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

Abstract

Background: Oxidative stress and inflammation are the predominant cause of chronic diseases including multiple forms of cancers. Due to the prominent roles, prevention of these oxidative stress and inflammation is considered to be a target for preventing these disorders. Various natural products and plant extracts prevent the process of free radical-induced damages. Objectives: 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 done 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 for the methanolic crude extract of T. siliquosa as DPPH radical scavenging (110.40 ± 4.5µg/mL), FRAP capacity (41.1 ± 6.2), peroxide scavenging (233.4 ± 14.2µg/mL). Besides, anti-inflammatory properties are also evident in terms of nitric oxide radical scavenging (28.76± 3.9 µg/mL) and lipoxygenase inhibition (39.2 ± 3.2µg/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 mediated through increased caspase and APAF-1 expression. 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.