Sphingosine 1-phosphate (S1P) is a highly active lysophospholipid implicated in various cardiocerebrovascular events such as coagulation, myocardial infarction and stroke. However, as the functional S1P receptor antagonist, whether the S1P mimetic FTY720 can modulate coagulation and/or thrombotic formation remains largely unknown. We investigated the effects of FTY720 on adenosine diphosphate (ADP)-induced platelet aggregation, coagulation parameters and thrombus formation in rats. Pretreatment with FTY720 (2.5 mg/kg) inhibited platelet aggregation induced by ADP, elongated the thrombin time and decreased the fibrinogen levels. However, FTY720 produced no significant effects on the arteriovenous bypass thrombus formation or the FeCl3-induced thrombus formation in the inferior vena cava and the common carotid artery. Our data suggest that FTY720 can exert an inhibitory effect on platelet aggregation and coagulation-related parameters. These characteristics of FTY720 could be useful as an adjunct in the treatment of ischemic diseases such as ischemic stroke and myocardial infarction.
Sphingosine 1‐phosphate (S1P) is an important signaling sphingolipid involved in the pathogenesis of various cardio cerebral vascular diseases such as ischemic stroke. In particular, the S1P mimetic FTY720 is protective for brain against ischemic conditions. However, whether and how FTY720 can modulate vascular tone and blood pressure remains to be determined. We showed that FTY720 (1 mg/kg) enhanced the contractile response of rat thoracic aortic rings induced by high potassium and phenylephrine, respectively. This enhancement involves the activation of extracellular signal‐regulated kinase (ERK) since ERK phosphorylation was also enhanced and application of PD98059 (10 μmol/L), an inhibitor of ERK activation abrogated the aforementioned enhanced response by FTY720. In parallel, FTY720 (1 mg/kg) led to a modest elevation of blood pressure in rats, effects also being prevented by PD98059. In contrast, FTY720 decreased the high potassium‐induced contractile response in basilarartery preparations from rabbits, an effect blocked by PD98059. Together, FTY720‐induced an enhanced response of artery contractility in aorta and in arterial pressure involving ERK activation, with an attenuation in basilarartery contractility. This action property of FTY720 would be endowed with a potential of facilitating more blood flow perfusion to the brain and improving blood supply to the ischemic brain region and could be useful as an adjuvant in the treatment of ischemic stroke in the clinics.
The Osmanthus fragrans flower (OFF) is commonly used as an additive for tea in China and as a traditional medicine to treat dysentery, asthma and hepatitis. In the current study, we have acquired the aqueous extract of the dried OFF (OFFE) and determined its enriched acteoside contents. However, whether OFFE and acteoside can modulate melanogenesis and pigmentation has yet to be determined. We here provide novel data revealing that OFFE and acteoside inhibit melanogenesis induced by α-MSH in B16 melanoma cells via the MITF-tyrosinase signaling pathway. Treatment with α-MSH (1μM) enhanced melanin levels and tyrosinase activity, up-regulated the mRNA levels of MITF and tyrosinase and increased the dendritic number in B16 melanoma cells, effects all being intervened by OFFE and acteoside. Of interest, OFFE and acteoside showed no direct inhibition of tyrosinase activity as revealed by our ex vivo tyrosinase activity assay. In addition, OFFE produced a depigmenting action on UVB-induced hyperpigmentation in guinea pigs, as shown by the improved skin brightness and the decreased melanin staining. Our data have demonstrated that OFFE can alter melanogenesis via modulating the MITF-tyrosinase signaling thereby leading to its depigmenting action in the in vivo model. OFFE could be a substitute for acteoside as a promising skin-whitening agent.
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