Anti-platelet effects of epigallocatechin-3-gallate in addition to the concomitant aspirin, clopidogrel or ticagrelor treatment.

BACKGROUND/AIMS: Although epigallocatechin-3-gallate (EGCG), which is found in high contents in the dried leaves of green tea, has been reported to have an anti-platelet effect, synergistic effects of EGCG in addition to current anti-platelet medications remains to be elucidated. METHODS: Blood samples were obtained from 40 participants who took aspirin (ASA, n = 10), clopidogrel (CPD, n = 10), ticagrelor (TCG, n = 10) and no anti-platelet medication (Control, n = 10). Ex vivo platelet aggregation and adhesion under various stimulators were analyzed by multiple electrode aggregometry (MEA) and Impact-R systems. PAC-1 and P-selectin expressions in human platelets were analyzed by flow cytometry. RESULTS: In MEA analysis, adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP)-induced platelet aggregations were lower in the CPD and the TCG groups; arachidonic acid (AA)-induced platelet aggregation was lower in the ASA group, whereas collagen (COL)-induced platelet aggregations were comparable among four groups. EGCG significantly reduced ADP- and COL-induced platelet aggregation in dose-dependent manner (ADP, p = 0.04; COL, p < 0.01). There were no additional suppressions of platelet aggregation stimulated by AA in the ASA group, and by ADP in the CPD and TCG groups. Moreover, EGCG suppressed shear stress-induced platelet adhesion on Impact-R, and had no effect on P-selectin and PAC-1 expressions. CONCLUSIONS: Ex vivo treatment of EGCG inhibited platelet adhesion and aggregation without changes in P-selectin and PAC-1 expression. There was no additional suppressions in platelet aggregation stimulated by AA in the ASA group and ADP in the CPD and TCG groups.

Platycodon grandiflorus Root Extract Improves Learning and Memory by Enhancing Synaptogenesis in Mice Hippocampus.

Platycodon grandiflorus (Jacq.) A.DC. (PG) has long been used as an ingredient of foods and is known to have beneficial effects on cognitive functions as well. The present study examined the effect of each PG extract (PGE) from root, aerial part, and seeds on cognitive functions in mice. Changes in spatial learning and memory using a Y-maze test, and markers of adult hippocampal neurogenesis and synaptogenesis were examined. Moreover, changes in neuritogenesis and activation of the ERK1/2 pathway were investigated. Results indicated that mice administered PGE (root) showed increased spontaneous alternation in the Y-maze test and synaptogenesis in the hippocampus. In addition, PGE (root) and platycodin D, the major bioactive compound from the PG root, significantly stimulated neuritic outgrowth by phosphorylation of the ERK1/2 signaling pathway in vitro. These results indicate that the PGE (root), containing platycodin D, enhances cognitive function through synaptogenesis via activation of the ERK1/2 signaling pathway.

Anti-inflammatory, anti-nociceptive, and anti-psychiatric effects by the rhizomes of Alpinia officinarum on complete Freund's adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance (Zingiberaceae) is an annual plant. Its rhizome has long been used as an anti-inflammatory, an analgesic, a stomachic and a carminative in traditional medicine. OBJECTIVE: The aim of this study was to test the anti-inflammatory effects of Alpinia officinarum rhizomes on acute and chronic arthritis in SD rats. METHODS: Alpinia officinarum rhizomes were extracted by refluxing using 80% ethanol. The fractions were prepared by the fractionation of ethyl acetate (EtOAc), n-butanol, and water. This extract was administrated to rats by peroral injection. Acute arthritis was induced by a subcutaneous injection of carrageenan into the hind paw of SD rats. Chronic arthritis was stimulated by a subcutaneous injection of complete Freund's adjuvant (CFA) into the hind paw of SD rats. The paw volume was measured using a plethysmometer, thermal hyperalgesia was tested using a thermal plantar tester, hyperalgesia was evaluated by ankle flexion evoked vocalizations, and the expression of c-Fos in the brain hippocampus was measured with the avidin-biotin-peroxidase technique. Nitric oxide (NO) production was evaluated on nitrite by a Griess assay in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. RESULTS: An 80% ethanolic extract showed acute anti-inflammatory activity that it reduced the edema volume in carrageenan-stimulated arthritis and inhibited NO generation in LPS-induced RAW 264.7 cells. In addition, this extract showed chronic anti-rheumatic and analgesic activities by suppressing the swelling volume, by recovering the paw withdrawal latency, and by inhibiting the flexion scores in CFA-induced arthritis. Particularly, this medicine had potent meaningful effects on the second signal of the left hind paw in the form of an immunological reaction compared to its effects on the first signal in the right hind paw after the CFA treatment. This also shows an anti-psychiatric effect through control of the expression of the c-Fos protein of the brain hippocampus in CFA-stimulated arthritis. On the other hand, each fraction showed acute anti-inflammatory effects; the action of the EtOAc fraction may have resulted from the suppression of NO production. CONCLUSIONS: Alpinia officinarum rhizomes may be viable therapeutic or preventive candidates for the treatment of acute and chronic arthritis.

Successful use of magnetic resonance-guided focused ultrasound surgery to relieve symptoms in a patient with symptomatic focal adenomyosis.

OBJECTIVE: To report a successful treatment of symptomatic adenomyosis using magnetic resonance-guided focused ultrasound surgery (MRgFUS). DESIGN: Case study. SETTING: General hospital. PATIENT(S): A 47-year-old premenopausal woman with focal symptomatic adenomyosis. INTERVENTION(S): MRgFUS. MAIN OUTCOME MEASURE(S): Score on the Uterine Fibroids Symptoms Quality of Life (UFS-QOL) questionnaire and the degree of menstrual pain. RESULT(S): Uterine Fibroids Symptoms reduced from 53 to 28 and the degree of menstrual pain reduced from 10 to 5. CONCLUSION(S): For adenomyosis patients who wish to preserve their uterus, MRgFUS may be a promising alternative to hysterectomy. Additional studies of the safety and efficacy of MRgFUS in this indication should be conducted.

Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes.

Oleanolic acid (OA) and ursolic acid (UA), triterpene acids having numerous pharmacological activities including anti-inflammatory, anti-cancer, and hepato-protective effects, were tested for their ability to modulate the activities of several cytochrome P450 (CYP) enzymes using human liver microsomes. OA competitively inhibited CYP1A2-catalyzed phenacetin O-deethylation and CYP3A4-catalyzed midazolam 1-hydroxylation, the major human drug metabolizing CYPs, with IC50 (Ki) values of 143.5 (74.2) microM and 78.9 (41.0) microM, respectively. UA competitively inhibited CYP2C19-catalyzed S-mephenytoin 4'-hydroxylation with an IC50 (Ki) value of 119.7 (80.3) microM. However, other CYPs tested showed no or weak inhibition by both OA and UA. The present study demonstrates that OA and UA have inhibitory effects on CYP isoforms using human liver microsomes. It is thus likely that consumption of herbal medicines containing OA or UA, or administration of OA or UA, can cause drug interactions in humans when used concomitantly with drugs that are metabolized primarily by CYP isoforms. In addition, it appears that the inhibitory effect of OA on CYP1A2 is, in part, related to its anti-inflammatory and anticancer activities.

Modulation of Chelidonii herba on glycine-activated and glutamate-activated ion currents in rat periaqueductal gray neurons.

BACKGROUND: Chelidonii herba is classified as Papaver somniferum L. Aqueous extract from C. herba is traditionally used for disorders with symptoms like pain, bloating, abdominal cramp after meals. METHODS: Modulation of C. herba on glycine-activated and glutamate-activated ion currents in the acutely dissociated periaqueductal gray (PAG) neurons was investigated by the nystatin-perforated patch-clamp technique. RESULTS: C. herba inhibited glycine-activated ion current and increased glutamate-activated ion current. C. herba-induced inhibition on glycine-activated ion current is implicated in opioid receptors and GTP-binding proteins (G-proteins). Increased glutamate-activated ion current induced by C. herba is linked neither by opioid receptors nor GTP-binding proteins. CONCLUSIONS: Suppressed glycine-induced response and elevated glutamate-induced response by C. herba may increase neuronal excitability in PAG, results in activation of descending pain control system, and this mechanism can be suggested as one of the analgesic actions of C. herba.