Pharmacological effects of biologically synthesized ginsenoside CK-rich preparation (AceCK40) on the colitis symptoms in DSS-induced Caco-2 cells and C57BL mice.

BACKGROUND: Despite the notable pharmacological potential of natural ginsenosides, their industrial application is hindered by low oral bioavailability. Recent research centers on the production of less-glycosylated minor ginsenosides. PURPOSE: This study aimed to explore the effect of a biologically synthesized ginsenoside CK-rich minor ginsenoside complex (AceCK40), on ameliorating colitis using DSS-induced colitis models in vitro and in vivo. METHODS: The ginsenoside composition of AceCK40 was determined by HPLC-ELSD and UHPLC-MS/MS analyses. In vitro colitis model was established using dextran sodium sulfate (DSS)-induced Caco-2 intestinal epithelial model. For in vivo experiments, DSS-induced severe colitis mouse model was established. RESULTS: In DSS-stimulated Caco-2 cells, AceCK40 downregulated mitogen-activated protein kinase (MAPK) activation (p < 0.05), inhibited monocyte chemoattractant protein-1 (MCP-1) production (p < 0.05), and enhanced MUC2 expression (p < 0.05), mediated via signaling pathway regulation. Daily AceCK40 administration at doses of 10 and 30 mg/kg/day was well tolerated by DSS-induced severe colitis mice. These doses led to significant alleviation of disease activity index score (> 36.0% decrease, p < 0.05), increased luminal immunoglobulin (Ig)G (> 37.6% increase, p < 0.001) and IgA (> 33.8% increase, p < 0.001), lowered interleukin (IL)-6 (> 65.7% decrease, p < 0.01) and MCP-1 (> 116.2% decrease, p < 0.05), as well as elevated serum IgA (> 51.4% increase, p < 0.001) and lowered serum IL-6 (112.3% decrease at 30 mg/kg, p < 0.001). Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining revealed that DSS-mediated thickening of the muscular externa, extensive submucosal edema, crypt distortion, and decreased mucin droplets were significantly alleviated by AceCK40 administration. Additionally, daily administration of AceCK40 led to significant recovery of colonic tight junctions damaged by DSS through the elevation in the expression of adhesion molecules, including occludin, E-cadherin, and N-cadherin. CONCLUSION: This study presents the initial evidence elucidating the anti-colitis effects of AceCK40 and its underlying mechanism of action through sequential in vitro and in vivo systems employing DSS stimulation. Our findings provide valuable fundamental data for the utilization of AceCK40 in the development of novel anti-colitis candidates.

Characteristics of Phenolic Compounds in Peucedanum japonicum According to Various Stem and Seed Colors.

Total polyphenol and total flavonoid assays were performed to characterize the relationships between the color of Peucedanum japonicum (PJ) seed coat and stem and the content of phytochemical compounds. The samples were divided into two groups based on their stem and seed coat color, with each group containing 23 samples. The stem color group was subdivided into green, light red, and red, whereas the seed coat color group was divided into light brown, brown, and dark brown. In the stem color group, the light red stems exhibited the highest content of phytochemical compounds, with levels over 10% higher than those of the stems of the other colors. Moreover, among the top ten samples with the highest total polyphenol content, eight samples were light red, and the light red group also exhibited the highest total flavonoid content among the examined color groups. In terms of the seed coat color, the plants grown from dark brown seeds exhibited the highest contents of both total polyphenols and total flavonoids. In conclusion, PJ plants with dark brown seeds and light red stems contained the highest levels of phytochemical compounds. Collectively, our findings provide a valuable basis for future seed selection of PJ for pharmaceutical purposes.

Antioxidant and Anti-Inflammatory Activities of Sargassum macrocarpum Extracts.

Oxidative stress and the inflammatory response are known to be the most important pathological factors for aging skin cells. Therefore, substances that protect skin cells from oxidative stress and inflammatory reactions of the skin have potential as functional ingredients for skin care. In the present study, we investigated the potential of Sargassum macrocarpum as an anti-inflammatory candidate for inflammatory skin disease. Antioxidant and anti-inflammatory activities are desirable properties in such functional materials. The total polyphenol content as well as antioxidant and anti-inflammatory activities were evaluated in hot-water (HES) and ethanol (EES) extracts of S. macrocarpum. The polyphenol content was higher in the HES (HES: 115.9 ± 15.3 mg GA/g, EES: 3.9 ± 0.5 mg GA/g), and the HES also had ABTS (HES: IC50 1.0 ± 0.0 mg/mL, EES: IC50 16.09 ± 0.7 mg/mL) and DPPH (HES: IC50 6.50 ± 0.3 mg/mL, EES: IC50 35.3 ± 3.1 mg/mL) radical scavenging capacities as well as FRAP activity (HES: IC50 18.8 ± 0.4 mg/mL, EES: IC50 n.d.). Compared with the EES at the equivalent concentration range (1.25-20 µg/mL), the HES exerted a more potent inhibitory activity on LPS-stimulated nitric oxide (10.3-43.1%), IL-6 (15.7-45.0%), and TNF-α (14.1-20.8%) in RAW 264.7 macrophage cells in addition to TNF-α and IFN-γ-facilitated IL-6 (10.9-84.1%) and IL-8 (7.7-73.2%) in HaCaT keratinocytes. These results suggested that water-soluble materials might be deeply involved in the antioxidant and anti-inflammatory activity in S. macrocarpum. General composition analysis indicated that the HES contains more carbohydrates and polyphenols than the EES, and the monosaccharide composition analysis suggested that fucose-containing sulfated polysaccharide and ß-glucan might be potent anti-inflammatory candidates in the HES. The present study presents important preliminary results and a valuable strategy for developing novel anti-skin dermatitis candidates using a hot-water extract of S. macrocarpum.

Phenolic acids and flavonoids from Salvia plebeia and HPLC-UV profiling of four Salvia species.

We isolated and purified phenolic acids and flavonoids from the ethanolic extract of Salvia plebeia using silica gel and a Sephadex LH-20 column chromatography. Spectroscopy revealed the isolated compounds were caffeic acid, rosmarinic acid, hispidulin, luteolin, jaceosidin, nepitrin, homoplantaginin, 6-hydroxyluteolin 7-O-glucoside, 6-methoxynaringenin 7-O-glucoside, naasanone, and cosmosiin. Quantitative analyses, using high-performance liquid chromatography coupled with UV (HPLC-UV), revealed that the major flavonoid from S. plebeia was 6-hydroxyluteolin 7-O-glucoside (100.63 mg/g) and the most abundant phenolic acid was rosmarinic acid (47.73 mg/g). Furthermore, among four other Salvia species, S. officinalis contained the highest overall phenolic acid and flavonoid level but these were still lower than S. plebeia. These results can help assess the potential of phenolic acids and flavonoids as potent sources of pharmacological ingredients from different Salvia species extracts.

Antioxidant Activity and Acteoside Analysis of Abeliophyllum distichum.

This study determined acteoside and its content in Abeliophyllum distichum via HPLC/UV and LC/ESI-MS to obtain insights into the potential use of this plant as an antioxidant agent. Moreover, 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (•OH), and O2- radical scavenging activity assays were performed to assess in vitro antioxidative activity. The DPPH, •OH, and O2- radical scavenging activities of A. distichum leaf EtOH extracts at a 250 µg/mL concentration were 88.32%, 94.48%, and 14.36%, respectively, whereas those of stem extracts at the same concentration were 88.15%, 88.99%, and 15.36%, respectively. The contents of acteoside in A. distichum leaves and stems were 162.11 and 29.68 mg/g, respectively. Acteoside was identified as the main antioxidant compound in A. distichum leaves, which resulted in DPPH, •OH, and O2- radical scavenging activities of 82.84%, 89.46%, and 30.31%, respectively, at a 25 µg/mL concentration. These results indicate that A. distichum leaves and stems containing the antioxidant acteoside can be used as natural ingredients for functional and nutritional supplements.

Cardioprotective effects of BMS-180448, a prototype mitoK(ATP) channel opener, and the role of salvage kinases, in the rat model of global ischemia and reperfusion heart injury.

To investigate the involvement of reperfusion-induced salvage kinases (RISK) as possible signaling molecules for the cardioprotective effects of BMS-180448, a prototype mitochondrial ATP-sensitive K+ (mitoK(ATP)) channel opener, we measured its cardioprotective effects in a rat model of ischemia/reperfusion (I/R) heart injury, together with western blotting analysis of five different signaling proteins. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, BMS-180448 (1, 3 and 10 microM) significantly increased reperfusion left ventricular developed pressure (LVDP) and 30-min reperfusion double product (heart rate x LVDP) in a concentration-dependent manner, while decreasing left ventricular end-diastolic pressure (LVEDP) throughout reperfusion period in a concentration-dependent manner. SDS-PAGE/western blotting analysis of left ventricle reperfused for 30 min revealed that BMS-180448 significantly decreased phospho-GSK3beta at high concentration, whereas it tended to increase slightly phospho-eNOS and phospho-p70S6K with concentration. However, BMS-180448 had no effect on phospho-Akt and phospho-Bad. These results suggest that the cardioprotective effects of BMS-180448 against I/R heart injury may result from direct activation of mitoK(ATP) channel in cardiomyocytes, with the minimal role of RISK pathway in the activation of this channel and the cardioprotective effects of BMS-180448.