Kumar Piyush, Kannakazhi Kantari Sai Anand, Biswal Ranendra Pratap, Ghanta Prasanth, Dharanikota Malleswara
Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh, India.
Research Executive Karkinos Healthcare, Navi Mumbai, Maharashtra, India.
Front Fungal Biol. 2025 Jan 28;6:1447609. doi: 10.3389/ffunb.2025.1447609. eCollection 2025.
There is a growing demand for new diabetes drugs with fewer side effects to replace current medications known for their adverse effects. Inhibition of α-glucosidase responsible for postprandial hyperglycemia among diabetes patients is a promising strategy for managing the disease. This study aims to explore and identify novel bioactive metabolites with anti-diabetes potential from BRN05, an endophytic fungus isolated from a well-known medicinal plant King. Ethyl acetate extracts of BRN05 grown in full-strength (EFS) and quarter-strength (EQS) media, respectively were evaluated for their α-glucosidase inhibitory activities. Based on IC values, EQS exhibited significantly greater inhibitory activity (0.01482 ± 1.809 mg/mL) as compared to EFS (1.16 ± 0.173 mg/mL) as well as acarbose control (0.494 ± 0.009 mg/mL). EFS and EQS were subjected to metabolic profiling using Ultra-High-Performance Liquid Chromatography - Electrospray Ionization - Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-ESI-QTOF-MS). A total of nineteen metabolites from EFS and twenty from EQS were tentatively identified based on MS/MS fragmentation. Molecular docking analysis revealed that twelve among these exhibited greater binding energies than that of acarbose (-6.6 kcal/mol). Molecular Dynamics (MD) simulations of 3',4',7-trihydroxyisoflavanone (THF) and alternariol 9-methyl ether (AME) from EQS, exhibiting high binding energies (-7.5 and -7 kcal/mol, respectively), were performed to investigate their interactions with human intestinal α-glucosidase. Results suggest THF possesses strong inhibitory potential, making it a promising candidate for diabetes management.
对副作用更少的新型糖尿病药物的需求日益增长，以取代目前已知有不良作用的药物。抑制糖尿病患者餐后高血糖的α-葡萄糖苷酶是治疗该疾病的一种有前景的策略。本研究旨在从BRN05中探索和鉴定具有抗糖尿病潜力的新型生物活性代谢物，BRN05是从一种著名的药用植物金中分离出的内生真菌。分别对在全强度（EFS）和四分之一强度（EQS）培养基中生长的BRN05的乙酸乙酯提取物进行α-葡萄糖苷酶抑制活性评估。基于IC值，与EFS（1.16±0.173mg/mL）以及阿卡波糖对照（0.494±0.009mg/mL）相比，EQS表现出显著更高的抑制活性（0.01482±1.809mg/mL）。使用超高效液相色谱-电喷雾电离-四极杆飞行时间质谱（UHPLC-ESI-QTOF-MS）对EFS和EQS进行代谢谱分析。基于MS/MS碎片，初步鉴定出EFS中的19种代谢物和EQS中的20种代谢物。分子对接分析表明，其中12种代谢物的结合能比阿卡波糖（-6.6 kcal/mol）更高。对EQS中表现出高结合能（分别为-7.5和-7 kcal/mol）的3',4',7-三羟基异黄酮（THF）和链格孢酚9-甲醚（AME）进行分子动力学（MD）模拟，以研究它们与人类肠道α-葡萄糖苷酶的相互作用。结果表明THF具有很强的抑制潜力，使其成为糖尿病治疗的一个有前景的候选物。
