Synthesis and antimicrobial evaluation of pogostone and its analogues

Pogostone (PO) is one of the secondary metabolites from Pogostemon cablin (Blanco) Benth. (Lamiaceae), serving as the effective component of the antimicrobial activity. In this study, PO and a series of its analogues were synthesized by the reaction of dehydroacetate and aldehydes in tetrahydrofuran under a nitrogen atmosphere. Their activities against Candida albicans, Gram positive bacteria and Gram negative bacteria were evaluated. The antifungal results demonstrated that PO (MIC ranged from 12 to 97 μg/mL against all strains, MFC ranged from 49 to 97 μg/mL against all strains) and A3 (MIC ranged from 12 to 49, MFC over 195 μg/mL) showed a strong activity against Candida albicans. While A1 (MIC ranged from 49 to 97 μg/mL) and A2 (MIC ranged from 24 to 49 μg/mL) have only shown effect against Guangzhou clinical isolates, the antibacterial results demonstrated that PO and its analogues showed no effects against the tested bacteria strains. This study suggests that pogostone analogues, with the appropriated structure modification, represented a kind of promising antifungal agents.     

Chemical constituents from Aphanamixis grandifolia

Four new terpenoids, nemoralisins D–G (1–4), were isolated from the leaves and stems of Aphanamixis grandifolia, along with two known diterpenoids, nemoralisin C and nemoralisin. Among them, compound 1 is the first example of norsesquiterpenoid with δ-lactone moiety, and nemoralisins E–G (2–4), are a class of acyclic diterpenoids, which are structurally related nemoralisin C and nemoralisin. These structures were established on the basis of spectroscopic methods and the absolute configuration of 1 was determined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Nemoralisins D–G (1–4) were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines (IC₅₀ > 40 μM), as well as the antimicrobial activities on Staphylococcus aureus, Pseudomonas aeruginosa, MRSA92^# and MRSA98^# (MIC > 50 μg/mL).     

The antibiofilm activity of lingonberry flavonoids against oral pathogens is a case connected to residual complexity

The antimicrobial activity of lingonberry (Vaccinium vitis-idaea L.) was evaluated against two oral pathogens, Streptococcus mutans and Fusobacterium nucleatum. Long-bed gel permeation chromatography (GPC; Sephadex LH-20) yielded purified flavonoids, with the most efficient minimum inhibitory concentrations (MICs) against planktonic cells in the anthocyanin and procyanidin primary fractions against F. nucleatum (63–125 μg/ml) and in the procyanidin rich fraction against S. mutans (16–31 μg/ml). The purified flavonol glycosides and procyanidins inhibited biofilm formation of S. mutans (MICs 16–31 μg/ml), while the corresponding reference compounds showed no activity. Secondary GPC purification yielded flavonol glycosides devoid of antibiofilm activity in the 50% MeOH fraction, while elution with 70% acetone recovered a brownish material with activity against S. mutans biofilm (MIC 8 μg/ml). Even after HPLC-PDA, NMR, and MALDI-TOF analyses, the structural identity of this material remained unknown, while its color and analytical characteristics appear to be consistent with flavonoid oxidation products.     

Effects of globularifolin on cell survival,nuclear factor-κB activity,neopterin production,tryptophan breakdown and free radicals in vitro

The potential effects of globularifolin, an acylated iridoid glucoside, on cell survival, inflammation markers and free radicals scavenging were investigated. Viability assay on human myelomomonocytic cell line THP-1 and human peripheral blood mononuclear cells (PBMC) using the Cell-Titer Blue assay proved that globularifolin had no toxic effect at the tested concentrations. Conversely, it is proportional to the dose globularifolin increased growth of THP-1 cells (p < 0.01). On human PBMC, globularifolin at 6.25 and 12.5 μM concentrations showed a stimulatory effect, while at 12.5–200 μM it suppressed response of PBMC to stimulation with phytohemagglutinin (PHA). Globularifolin (50–200 μM) enhanced neopterin formation dose-dependently, whereas tryptophan breakdown was not influenced. At 50–200 μM in unstimulated PBMC in THP-1 cells, globularifolin induced a significant expression of nuclear factor-κB (NF-κB) as was quantified by Quanti-Blue assay. By contrast, in lipopolysaccharide (LPS)-stimulated cells, the higher concentrations of globularifolin suppressed NF-κB expression dose-dependently and a significant decrease was observed at 200 μM concentration. A positive correlation was found between increased neopterin and NF-κB activity (p < 0.01). Similarly, a positive correlation was observed between neopterin levels in mitogen-induced cells and NF-κB activity in LPS-stimulated cells after treatment with globularifolin (p = 0.001). The free radical scavenging capacity of globularifolin evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay showed relative ORAC values of 0.36 ± 0.05 μmol Trolox equivalent/μmol. All together, results show that natural antioxidant globularifolin might represent a potential immunomodulatory as well as proliferative agent, which deserves further in vitro and in vivo studies.     

Pharmacokinetic and metabolism studies of rohitukine in rats by high performance liquid-chromatography with tandem mass spectrometry

A sensitive, selective, and rapid high performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed for the quantification of rohitukine in rat plasma. HPLC was performed using a Symmetry-Shield C₁₈ (5 μ, 4.6 × 150 mm) column, and isocratic elution with ammonium acetate buffer (pH 4; 10 mM):methanol (08:92, v/v) at a flow rate of 0.6 mL/min. Sample clean-up involved solid phase extraction (SPE) of analyte and internal standard (phenacetin) from 100 μL plasma. The parent → product ion transitions (MRM) for analyte and IS were 306.1 → 245.1 m/z and 180.1 → 138.1 m/z respectively, and were monitored on a triple quadrupole mass spectrometer, operating in positive ion mode. The method was validated across the dynamic concentration range of 5–500 ng/mL for rohitukine, with a fast run time of 4.5 min. The analytical method measured concentrations of rohitukine with accuracy (% bias) of <± 10% and precision (% RSD) of <± 12%. Rohitukine was stable during the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and 30 days of storage in a freezer at − 70 ± 10 °C. Finally, the applicability of this assay has been successfully demonstrated in vivo pharmacokinetic and in vitro metabolism studies in Sprague–Dawley rat. This method will therefore be highly useful for future preclinical and clinical pharmacokinetic studies of rohitukine.     

Modulation of COX,LOX and NFκB activities by Xanthium spinosum L. root extract and ziniolide

Xanthium spinosum L. (Asteraceae) is a medicinal weed distributed worldwide. Many of its diverse ethnopharmacological uses – namely diarrhoea, inflammation, liver disorders, snake bite and fever – are linked – at least in part – to an uncontrolled release of arachidonic acid metabolites. The crude extract of X. spinosum roots from Jordanian origin dose-dependently inhibited the 5-LOX (IC₅₀ ≅ 10 μg/mL), COX-1(IC₅₀ ≅ 50 μg/mL), and 12-LOX (IC₅₀ ≅ 170 μg/mL) enzymatic pathways in intact pro-inflammatory cells. A direct activity at the level of PLA₂ is not probable, but the extract induced the synthesis of the anti-inflammatory eicosanoid 15(S)-HETE, which may in turn inhibit this enzyme. 5-LOX bioguided fractionation of the crude extract led to the isolation of ziniolide, a known 12,8-guaianolide sesquiterpene lactone, from the hydro-alcoholic fraction of the n-hexane extract (IC₅₀ = 69 μM). Both the plant extract and ziniolide are in vitro inhibitors of the phorbol-induced NFκB activation, a key regulator of the arachidonic pathway.     

Pharmacokinetic study of eight coumarins of Radix Angelicae Dahuricae in rats by gas chromatography–mass spectrometry

A sensitive, specific gas chromatography–mass spectrometry (GC–MS) method was established for the quantitative determination of eight coumarins of Radix Angelicae Dahuricae including coumarin, isopsoralen, psoralen, xanthotoxin, bergapten, osthole, imperatorin and oxypeucedanin in rat plasma. Nitrendipine was used as the internal standard (IS). The plasma samples were extracted by acetonitrile. GC separation was accomplished on a DB-5MS column with temperature programmed from 160 °C (17 min) to 190 °C (10 min) at the rate of 20 °C/min, then to 240 °C (5 min) at 20 °C/min, and finally to 280 °C (14 min) at 20 °C/min. The detection was performed on a quadrupole mass spectrometer detector operated by full-scan mode (m/z 50–500). The lower limit of quantitation was 5–10 ng/mL for eight coumarins, and the linear range was 5–1000 ng/mL for the coumarins (R² > 0.9990). All the validation data were within the required limits. After oral administration, the plasma concentration–time curves showed that the time for maximum concentration (T_max) was 1.29 for coumarin, 1.83 for isopsoralen, 1.93 for psoralen, 1.30 for xanthotoxin, 2.04 for bergapten, 0.64 for osthole, 1.41 for imperatorin and 0.51 h for oxypeucedanin. The plasma concentration of the eight coumarins was low, with a mean maximum plasma concentration (C_max) < 6.41 μg/mL. Pharmacokinetic data analysis showed that the eight coumarins had different pharmacokinetic characteristics after oral administration. The method was successfully applied to pharmacokinetic studies of eight coumarins after oral administration in rats.     

Bioactive cis-stilbenoids from the tubers of Scirpus yagara

Two new cis-stilbenoids, sciryagarol I (1) and II (2) were isolated from the EtOAc extract of the tubers of Scirpus yagara, together with four known compounds. The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and comparison with literature information. The compounds 3, 4 and 6 were isolated for the first time from this genus. Some compounds were tested for their cytotoxicity against human tumor cell lines and antimicrobial activity. Compounds 1–4 showed significant cytotoxicity against the Hela cell lines with IC₅₀ values ranging from 7.21 to 61.21 μM. 1 and 2 exhibited some antimicrobial activity against Staphylococcus aureus and Candida albicans with uniform MICs of 79.3 μl/ml for 2, and 152 μl/ml for 1, respectively.     

Nitrate concentrations in soil solutions below Danish forests

Nitrate in the soil water below the root zone is a pre-condition for nitrate leaching, and it indicates loss of nutrients from the forest ecosystem. Nitrate leaching may potentially cause eutrophication of surface water and contamination of ground water. In order to evaluate the extent of nitrate leaching in relation to land-use, a national monitoring programme has established sampling routines in a 7×7 km grid including 111 points in forests. During winters of 1986–1993, soil samples were obtained from a depth of 0–25, 25–50, 50–75 and 75–100 cm. Nitrate concentrations in soil solutions were determined by means of a 1 M KCl extraction. The influence of forest size, forest-type, soil-type, tree species and sampling time on the nitrate concentrations was analysed in a statistical model. The analysis focused on data from depth 75–100 cm, as nitrate is considered potentially lost from the ecosystem at this depth. The range of nitrate concentrations was 0–141 mg NO⁻₃–N dm⁻³ and the estimated mean value was 1.51 mg NO⁻₃–N dm⁻³. The concentration was influenced by (1) forest size (concentrations in forests <10 ha were higher than concentrations in forests >50 ha), (2) forest-type (afforested arable land had higher concentrations than forest-type `other woodland'), (3) soil-type (humus soils showed above average concentrations, and fine textured soils had higher concentrations than coarse textured soils), and (4) sampling time. Unlike other investigations, there was no significant effect of tree species. A few sites deviated radically from the general pattern of low concentrations. The elevated concentrations recorded there were probably caused by high levels of N deposition due to emission from local sources or temporal disruptions of the N cycle. The nitrate concentration in the soil solution below the root zone was mostly rather low, indicating that, generally, N saturation has not yet occurred in Danish forest ecosystems. However, median concentrations exceeding drinking water standards (11.3 mg NO⁻₃–N dm⁻³) were found at 7% of the sites. Furthermore, 30% of the sites had median concentrations above 2 mg NO⁻₃–N dm⁻³, suggested as an elevated level for Danish forest ecosystems, equalling annual N losses of more than 2–6 kg ha⁻¹ year⁻¹.     

Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation

Isoliquiritigenin, a herbal ingredient with chalcone structure, has been speculated to be able to inhibit one of the most drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferase (UGT). Therefore, the aim of the present study was to investigate the inhibition of isoliquiritigenin towards important UGT isoforms in the liver and intestine, including UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as probe reactions. The results showed that 100 μM of isoliquiritigenin inhibited the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 by 95.2%, 76.1%, 78.9%, 87.2%, 67.2%, 94.8%, and 91.7%, respectively. The data fitting using Dixon plot and Lineweaver–Burk plot showed that the inhibition of UGT1A1, UGT1A9 and UGT1A10 by isoliquiritigenin was all best fit to the competitive inhibition, and the second plot using the slopes from the Lineweaver–Burk plot versus isoliquiritigenin concentrations was used to calculate the inhibition kinetic parameter (K_i) to be 0.7 μM, 0.3 μM, and 18.3 μM for UGT1A1, UGT1A9, and UGT1A10, respectively. All these results indicated the risk of clinical application of isoliquiritigenin on the drug–drug interaction and other possible diseases induced by the inhibition of isoliquiritigenin towards these UGT isoforms.     

Antibacterial tetraoxygenated xanthones from the immature fruits of Garcinia cowa

A phytochemical investigation of the acetone extract from the immature fruits of Garcinia cowa led to the isolation of two novel tetraoxygenated xanthones, garcicowanones A (1) and B (2), together with eight known tetraoxygeanted xanthones. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their antibacterial activity against Bacillus cereus TISTR 688, Bacillus subtilis TISTR 008, Micrococcus luteus TISTR 884, Staphylococcus aureus TISTR 1466, Escherichia coli TISTR 780, Pseudomonas aeruginosa TISTR 781, Salmonella typhimurium TISTR 292 and Staphylococcus epidermidis ATCC 12228. α-Mangostin showed potent activity (MIC 0.25–1 μg/mL) against three Gram–positive strains and garcicowanone A and β-mangostin exhibited strong antibacterial activity against B. cereus with the same MIC values of 0.25 μg/mL.     

Improving permeability and oral absorption of mangiferin by phospholipid complexation

Mangiferin is an active ingredient of medicinal plant with poor hydrophilicity and lipophilicity. Many reports focused on improving aqueous solubility, but oral bioavailability of mangiferin was still limited. In this study, we intended to increase not only solubility, but also membrane permeability of mangiferin by a phospholipid complexation technique. The new complex's physicochemical properties were characterized in terms of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), aqueous solubility, oil–water partition coefficient and in vitro dissolution. The intestinal absorption of the complex was studied by the rat in situ intestinal perfusion model. After oral administration of mangiferin–phospholipid complex and crude mangiferin in rats, the concentrations of mangiferin were determined by a validated RP-HPLC method. Results showed that the solubility of the complex in water and in n-octanol was enhanced and the oil–water partition coefficient was improved by 6.2 times and the intestinal permeability in rats was enhanced significantly. Peak plasma concentration and AUC of mangiferin from the complex (C_max: 377.66 μg/L, AUC: 1039.94 μg/L*h) were higher than crude mangiferin (C_max: 180 μg/L, AUC: 2355.63 μg/L*h). In view of improved solubility and enhanced permeability, phospholipid complexation technique can increase bioavailability of mangiferin by 2.3 times in comparison to the crude mangiferin.     

Comparison of in vitro antiviral activity of tea polyphenols against influenza A and B viruses and structure–activity relationship analysis

Influenza poses a particular risk of severe outcomes in the elderly, the very young and those with underlying diseases. Tea polyphenols are the natural phenolic compounds in teas, and principally consist of catechins, proanthocyanidins, flavonols, and theaflavins, which antiviral activities have been reported recently. This study is to gain a further insight into potential of various tea polyphenols for inhibiting influenza virus infection. Five tea polyphenols exhibited inhibitory activity against influenza A virus in the trend of theaflavin > procyanidin B-2 > procyanidin B-2 digallate > (−)-epigallocatechin(EGC) > (−)-epigallocatechingallate(EGCG) with IC₅₀ values in the range of 16.2–56.5 μg/ml. Six of the tested compounds showed anti-influenza B virus activity in the order of kaempferol > EGCG > procyanidin B-2 > (−)-EGC ~ methylated EGC > theaflavin with IC₅₀ values in the range of 9.0–49.7 μg/ml. Based on these results, the structure–activity relationship (SAR) was explained as follows. First, the dimeric molecules, such as theaflavin and procyanidin B-2, generally displayed more potent antiviral activity against both influenza A and B viruses than the catechin monomers. Second, the kaempferol for inhibition of influenza B virus indicated that the more planar flavonol structure with only one C-4′ phenolic hydroxyl group in the B ring is necessary for the anti-influenza B virus activity. A similar SAR can be drawn from the assays of another enveloped RNA virus, such as respiratory syncytial virus. These results are expected to provide guides for rational design of antiviral drugs based on polyphenols.     

Carapanolides C–I from the seeds of andiroba (Carapa guianensis,Meliaceae)

Five new mexicanolide-type limonoids, carapanolides C–G (1–5), together with two new phragmalin-type limonoids, carapanolides H–I (6, 7), were isolated from the oil of Carapa guianasis AUBLET (Meliaceae) seeds. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR spectra and FABMS. Carapanolides C (1), E (3), and I (7) exhibited moderate activity in the P388 (IC₅₀ 17.9 μM in 1, 15.8 μM in 3) and L1210 cell lines (IC₅₀ 13.3 μM in 1, 18.1 μM in 3, 16.9 μM in 7). On the other hand, Carapanolide D (2) exhibited a strong inhibitory effect in the HL-60 cell line (IC₅₀ 11.0 μM), Carapanolides F (4) showed inhibitory activity in the L1210 cell line (IC₅₀ 15.9 μM), and the cytotoxic activity of Carapanolides I (7) was moderate in all cell lines.     

Different pharmacokinetics of the two structurally similar dammarane sapogenins,protopanaxatriol and protopanaxadiol,in rats

Dammarane Sapogenins (DS), with main ingredients of protopanaxatriol (PPT, 33%) and protopanaxadiol (PPD, 16%), is an alkaline hydrolyzed product of ginsenosides and had significant activities in improving learning and memory and decreasing chemotherapy-induced myelosuppression. In the present study, the pharmacokinetics and oral bioavailabilities of PPT and PPD were investigated when a single dose of DS was administrated orally (75 mg/kg) and intravenously (i.v., 30 mg/kg) to rats. Their in vitro stabilities in the GI tract were also investigated. PPT and PPD concentrations were measured by LC–MS. The results showed that PPT was eliminated rapidly from the body with an average t_{1/2, λz} value of 0.80 h and CL of 4.27 l/h/kg after i.v. administration, while PPD was eliminated relatively slowly with a t_{1/2, λz} of 6.25 h and CL of 0.98 l/h/kg. After oral administration, both PPD and PPT could be absorbed into the body, but their systemic exposures were quite different. PPT was absorbed into the body quickly, with a T_max of 0.58 h and a C_max of 0.13 μg/ml, while PPD was absorbed relatively slowly with a T_max of 1.82 h and a C_max of 1.04 μg/ml. The absolute bioavailabilities of PPT and PPD were estimated as 3.69% and 48.12%, respectively. The stability test found that PPT was instable in the stomach with 40% degradation after 4 h incubation at 37 °C, both in pH 1.2 buffer and in the stomach content solution. The instability in the stomach might be one of the reasons for PPT's poor bioavailability.     

New antimicrobial pregnane glycosides from the stem of Ecdysanthera rosea

Phytochemical investigation on the stem of Ecdysanthera rosea led to the isolation of eight new C-21 pregnane glycoside ecdysosides A–H (1–8), together with one known pregnane glycoside ecdysantheroside A (9). Their structures were elucidated based on extensive spectroscopic data (MS, IR, 1D and 2D NMR) analysis, as well as comparison with the reported literature data. Antimicrobial activities of all the compounds were evaluated against bacteria and yeasts. Compounds 1, 9, 3 and 5 exhibited moderate antibacterial activities against respective Enterococcus faecalis and Providensia smartii, with MIC value of 12.5 μg/mL. Compound 8 showed significant anti-yeast activity against Cryptococcus neoformans with MIC value of 12.5 μg/mL.     

Cytotoxic sesquiterpenes from Hedychium spicatum: Isolation,structure elucidation and structure–activity relationship studies

Phytochemical investigation of chloroform extract from rhizomes of Hedychium spicatum resulted in the isolation of six new sesquiterpenes (1–6) along with fifteen known compounds (7–21). Their structures were elucidated on the basis of the extensive spectroscopic analyses (IR, Mass and NMR) and by comparison of the data with those reported in the literature. Further, cytotoxic activities of all the isolates were evaluated by determining their inhibitory effects against A-549, B-16, Hela, HT-29, NCI-H460, PC-3, IEC-6 and L-6 cancer cell lines. Results indicated that compounds 1 and 3 may serve as an important natural lead compounds for future development as they showed potent cytotoxic activity against Hela cell lines with an IC₅₀ value of 0.3 μg/mL and 1.80 μg/mL, respectively.     

A potent acetylcholinesterase inhibitor from Pancratium illyricum L.

Plants belonging to the Amaryllidaceae contain an exclusive group of alkaloids, known as sources of important biological activities. In the present work, Pancratium illyricum L., a species belonging to this family and endemic of Sardinia (Italy), was investigated for its alkaloid content. Fresh bulbs and leaves were processed separately. Standard extraction and purification procedures were applied to obtain fractions and compounds for GC–MS and NMR analysis. In addition to eight already known alkaloids (1–8), 11α-hydroxy-O-methylleucotamine (9) was isolated for the first time and its structure completely determined by one and two-dimensional ¹H and ¹³C NMR spectroscopy. This new galanthamine-type compound exhibited a pronounced in vitro acetylcholinesterase (AChE) inhibitory activity (IC₅₀ = 3.5 ± 1.1 μM) in comparison to the reference standard galanthamine hydrobromide (IC₅₀ = 1.5 ± 0.2 μM).     

Phytic acid enhances the oral absorption of isorhamnetin,quercetin, and kaempferol in total flavones of Hippophae rhamnoides L.

AimTotal flavones of Hippophae rhamnoides L. (TFH) have a clinical use in the treatment of cardiac disease. The pharmacological effects of TFH are attributed to its major flavonoid components, isorhamnetin, kaempferol, and quercetin. However, poor oral bioavailability of these flavonoids limits the clinical applications of TFH. This study explores phytic acid (IP₆) enhancement of the oral absorption in rats of isorhamnetin, kaempferol, and quercetin in TFH.MethodsIn vitro Caco-2 cell experiments and in vivo pharmacokinetic studies were performed to investigate the effects of IP₆. The aqueous solubility and lipophilicity of isorhamnetin, quercetin, and kaempferol were determined with and without IP₆, and mucosal epithelial damage resulting from IP₆ addition was evaluated by MTT assays and morphology observations.ResultsThe P_app of isorhamnetin, kaempferol, and quercetin was improved 2.03-, 1.69-, and 2.11-fold in the presence of 333 μg/mL of IP₆, respectively. Water solubility was increased 22.75-, 15.15-, and 12.86-fold for isorhamnetin, kaempferol, and quercetin, respectively, in the presence of 20 mg/mL IP₆. The lipophilicity of the three flavonoids was slightly decreased, but their hydrophilicity was increased after the addition of IP₆ in the water phase as the logP values of isorhamnetin, kaempferol, and quercetin decreased from 2.38 ± 0.12 to 1.64 ± 0.02, from 2.57 ± 0.20 to 2.01 ± 0.04, and from 2.39 ± 0.12 to 1.15 ± 0.01, respectively. The absorption enhancement ratios were 3.21 for isorhamnetin, 2.98 for kaempferol, and 1.64 for quercetin with co-administration of IP₆ (200 mg/kg) in rats. In addition, IP₆ (200 mg/kg, oral) caused neither significant irritation to the rat intestines nor cytotoxicity (400 μg/mL) in Caco-2 cells.ConclusionsThe oral bioavailability of isorhamnetin, kaempferol, and quercetin in TFH was enhanced by the co-administration of IP₆. The main mechanisms are related to their enhanced aqueous solubility and permeability in the presence of IP₆. In summary, IP₆ is a potential absorption enhancer for pharmaceutical formulations that is both effective and safe.     

Coreosides A–D,C14-polyacetylene glycosides from the capitula of Coreopsis tinctoria and its anti-inflammatory activity against COX-2

Four new C₁₄-polyacetylene glycosides, namely coreosides A–D (1–4), were isolated from the capitula of Coreopsis tinctoria, a Snow chrysanthemum or Snow tea that is used as a folk tea for prevention of cardiovascular disease in southern Xinjiang, China. Coreosides A–D feature a long chain structure as its aglycon with two acetylenes on C-8 and C-10 and two olefinics on C-6 and C-12 sites, which construct a large conjugate system. The structures were elucidated on the basis of spectroscopic evidences and hydrolysis. Compounds 1–4 exhibited significant inhibition against cyclooxygenase-2 at the concentration of 1 × 10^− 6 mol/L, with its IC₅₀ values of 0.22–8.8 × 10^− 2 μmol/L.