索特西亚醇提物的抗氧化、抗炎和抗癌活性：体外和计算机模拟研究。

Antioxidant, Anti-Inflammatory and Anticancer Activities of the Methanolic Extract of Thottea siliquosa: An In Vitro and In Silico Study.

机构信息

Division of Cell and Molecular Biology PG & Research Department of Zoology, St. Joseph's College (Autonomous), Devagiri, Calicut, Kerala, India.

出版信息

Recent Pat Anticancer Drug Discov. 2021;16(3):436-444. doi: 10.2174/1574892816666210401143750.

DOI:10.2174/1574892816666210401143750

PMID:33797378

Abstract

BACKGROUND

Oxidative stress and inflammation are the predominant cause of chronic diseases, including multiple forms of cancers. Prevention of oxidative stress and inflammation is considered to be a target for preventing these disorders due to their significant roles in various degenerative diseases. Various natural products and plant extracts prevent the process of free radical- induced damages.

OBJECTIVE

The present study evaluated the biological properties of Thottea siliquosa, belonging to the family Aristolochiaceae, which is a traditionally used Ayurvedic plant.

METHODS

Antioxidant assays carried out were DPPH, FRAP, hydrogen peroxide scavenging, and hemolysis inhibition assay; nitric oxide and lipoxygenase inhibition assays were used for anti-inflammatory studies. Anticancer activity was evaluated using human endometrial and breast cancer cells by MTT assay. Bioactive compounds present in T. siliquosa were identified by LCMS and each was docked with various cancer targets, including EGFR, VEGFR, GST, COX2, and Lipooxygenase.

RESULTS

The results of the present study showed antioxidant properties of the methanolic crude extract of T. siliquosa as DPPH radical scavenging (110.40 ± 4.5 μg/mL), FRAP capacity (41.1 ± 6.2), and peroxide scavenging (233.4 ± 14.2 μg/mL). Besides, anti-inflammatory properties were also evident in terms of nitric oxide radical scavenging (28.76± 3.9 μg/mL) and lipoxygenase inhibition (39.2 ± 3.2 μg/mL) assays. In silico analysis confirmed the inhibitory potential of the bioactive compounds of T. siliquosa against cancer drug targets such as EGFR, VEGFR, and inflammatory enzymes cyclooxygenase as well as lipooxygenase. Further, the anticancer activity of the extract has been identified against human endometrial and breast cancer cells. The possible mechanism of anticancer action of the extract is mediated through the apoptosis induction mechanism acting through increased caspase and APAF-1 expressions.

CONCLUSION

The study thus concludes that T. siliquosa showed significant antioxidant, anti-inflammatory and anticancer properties. Further studies together with a bioassay-guided fractionation may identify possible bioactive compounds.

摘要

背景

氧化应激和炎症是导致慢性疾病的主要原因，包括多种癌症。由于它们在各种退行性疾病中起着重要作用，因此预防氧化应激和炎症被认为是预防这些疾病的目标。各种天然产物和植物提取物可防止自由基诱导的损伤过程。

目的

本研究评估了属于马兜铃科的 Thottea siliquosa 的生物学特性，这是一种传统的印度草医学植物。

方法

进行了抗氧化测定，包括 DPPH、FRAP、过氧化氢清除和溶血抑制测定；使用一氧化氮和脂氧合酶抑制测定来研究抗炎作用。通过 MTT 测定评估了 T. siliquosa 对人子宫内膜和乳腺癌细胞的抗癌活性。通过 LCMS 鉴定了 T. siliquosa 中的生物活性化合物，并将每种化合物与各种癌症靶点（包括 EGFR、VEGFR、GST、COX2 和脂氧合酶）对接。

结果

本研究结果表明，T. siliquosa 甲醇粗提取物具有抗氧化特性，DPPH 自由基清除能力（110.40 ± 4.5 μg/mL）、FRAP 能力（41.1 ± 6.2）和过氧化物清除能力（233.4 ± 14.2 μg/mL）。此外，在一氧化氮自由基清除（28.76± 3.9 μg/mL）和脂氧合酶抑制（39.2 ± 3.2 μg/mL）测定中也显示出抗炎特性。计算机分析证实了 T. siliquosa 生物活性化合物对癌症药物靶点（如 EGFR、VEGFR 和炎症酶环氧化酶和脂氧合酶）的抑制潜力。此外，还确定了提取物对人子宫内膜和乳腺癌细胞的抗癌活性。提取物的抗癌作用机制可能是通过增加半胱天冬酶和 APAF-1 的表达来诱导细胞凋亡。