Antibacterial plant compounds, extracts and essential oils: An updated review on their effects and putative mechanisms of action.

BACKGROUND: Antibiotic-resistant bacteria pose a global health threat. Traditional antibiotics can lose their effectiveness, and the development of novel effective antimicrobials has become a priority in recent years. In this area, plants represent an invaluable source of antimicrobial compounds with vast therapeutic potential. PURPOSE: To review the full possible spectrum of plant antimicrobial agents (plant compounds, extracts and essential oils) discovered from 2016 to 2021 and their potential to decrease bacterial resistance. Their activities against bacteria, with special emphasis on multidrug resistant bacteria, mechanisms of action, possible combinations with traditional antibiotics, roles in current medicine and future perspectives are discussed. METHODS: Studies focusing on the antimicrobial activity of compounds of plant origin and their mechanism of action against bacteria were identified and summarized, including contributions from January 2016 until January 2021. Articles were extracted from the Medline database using PubMed search engine with relevant keywords and operators. RESULTS: The search yielded 11,689 articles from 149 countries, of which 101 articles were included in this review. Reports from 41 phytochemicals belonging to 20 families were included. Reports from plant extracts and essential oils from 39 plant species belonging to 17 families were also included. Polyphenols and terpenes were the most active phytochemicals studied, either alone or as a part of plant extracts or essential oils. Plasma membrane disruption was the most common mechanism of antimicrobial action. Number and position of phenolic hydroxyl groups, double bonds, delocalized electrons and conjugation with sugars in the case of flavonoids seemed to be crucial for antimicrobial capacity. Combinations of phytochemicals with beta-lactam antibiotics were the most studied, and the inhibition of efflux pumps was the most common synergistic mechanism. CONCLUSION: In recent years, terpenes, flavones, flavonols and some alkaloids and phenylpropanoids, either isolated or as a part of extracts, have shown promising antimicrobial activity, being membrane disruption their most common mechanism. However, their utilization as appropriate antimicrobials need to be boosted by means of new omics technologies and network pharmacology to find the most effective combinations among them or in combination with antibiotics.

Protective effects of citrus and rosemary extracts on UV-induced damage in skin cell model and human volunteers.

Ultraviolet radiation absorbed by the epidermis is the major cause of various cutaneous disorders, including photoaging and skin cancers. Although topical sunscreens may offer proper skin protection, dietary plant compounds may significantly contribute to lifelong protection of skin health, especially when unconsciously sun UV exposed. A combination of rosemary and citrus bioflavonoids extracts was used to inhibit UV harmful effects on human HaCaT keratinocytes and in human volunteers after oral intake. Survival of HaCaT cells after UVB radiation was higher in treatments using the combination of extracts than in those performed with individual extracts, indicating potential synergic effects. The combination of extracts also decreased UVB-induced intracellular radical oxygen species (ROS) and prevented DNA damage in HaCaT cells by comet assay and decreased chromosomal aberrations in X-irradiated human lymphocytes. The oral daily consumption of 250 mg of the combination by human volunteers revealed a significant minimal erythema dose (MED) increase after eight weeks (34%, p<0.05). Stronger protection was achieved after 12 weeks (56%, p<0.01). The combination of citrus flavonoids and rosemary polyphenols and diterpenes may be considered as an ingredient for oral photoprotection. Their mechanism of action may deserve further attention.

A metabolite-profiling approach to assess the uptake and metabolism of phenolic compounds from olive leaves in SKBR3 cells by HPLC-ESI-QTOF-MS.

Olive leaves, an easily available natural low-cost material, constitute a source of extracts with significant antitumor activity that inhibits cell proliferation in several breast-cancer-cell models. In this work, a metabolite-profiling approach has been used to assess the uptake and metabolism of phenolic compounds from an olive-leaf extract in the breast-cancer-cell line SKBR3 to evaluate the compound or compounds responsible for the cytotoxic activity. For this, the extract was firstly characterized quantitatively by high-performance liquid chromatography coupled to electrospray ionization-quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS). Then, SKBR3 cells were incubated with 200 µg/mL of the olive-leaf extract at different times (15 min, 1, 2, 24, and 48 h). A metabolite-profiling approach based on HPLC-ESI-QTOF-MS was used to determine the intracellular phenolic compounds, enabling the identification of 16 intact phenolic compounds from the extract and four metabolites derived from these compounds in the cell cytoplasm. The major compounds found within the cells were oleuropein, luteolin-7-O-glucoside and its metabolites luteolin aglycone and methyl-luteolin glucoside, as well as apigenin, and verbascoside. Neither hydroxytyrosol nor any of its metabolites were found within the cells at any incubation time. It is proposed that the major compounds responsible for the cytotoxic activity of the olive-leaf extract in SKBR3 cells are oleuropein and the flavones luteolin and apigenin, since these compounds showed high uptake and their antitumor activity has been previously reported.

High-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-trap tandem mass spectrometry to identify phenolic compounds from a Cistus ladanifer aqueous extract.

INTRODUCTION: Cistus ladanifer is an aromatic shrub that is widespread in the Mediterranean region. The labdanum exudate is used in the fragrance industry and has been characterised. However, there is not enough information about the phenolic content of the raw plant, the aerial part of it being a very rich source of bioactive compounds. OBJECTIVE: Characterisation of the bioactive compounds of the raw plant and its aerial parts. METHODOLOGY: High-performance liquid chromatography with diode array and electrospray ionisation mass spectrometric detection was used to carry out the comprehensive characterisation of a Cistus ladanifer shrub aqueous extract. Two different MS techniques were coupled to HPLC: time-of-flight mass spectrometry and tandem mass spectrometry. RESULTS: Many well-known compounds present in Cistus ladanifer were characterised, such as flavonoids, phenolic acids, ellagitanins, hexahydroxydiphenoyl and derivatives, and other compounds. CONCLUSION: The method described simultaneously separated a wide range of phenolic compounds and the proposed characterisation of the major compounds of this extract was carried out. It is important to highlight that, to our knowledge, this is the first time that a Cistus ladanifer aqueous extract from the raw plant has been characterised.