Abstract:
BACKGROUND : Sarcocephalus pobeguinii (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 S. pobeguinii induced significant cytotoxic effect against several cancerous cells
with high selectivity indexes towards non-cancerous cells.
AIM : The current study aims to isolate natural compounds from S. pobeguinii, and
to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as
searching for potential target proteins of bioactive compounds.
METHODS : Natural compounds were isolated from leaf, fruit and bark extracts of S.
pobeguinii 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.
RESULTS : Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and
quinovic acid 3-O-[β-D-quinovopyranoside] (9) exhibited significant cytotoxic
effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by
increasing caspase-3/-7 activity. (6) showed the highest efficacy against all
cancerous cells with poor selectivity (except for A549 cells) towards noncancerous
Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) 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 (1), hederagenin (2) and chletric acid (3)
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.
CONCLUSION : Overall, hederagenin (2), 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.
