Nobiletin represses change in the levels of blood coagulation markers in the LPS-induced rat DIC model
DOI:
https://doi.org/10.31989/ffhd.v10i9.732Abstract
Background: Nobiletin is contained in Shiikuwasa fruit, a popular citrus fruit from Okinawa Prefecture in Japan. Nobiletin reportedly acts as a strong antioxidant, an anti-inflammatory agent, and an anti-cancer agent, and it suppresses the expression of TF which triggers blood coagulation. However, in vivo verification of in vitro reports is necessary. This study used a rat model of LPS-induced microthrombosis based on the in vivo studies as previously reported. Sustained intravenous injection of LPS changed all blood coagulation indicators in the direction of thrombus formation. The aim of this study was to determine if intake of nobiletin could suppress DIC-like symptoms.
Methods: Experimental SD rats were fully anesthetized and fixed to an operating table. Either LPS alone or nobiletin (50 mg/kg) plus LPS was given to rats to investigate the repressive effects of nobiletin on the expression of blood coagulation factors.
Results: After 4 h of LPS infusion (12.5 mg/kg/h, i.v.), PLT counts and Fbg levels in rat plasma decreased by 80% and 74%, respectively. PT and APTT were extended by 180% and 256%, respectively. TF activity and PAI-1 antigen levels were remarkably increased (54- and 86-fold, respectively vs. control). Pretreatment on nobiletin (50 mg/kg, p.o.) reduced or suppressed fluctuations in blood coagulation indices caused by LPS. TF activity was repressed almost completely by nobiletin pretreatment. After 4 h, PAI-1 antigen levels in nobiletin-treated animals were repressed 82.6% compared to LPS-treated rats. Nobiletin repressed LPS-induced changes in TF and PAI-1 more effectively than other parameters. Further, nobiletin repressed fibrin thrombi formation in the renal glomeruli induced by LPS treatment.
Conclusions: Nobiletin was found to reduce LPS-induced DIC-like symptoms in rats. In the fluctuations of blood indices related to the coagulation cascade, nobiletin suppressed the LPS-induced expression of PAI-1 and TF more effectively than other indices. The binding sites of transcription factors that are activated by LPS-induced signals reside in the promoter areas of TF and PAI-1 gene sequences. Thus, the suppression of TF and PAI-1 expression by nobiletin appears similar to mechanisms previously evaluated during in vitro experiments. Importantly, nobiletin repressed fibrin deposition in the renal glomeruli induced by LPS treatment and improved overall health. Nobiletin may function as an anti-thrombogenic agent when ingested daily.
Keywords: nobiletin; LPS; DIC model; blood coagulation; anti-thrombogenic
Downloads
Published
Issue
Section
License
Any manuscripts or substantial parts of it, submitted to the journal must not be under consideration by or previously published in any other journal or citable form. Authors are required to ensure that no material submitted as part of a manuscript infringes existing copyrights or the rights of a third party. In submitting one's article in any form, the author has assigned the FFC publishing rights and has agreed to an automatic transfer of the copyright to the publisher. This is so that the FFC may create print option journals, for example, at the FFC’s discretion. If the author wishes to distribute their works by means outside of the FFC, for example within their community, they will have to place a request.
Correspondence concerning articles published in Functional Foods in Health and Disease is encouraged. While derivative works (adaptations, extensions on the current work, etc.) are allowed, distribution of the modified material is not allowed without permission from the FFC.