Pharmacognostic investigation on the biomolecular activities of Gundelia tournefortii L. var. armata Freyn & Sint (Asteraceae)

Bioprospecting in traditional medicinal plants has led to the discovery of novel therapeutic leads against an array of human diseases. This study determined the pharmacognostic bioactivities of the historical medicinal herb, Gundelia tournefortii L. var. armata. The chemical composition of the aqueous, ethanol and dichloromethane (DCM) extracts from young edible stems was investigated. Mass spectrometry revealed gallic acid, chlorogenic acid, quercetin and myricetin in the aqueous extract, which were also present in the ethanol extract in addition to aesculin, catechin and ferulic acid. Non-polar compounds were present in the DCM extract, which were β- sitosterol, stigmasterol, β-amyrin, oleic and linoleic acids. The extracts were investigated for anti-proliferative activity against four human cancer cell lines, breast (MCF-7), colon (HT-29 and HCT-116) and monocytic leukemia (THP-1), and normal human dermal fibroblasts (HDFn). The DCM extract was cytotoxic with IC50 in μg/mL of 19.97 for MCF-7, 5.84 for HCT-116, 7.81 for HT-29 and 10.58 for THP-1. Ethanol extract was cytotoxic with IC50 of 18.37 μg/mL for MCF-7, 5.56 μg/mL for HCT-116 and 7.33 μg/mL for HT-29, but was not cytotoxic to THP-1 (\u3e100 μg/mL). The aqueous extract produced IC50 of 73.90 μg/mL for MCF-7, 57.53 μg/mL for HCT-116, 55.50 μg/mL for HT-29 and \u3e100 μg/mL for THP-1. All extracts were non-cytotoxic to HDFn (IC50 \u3e100 μg/mL). Quantification of expressed cfos and cjun early apoptotic genes by qRT-PCR showed significant upregulation in cancer cells treated with extracts compared to untreated controls (p \u3c 0.05). Moreover, HDFn pre-treated with the extracts exhibited protection against H2O2-induced oxidative stress at half-maximal concentrations of 29.16, 15.88 and 22.36 μg/mL for aqueous, ethanol and DCM extracts, respectively. Lactate dehydrogenase leakage was significantly low compared with H2O2-treated control (p \u3c 0.05), while mitochondrial membrane potential was also unaffected shown by significant levels of green JC-1 aggregates (p \u3c 0.05). Cytoprotection was abrogated in the presence of benzimidazole confirming the role of Akt. The extracts also exhibited repression of IL-1β and TNF-α expression in LPS-induced macrophage compared to controls (p \u3c 0.05) suggesting anti-inflammatory activity. Meanwhile, antiquorum sensing activity against Entropathogenic E. coli (EPEC) was also observed as shown by significant downregulation of eaeAg (intimin), escC (type III secretion biogenesis) and tir (translocated intimin receptor) virulence genes compared to controls (p \u3c 0.05). Furthermore, pre-treatment of the human enterocyte CRL-1831 with extracts afforded cytoprotection against EPEC pathogenesis through blockade of intimin-mediated host cell attachment through fluorescence microscopy accompanied by downregulated expression of IL-8 and TNF-α