Qingli Wu

AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-β peptide metabolism.

Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Aβ levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Aβ metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-β. Direct pharmacological and genetic activation of AMPK lowered extracellular Aβ accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Aβ levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Aβ. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Aβ levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease.

Recent Advances in Anthocyanin Analysis and Characterization

Anthocyanins are a class of polyphenols responsible for the orange, red, purple and blue colors of many fruits, vegetables, grains, flowers and other plants. Consumption of anthocyanins has been linked as protective agents against many chronic diseases and possesses strong antioxidant properties leading to a variety of health benefits. In this review, we examine the advances in the chemical profiling of natural anthocyanins in plant and biological matrices using various chromatographic separations (HPLC and CE) coupled with different detection systems (UV, MS and NMR). An overview of anthocyanin chemistry, prevalence in plants, biosynthesis and metabolism, bioactivities and health properties, sample preparation and phytochemical investigations are discussed while the major focus examines the comparative advantages and disadvantages of each analytical technique.

Green Tea Protects Rats against Autoimmune Arthritis by Modulating Disease-Related Immune Events

Green tea, a product of the dried leaves of Camellia sinensis, is the most widely consumed beverage in the world. The polyphenolic compounds from green tea (PGT) possess antiinflammatory properties. We investigated whether PGT can afford protection against autoimmune arthritis and also examined the immunological basis of this effect using the rat adjuvant arthritis (AA) model of human rheumatoid arthritis (RA). AA can be induced in Lewis rats (RT.1(l)) by immunization with heat-killed Mycobacterium tuberculosis H37Ra (Mtb), and arthritic rats raise a T cell response to the mycobacterial heat-shock protein 65 (Bhsp65). Rats consumed green tea (2-12 g/L) in drinking water for 1-3 wk and then were injected with Mtb to induce disease. Thereafter, they were observed regularly and graded for signs of arthritis. Subgroups of these rats were killed at defined time points and their draining lymph node cells were harvested and tested for T cell proliferative and cytokine responses. Furthermore, the sera collected from these rats were tested for anti-Bhsp65 antibodies. Feeding 8 g/L PGT to Lewis rats for 9 d significantly reduced the severity of arthritis compared with the water-fed controls. Interestingly, PGT-fed rats had a lower concentration of the proinflammatory cytokine interleukin (IL)-17 but a greater concentration of the immunoregulatory cytokine IL-10 than controls. PGT feeding also suppressed the anti-Bhsp65 antibody response. Thus, green tea induced changes in arthritis-related immune responses. We suggest further systematic exploration of dietary supplementation with PGT as an adjunct nutritional strategy for the management of RA.

Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson׳s disease.

Neuropathological evidence indicates that dopaminergic cell death in Parkinson׳s disease (PD) involves impairment of mitochondrial complex I, oxidative stress, microglial activation, and the formation of Lewy bodies. Epidemiological findings suggest that the consumption of berries rich in anthocyanins and proanthocyanidins may reduce PD risk. In this study, we investigated whether extracts rich in anthocyanins, proanthocyanidins, or other polyphenols suppress the neurotoxic effects of rotenone in a primary cell culture model of PD. Dopaminergic cell death elicited by rotenone was suppressed by extracts prepared from blueberries, grape seed, hibiscus, blackcurrant, and Chinese mulberry. Extracts rich in anthocyanins and proanthocyanidins exhibited greater neuroprotective activity than extracts rich in other polyphenols, and a number of individual anthocyanins interfered with rotenone neurotoxicity. The blueberry and grape seed extracts rescued rotenone-induced defects in mitochondrial respiration in a dopaminergic cell line, and a purple basal extract attenuated nitrite release from microglial cells stimulated by lipopolysaccharide. These findings suggest that anthocyanin- and proanthocyanidin-rich botanical extracts may alleviate neurodegeneration in PD via enhancement of mitochondrial function.

Phytochemical and biological studies of Lycium medicinal plants.

by Xia Yaoa), Yong Penga), Li-Jia Xua), Li Lia), Qing-Li Wub), and Pei-Gen Xiao*a) a) Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, 151 Malianwa North Road, Beijing 100193, P. R. China (phone: þ86-10-63011294; e-mail: xiaopg@public.bta.net.cn) b) New Use Agriculture and Natural Plant Products Program, Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901, USA

Anti-inflammatory activity of edible oyster mushroom is mediated through the inhibition of NF-κB and AP-1 signaling

BackgroundMushrooms are well recognized for their culinary properties as well as for their potency to enhance immune response. In the present study, we evaluated anti-inflammatory properties of an edible oyster mushroom (Pleurotus ostreatus) in vitro and in vivo.MethodsRAW264.7 murine macrophage cell line and murine splenocytes were incubated with the oyster mushroom concentrate (OMC, 0-100 μg/ml) in the absence or presence of lipopolysacharide (LPS) or concanavalin A (ConA), respectively. Cell proliferation was determined by MTT assay. Expression of cytokines and proteins was measured by ELISA assay and Western blot analysis, respectively. DNA-binding activity was assayed by the gel-shift analysis. Inflammation in mice was induced by intraperitoneal injection of LPS.ResultsOMC suppressed LPS-induced secretion of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6), and IL-12p40 from RAW264.7 macrophages. OMC inhibited LPS-induced production of prostaglandin E2 (PGE2) and nitric oxide (NO) through the down-regulation of expression of COX-2 and iNOS, respectively. OMC also inhibited LPS-dependent DNA-binding activity of AP-1 and NF-κB in RAW264.7 cells. Oral administration of OMC markedly suppressed secretion of TNF-α and IL-6 in mice challenged with LPS in vivo. Anti-inflammatory activity of OMC was confirmed by the inhibition of proliferation and secretion of interferon-γ (IFN-γ), IL-2, and IL-6 from concanavalin A (ConA)-stimulated mouse splenocytes.ConclusionsOur study suggests that oyster mushroom possesses anti-inflammatory activities and could be considered a dietary agent against inflammation. The health benefits of the oyster mushroom warrant further clinical studies.

Survey of Polyphenol Constituents in Grapes and Grape-Derived Products

A rapid and comprehensive qualitative method has been developed to characterize the different classes of polyphenols, such as anthocyanins, flavonols, phenolic acids, and flavanols/proanthocyanidins, in grape products. The detection was achieved by two runs with the same LC gradient in different MS ionization modes and mobile phase modifiers (positive ionization mode and 0.4% trifluoroacetic acid for anthocyanins and flavonols; negative ionization mode and 0.1% formic acid for phenolic acids and flavanols). From an analysis of the MS and UV data and in comparison with the authenticated standards, a total of 53 compounds were identified, including 33 anthocyanins, 12 flavonols, 4 phenolic acids, and 4 flavanols/proanthocyanidins. With the method developed, a survey was then conducted to qualitatively assess the composition of polyphenols among 29 different grape products including original grape, grape juice, grape wine, and grape-derived dietary supplements, and their chemical profiles were systematically compared. This method provided a comprehensive qualitative insight into the composition of polyphenols in grape-derived products.

Phytochemistry, antioxidant capacity, total phenolic content and anti-inflammatory activity of Hibiscus sabdariffa leaves

A liquid chromatography-mass spectrometry method was developed for the simultaneous separation, and determination of natural compounds including phenolic acids and flavonoids in the leaves of Hibiscus sabdariffa. By analyzing the UV and MS data, and comparison with authenticated standards, 10 polyphenols including neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, quercetin, kaempferol and their glycosides were identified together with 5-(hydroxymethyl)furfural. Major constituents in the leaves of 25 different populations from worldwide accessions were quantified and compared with each other. The total phenolic content of each accession was determined using Folin-Ciocalteu assay, ranging from 18.98 ± 2.7 to 29.9 ± 0.5 mg GAE/g. Their in vitro antioxidant activities were measured by ABTS radical cation decolorization assay, varying from 17.5 to 152.5 ± 18.8 μmol Trolox/g. After the treatment of H. sabdariffa leaf extract, the reduction of LPS-induced NO production dose-dependently in RAW 264.7 cell indicates the extracts potential anti-inflammatory activity.

Chemistry and quality of Hibiscus (Hibiscus sabdariffa) for developing the natural-product industry in Senegal.

The objectives of this study were to assess and improve the quality of the hibiscus calyces from Senegal over 2 production seasons (2004 to 2005), to develop and adapt new procedures for the determination of hibiscus anthocyanins and analysis of the 2 major ones, delphinidin-3-sambubioside and cyanidin-3-sambubioside. The foreign matter, total ashes, and acid insoluble ashes showed that the calyces harvested in 2005 were produced following hygienic practices, while the color assessment of the calyces and analysis of hibiscus active principles also showed higher amounts of anthocyanins in 2005. A protocol to measure anthocyanins by pH-differential UV-Vis spectrophotometry was adapted to measure the hibiscus anthocyanins from a water extract. The spectrophotometric method for quantitation of total anthocyanins showed a close correlation (r(2)= 0.82) when compared with the HPLC method, suggesting the use of the colorimetric method in quality control programs as an affordable alternative method to assess anthocyanin content in hibiscus. New and raised standards for the cleanliness and active principle content in hibiscus are also proposed. This study demonstrated that the implementation of a quality control program and the application of agricultural good practices in the production and processing of hibiscus calyces can lead to higher quality natural plant products.

LC-MS Method for the Simultaneous Quantitation of the Anti-inflammatory Constituents in Oregano (Origanum Species)

Oregano (Origanum spp.), a popular herb in western and Middle Eastern cuisine, was reported to show anti-inflammatory activities in vitro and in vivo but without any information as to the compounds responsible, whether the plants were authenticated or only contained true Origanum spp. Using a wide range of botanically authenticated oregano, we were able to show that oregano had anti-inflammatory activity and then using biodirected-guided fractionation, identified the anti-inflammatory agents in oregano as rosmarinic acid, oleanolic acid, and ursolic acid. In this study, we successfully developed an LC-MS (SIM mode) method to achieve coquantitation of these three organic acids with the application of a unique tandem column system. The detection of rosmarinic acid was optimal under negative ion mode of SIM, whereas oleanolic acid and ursolic acid were sensitive to positive ion mode. The simultaneous quantitation was attained by setting two time segments in one run to facilitate the ESI polarity switch. For the investigated analytes romarinic acid, oleanolic acid, and ursolic acid, good linearities (r(2) > 0.999) were obtained for each calibration curve. Validation for this method showed a precision (relative standard deviation) ranging from 4.84 to 6.41%, and the recoveries varied from 92.2 to 100.8% for the three analytes. A quantitative survey of these anti-inflammatory constituents in different oregano species (O. vulgare ssp. hirtum, O. vulgare, and O. syriacum) and chemotypes within the species varied significantly in their accumulation of rosmarinic, oleanolic, and ursolic acids. Significant variation in chemical composition between species and within a species was found.