Rubinoboletus ballouii polysaccharides exhibited immunostimulatory activities through toll-like receptor-4 via NF-κB pathway.

The biological activities of water-soluble components of edible mushroom Rubinoboletus ballouii (RB) were seldom reported. Polysaccharides of RB (RBP) were prepared and well-characterized using chemical analyses. The immunomodulatory properties of RBP were investigated using human monocyte-derived dendritic cells (moDC) in vitro, and cyclophosphamide (CTX)-induced immunosuppressive mouse model. Results showed that RBP was found to contain 80.6% (w/w) of neutral sugars including D-fucose, D-mannose, D-glucose and D-galactose (1.7:1.4:1.0:1.8), and 12.5% (w/w) of proteins, which composed of glutamine, threonine, serine, etc. RBP could promote the maturation of moDC and increase the secretion of IL-12p40, IL-10, and TNF-α. Furthermore, the stimulation of IL-12p40 production was inhibited by pretreatment with toll-like receptor (TLR)-4 blocker or NF-κB pathway blocker, suggesting that the activation of moDC by RBP was mediated through NF-κB pathway via TLR-4 receptor. On the other hand, in CTX-treated mice, RBP restored the loss of CD34bright CD45dim hematopoietic stem cells and increased IL-2 production in sera and splenocytes culture supernatant, as well as up-regulated the percentage of CD4+ T helper lymphocyte in mice splenocytes. These findings strongly suggested that RBP are the active ingredients of RB responsible for its immunostimulatory actions and deserved to be further investigated as cancer supplements.

Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

Palladium-Catalyzed Arylation of Carbasugars Enables the Discovery of Potent and Selective SGLT2 Inhibitors.

Selective inhibition of the transporter protein sodium-glucose cotransporter 2 (SGLT2) has emerged as a promising way to control blood glucose level in diabetes patients. Reported herein is a short and convergent synthetic route towards some small-molecule SGLT2 inhibitors by a chemo- and diastereospecific palladium-catalyzed arylation reaction. This synthetic strategy enabled the discovery of two highly selective and potent SGLT2 inhibitors, thereby paving the way towards the development of carbasugar SGLT2 inhibitors as potential antidiabetic/antitumor agents.

Transport in Caco-2 cell monolayers of antidiabetic cucurbitane triterpenoids from Momordica charantia fruits.

Bitter melon, the fruit of Momordica charantia L. (Cucurbitaceae), is a widely-used treatment for diabetes in traditional medicine systems throughout the world. Various compounds have been shown to be responsible for this reputed activity, and, in particular, cucurbitane triterpenoids are thought to play a significant role. The objective of this study was to investigate the gastrointestinal transport of a triterpenoid-enriched n-butanol extract of M. charantia using a two-compartment transwell human intestinal epithelial cell Caco-2 monolayer system, simulating the intestinal barrier. Eleven triterpenoids in this extract were transported from the apical to basolateral direction across Caco-2 cell monolayers, and were identified or tentatively identified by HPLC-TOF-MS. Cucurbitane triterpenoids permeated to the basolateral side with apparent permeability coefficient (P app) values for 3-ß-7-ß,25-trihydroxycucurbita-5,23(E)-dien-19-al and momordicines I and II at 9.02 × 10(-6), 8.12 × 10(-6), and 1.68 × 10(-6)cm/s, respectively. Also, small amounts of these triterpenoids were absorbed inside the Caco-2 cells. This is the first report of the transport of the reputed antidiabetic cucurbitane triterpenoids in human intestinal epithelial cell monolayers. Our findings, therefore, further support the hypothesis that cucurbitane triterpenoids from bitter melon may explain, at least in part, the antidiabetic activity of this plant in vivo.

Immunomodulatory activities of Ganoderma sinense polysaccharides in human immune cells.

Medicinal mushrooms have been traditionally used as food nutrient supplements in China for thousands of years. The present study aimed to evaluate the immunomodulatory activities of Ganoderma sinense (GS), an allied species of G. lucidum, using human peripheral blood mononuclear cells (PBMC). Our results showed that the polysaccharide-enriched fraction of GS hot water extract (400 µg/ml) exhibited significant stimulatory effects on PBMC proliferation. When the fruiting bodies of GS were divided into pileus and stipe parts and were separately extracted, the GS stipe polysaccharide-enriched fraction (50-400 µg/ml) showed concentration-dependent immunostimulating effects in PBMC. The productions of tumor necrosis factor-α, interleukin (IL)-10, and transforming growth factor -ß were significantly enhanced by this fraction. In addition, the proportion of CD14(+) monocyte subpopulation within the PBMC was specifically increased. The IL-10 and IL-12 productions in monocyte-derived dendritic cells were significantly enhanced by GS stipe fraction. The composition of monosaccharides of this fraction was determined by ultra performance liquid chromatography and ion exchange chromatography. Our study demonstrated for the first time the immunostimulatory effects of GS stipe polysaccharide-enriched fraction on PBMC and dendritic cells. The findings revealed the potential use of GS (especially including the stipes of fruiting bodies) as adjuvant nutrient supplements for patients, who are receiving immunosuppressive chemotherapies.

Anti-inflammatory and anti-allergic activities of Pentaherb formula, Moutan Cortex (Danpi) and gallic acid.

Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 µg/mL) and GA (10 µg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-kB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects.

Molecular studies of the congenital malformation induced by Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese herbal medicine for threatened miscarriage. Potential reproductive toxicity of LAR was identified in early pregnancy in animals. Skeletal anomalies including loss of ulna and distal digits, shortening of humerus and radius were observed in higher clinical dose groups. Here, we aimed to study the molecular mechanism of the congenital malformation induced by LAR. In vitro whole mouse embryo culture was used to confirm the embryotoxicity effects of LAR on developing limb buds during early organogenesis. A pregnant mouse model was employed to study the developmental gene expression by quantitative PCR and whole hybridization and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, in the forelimbs and hindlimbs during development in vivo. Severe growth retardation, multiple embryonic malformations and delayed limb bud development were observed. Limb-specific Tbx gene expressions in both developing forelimbs and hindlimbs were significantly decreased. Increased developmental apoptosis in apical ectodermal ridge and mesenchymal mesoderm of the developing limb buds was identified. Overexpressions of Tbx2 and Tbx3 in embryos in vitro rescued LAR-induced abnormal limb development and reduced apoptosis in the developing forelimb buds. In conclusion, LAR affects limb development by suppressing the expression of limb developmental genes and disturbing programmed cell death during limb formation in mice.

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways.

Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment.

Synthesis of chiral hydroxylated enones as potential anti-tumor agents.

A series of chiral hydroxylated enones were synthesized as COTC ether analogues to investigate the structural features required for optimal and selective anti-tumor activity. The cytotoxicity of the seven COTC ether analogues against WRL-68 normal and HepG2, HL-60 cancer cell lines were measured. C-4 ether analogues with an aliphatic chain substituent were found to be more favorable than their aromatic counterparts. Inversion of the configuration at C-4 in 5e to give 5f only resulted in reduced selectivity towards cancer cells. These results show that 4-O-pentyl-gabosine D (5e) has optimum selectivity and cytotoxicity towards two cancer cell lines.

Screening for anti-inflammatory and bronchorelaxant activities of 12 commonly used Chinese herbal medicines.

The use of health supplements derived from medicinal herbs as self-medication for the relief of respiratory tract pathology symptoms is increasing in Chinese communities as air pollution is worsening. Twelve herbs from two formulae of our previous studies were evaluated for their anti-inflammatory, immunomodulatory and bronchorelaxant activities in this study. Among the extracts tested, those of Herba Schizonepetae and Radix Glycyrrhizae showed significant inhibitory effects on LPS-induced nitric oxide production (p < 0.05) in mouse macrophage RAW264.7 cells, suggesting their anti-inflammatory activities. Radix Scutellariae and Radix Glycyrrhizae extracts showed significant inhibitory effects on phytohaemagglutinin-induced proliferation in human peripheral blood mononuclear cells (p < 0.05). These extracts also showed inhibition of TNF-α, IFN-γ and IL-10 production. For the bronchorelaxant assay, Rhizoma Cynanchi Stauntonii and Radix Glycyrrhizae extracts showed potent attenuation of the acetylcholine- and carbachol-induced contractions in rat trachea (p < 0.05), implying their relaxant activities. In conclusion, Herba Schizonepetae, Radix Glycyrrhizae, Radix Scutellariae and Rhizoma Cynanchi Stauntonii extracts were demonstrated to exert anti-inflammatory, immunomodulatory and bronchorelaxant activities, which may help to ameliorate the symptoms of respiratory tract pathologies. The findings have thus provided some scientific evidence on the efficacy and mechanisms of action of these herbs, which are useful for the further development of clinical applications.

Extracts from Radix Astragali and Radix Rehmanniae promote keratinocyte proliferation by regulating expression of growth factor receptors.

Chinese herbal medicine has long been used as a treatment for wounds. However, the underlying cellular and molecular mechanisms remain largely unknown. In this study it was shown that the proliferation of keratinocytes, which is known to play an important role in wound healing as the major cell type in the epidermis, was promoted by three herbal extracts/natural compounds: NF3 (an extract from the mixture of Radix Astragali (RA) and Radix Rehmanniae (RR) in the ratio of 2:1), stachyose (an isolated compound from Radix Rehmanniae) and extract P2-2 (a sub-fraction from the extract of Radix Astragali). The effect of the herbal extracts/natural compounds on the growth of keratinocytes was not influenced by a high glucose level, a condition similar to diabetic patients who usually suffer from diabetic foot ulcers. Real time RT-PCR results showed that the expression of epidermal growth factor (EGF) receptor, but not transforming growth factor-ß (TGF-ß) receptor, was up-regulated by NF3. Moreover, treatments with the EGF receptor kinase inhibitor AG1478 and the MEK inhibitor U0126 resulted in the diminishment of the effect of the three herbal extracts/natural compounds on keratinocyte proliferation, indicating that EGF receptor might have a significant role in this action. This study has further elucidated the molecular mechanism under which herbal extracts/natural compounds exert their effects on the wound healing process.

Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

BACKGROUND: Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth. METHODS: Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied. RESULTS: In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats. CONCLUSIONS: Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

The known immunologically active components of Astragalus account for only a small proportion of the immunological adjuvant activity when combined with conjugate vaccines.

The 95 % ethanol extract of Astragalus has been demonstrated to have potent activity as an immunological adjuvant when administered with vaccines of various types. We endeavor here to identify the components of this extract that are responsible for this adjuvant activity. Mice were immunized with KLH conjugated to cancer carbohydrate antigens globo H and GD3 and cancer peptide antigen MUC1 combined with different Astragalus fractions or with commercially available Astragalus saponins and flavonoids. The antibody responses against cancer antigens and KLH were quantitated in ELISA assays, and toxicity was calculated by weight loss. Astragalosides II and IV were the most active components, but the toxicity of these two differed dramatically. Astragaloside II was the most toxic Astragalus component with 5-10 % weight loss at a dose of 500 µg while astragaloside IV showed no weight loss at all at this dose, suggesting that astragaloside IV might be utilized as an immunological adjuvant in future studies. Several flavonoids also had significant adjuvant activity. However, when the activities of these known immunologically active components of Astragalus (and of endotoxin) are calculated based on the extent of their presence in the 95 % ethanol extract, they provide only a small proportion of the immunological activity. This raises the possibility that additional uniquely active components of Astragalus may contribute to adjuvant activity, or that the adjuvant activity of Astragalus is greater than the activity of the sum of its parts.

Baicalein-modified hydroxyapatite nanoparticles and coatings with antibacterial and antioxidant properties.

Aseptic loosening and bacterial infections are the two main causes of failure for metallic implants used for joint replacement. A coating that is both bioactive and possesses antimicrobial properties may address such shortcomings and improve the performance of the implant. We have sought to study the properties of combining hydroxyapatite-based nanoparticles or coatings with baicalein, a plant-extracted molecule with both antibacterial and antioxidant properties. (B-type) carbonated hydroxyapatite nanoparticles prepared by a chemical wet method could subsequently adsorbed by soaking in a baicalein solution. The amount of adsorbed baicalein was determined to be 63 mg.g-1 by thermogravimetric measurements. In a second approach, baicalein was adsorbed on a biomimetic calcium-deficient hydroxyapatite planar coating (12 µm thick) deposited on Ti6Al4V alloy from an aqueous solution of calcium, phosphate, sodium and magnesium salts. Soaking of the hydroxyapatite coated on titanium alloy in a baicalein solution induced partial dissolution/remodeling of the upper surface of the coating. However, the observed remodeling of the surface was much more pronounced in the presence of a baicalein solution, compared to pure water. The presence of adsorbed baicalein on the HAp layer, although it could not be precisely quantified, was assessed by XPS and fluorescence analysis. Planar coatings exhibited significant antibacterial properties against Staphylococcus epidermidis. Baicalein-modified nanoparticles exhibited significant antioxidant properties. These results illustrate the potential of hydroxyapatite used as a carrier for natural biologically-active molecules and also discuss the challenges associated with their applications as antibacterial agents.

Development of thermosensitive hydrogel containing methylene blue for topical antimicrobial photodynamic therapy.

Due to the emergence of antibiotic resistance, antimicrobial photodynamic therapy (aPDT) has recently been demonstrated as a promising alternative to antibiotics to treat wound infections caused by multidrug-resistant (MDR) pathogens. This study aimed to evaluate the bacterial killing efficiency of aPDT mediated by methylene blue (MB) loaded thermosensitive hydrogels against methicillin-resistant Staphylococcus aureus (MRSA). Box-Behnken Design method was employed to investigate the impacts of the polymer compositions, Poloxamer 407, Poloxamer 188 and Carbopol 934P, on the gelation temperature (Tsol-gel) and release rate of MB. The viscosity and in vitro bacterial killing efficiency of three selected formulations with Tsol-gel ranged 25-34 °C and MB release in 2 h (the incubation time used for aPDT experiment) ≥ 70%, were assessed. The viscosity was found to increase with increasing P407 content and increasing total gel concentration. In the in vitro aPDT experiment, all tested MB-hydrogels demonstrated >2.5 log10 colony forming unit (CFU) reduction against three clinical relevant MRSA strains. Interestingly, the bacterial reduction increased with decreasing amount of gel added (reduced MB concentration). This was possibly attributed to the increased viscosity at higher gel concentration reducing the diffusion rate of released MB towards bacterial cells leading to reduced aPDT efficiency. In summary, aPDT with the thermosensitive MB hydrogel formulations is a promising treatment strategy for wound infections.

Monosubstituted tricationic Zn(II) phthalocyanine enhances antimicrobial photodynamic inactivation (aPDI) of methicillin-resistant Staphylococcus aureus (MRSA) and cytotoxicity evaluation for topical applications: in vitro and in vivo study.

Antimicrobial photodynamic therapy (aPDT) is an innovative approach to combat multi-drug resistant bacteria. It is known that cationic Zn(II) phthalocyanines (ZnPc) are effective in mediating aPDT against methicillin-resistant Staphylococcus aureus (MRSA). Here we used ZnPc-based photosensitizer named ZnPcE previously reported by our research group to evaluate its aPDT efficacy against broad spectrum of clinically relevant MRSAs. Remarkably, in vitro anti-MRSA activity was achieved using near-infrared (NIR, >610 nm) light with minimal bactericidal concentrations ranging <0.019-0.156 µM against the panel of MRSAs. ZnPcE was not only significantly (p < .05) more potent than methylene blue, which is a clinically approved photosensitizer but also demonstrated low cytotoxicity against human fibroblasts cell line (Hs-27) and human immortalized keratinocytes cell line (HaCaT). The toxicity was further evaluated on human 3-D skin constructs and found ZnPcE did not manifest in vivo skin irritation at ≤7.8 µM concentration. In the murine MRSA wound model, ZnPcE with PDT group demonstrated > 4 log10 CFU reduction and the value is significantly higher (p < .05) than all test groups except positive control. To conclude, results of present study provide a scientific basis for future clinical evaluation of ZnPcE-PDT on MRSA wound infection.

Synthesis and In Vitro Photodynamic Activity of Cationic Boron Dipyrromethene-Based Photosensitizers against Methicillin-Resistant Staphylococcus aureus.

A series of cationic boron dipyrromethene (BODIPY) derivatives were synthesized and characterized with various spectroscopic methods. Having the ability to generate singlet oxygen upon irradiation, these compounds could potentially serve as photosensitizers for antimicrobial photodynamic therapy. Of the five BODIPYs being examined, the dicationic aza-BODIPY analogue (compound 5) demonstrated the highest potency against a broad spectrum of clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), including four ATCC-type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two strains carrying specific antibiotic resistance mechanisms [-AAC(6')-APH(2") and RN4220/pUL5054], and ten non-duplicate clinical strains from hospital- and community-associated MRSAs of the important clonal types ST239, ST30, and ST59, which have previously been documented to be prevalent in Hong Kong and its neighboring countries. The in vitro anti-MRSA activity of compound 5 was achieved upon irradiation with near-infrared light (>610 nm) with minimal bactericidal concentrations (MBCs) ranging from 12.5 to 25 µM against the whole panel of MRSAs, except the hospital-associated MRSAs for which the MBCs were in the range of 50-100 µM. Compound 5 was significantly (p < 0.05) more potent than methylene blue, which is a clinically approved photosensitizer, indicating that it is a promising antimicrobial agent that is worthy of further investigation.

Search for antimycobacterial constituents from a Tibetan medicinal plant, Gentianopsis paludosa.

From the whole plant of Gentianopsis paludosa seven compounds were isolated and identified to be 1,7-dihydroxy-3,8-dimethoxyxanthone (1), 1,7,8-trihydroxy-3-methoxyxanthone (2), 1-hydroxy-3,7,8-trimethoxyxanthone (3), 1,8-dihydroxy-2,6-dimethoxyxanthone (4), oleanolic acid (5), 4',5,7-trihydroxyflavone (6) and luteolin-7-O-glucoside (7). Compounds 1, 2, 3 and 5 showed modest inhibitory effect against the growth of Mycobacterium smegmatis and M. tuberculosis.

Jaboticabin and Related Polyphenols from Jaboticaba ( Myrciaria cauliflora) with Anti-inflammatory Activity for Chronic Obstructive Pulmonary Disease.

Myrciaria cauliflora (jaboticaba) is an edible fruit common in Brazil that has been used for treating respiratory diseases, including chronic tonsillitis and asthma. This study explores the distribution of an anti-inflammatory depside, jaboticabin, in different parts of the jaboticaba plant as well as major polyphenols from the wood of jaboticaba, some with biological activity similar to jaboticabin. The peel of the fruit was found to be the major source of jaboticabin. This is the first phytochemical study of the wood of M. cauliflora. The antioxidant-activity-guided fractionation strategy successfully identified 3,3'-dimethylellagic acid-4- O-sulfate from jaboticaba wood. This ellagic acid derivative, in a manner similar to jaboticabin, showed antiradical activity and inhibited the production of the chemokine interleukin-8 after treating the human small airway epithelial cells with cigarette smoke extract. The human intestinal Caco-2 cell studies demonstrated the jaboticabin transport in vitro. The polyphenols, jaboticabin and 3,3'-dimethyellagic acid-4- O-sulfate, from jaboticaba were both found to exhibit anti-inflammatory activities, thus suggesting the potential use of these compounds or even the fruits themselves for chronic obstructive pulmonary disease.

Enantiospecific synthesis of pseudoacarviosin as a potential antidiabetic agent.

A pseudo-1,4'- N-linked disaccharide, pseudoacarviosin 5, was constructed via a key palladium-catalyzed coupling reaction of pseudoglycosyl chloride 8 (prepared from d-glucose via a novel direct intramolecular aldol addition in 12 steps) and pseudo-4-amino-4,6-dideoxy-alpha- d-glucose 9 (prepared from l-arabinose via an unusual trans-fused isoxazolidine-selective intramolecular nitrone-alkene cycloaddition in 11 steps). Pseudoacarviosin 5 has been shown to be a potent inhibitor of alpha-glucosidases, particularly the intestinal mucosal enzymes sucrase and glucoamylase of relevance to blood glucose control.