ABSTRACT
Introduction: IFN-α is the main cytokine in SLE, and single nucleotide polymorphisms (SNP) in different genes could induce it. Aim: To determine the association of rs2004640 (IRF5), rs179008 (TLR7), rs1800795 (IL-6) and rs2280788 (CCL5) with SLE in Mexican women with Mayan ethnicity. Methods: DNA and RNA were isolated from the peripheral blood of 110 patients and 200 healthy control subjects. SNP genotyping and gene expression analysis of IRF5, TLR7, IL-6 and IFN-α were determined by real-time PCR and analyzed with SNP Stat, Stata 10.1 and Graph Pad Prism v5. Results: rs2004640, rs179008, and rs1800795 in both groups were according to Hardy-Weinberg equilibrium. Risk alleles rs179008T and rs2004640T frequencies were higher in controls (p = 0.015 and p = 0.028, respectively), whereas rs179008A frequency was higher in patients (p = 0.015). Allelic combination AGT frequency was higher in patients (p = 0.001). IL-6 rs1800795C > G and CCL5 rs2280788G > C frequencies did not show significant differences (p > 0.05), being rs2280788G (CCL5) monomorphic in controls. SLE patients showed higher TLR7, IRF5, IL6, and IFN-α mRNA levels. IRF5 expression was higher in SLE patients homozygous for rs2004640T (IRF5). Conclusion: This work showed the contribution of TLR7 and IRF5 in SLE pathogenesis in Mayan females from Yucatan.
ABSTRACT
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Conventional antithrombotic therapy has reported hemorrhagic accidents. Ethnobotanical and scientific reports point to Cnidoscolus aconitifolius as an antithrombotic adjuvant. Previously, C. aconitifolius leaves ethanolic extract displayed antiplatelet, anticoagulant, and fibrinolytic activities. This work aimed to identify compounds from C. aconitifolius with in vitro antithrombotic activity through a bioassay-guided study. Antiplatelet, anticoagulant, and fibrinolytic tests guided the fractionation. Ethanolic extract was subjected to a liquid-liquid partitioning, followed by vacuum liquid, and size exclusion chromatography to obtain the bioactive JP10B fraction. The compounds were identified through UHPLC-QTOF-MS, and their molecular docking, bioavailability, and toxicological parameters were determined computationally. Kaempferol-3-O-glucorhamnoside and 15(S)-HPETE were identified; both showed affinity for antithrombotic targets, low absorption, and safety for human consumption. Further in vitro and in vivo evaluations will better understand their antithrombotic mechanism. This bioassay-guided fractionation demonstrated that C. aconitifolius ethanolic extract has antithrombotic compounds.Communicated by Ramaswamy H. Sarma.
Subject(s)
Fibrinolytic Agents , Plant Extracts , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Molecular Docking Simulation , Fibrinolytic Agents/pharmacology , Biological Availability , Ethanol/chemistry , Anticoagulants/pharmacologyABSTRACT
In Mexico, Cnidoscolus aconitifolius (chaya) has been used to treat cardiovascular diseases (CVD). Because CVD are the number one cause of mortality, chaya use has become a health strategy. The aim of this study was to evaluate the antithrombotic activity and identify the metabolites in the most active extract. Aqueous (Aq), ethanolic (EtOH), acetonic (An), ethyl acetate (AcOEt), diethyl ether (Et2O), and hexanic (Hx) extracts were obtained. Platelet aggregation, phospholipase A2, prothrombin time (PT), activated partial thromboplastin time (aPTT), and clot lysis were evaluated. Metabolites were identified by gas chromatography-mass spectrometry (GC-MS). EtOH showed the greatest inhibition of platelet aggregation and phospholipase A2. Ac had the greatest effect on PT and aPTT. AcOEt had the greatest effect on clot lysis. EtOH, with the highest potential, was analyzed by GC-MS; fatty acids and triterpenes were identified. Thus, EtOH showed greater antiplatelet activity and other extracts showed moderate activity. This is a preliminary antithrombotic study. Future research will allow the development of nutraceuticals or functional ingredients for the prevention and treatment of thrombosis.
