However, in terms of its own methylation, danshensu could elevate tHcy level, which would act against its cardiovascular benefit, thus posing a ‘therapeutic paradox’. As this paradox has not been fully assessed, we have evaluated
the effects of danshensu on tHcy levels to uncover the underlying mechanisms.\n\nWe evaluated the influence of danshensu on INCB018424 purchase homocysteine (Hcy) metabolism in rats with normal tHcy levels and in rat models of elevated tHcy (single intravenous methionine loading model and a hyperhomocysteinemic model after 3 weeks methionine dosing, with and without 3 weeks of danshensu treatment). We also quantified some metabolic intermediates (S-adenosyl methionine, S-adenosyl-l-homocysteine, cysteine and glutathione) relevant to Hcy metabolism in rat liver and kidney.\n\nAcute treatment with a single dose of danshensu in rats with normal tHcy did not change plasma
tHcy. In contrast, danshensu SNX-5422 mouse significantly lowered tHcy in rats with elevated tHcy. The relatively higher cysteine and glutathione levels after treatment with danshensu indicated that its tHcy-lowering effect was via increased activity of the trans-sulphuration pathway.\n\nOur results suggested that danshensu may act both acutely to increase trans-sulphuration and after chronic exposure to up-regulate the activity of the trans-sulphuration enzymes. The tHcy-lowering effect of danshensu is another cardiovascular benefit provided by S. miltiorrhiza and suggests a potential tHcy-lowering therapy.”
“A promising therapeutic approach to reduce pathological inflammation is to inhibit the increased production of pro-inflammatory cytokines (e.g.. TNF-alpha, IL-6). In this study, we investigated the anti-inflammatory potential of 7-hydroxyfrullanolide (7HF). 7HF is an orally bioavailable, small molecule sesquiterpene lactone isolated from the fruit of Sphaeranthus indicus. 7HF significantly and dose-dependently diminished induced and spontaneous production of TNF-alpha and IL-6 from freshly isolated human mononuclear cells, synovial tissue cells isolated from patients selleck products with active
rheumatoid arthritis and BALB/c mice. Oral administration of 7HF significantly protected C57BL/6J mice against endotoxin-mediated lethality. In the dextran sulfate sodium (DSS) model of murine colitis, oral administration of 7HF prevented DSS-induced weight loss, attenuated rectal bleeding, improved disease activity index and diminished shortening of the colon of C57BL/6J mice. Histological analyses of colonic tissues revealed that 7HF attenuated DSS-induced colonic edema, leukocyte infiltration in the colonic mucosa and afforded significant protection against DSS-induced crypt damage. 7HF was also significantly efficacious in attenuating carrageenan-induced paw edema in Wistar rats after oral administration.