Thymus zygis subsp. zygis an Endemic Portuguese Plant: Phytochemical Profiling, Antioxidant, Anti-Proliferative and Anti-Inflammatory Activities

Abstract

Thymus zygis subsp. zygis is an endemic Portuguese plant belonging to the Thymus zygis species. Although T. zygis is commonly used as a condiment and as a medicinal herb, a detailed description of the polyphenol composition of hydroethanolic (HE) and aqueous decoction (AD) extracts is not available. In this work, we describe for the first time a detailed phenolic composition of Thymus zygis subsp. zygis HE and AD extracts, together with their antioxidant, anti-proliferative and anti-inflammatory activities. Unlike other Thymus species, T. zygis subsp. zygis extracts contain higher amounts of luteolin-(?)-O-hexoside. However, the major phenolic compound is rosmarinic acid, and high amounts of salvianolic acids K and I were also detected. T. zygis subsp. zygis extracts exhibited significant scavenging activity of ABTS+, hydroxyl (•OH), and nitric oxide (NO) radicals. Regarding the anti-proliferative/cytotoxic effect, tested against Caco-2 and HepG2 cells, the AD extract only slightly reduced cell viability at higher concentrations (IC50 > 600 µg/mL, 48 h exposure), denoting very low toxicity, while the HE extract showed a high anti-proliferative effect, especially at 48 h exposure (IC50 of 85.01 ± 15.10 μg/mL and 82.19 ± 2.46 μg/mL, for Caco-2 and HepG2, respectively). At non-cytotoxic concentrations, both extracts reduced the nitric oxide (NO) release by lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (at 50 μg/mL, HE and AD extracts inhibited NO release in ~89% and 48%, respectively). In conclusion, the results highlight the non-toxic effect of aqueous extracts, both resembling the consumption of antioxidants in foodstuff or in functional food. Furthermore, the HE extract of T. zygis subsp. zygis is a source of promising molecules with antioxidant, anti-inflammatory and anticancer activities, highlighting its potential as a source of bioactive ingredients for nutraceutical and pharmaceutical industries.

Red Propolis and Its Dyslipidemic Regulator Formononetin: Evaluation of Antioxidant Activity and Gastroprotective Effects in Rat Model of Gastric Ulcer

“…Free radicals are chemical entities capable of causing irreversible damage to the cell [ 4 , 54 ]. The antioxidant process includes the scavenging of these radicals (preventing their propagation), enzymatic hydrolysis of the ester linkage to remove peroxidized fatty acids from lipids, scavenging of transition metal ions, and reduction of peroxide catalyst enzymes.…”

“…The interest in natural products as sources of new drugs and therapeutic strategies for chronic diseases is increasingly growing. Among those sources, natural antioxidants from different plants (e.g., Dirmophandra mollis Benth, Ruta graveolens L., Ginkgo biloba L., Vitis vinifera L, Thymus zygis , Croton argyrophyllus Kunth, Hordeum vulgare, Dalbergia ecastophyllum, Origanum vulgare L.) are receiving particular attention [ 2 , 3 , 4 , 5 , 6 , 7 ].…”

Health-Promoting Effects of Thymus Phenolic-Rich Extracts: Antioxidant, Anti-inflammatory and Antitumoral Properties

“…In addition, a significant scavenging activity of ABTS •+ (expressed as mmol Trolox eq./g extract) was observed for hydroethanolic/aqueous decoction extracts of Thymus pulegioides (1.53/1.58) [61], Thymus citriodorus (1.52/1.21) and T. vulgaris (0.92/0.79) [51], T. mastichina (1.48/0.96) [54], and Thymus zygis subsp. zygis (1.08/0.76) [60]. These authors also noted the high inhibitory ability of some of these extracts (at 0.1 mg/mL) against hydroxyl radical in the presence of EDTA, namely the decoctions of T. zygis subsp.…”

“…These authors also noted the high inhibitory ability of some of these extracts (at 0.1 mg/mL) against hydroxyl radical in the presence of EDTA, namely the decoctions of T. zygis subsp. zygis (66%) [60] and T. citriodorus (37.9%) [51], as well the hydroethanolic and decoctions of T. mastichina (43.2 and 48.5%, respectively) [54] and T. pulegioides (34.8 and 34.0%, respectively) [61].…”

“…were also tested for their cytotoxicity in MCF-7, BT-474 and RAW 264.7 cells using Alamar Blues assay, with best results being obtained for the hydroethanolic extracts rich in salvianolic acids and rosmarinic acid [69]. T. zygis extracts, containing similar phenolic composition, displayed promising results in Caco-2 and HepG2 cells (IC 50 = 85.01 and 82.19 µg/mL, respectively), especially at 48 h of exposure [60]. The same group reported high cytotoxic ability of aqueous decoction and hydroethanolic extracts from different Thymus species towards Caco-2, namely T. pulegioides (IC 50 of 82.25 and 105.44 µg/mL respectively) [61] and T. citriodorus (IC 50 of 159.40 and 114.6 µg/mL respectively) [51], albeit both were less active against HepG2 cells [51].…”