candida albicans and killing fungi through destroying the cell membrane.

[A new indole alkaloid glycoside from stems of Nauclea officinalis].

AIM: To investigate the chemical constituents of water-soluble part of stem of Nauclea officinalis. METHODS: The compounds were isolated and purified by resins, silica gel, and Sephadex LH20 column chromatography repeatedly, and their structures were identified by spectral analysis. RESULTS: Seven compounds were isolated and identified as: naucleamide A-10-O-beta-D-glucopyranoside (I), 5-beta-carboxystrictosidin (II), sweroside (III), loganin (IV), 3,4-dimethoxyphenyl-beta-D-glucopyranoside (V), 3, 4, 5-trimethoxyphenyl-beta-D-glucopyranoside (VI), 2-phenethylrutinoside (VII). CONCLUSION: Compound I is a new indole alkaloid glucoside, compounds I-VII were isolated from this plant for the first time.

A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes.

Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations.

[Studies on chemical constituents of Ervatamia hainanensis].

OBJECTIVE: To study the chemical constituents of Ervatamia hainanensis. METHOD: The compounds were separated and purified by column chromatography with silica gel, and identified by IR, MS, NMR and 2D-NMR. RESULT: Five compounds were identified as I (isolariciresinol 9-O-beta-D-glucopyranoside), II (cycloartenol), III (beta-amyrin acetate), IV (beta-sitosterol), V (daucosterol), respectively. CONCLUSION: All the compounds were isolated from this plant for the first time.

[Studies on liver-toxicity in rhigoma of Dioscorea bulbifera].

OBJECTIVE: To explore the liver-toxic fraction in Rhigoma of Dioscorea bulbifera. METHOD: The rats were randomized into four groups: control group (20% PVP-water), T001(10% total methanol extraction), F002(5% chloroform fraction) and F003(5% methanol fraction). Direct bilirubin (DBil) and Glutamic-pyruvic transaminase (GPT) were examined, and liver index was measured. The histological and morphological observations were performed with optical and electrical microscope. RESULT: T001 and F002 showed significant liver toxicity. CONCLUSION: The chloroform fraction was the liver-toxic fraction of D. bulbifera.

[Studies on chemical constituents in bulbs of Bolbostemma paniculatum].

OBJECTIVE: To investigate the chemical constituents of the bulbs of Bolbostemma panicultum. METHOD: The compounds were isolated by column chromatography on silica gel, C18, Sephadex LH-20 separately and their structures were elucidated by chemical and spectroscopic technologies. RESULT: Eight compounds were isolated and identified as maltol(I), emodin(II), cucurbitacin B(III), cucurbitacin E(IV), stigmasta-7, 22, 25-triene-3-ol(V), stigmasta-7, 22, 25-triene-3-nonadecanoic acid ester(VI), stigmasta-7, 22, 25-triene-3-O-beta-D-glucopyranoside(VII), stigmasta-7, 22, 25-triene-3-O-beta-D-(6'-palmitoyl) glucopyranoside(VIII). CONCLUSION: I-VIII were obtained from this plant for the first time; VI and VIII are new compounds.