In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

Abstract

<b>Background:</b> <i>Sarcocephalus pobeguinii</i> (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of <i>S. pobeguinii</i> induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. <b>Aim:</b> The current study aims to isolate natural compounds from <i>S. pobeguinii</i>, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. <b>Methods:</b> Natural compounds were isolated from leaf, fruit and bark extracts of <i>S. pobeguinii</i> and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. <b>Results:</b> Hederagenin (<b>2</b>), quinovic acid 3-O-[α-D-quinovopyranoside] (<b>6</b>) and quinovic acid 3-O-[β-D-quinovopyranoside] (<b>9</b>) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (<b>6</b>) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards non-cancerous Vero cells; while (<b>2</b>) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (<b>6</b>) and (<b>9</b>) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (<b>1</b>), hederagenin (<b>2</b>) and chletric acid (<b>3</b>) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. <b>Conclusion:</b> Overall, hederagenin (<b>2</b>), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.