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Immune responses to infection or to localized injury or trauma are among the main causes of local or systemic inflammation. Despite the beneficial effect of inflammation in limiting responses to cellular and organ damage, a breakdown in the regulation of the inflammatory response may result in a wide range of chronic diseases such as arthritis, inflammatory bowel diseases, asthma and others. 1)Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, sulindac and indomethacin, are widely believed to have anti-inflammatory effects due to their ability to inhibit prostanoid production, and relieve inflammation by inhibiting cyclooxygenase (COX).COX are the rate-limiting enzymes that catalyze the formation of prostaglandins from arachidonic acid.2-5) Levels of prostaglandins increase early in the course of the inflammatory process. The constitutive isoform, COX-1, is expressed in most tissues predominantly in platelets, gastrointestinal tract, kidney, and liver.2-4) The inducible isoform, COX-2, is activated in response to pro-inflammatory cytokines and growth factors.3,4) Because COX-2 protein is induced by several kinds of stimuli in inflammatory cells, inhibitors of COX-2 protein induction might be candidates for the new-type NSAIDs. Also, inflammation is associated with inducible nitric oxide synthase (iNOS). Especially, nitric oxide (NO) produced by activated macrophages via iNOS was initially considered a component of innate immunity in the fight against infections. 6) It has been well accepted that nuclear-factor-kB (NF-kB) signaling pathway plays important roles in the inflammation, control of cell growth, apoptosis, stress response, and many other physiological processes. [7][8][9][10][11] There are several important molecules such as NF-kB, inhibitor kB (IkB), IKK, within NF-kB signaling pathway.12) NF-kB is a key protein in the pathway, and has been described as a major culprit and a therapeutic target in inflammation and cancer. [13][14][15][16] It is activated by lipopolysaccharide (LPS), which is a mammalian transcription factor that controls various genes that are important for immunity and inflammation.17) NF-kB is mainly composed of p50 and p65. 17) In unstimulated cells, NF-kB is present in the cytoplasm through interactions with an inhibitory protein, IkB. NF-kB is activated by IkBa degradation following phosphorylation of IkBa. 18)Platycodi Radix is the root of Platycodon grandiflorum A. DE (Campanulaceae).19) It is edible and the principal herb in Oriental medicine for diseases of the lungs and throat, and is commonly used for the inflammatory conditions of the eyes, ears, and sinuses.19) Saponins (PS) are the primary constituents of Platycodi Radix, [20][21][22] and they are responsible for diverse effects including anti-inflammation, [23][24][25][26] anti-allergy, 23) anti-tumor, 27) augmentation of immune response, [28][29][30] and stimulating the apoptosis in skin cells. 27) In the last decade, PS has generated renewed interests due to their pharmacological potentials for healing the...

ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.

Platycodon grandiflorum A. DC (Campanulaceae) is a traditional medicinal plant. Its root, Platycodi Radix, contains an abundant amount of saponin glycosides, platycodins, of which platycodin D is one of the major components. The chemical structures of platycodins can be modified by various types of chemical processing, but a modification mediated with microorganisms has been not reported yet. In this study, platycodin D was modified to several partially degraded platycodin glycosides after treatment with a crude enzyme extract from Aspergillus niger (A. niger). The modified platycodin D possessed a shorter sugar side-chain, and presented a remarkably reduced V79-4 cell (Chinese hamster lung fibroblasts) cytotoxicity and erythrocyte hemolytic toxicity, whereas the nitrite-scavenging activity was increased in the modified platycodin D. Sensory scores for pungency, bitterness and after-taste were improved as well in the modified platycodin D. Results suggest that A. niger mediated modification yielded a novel partially degraded platycodin glycoside which possesses increased bioactivities and improved sensory values, yet with reduced toxic profiles.

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to investigate the effects of puerarin on hepatic oxidative stress and hyperlipidaemia in mice exposed to carbon tetrachloride (CCl4). Male ICR mice were injected with CCl4 with or without puerarin co-administration (200 and 400 mg/kg intragastrically once-daily) for 8 weeks. Our data showed that puerarin significantly prevented CCl4-induced hepatotoxicity, indicated by both diagnostic indicators of the liver damage (serum aminotransferase levels) and histopathological analysis. Puerarin decreased the thiobarbituric acid reactive substances (TBARS) and the protein carbonyl content (PCO) in the liver of CCl4-treated mice. Puerarin also restored the levels of reduced glutathione (GSH) and total antioxidant capacity (TAC) in the liver. Furthermore, the increase in serum cholesterol, triglycerides and low-density lipoproteins (LDL) induced by CCl4 was effectively suppressed by puerarin. The high-density lipoprotein (HDL) level in the CCl4 treatment mice was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidaemia by regulating the expression of phosphorylated Jun N-terminal kinases (JNK), phosphorylated c-Jun protein and cholesterol 7a-hydroxylase (CYP7A1) in the liver of CCl4-treated mice. Altogether, these results suggest that puerarin could protect the CCl4-induced liver injury and hyperlipidaemia by reducing reactive oxygen species S production, renewing the total antioxidant capacity and influencing expression of hepatic lipid biosynthesis and metabolism genes.

A 1, 2-diglyceride-based multi-step colorimetric assay to measure the pancreatic lipase activity was applied for the determination of the kinetic profiles of the lipase inhibition with a slight modification and the validity verification. With this assay method, our study revealed that platycodin D, one of major constituents of Platycodi Radix, inhibits the pancreatic lipase activity in a competitive type, with the value of Kl being 0.18 +/- 0.02 mM. In addition, PD has affected the values of Km,app and Kcat/Km in a dose- dependent manner. The results shed a meaningful light on how PD mediates lipid metabolism in the intestinal tracts. On the other hand, since the revised assay is sensitive, rapid, and does not affect the accuracy to the kinetic properties, it is applicable not only to evaluation of the kinetic properties of the pancreatic lipase, but also to high-throughput screening of pancreatic lipase activity.

Background Chondrocyte apoptosis and catabolism are 2 major factors that contribute to the progression of osteoarthritis (OA). Loganin, an iridoid glycoside present in several herbs, including Flos lonicerae , Cornus mas L , and Strychnos nux vomica, is a valuable medication with anti-inflammatory and anti-apoptotic effects . Our study examines these effects and explores the potential benefits of loganin in the OA treatment. Material/Methods To clarify the roles of loganin in OA and its specific signaling pathway, chondrocytes were administrated with IL-1β and supplemented with or without LY294002 (a classic PI3K/Akt inhibitor). The apoptotic level, catabolic factors (MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5), extracellular matrix (ECM) degradation, and activation of the PI3K/Akt pathway were evaluated using western blotting, PCR, and an immunofluorescent assay. The degenerative condition of the cartilage was evaluated using the Safranin O assay in vivo . The expression of cleaved-caspase-3 (C-caspase-3) was measured using immunochemistry. Results The data suggested that loganin suppressed the apoptotic level, reduced the release of catabolic enzymes, and decreased the ECM degradation of IL-1β-induced chondrocytes. However, suppressing PI3K/Akt signaling using LY294002 alleviated the therapeutic effects of loganin in chondrocytes. Our in vivo experiment showed that loganin partially attenuated cartilage degradation while inhibiting the apoptotic level. Conclusions This work revealed that loganin treatment attenuated IL-1β-treated apoptosis and ECM catabolism in rat chondrocytes via regulation of the PI3K/Akt signaling, revealing that loganin is a potentially useful treatment for OA.