Abstract：
BACKGROUND: Oral cancer poses a significant threat to public health worldwide. In addition, because many chemotherapy treatments have negative side effects, natural herbs may be beneficial for oral cancer therapy. Achyranthes aspera (AA), a potential medicinal herb, exerts various pharmacological and biochemical activities.
OBJECTIVE: The present study aimed to predict the anti-oral cancer potential of AA using in silico tools and cell death by in vitro testing.
METHODS: A total of fourteen bioactive constituents from AA herb were selected using phytochemical databases. The toxicity of AA herb extract was analysed through MTT assay against oral carcinoma A253 cell line. The binding activities of the phytocomponents against serine/ threonine-specific protein kinases isoforms, namely Akt1 (PDB ID: 3qkk) and Akt2 (PDB ID: 2jdo) proteins, were analysed using Discovery Studio 2021 and PyRx docking software.
RESULTS: Cell viability data revealed that AA extract decreased the viability and reduced the number of live cells of the oral carcinoma A253 cell line in a dose-dependent manner. The halfmaximal concentration (IC50) value of AA was assessed as 204.74 μg/ml. Based on binding affinity, saponin C (-CDOCKER energy = -77.9862), oleanolic acid (-CDOCKER energy = - 49.4349), spinasterol (-CDOCKER energy = -38.1246), 36,47-dihydroxyhenpentacontan-4-one (-CDOCKER energy = -32.4386), and 20-hydroxyecdysone (-CDOCKER energy = -31.9138) were identified as the best compounds against Akt1, while, compounds saponin C (-CDOCKER energy = -134.412), oleanolic acid (-CDOCKER energy = -90.0846), spinasterol (-CDOCKER energy = -78.3213), 20-hydroxyecdysone (-CDOCKER energy = -80.1049), and ecdysone (- CDOCKER energy = -73.3885) were identified as Akt2 inhibitors. These top compounds fulfilled drug score values, pharmacokinetic and physicochemical characteristics, and druglikeness parameters.
CONCLUSIONS: The present findings reveal that the lead phytomolecules of AA could be effective and developed as a prospective drug against oral cancer.
OBJECTIVE: The present study aimed to predict the anti-oral cancer potential of AA using in silico tools and cell death by in vitro testing.
METHODS: A total of fourteen bioactive constituents from AA herb were selected using phytochemical databases. The toxicity of AA herb extract was analysed through MTT assay against oral carcinoma A253 cell line. The binding activities of the phytocomponents against serine/ threonine-specific protein kinases isoforms, namely Akt1 (PDB ID: 3qkk) and Akt2 (PDB ID: 2jdo) proteins, were analysed using Discovery Studio 2021 and PyRx docking software.
RESULTS: Cell viability data revealed that AA extract decreased the viability and reduced the number of live cells of the oral carcinoma A253 cell line in a dose-dependent manner. The halfmaximal concentration (IC50) value of AA was assessed as 204.74 μg/ml. Based on binding affinity, saponin C (-CDOCKER energy = -77.9862), oleanolic acid (-CDOCKER energy = - 49.4349), spinasterol (-CDOCKER energy = -38.1246), 36,47-dihydroxyhenpentacontan-4-one (-CDOCKER energy = -32.4386), and 20-hydroxyecdysone (-CDOCKER energy = -31.9138) were identified as the best compounds against Akt1, while, compounds saponin C (-CDOCKER energy = -134.412), oleanolic acid (-CDOCKER energy = -90.0846), spinasterol (-CDOCKER energy = -78.3213), 20-hydroxyecdysone (-CDOCKER energy = -80.1049), and ecdysone (- CDOCKER energy = -73.3885) were identified as Akt2 inhibitors. These top compounds fulfilled drug score values, pharmacokinetic and physicochemical characteristics, and druglikeness parameters.
CONCLUSIONS: The present findings reveal that the lead phytomolecules of AA could be effective and developed as a prospective drug against oral cancer.
摘要：
背景：口腔癌对全球公共卫生构成重大威胁。此外,因为许多化疗都有副作用，天然草药可能对口腔癌治疗有益。牛膝（AA），一种潜在的药草，发挥各种药理和生化活性。
目的：本研究旨在通过体外试验预测AA的抗口腔癌潜能和细胞死亡。
方法：使用植物化学数据库从AA草本植物中选择了总共14种生物活性成分。通过MTT法分析AA草药提取物对口腔癌A253细胞的毒性。植物成分对丝氨酸/苏氨酸特异性蛋白激酶同工型的结合活性，即Akt1（PDBID：3qkk）和Akt2（PDBID：2jdo）蛋白，使用DiscoveryStudio2021和PyRx对接软件进行了分析。
结果：细胞活力数据显示，AA提取物以剂量依赖性方式降低了口腔癌A253细胞系的活力并减少了活细胞的数量。AA的半最大浓度(IC50)值被评估为204.74μg/ml。基于结合亲和力，皂苷C（-CDOCKER能量=-77.9862），齐墩果酸（-CDOCKER能量=-49.4349），spinasterol（-CDOCKER能量=-38.1246），36,47-二羟基苯戊酮-4-酮（-CDOCKER能量=-32.4386），和20-羟基蜕皮激素（-CDOCKER能量=-31.9138）被确定为针对Akt1的最佳化合物，而，化合物皂苷C（-CDOCKER能量=-134.412），齐墩果酸（-CDOCKER能量=-90.0846），spinasterol（-CDOCKER能量=-78.3213），20-羟基蜕皮激素（-CDOCKER能量=-80.1049），和蜕皮激素(-CDOCKER能量=-73.3885)被鉴定为Akt2抑制剂。这些顶级化合物达到了药物评分值，药代动力学和物理化学特征，和药物相似度参数。
结论：目前的发现表明，AA的先导分子可能是有效的，并可作为抗口腔癌的前瞻性药物开发。
目的：本研究旨在通过体外试验预测AA的抗口腔癌潜能和细胞死亡。
方法：使用植物化学数据库从AA草本植物中选择了总共14种生物活性成分。通过MTT法分析AA草药提取物对口腔癌A253细胞的毒性。植物成分对丝氨酸/苏氨酸特异性蛋白激酶同工型的结合活性，即Akt1（PDBID：3qkk）和Akt2（PDBID：2jdo）蛋白，使用DiscoveryStudio2021和PyRx对接软件进行了分析。
结果：细胞活力数据显示，AA提取物以剂量依赖性方式降低了口腔癌A253细胞系的活力并减少了活细胞的数量。AA的半最大浓度(IC50)值被评估为204.74μg/ml。基于结合亲和力，皂苷C（-CDOCKER能量=-77.9862），齐墩果酸（-CDOCKER能量=-49.4349），spinasterol（-CDOCKER能量=-38.1246），36,47-二羟基苯戊酮-4-酮（-CDOCKER能量=-32.4386），和20-羟基蜕皮激素（-CDOCKER能量=-31.9138）被确定为针对Akt1的最佳化合物，而，化合物皂苷C（-CDOCKER能量=-134.412），齐墩果酸（-CDOCKER能量=-90.0846），spinasterol（-CDOCKER能量=-78.3213），20-羟基蜕皮激素（-CDOCKER能量=-80.1049），和蜕皮激素(-CDOCKER能量=-73.3885)被鉴定为Akt2抑制剂。这些顶级化合物达到了药物评分值，药代动力学和物理化学特征，和药物相似度参数。
结论：目前的发现表明，AA的先导分子可能是有效的，并可作为抗口腔癌的前瞻性药物开发。
