Carvacrol, a monoterpene known for its pharmacological activities, is present in the essential oil of Origanum majorana, Origanum vulgare, Thymus vulgaris, and Lippia graveolens. It is used in food as a flavoring and preservative agent in cosmetics and medicines because of its useful bioactivities in clinical practice. However, carvacrol was not much explored for its anticancer potential. Targeting enzymes involved in carcinogenesis, such as ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2), lipoxygenase-5 (LOX-5), and hyaluronidase (HYAL) by monoterpenes are amongst the efficient approaches for cancer prevention and treatment. In this study, the efficacy of carvacrol was investigated against deregulated cancer biomarkers/targets in organ-specific human cancer cell lines (FaDu, K562, and A549) utilizing in vitro, in silico, and in vivo approaches. The efficacy of carvacrol was evaluated on human cancer cell lines using neutral red uptake (NRU), sulpho rhodamine B (SRB), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. The mechanistic study was carried out in cell-based test systems. Further, the potency of carvacrol was confirmed by the quantitative real-time PCR analysis and molecular docking studies. The in vivo anti-tumor potential of carvacrol was performed on mice S-180 model, and the toxicity examination was accomplished through in silico approach. Carvacrol significantly impeded the growth of FaDu, K562, and A549 cell lines with IC50 values ranging from 9.61 ± 0.05 to 81.32 ± 11.83 μM. Further, the efficacy of carvacrol was explored against different cancer targets in FaDu, K562, and A549 cell lines. Carvacrol inhibits the ODC, COX-2, LOX-5, and HYAL activities in FaDu cell line and ODC, COX-2, and HYAL activities in K562 cell line. The results were validated by expression analysis revealing the downregulation of the targeted gene with a significant change in the transcript level of ODC and HYAL in FaDu cell line with a fold change of 1.56 and 1.61, respectively. A non-significant effect of carvacrol was observed on the downstream signaling pathway of PI3K and HIF-1α/vascular endothelial growth factor (VEGF) in FaDu cells. The cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and Annexin V-fluorescein isothiocyanate (FITC) experiments demonstrate that carvacrol induces apoptosis of FaDu cells. Further, the potency of carvacrol was also evaluated in vivo on mice S-180 tumor model, wherein it inhibits tumor growth (72%) at 75 mg/kg body weight (bw). ADMET studies predicted carvacrol as a safe molecule. Overall, carvacrol delayed the growth of FaDu, K562, and A549 cell lines by targeting enzymes involved in the carcinogenesis process. The existence of one hydroxyl group at the para position of carvacrol could be responsible for the anti-proliferative activity. Thus, carvacrol could be used as a pharmacophore to develop a safe and effective multi-targeted anti-cancer medicament.
Copyright © 2022 Fatima, Luqman and Meena.

Gastric ulceration is among the most serious humanpublic health problems. Olea europea L. cv. Arbequina is one of the numerous olive varieties which have scarcely been studied. The reported antioxidant and anti-inflammatory potential of the olive plant make it a potential prophylactic natural product against gastric ulcers. Consequently, the main goal of this study is to investigate the gastroprotective effect of Olea europea L. cv. Arbequina leaf extract. LC-HRMS-based metabolic profiling of the alcoholic extract of Olea europea L. cv. Arbequina led to the dereplication of 18 putative compounds (1-18). In vivo indomethacin-induced gastric ulcer in a rat model was established and the Olea europea extract was tested at a dose of 300 mg kg-1 compared to cimetidine (100 mg kg-1). The assessment of gastric mucosal lesions and histopathology of gastric tissue was done. It has been proved that Olea europea significantly decreased the ulcer index and protected the mucosa from lesions. The antioxidant potential of the extract was evaluated using three in vitro assays, H2O2 scavenging, xanthine oxidase inhibitory, and superoxide radical scavenging activities and showed promising activities. Moreover, an in silico based study was performed on the putatively dereplicated compounds, which highlighted that 3-hydroxy tyrosol (4) and oleacein (18) can target the 5-lipoxygenase enzyme (5-LOX) as a protective mechanism against the pathogenesis of ulceration. Upon experimental validation, both compounds 3-hydroxy tyrosol (HT) and oleacein (OC) (4 and 18, respectively) exhibited a significant in vitro 5-LOX inhibitory activity with IC50 values of 8.6 and 5.8 µg/mL, respectively. The present study suggested a possible implication of O. europea leaves as a potential candidate having gastroprotective, antioxidant, and 5-LOX inhibitory activity for the management of gastric ulcers.

Sargassum is a brown algal genus inhabiting tropical region. Metabolomic profiling of Sarragassum cinnerum “ Sargassaceae ” , dereplicated eleven compounds 1-11 , further phytochemical investigation afforded two new aryl cresol 12-13 , along with eight known compounds 14-21 . Both new metabolites along with 19 showed moderate in vitro antiproliferative activity against HEPG2, MCF7, and CACO2. Molecular targets of the bioactive compounds using a pharmacophore-based virtual screening, predicts 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The validation step revealed 12 and 13 inhibited 5-LOX more prudentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico analysis revealed the molecular interactions inside both enzymes active sites and explained the varying inhibitory activity for 12 , and 13 toward 5-LOX and 15-LOX. Taken together, unique metabolites in S. cinnerum had potential anticancer activity supported with in-silico investigations to facility drug discovery and development processes.

Lithraea caustica (Molina) Hook. and Arn. (Anacardiaceae), common name Litre, is an evergreen endemic plant used in the Mapuche Chilean folk medicine. The stem juice of L. caustica mixed with Rubus ulmifolius (blackberry) is used to treat cough and the infusion of leaves is used in baths to treat joint inflammations. In this study, the activities of 3-n-alk(en)yl-catechols, obtained from the dichloromethane extract of the epicuticular compounds of fresh leaves (DCME), stem bark petroleum ether extract (PEE), fractions of phenols and phenol-acid compounds obtained from the methanolic extract (methanolic extract) of defatted leaves and aqueous infusion (AE) from fresh leaves, were evaluated as in vitro inhibitors of soybean 15-lipoxygenase (15-sLOX) and human 5-lipoxygenase (5-hLOX), one of the inflammation pathways. The 3-n-alk(en)yl-catechols were characterized by gas chromatography-mass spectrometry and 1D and 2D nuclear magnetic resonance analysis as mixtures of 3-[(10E)-pentadec-10'-en-1-yl]-catechol, 3-[(10Z)-pentadec-10'-en-1-yl]-catechol and 3-n-pentadecylcatechol. In addition, two fractions, obtained from MeOHE, were characterized by liquid chromatography electrospray ionization tandem mass spectrometric as complex mixtures of known acids and phenolic compounds. DCME, MeOHE and ethyl acetate extract (AcOEtE) extracts showed inhibition against 15-sLOX, and the AE of fresh leaves, showed the best inhibition against 5-hLOX. The mixture of 3-n-alk(en)yl-catechols showed inhibition of 15-sLOX and 5-hLOX. The compounds 3-[(10Z)-pentadec-10'-en-1-yl]-catechol (IC50 2.09 µM) and 3-n-pentadecylcatechol (IC50 2.74 µM) showed inhibition against 5-hLOX. The inhibition values obtained for the 3-n-alk(en)yl-catechols are in the range of well-known inhibitors of 5-hLOX. Acetylation of the 3-n-alk(en)yl-catechols blocks the inhibitory activity, indicating that the free catechol function is necessary for the enzyme inhibition. In addition, the fractions of phenols and phenol-acid compounds showed inhibitory activity against 15-sLOX and the AE, showed a good inhibition against 5-hLOX. These results would be in agreement with the use of L. caustica, as an anti-inflammatory in Mapuche ethnomedicine.
Copyright © 2020 Muñoz Ramírez, Mascayano, Barriga, Echeverria and Urzua.

Weinmannia trichosperma Cav. (Cunoniaceae) (local name, tineo; Mapuche names, madén, mëdehue) is an endemic species of Chile and Argentina used in Mapuche traditional medicine in the treatment of chronic diarrhea, inflammation, and wound healing. This study focused on the isolation, analysis, and characterization of the biological activity of compounds and bark extracts from this plant for the first time. The infusion and tincture of the bark were characterized regarding antioxidant and important enzyme inhibitory activities, phenolics, and flavonoids content and UHPLC-ESI-OT-MS metabolite profiling. Twenty-five metabolites were detected in the medicinal infusion of W. trichosperma, three flavonols were isolated: isoastilbin, neoisoastilbin, and neoastilbin ((2R,3S)-, (2S,3R)-, and (2S,3S)-dihydroquercetin 3-O-alpha-l-rhamnoside) by countercurrent chromatography, and the isomers were quantified in the bark using a validated analytical HPLC methodology. The antioxidant properties were measured by ABTS, DPPH, FRAP, ORAC, and TEAC methods. The infusion displayed a strong DPPH and ABTS scavenging activity (IC50 = 20.58 and 3.070 µg ml-1, respectively) while a moderated effect was observed in the FRAP, ORAC, and ABTS assays. The infusion showed a content of phenolic and flavonoid compounds of 442.1 mg GAE g-1 and 15.54 mg QE g-1, respectively. Furthermore, the infusion showed a good and promissory inhibitory activity (33.80%, 33.12%, and 82.86% for AChE, BuChE, and 5-hLOX, respectively) and isoastilbin (51.70%, 50.10%, and 34.29-80.71% for AChE, BuChE, and 5-hLOX, respectively). The biomolecules identified in this study support the traditional uses of this bark and the potential industrial interest from this Valdivian plant species.
Copyright © 2020 Barrientos, Fernández-Galleguillos, Pastene, Simirgiotis, Romero-Parra, Ahmed and Echeverría.