PDF(Pubmed)
Abstract：
BACKGROUND: Shyonaka (Oroxylum indicum Vent) is widely used in Ayurveda and in ethnomedical practice for the treatment of inflammation, pain, diarrhea, non-healing ulcers, and cancer. Owing to the high prevalence of Epstein-Barr virus (EBV) infection in Nasopharyngeal carcinoma (NPC) patients, simultaneous targeting of proteins involved in both EBV replication and NPC proliferation might help to manage the disease effectively.
OBJECTIVE: This study is designed to identify potential dual targeting inhibitors from Oroxylum indicum having the potential to inhibit both EBV and NPC. This study also attempted quantitative analysis of Shyonaka Bark Decoction (SBD) to confirm the presence of Baicalein and Chrysin which are predominant marker compounds of Shyonaka.
METHODS: The HPLC analysis of stem bark and root bark of Oroxylum indicum was done to estimate the presence of marker compounds Baicalein and Chrysalin. The in-silico analysis included ADMET analysis followed by molecular docking of known compounds from Oroxylum indicum (retrieved from IMPPAT database) onto the target proteins of EBV (BHRF1, NEC1, dUTPase, Uracil DNA glycosylase) and NPC (COX-2, EGFR, and MDM2) using DOCK6 tool. Further validations were done using the molecular dynamics simulations of top screened molecules onto the selected target proteins using AMBER20 package and their corresponding MMGBSA binding free-energy values were calculated.
RESULTS: The molecular docking revealed that the key molecules from the plant, scutellarein 7-rutinoside (S7R), scutellarin (SCU) and 6-hydroxyluteolin, Baicalein and 5,7-Dihydroxy-2-phenyl-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one (57D) are effectively intervening with the target proteins of EBV, one of the key causative factors of NPC and the NPC specific targets which have the potential to reduce tumor size and other consequences of NPC. The molecular dynamics simulations of S7R, Baicalein and 57D, Baicalein with MDM-2 protein and dUTPase protein, respectively, showed stable interactions between them which were further assessed by the binding energy calculations.
CONCLUSIONS: Overall, the in-silico evaluation of these phytochemicals with target proteins indicates their potential to inhibit both EBV and NPC which needs further in-vitro and in-vivo validations.
OBJECTIVE: This study is designed to identify potential dual targeting inhibitors from Oroxylum indicum having the potential to inhibit both EBV and NPC. This study also attempted quantitative analysis of Shyonaka Bark Decoction (SBD) to confirm the presence of Baicalein and Chrysin which are predominant marker compounds of Shyonaka.
METHODS: The HPLC analysis of stem bark and root bark of Oroxylum indicum was done to estimate the presence of marker compounds Baicalein and Chrysalin. The in-silico analysis included ADMET analysis followed by molecular docking of known compounds from Oroxylum indicum (retrieved from IMPPAT database) onto the target proteins of EBV (BHRF1, NEC1, dUTPase, Uracil DNA glycosylase) and NPC (COX-2, EGFR, and MDM2) using DOCK6 tool. Further validations were done using the molecular dynamics simulations of top screened molecules onto the selected target proteins using AMBER20 package and their corresponding MMGBSA binding free-energy values were calculated.
RESULTS: The molecular docking revealed that the key molecules from the plant, scutellarein 7-rutinoside (S7R), scutellarin (SCU) and 6-hydroxyluteolin, Baicalein and 5,7-Dihydroxy-2-phenyl-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one (57D) are effectively intervening with the target proteins of EBV, one of the key causative factors of NPC and the NPC specific targets which have the potential to reduce tumor size and other consequences of NPC. The molecular dynamics simulations of S7R, Baicalein and 57D, Baicalein with MDM-2 protein and dUTPase protein, respectively, showed stable interactions between them which were further assessed by the binding energy calculations.
CONCLUSIONS: Overall, the in-silico evaluation of these phytochemicals with target proteins indicates their potential to inhibit both EBV and NPC which needs further in-vitro and in-vivo validations.
摘要：
背景：Shyonaka（OroxylumindicumVent）广泛用于阿育吠陀和用于治疗炎症的民族医学实践，疼痛,腹泻,不愈合的溃疡，和癌症。由于鼻咽癌（NPC）患者中EB病毒（EBV）感染的高患病率，同时靶向参与EBV复制和NPC增殖的蛋白质可能有助于有效控制疾病.
目的：本研究旨在鉴定具有抑制EBV和NPC的潜力的来自Oroxylum的潜在双重靶向抑制剂。本研究还尝试了Shyonaka树皮汤（SBD）的定量分析，以确认黄芩素和白杨素的存在，这是Shyonaka的主要标记化合物。
方法：采用高效液相色谱法对番木瓜的茎皮和根皮进行分析，以评估标记化合物黄芩素和Chrysalin的存在。计算机分析包括ADMET分析，然后将来自Oroxylumindicum的已知化合物（从IMPPAT数据库检索）分子对接到EBV的靶蛋白（BHRF1，NEC1，dUTPase，尿嘧啶DNA糖基化酶）和NPC（COX-2，EGFR，和MDM2）使用DOCK6工具。使用AMBER20包装在选择的靶蛋白上使用顶部筛选的分子的分子动力学模拟进行进一步的验证,并计算其相应的MMBGBSA结合自由能值。
结果：分子对接显示，来自植物的关键分子，黄芩苷7-rutinoside(S7R),灯盏总素（SCU）和6-羟基乌托林，黄芩素和5,7-二羟基-2-苯基-6-[3,4,5-三羟基-6-（羟甲基）氧代色烯-4-酮（57D）有效地干预了EBV的靶蛋白，NPC的关键致病因素之一和NPC特异性靶标，这些靶标有可能减少NPC的肿瘤大小和其他后果。S7R的分子动力学模拟,黄芩素和57D，黄芩素与MDM-2蛋白和dUTPase蛋白，分别,显示它们之间稳定的相互作用，通过结合能计算进一步评估。
结论：总体而言，这些植物化学物质与靶蛋白的计算机评估表明，它们具有抑制EBV和NPC的潜力，这需要进一步的体外和体内验证。
目的：本研究旨在鉴定具有抑制EBV和NPC的潜力的来自Oroxylum的潜在双重靶向抑制剂。本研究还尝试了Shyonaka树皮汤（SBD）的定量分析，以确认黄芩素和白杨素的存在，这是Shyonaka的主要标记化合物。
方法：采用高效液相色谱法对番木瓜的茎皮和根皮进行分析，以评估标记化合物黄芩素和Chrysalin的存在。计算机分析包括ADMET分析，然后将来自Oroxylumindicum的已知化合物（从IMPPAT数据库检索）分子对接到EBV的靶蛋白（BHRF1，NEC1，dUTPase，尿嘧啶DNA糖基化酶）和NPC（COX-2，EGFR，和MDM2）使用DOCK6工具。使用AMBER20包装在选择的靶蛋白上使用顶部筛选的分子的分子动力学模拟进行进一步的验证,并计算其相应的MMBGBSA结合自由能值。
结果：分子对接显示，来自植物的关键分子，黄芩苷7-rutinoside(S7R),灯盏总素（SCU）和6-羟基乌托林，黄芩素和5,7-二羟基-2-苯基-6-[3,4,5-三羟基-6-（羟甲基）氧代色烯-4-酮（57D）有效地干预了EBV的靶蛋白，NPC的关键致病因素之一和NPC特异性靶标，这些靶标有可能减少NPC的肿瘤大小和其他后果。S7R的分子动力学模拟,黄芩素和57D，黄芩素与MDM-2蛋白和dUTPase蛋白，分别,显示它们之间稳定的相互作用，通过结合能计算进一步评估。
结论：总体而言，这些植物化学物质与靶蛋白的计算机评估表明，它们具有抑制EBV和NPC的潜力，这需要进一步的体外和体内验证。
