Kapoor Neha, Saxena Sanjai
Department of Biotechnology, Thapar University, Patiala, Punjab, 147004, India.
Appl Biochem Biotechnol. 2014 Jul;173(6):1360-74. doi: 10.1007/s12010-014-0927-x. Epub 2014 May 7.
Xanthine oxidase is considered as a potential target for treatment of hyperuricemia. Hyperuricemia is predisposing factor for gout, chronic heart failure, atherosclerosis, tissue injury, and ischemia. To date, only two inhibitors of xanthine oxidase viz. allopurinol and febuxostat have been clinically approved for used as drugs. In the process of searching for new xanthine oxidase inhibitors, we screened culture filtrates of 42 endophytic fungi using in vitro qualitative and quantitative XO inhibitory assays. The qualitative assay exhibited potential XO inhibition by culture filtrates of four isolates viz. #1048 AMSTITYEL, #2CCSTITD, #6AMLWLS, and #96 CMSTITNEY. The XO inhibitory activity was present only in the chloroform extract of the culture filtrates. Chloroform extract of culture filtrate #1048 AMSTITYEL exhibited the highest inhibition of XO with an IC50 value of 0.61 μg ml(-1) which was better than allopurinol exhibiting an IC50 of 0.937 μg ml(-1) while febuxostat exhibited a much lower IC50 of 0.076 μg ml(-1). Further, molecular phylogenetic tools and morphological studies were used to identify #1048 AMSTITYEL as Lasiodiplodia pseudotheobromae. This is the first report of an endophytic Lasiodiplodia pseudotheobromae from Aegle marmelos exhibiting potential XO Inhibitory activity.
黄嘌呤氧化酶被认为是治疗高尿酸血症的一个潜在靶点。高尿酸血症是痛风、慢性心力衰竭、动脉粥样硬化、组织损伤和局部缺血的诱发因素。迄今为止,仅有两种黄嘌呤氧化酶抑制剂,即别嘌醇和非布索坦已被临床批准用作药物。在寻找新型黄嘌呤氧化酶抑制剂的过程中,我们使用体外定性和定量XO抑制试验筛选了42种内生真菌的培养滤液。定性试验显示,四种分离株即#1048 AMSTITYEL、#2CCSTITD、#6AMLWLS和#96 CMSTITNEY的培养滤液具有潜在的XO抑制作用。XO抑制活性仅存在于培养滤液的氯仿提取物中。培养滤液#1048 AMSTITYEL的氯仿提取物对XO的抑制作用最强,IC50值为0.61μg ml(-1),优于别嘌醇(IC50为0.937μg ml(-1)),而非布索坦的IC50值则低得多,为0.076μg ml(-1)。此外,利用分子系统发育工具和形态学研究将#1048 AMSTITYEL鉴定为拟可可球座菌。这是首次报道来自印度枳椇的内生拟可可球座菌具有潜在的XO抑制活性。