The Microbiota-Derived Metabolite of Quercetin, 3,4-Dihydroxyphenylacetic Acid Prevents Malignant Transformation and Mitochondrial Dysfunction Induced by Hemin in Colon Cancer and Normal Colon Epithelia Cell Lines

Meat diet plays a pivotal role in colorectal cancer (CRC). Hemin, a metabolite of myoglobin, produced after meat intake, has been involved in CRC initiation. The compound, 3,4-dihydroxyphenylacetic acid (3,4HPAA) is a scarcely studied microbiota-derived metabolite of the flavonoid quercetin (QUE), which exert antioxidant properties. The aim of this study was to determine the protective effect of 3,4HPAA against malignant transformation (increased cell proliferation, decreased apoptosis, DNA oxidative damage and augmented reactive oxidative species (ROS) levels) and mitochondrial dysfunction induced by hemin in normal colon epithelial cells and colon cancer cells. The effect of 3,4HPAA was assessed in comparison to its precursor, QUE and to a known CRC protective agent, sulforaphane (SFN). The results showed that both, tumor and normal cells, exposed to hemin, presented increased cell proliferation, decreased caspase 3 activity and cytochrome c release, as well as augmented production of intracellular and mitochondrial ROS. In addition, hemin decreased the mitochondrial membrane potential (MMP) and the activity of complexes I and II of the electron transport chain. These effects of hemin were prevented by the action of 3,4HPAA. The metabolite showed to be more active than QUE and slightly less active than SFN. In conclusion, 3,4HPAA administration could represent a promising strategy for preventing malignant transformation and mitochondrial dysfunction in colon epithelia induced by hemin.

Saudi Rosmarinus officinalis and Ocimum basilicum L. Polyphenols and Biological Activities

Investigating the polyphenolic profile of natural Rosmarinus officinalis and Ocimum basilicum populations may reveal essential compounds that have biological activities. Natural populations of R. officinalis and O. basilicum in Northern Riyadh were investigated by HPLC-DAD analyses. Several polyphenols, including rosmarinic acid, gentisic acid, 3,4-dihydroxyphenylacetic acid, rutoside, and others, out of 38 screened were confirmed. Rosmarinic acid was the major polyphenol in both of R. officinalis and O. basilicum. R. officinalis methanolic leaf extracts contained other phenols such as gentisic acid while O. basilicum contained also 3,4-dihydroxyphenylacetic acid and rutoside as well as others. R. officinalis showed higher antioxidant activities than O. basilicum using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and β-carotene bleaching assays. These higher activities are associated with a higher composition of rosmarinic acid in leaf extracts. The antioxidant activities of O. basilicum were attributed to identified phenols of rosmarinic acid, 3,4-dihydroxyphenylacetic acid, and rutoside. There were antiproliferative and cytotoxic activities of leaf extracts, as well as identified polyphenols, against several cancer cells. These activities were attributed to the accumulation of necrotic and apoptotic cells in treated cancer cells with leaf extracts as well as identified polyphenols. The antibacterial and antifungal activities of leaf extracts were mainly attributed to 3,4-dihydroxyphenylacetic acid and rutoside in O. basilicum and rosmarinic acid and caffeic acid in R. officinalis. This study proved that R. officinalis and O. basilicum natural populations might be considered as promising sources of natural polyphenols with biological activities.

Antiproliferative, Antimicrobial, and Antifungal Activities of Polyphenol Extracts from Ferocactus Species

Polyphenols, obtained from natural resources, may possess important pharmacological effects. The polyphenolic profiles of the stem extracts of six Ferocactus species (sp.): F. gracilis, F. pottsii, F. herrerae, F. horridus, F. glaucescens, and F. emoryi, were measured using high-performance liquid chromatography (HPLC) with diode-array detection (DAD). Additionally, anticancer, antibacterial, and antifungal activities were examined. Results showed the presence of high to moderate amounts of polyphenols in the extracts (phenolic acids: Protocatechuic acid, 3,4-dihydroxyphenylacetic acid, caffeic acid, and vanillic acid; flavonoids: Rutoside and quercitrin). The highest amounts of 3,4-dihydroxyphenylacetic acid were found in F. glaucescens ((132.09 mg 100 g−1 dry weight (DW)), F. pottsii (75.71 mg 100 g−1 DW), and F. emoryi (69.14 mg 100 g−1 DW) while rutoside content was highest in F. glaucescens (107.66 mg 100 g−1 DW). Maximum antiproliferative activities were observed against HeLa and Jurkat cancer cells, with F. glaucescens, F. emoryi, and F. pottsii showing the highest anticancer activity. Most bacteria were sensitive to Ferocactus sp. stem extracts. Escherichia coli and Staphylococcus aureus were the most sensitive. Excellent antifungal effects were observed against Aspergillus ochraceus and A. niger. However, Penicillium funiculosum, P. ochrochloron, and Candida albicans were relatively resistant. This is the first study reporting novel sources of polyphenols in Ferocactus sp. with anticancer and antimicrobial activities.