Hui Teng

Modifications of Dietary Flavonoids towards Improved Bioactivity: An Update on Structure-activity Relationship

ABSTRACT Over the past two decades, extensive studies have revealed that inflammation represents a major risk factor for various human diseases. Chronic inflammatory responses predispose to pathological progression of chronic illnesses featured with penetration of inflammatory cells, dysregulation of cellular signaling, excessive generation of cytokines, and loss of barrier function. Hence, the suppression of inflammation has the potential to delay, prevent, and to treat chronic diseases. Flavonoids, which are widely distributed in humans daily diet, such as vegetables, fruits, tea and cocoa, among others, are considered as bioactive compounds with anti-inflammatory potential. Modification of flavonoids including hydroxylation, o-methylation, and glycosylation, can alter their metabolic features and affect mechanisms of inflammation. Structure–activity relationships among naturally occurred flavonoids hence provide us with a preliminary insight into their anti-inflammatory potential, not only attributing to the antioxidant capacity, but also to modulate inflammatory mediators. The present review summarizes current knowledge and underlies mechanisms of anti-inflammatory activities of dietary flavonoids and their influences involved in the development of various inflammatory-related chronic diseases. In addition, the established structure–activity relationships of phenolic compounds in this review may give an insight for the screening of new anti-inflammatory agents from dietary materials.

Agrimonolide from Agrimonia pilosa suppresses inflammatory responses through down-regulation of COX-2/iNOS and inactivation of NF-κB in lipopolysaccharide-stimulated macrophages

BACKGROUND Agrimonolide from Agrimonia pilosa showed a strong anti-inflammatory activity, and the present study aims to reveal potential mechanisms on molecular level explaining its anti-inflammatory effect. HYPOTHESIS/PURPOSE To investigate the mechanism of anti-inflammatory activity of agrimonolide. STUDY DESIGN Anti-inflammatory activity of agrimonolide in cells was applied. METHODS Anti-inflammatory activity of agrimonolide isolated from Agrimonia pilosa was evaluated using lipopolysaccharide (LPS) stimulated RAW 264.7 cell models. The productions of IL-1β, IL-6, TNF-α and NO were determined by ELISA and nitrite analysis, respectively. The expressions of iNOS and COX-2 were measured by western blotting and RT-PCR analysis. RESULTS The pre-treatment with agrimonolide significantly reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), as well as attenuated the expression of iNOS and COX-2 in LPS-stimulated macrophages. Furthermore, agrimonolide inhibited the activation of JNK and p38 MAPKs and decreased the activation of JAK-STAT and NF-κB in LPS-stimulated macrophages. CONCLUSION The present study suggested that agrimonolide exerted anti- inflammatory activity, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signaling pathway.

Intracellular signaling pathways of inflammation modulated by dietary flavonoids: The most recent evidence

ABSTRACT Dietary flavonoids, which occur in many plant foods, are considered as the most active constituents among the plant-derived ones in vitro and in vivo. To date, many studies have addressed the anti-inflammatory activity of flavonoids. However, their considerable structural diversity and in vivo bioavailability make them able to modulate different signaling pathways. The present review attempted to summarize and highlight a broad range of inflammation-associated signaling pathways modulated by flavonoids. Finally, based on the current scientists literature, structure-activity relationships were concluded. Dietary flavonoids have the ability to attenuate inflammation by targeting different intracellular signaling pathways triggered by NF-κB, AP-1, PPAR, Nrf2, and MAPKs. Identification of the main structural features required for the modulation of these inflammation-related pathways (hydroxylation pattern, C2=C3 double bond) have an important role to play in the development of new anti-inflammatory drugs.

α-Glucosidase and α-amylase inhibitors from seed oil: a review of liposoluble substance to treat diabetes

ABSTRACT One of the effective managements of diabetes mellitus, in particular, noninsulin-dependent diabetes mellitus, is to retard the absorption of glucose by inhibition of carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase, in the digestive organs. Currently, there is renewed interest in plant-based medicines and functional foods modulating physiological effects in the inhibition of α-glucosidase and α-amylase. Accordingly, inhibitors of α-glucosidase or α-amylase derived from various sources have also been isolated, and majority of phenolic compounds and their effects have been investigated in animals as well. As such, when the presence of α-glucosidase inhibitor in many foodstuffs was screened for, we found that vegetable seed oil also strongly inhibited α-glucosidase and α-amylase. Seed oil is an important source of liposoluble constituents with potential for inhibition of these enzymes, hence can also be used as therapeutic or functional food sources. Therefore, this review is aimed at highlighting the main liposoluble classes of α-glucosidase and α-amylase inhibitors, but it is not intended to be an exhaustive review on the subject.

Ultrasonic-Assisted Extraction of Raspberry Seed Oil and Evaluation of Its Physicochemical Properties, Fatty Acid Compositions and Antioxidant Activities

Ultrasonic-assisted extraction was employed for highly efficient separation of aroma oil from raspberry seeds. A central composite design with two variables and five levels was employed and effects of process variables of sonication time and extraction temperature on oil recovery and quality were investigated. Optimal conditions predicted by response surface methodology were sonication time of 37 min and extraction temperature of 54°C. Specifically, ultrasonic-assisted extraction (UAE) was able to provide a higher content of beneficial unsaturated fatty acids, whereas conventional Soxhlet extraction (SE) resulted in a higher amount of saturated fatty acids. Moreover, raspberry seed oil contained abundant amounts of edible linoleic acid and linolenic acid, which suggest raspberry seeds could be valuable edible sources of natural γ-linolenic acid products. In comparison with SE, UAE exerted higher free radical scavenging capacities. In addition, UAE significantly blocked H2O2-induced intracellular reactive oxygen species (ROS) generation.

Inhibition of cell proliferation and triggering of apoptosis by agrimonolide through MAP kinase (ERK and p38) pathways in human gastric cancer AGS cells

Data from the present study showed that agrimonolide exhibited a high anti-proliferation effect against human gastric cancer AGS cells. Flow cytometric analysis revealed that the number of total apoptotic cells increased after the treatment with the agrimonolide in a dose-dependent manner. In addition, it was found that agrimonolide-induced cell apoptosis was associated with the increase in the (Bcl-2 Associated X Protein, BAX)/(B-cell lymphoma-2, Bcl-2) ratio and the activation of cleaved caspase-3. MAPK (p38, c-Jun N-terminal kinase, and ERK1/2) signaling pathways were involved in agrimonolide-induced apoptosis. Cells were exposed to 40 μM of agrimonolide and the level of phospho-ERK/ERK protein was increased to 7.0-fold as compared to the control, and the expression of phospho-p38 protein showed a significant 6.2-fold increase after 24 h incubation, as compared to the control. The employment of protein kinase inhibitors of PD98059 and SB203580, showed the block effects of agrimonolide on the activation of caspase-3 and apoptosis.

The potential beneficial effects of phenolic compounds isolated from A. pilosa Ledeb on insulin-resistant hepatic HepG2 cells

Agrimonia pilosa Ledeb (AP) has already been applied in practice for the treatment of different disorders and is available to access without the provision of a medical prescription. The present study aims at investigating the effect of bioactive compounds isolated from AP on the improvement of insulin resistance, figuring out the mechanism in insulin-responsive cell lines. Five compounds were isolated from AP using column chromatography, including agrimonolide (K1), desmethylagrimonolide (K2), tormentic acid (K3), ursolic acid (K4), and quercetin (K5). Glucose metabolism was evaluated in insulin-resistant HepG2 cells. Ursolic acid had the strongest activity among all isolated compounds with the lowering value of 71.5% (1.24 mM glucose in DMEM) and 71.7% (1.23 mM) when compared to the control. K1 consisting of K2 effectively increased the insulin-mediated glycogen level in hepatocytes. At a concentration level of 20 μM, K2 significantly elevated the hepatic glucokinase (GK) activity (3.2 U min-1 mg-1 protein), followed by K1 (3.0 U min-1 mg-1 protein). Both of them significantly increased (p < 0.05) the GK activity as compared to the control. On the same lines, K2 and K1 caused a significant reduction of the glucose-6-phosphatase (G6Pase) activity and a significant change in the phosphoenolpyruvate carboxykinase (PEPCK) activity. In summary, bioactive compounds in AP may play an important role in regulating the glucose metabolism in insulin-resistant HepG2 cells and could be developed as a promising natural material for diabetes prevention and treatment.

Effect of Different Drying Method on Volatile Flavor Compounds of Lactarius deliciosus

The effect of different drying methods on volatile flavor compounds of Lactarius deliciosus was investigated, such as hotair drying, vacuum freeze drying and sunshine drying. By adopting the solid-phase micro-extraction method, volatile flavor compounds were extracted from Lactarius deliciosus, then analyzed and identified through the application of gas chromatography-mass spectrometer (GC-MS). Results indicated that different drying methods could lead to large differences in volatile flavor compounds. Main volatile flavor compounds of fresh Lactarius deliciosus involved acids and aldehydes, which accounted for 86.31%; Hot-air dried Lactarius deliciosus mainly included acids and alkene, which accounted for 87.16%; Lactarius deliciosus dried with vacuum freezed Lactarius deliciosus was mostly composed of acids, esters and aromatic substance, which accounted for 94.74%; Lactarius deliciosus dried with sunshine was constituted by acid and aldehydes, which was as high as 90.67%.

Agrimonolide and Desmethylagrimonolide Induced HO-1 Expression in HepG2 Cells through Nrf2-Transduction and p38 Inactivation

Agrimonolide and desmethylagrimonolide are the main bioactive polyphenols in agrimony with well-documented antioxidant, anti-diabetic, and anti-inflammatory potential. We report here for the first time that agrimonolide and desmethylagrimonolide stimulate the expression of phase II detoxifying enzymes through the Nrf2-dependent signaling pathway. Agrimonolide and desmethylagrimonolide also possess considerable protective activity from oxidative DNA damage. In order to explore the cytoprotective potential of agrimonolide and desmethylagrimonolide on oxidative stress in liver, we developed an oxidative stress model in HepG2 cells, and check the hypothesis whether Nrf2 pathway is involved. Western blotting and luciferase assay revealed that exposure of HepG2 cells to agrimonolide or desmethylagrimonolide leads to increased heme oxygenase-1 (HO-1) expression by activating ARE through induction of Nrf2 and suppression of Kelch-like ECH-associated protein 1 (Keap1). Moreover, agrimonolide and desmethylagrimonolide also activated ERK signaling pathways and significantly attenuated individual p38 MAPK expression, subsequently leading to Nrf2 nuclear translocation. In conclusion, our results indicated that transcriptional activation of Nrf2/ARE is critical in agrimonolide and desmethylagrimonolide-mediated HO-1 induction, which can be regulated partially by the blockade of p38 MAPK signaling pathway and inhibiting nuclear translocation of Nrf2.

Polyphenols and Bioavailability: an update

Abstract Based on many cell culture, animal and human studies, it is well known that the most challenge issue for developing polyphenolics as chemoprevention or anti-diabtetic agents is the low oral bioavailability, which may be the major reason relating to its ambiguous therapeutic effects and large inter-individual variations in clinical trials. This review intends to highlight the unscientific evaluation on the basis of the published data regarding in vitro bioactivity of polyphenols, which may sometimes mislead the researchers and to conclude that: first, bio-accessibilities values obtained in the studies for polyphenols should be highly reconsidered in accordance with the abundant newly identified circulating and excreted metabolites, with a particular attention to colonic metabolic products which are obviously contributing much more than expected to their absorptions; second, it is phenolic metabolites, which are formed in the small intestine and hepatic cells,low molecular weight catabolic products of the colonic microflora to travel around the human body in the circulatory system or reach body tissues to elicit bioactive effects. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.