Salimi Fatemeh, Hamedi Javad, Motevaseli Elaheh, Mohammadipanah Fatemeh
Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
Microbial Technology and Products Research Center, University of Tehran, Tehran, Iran.
Iran J Pharm Res. 2019 Winter;18(1):459-468.
Thrombotic disorders increase the risk of cardiovascular/cerebrovascular complications and represent a major health problem worldwide. Anticoagulants are extensively used in treatment of these disorders. Vitamin K antagonists, like Warfarin, are frequently used in medication. Vascular calcification (VC) is a significant side-effect of vitamin K antagonists especially Warfarin. There is an urgent need to find natural, efficient, non-toxic, and cost effective anticoagulants without dangerous side-effect like VC. In the present study, we evaluated the potential of thirteen fermentation broth extracts of actinobacteria (FBEA) (200 µg mL) to prolong whole blood prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (APTT). The fractions of the most effective FBEA were further investigated for their inhibitory effect on VC. The results showed PT/INR of the healthy blood samples was sensitive to the presence of five FBEA. Their INR index fell in the 1.2 to 8.6 range and six FBEA prolonged both PT/INR and APTT parameters (1.7-5 INR, and 46-59 s for APTT). The fractions of sp. UTMC 267 FBE (200 µg mL), as the most efficient FBE, only inhibited intrinsic and common pathways of coagulation (APTT). Under calcification condition, sp. UTMC 267 fractions (20 µg mL) showed significant inhibitory effect on VC in alizarin red staining (13.3-76 %) and alkaline phosphatase activity of VSMCs (33-62%). They also inhibited osteopontin mRNA expression in treated vascular smooth muscle cells (VSMCs) under that situation. So, we can introduce sp. UTMC 267 FBE as a good candidate for more investigation on thrombotic medication.
血栓形成性疾病会增加心血管/脑血管并发症的风险，是全球范围内的一个主要健康问题。抗凝剂被广泛用于治疗这些疾病。维生素K拮抗剂，如华法林，常用于药物治疗。血管钙化（VC）是维生素K拮抗剂尤其是华法林的一个显著副作用。迫切需要找到天然、高效、无毒且具有成本效益的抗凝剂，且没有像VC这样的危险副作用。在本研究中，我们评估了13种放线菌发酵液提取物（FBEA）（200 µg/mL）延长全血凝血酶原时间（PT）/国际标准化比值（INR）和活化部分凝血活酶时间（APTT）的潜力。对最有效的FBEA的组分进一步研究其对VC的抑制作用。结果显示，健康血样的PT/INR对5种FBEA的存在敏感。它们的INR指数在1.2至8.6范围内，6种FBEA延长了PT/INR和APTT参数（INR为1.7 - 5，APTT为46 - 59秒）。作为最有效的FBE，sp. UTMC 267 FBE的组分（200 µg/mL）仅抑制凝血的内源性和共同途径（APTT）。在钙化条件下，sp. UTMC 267组分（20 µg/mL）在茜素红染色（13.3 - 76%）和血管平滑肌细胞（VSMC）的碱性磷酸酶活性方面对VC显示出显著的抑制作用（33 - 62%）。在那种情况下，它们还抑制了经处理的血管平滑肌细胞（VSMC）中骨桥蛋白mRNA的表达。因此，我们可以将sp. UTMC 267 FBE作为血栓治疗药物进一步研究的良好候选物。
