Structural characterization and evaluation of antimicrobial and cytotoxic activity of six plant phenolic acids

Monika Kalinowska; Renata Świsłocka; Elżbieta Wołejko; Agata Jabłońska-Trypuć; Urszula Wydro; Maciej Kozłowski; Kamila Koronkiewicz; Jolanta Piekut; Włodzimierz Lewandowski

doi:10.1371/journal.pone.0299372

Abstract

Phenolic acids still gain significant attention due to their potential antimicrobial and cytotoxic properties. In this study, we have investigated the antimicrobial of six phenolic acids, namely chlorogenic, caffeic, p-coumaric, rosmarinic, gallic and tannic acids in the concentration range 0.5–500 μM, against Escherichia coli and Lactobacillus rhamnosus. The antimicrobial activity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Additionally, the cytotoxic effects of these phenolic acids on two cancer cell lines, the colorectal adenocarcinoma Caco-2 cell line and Dukes’ type C colorectal adenocarcinoma DLD-1 cell line was examined. To further understand the molecular properties of these phenolic acids, quantum chemical calculations were performed using the Gaussian 09W program. Parameters such as ionization potential, electron affinity, electronegativity, chemical hardness, chemical softness, dipole moment, and electrophilicity index were obtained. The lipophilicity properties represented by logP parameter was also discussed. This study provides a comprehensive evaluation of the antimicrobial and cytotoxic activity of six phenolic acids, compounds deliberately selected due to their chemical structure. They are derivatives of benzoic or cinnamic acids with the increasing number of hydroxyl groups in the aromatic ring. The integration of experimental and computational methodologies provides a knowledge of the molecular characteristics of bioactive compounds and partial explanation of the relationship between the molecular structure and biological properties. This knowledge aids in guiding the development of bioactive components for use in dietary supplements, functional foods and pharmaceutical drugs.

Citation: Kalinowska M, Świsłocka R, Wołejko E, Jabłońska-Trypuć A, Wydro U, Kozłowski M, et al. (2024) Structural characterization and evaluation of antimicrobial and cytotoxic activity of six plant phenolic acids. PLoS ONE 19(6): e0299372. https://doi.org/10.1371/journal.pone.0299372

Editor: Jorddy Neves Cruz, Universidade Federal do Para, BRAZIL

Received: November 2, 2023; Accepted: February 8, 2024; Published: June 17, 2024

Copyright: © 2024 Kalinowska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Relevant data are within the paper and Supporting Information files. Relevant data may also be accessed via the Bialystok University of Technology repository at DOI: 10.24427/2018/29/b/nz9/01997_pb (https://bazawiedzy.pb.edu.pl/info/researchdata/BUT1d8312e294574d51aee166b78f760993/).

Funding: This research was funded by The Polish Ministry of Education and Science, project number WZ/WB-IIS/3/2020 and National Science Center no. 2018/29/B/NZ9/01997.

Competing interests: The authors have declared that no competing interests exist.

Introduction

There has been a growing interest in natural compounds as potential pharmaceutics or chemical agents including antioxidant or preservatives that can be applied in food industry. One of the known natural bioactive substances are phenolic compounds, which include flavonoids, phenolic acids, or tannins [1, 2]. Phenolic compounds are secondary metabolites that are involved primarily in protecting plants against UV radiation, viruses, bacteria and insects. In the past decade, scientific publications taking a closer look at phenolic compounds have increasingly highlighted their antibacterial and cytotoxic properties and the potential for their use. Hence, there is a great deal of co-occurrence of these keywords in many global studies (S1 Fig) [3]. Phenolic acids are among the most widely distributed plant non-flavonoid phenolic compounds present in the free, conjugated-soluble and insoluble-bound forms.

Chlorogenic acid (5-CQA) (S2 Fig) [4], an ester of caffeic acid and (−)-quinic acid, one of the most abundant phenolic acids, is widely distributed in fruits and vegetables like: apples, pears, carrots, or potatoes. Additionally, it can be found in most consumed beverages in the world: wine, tea and coffee [5–7]. Notably, chlorogenic acid demonstrates antimicrobial activity against bacteria (S1 Table) like Gram-negative Escherichia coli (MIC 7.06 mg/mL) [8], Gram-positive Alicyclobacillus acidoterrestris (MIC 2 μg/mL) [9] and fungi Candida albicans with MIC (80 μg/mL) [10]. 5-CQA exhibits antimicrobial activity by disrupting membrane, leading to permeability changes and release of cytoplasmic macromolecules, resulting in cell death [11]. 5-CQA main cytotoxic effects on cancer cells are triggering apoptosis, suppressing cell proliferation, or inhibiting the cell cycle. Studies show (S2 Table) lack of cytotoxicity of 5-CQA towards HaCaT cell line in concentration range of 0.15–1000 nM [5], HL-60 and Jurkat cells in concentrations of 1–100 μM [12].

Caffeic acid (CA) (S2 Fig), is a well-studied phenolic acid present in numerous plant species. It can be found in herbs like basil, rosemary, sage, oregano and even in vegetable like carrots, potatoes, and also in propolis [13]. Its antimicrobial abilities studied by Arciszewska et al (S1 Table) showed inhibitory effect against E. coli (MIC 13 mg/mL), Bacillus subtilis (MIC 18 mg/mL) and antifungal inhibiting growth of Candida albicans (MIC 29 mg/mL) [14]. Another research showed that CA completely inhibits growth of Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Candida albicans, Aspergillus brasiliensis at concentration of 5 mM [15]. CA possesses nucleophilic properties and can donate an electron pair to plasma membrane proteins and lipids, potentially leading to membrane dysfunction. CA may physically damage the cytoplasmic membrane, resulting in the leakage of intracellular components and affecting various cellular processes [16]. CA has been investigated in various cancer cell lines (S2 Table), including MDAMB-231, SK-BR-3, HeLa, HT-29, Neuro 2A, PC-3, and Vero cells. In these cell lines, it exhibited IC₅₀ values ranging from 104 μg/mL to 261 μg/mL, indicating its potential cytotoxic effects against various type of human cancer cells but also animal ones [17]. CA’s anticancer effects are attributed to its both antioxidant and pro-oxidant capacities, its chemical structure that possesses phenolic hydroxyl groups and a double bond in the carbon chain. These factors enable the elimination of free radicals and prevention of reactive oxygen species production as well its ability to stimulate the expression of P53 and P21 genes while inhibiting CDK2 gene expression, leads to cell cycle arrest in the G0/G1 phase and the inhibition of MMP-2 and MMP-9 expression, which are involved in cancer invasion and metastasis [18, 19].

p-Coumaric acid (p-CA) (S2 Fig) is commonly found in cherries, walnuts, onions, pear, grapes and wine either as an esterified form or as a free acid. Experimental and clinical studies have demonstrated that p-CA possesses a range of beneficial properties, including antioxidant and anti-inflammatory activities, making it highly valuable for industries such as food, health, cosmetics and pharmaceuticals [20, 21]. Antimicrobial properties of p-CA have attracted the attention of many researchers (S1 Table). For example, Bag et al. have examined p-CA growth inhibitory capabilities on Bacillus cereus and Salmonella typhimurium with results of respectively MIC equal to 0.041 mg/mL and 0.104 mg/mL [22]. In studies conducted by Abdel-Wareth et al. p-CA showed no antimicrobial action against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Aspergillus niger or Candida albicans but exhibited ability to inhibit growth of Bacillus cereus (IZ = 9 mm) [23]. p-CA antibacterial mechanism was investigated by Lou et al. The results showed that p-CA caused an efflux of potassium ions from cells, indicating an increase in membrane permeability. It was revealed that p-CA caused membrane damage, leading to the release of cellular contents. Furthermore, their studies showed that p-CA can bind to DNA, potentially affecting its structure and function leading to death of a cell [24]. p-CA exhibits significant cytotoxic abilities against various cancer cell lines (S2 Table). p-CA demonstrated its great efficacy in inhibiting the growth of HeLa cells, with an IC₅₀ value of 1 μg/mL. HT-29 cells exhibited an IC₅₀ value of 25 μg/mL suggesting a substantial cytotoxic effect. Karakurt et al. evaluated cytotoxic effects of p-CA using the Alamar Blue assay. The study determined that p-CA exhibited cytotoxic abilities against DLD-1 cells with an IC₅₀ value of 254.3 μg/mL Caco-2 cells with IC₅₀ of 714.6 μg/mL [25].

Rosmarinic acid (RA) (S2 Fig) is predominantly found in herbs such as rosemary, sage, basil, oregano, marjoram, and lemon balm [26]. Some of its notable properties include neuroprotective effects, antioxidant activity, anti-inflammatory properties, antimicrobial effects, anti-angiogenic properties, heptatoprotective and anticancer potential [27–29]. RA showed notable antimicrobial activity against various microorganisms (S1 Table). RA induces membrane depolymerization upon contact. Furthermore, RA inhibits the activity of Na⁺/K⁺-ATPase in bacterial cells [19]. In terms of antifungal mechanisms, RA may hinder mitochondrial activity, compromises membrane integrity [19]. RA demonstrated an IC₅₀ value of 2.9 μmol/L for the MOLM-13 cell line, the MOLM-14 cell line showed an IC₅₀ value of 7.1 μmol/L [30]. MDAMB-231, SK-BR-3, and HeLa cells also showed notable susceptibility to RA, with IC₅₀ values of 121 μg/mL, 147 μg/mL, and 139 μg/mL, respectively. Similarly, the IC₅₀ values for RA against HT-29 and Vero cells were 150 and 388 μg/ml, respectively [17]. Numerous mechanisms have been suggested to explain the anticancer effects of RA. RA inhibits colony formation, cell viability, and spheroid creation by targeting HDAC2 [31]. This leads to cell cycle arrest and apoptosis. RA also demonstrates dose-dependent inhibition of certain cells while being less toxic to normal lymphocytes [32].

Gallic acid (S2 Fig) (GA) is the most popular of trihydroxybenzoic acids that is found in the leaves of pomegranate bark, gall nuts, Indian gooseberry, witch hazel, sumac, tea leaves, oak bark, and many other plants, both in free form and as part of tannin molecules. It occurs in abundance in processed beverages such as red wine or green tea [33]. GA exhibits significant antimicrobial abilities against a wide range of microorganisms, including bacteria and fungi (S2 Table). In studies conducted by Kalinowska et al it displayed a MIC of 3 mg/mL against E. coli, B. subtilis, Salmonella enteritidis, and C. albicans, however S. aureus was more resistant to GA antibacterial abilities with MIC 6 mg/mL [34]. Furthermore, it generates an IZ of 11 mm against Pseudomonas fluorescens, 13.2 mm against P30-4, 15 mm against Pseudomonas fragi, and 14.8 against Pseudomonas putida [35]. In case of fungal infections, GA demonstrated its effectiveness by inhibiting the growth of Streptococcus mutans and Pseudomonas aeruginosa, with MIC values of 62.5 μg/mL and 100 μg/mL, respectively [36]. One of GA antimicrobial mechanisms is the inhibition of efflux pumps, which contribute to antimicrobial resistance in bacteria [37]. GA might cause impairing in the permeability of cellular membranes and also altering its charge or hydrophobicity. This might lead to DNA degradation, impairment of gene expression and cell signaling, disruption of energy metabolism, and ATP depletion [38, 39]. GA has been evaluated for its cytotoxicity in various cell lines using different assays (S2 Table). In the research conducted by Pham et al. on A2780, H460, A431, MCF-7, and MCF10A cell lines using the MTT assay, the concentration of 50 μM GA did not exhibit any cytotoxic properties after 72 h of incubation [40]. However, studies by Rezaei-Seresht et al. on breast cancer MCF-7 line showed that GA possess cytotoxic activity against this specific cell line with IC₅₀ value of 18 μg/mL [18]. GA has been found to increase the expression of p53 and disrupts mitochondrial membranes, which may lead to cytochrome C release, caspase-3 activation, and subsequent apoptotic cell death. Additionally, GA can mediate in DNA damage-related regulations and overexpression of the P21 gene. The P21 can promote cellular differentiation and inhibition of cell proliferation [18].

Tannic acid (TA) (S2 Fig) is a naturally occurring plant polyphenol that can be found in various plants, notably in certain tree species such as sumac, oak, and myrobalan, particularly their barks, are rich sources of it. Additionally, tannic acid can be found in galls formed on plants [41]. It has a rich history of medicinal use, including the treatment of diarrhea, burns, and rectal disorders [42]. Additionally, it has been associated with various health benefits, including modulating immune responses, reducing allergen levels, and accelerating blood clotting [42–44]. Tannic acid exhibits antibacterial abilities against various bacterial strains. The minimum inhibitory concentrations [MICs] of tannic acid in studies conducted by Sahiner et al. were as follows: 60 μg/mL for P. aeruginosa, 60 μg/mL for B. subtilis, 40 μg/mL for S. aureus and 70 μg/mL for C. albicans. However, in the same study TA expressed no antimicrobial activity against E. coli [44]. On the other hand, tannic acid demonstrated inhibitory effects against E. coli with an average diameter of 13.33 mm and against S. aureus with a diameter of 10.16 mm [45]. Moreover, TA exhibits a moderately inhibitory effect against S. typhimurium 400 μg/mL (MQIC value, minimal quorum inhibitory concentration). In case of methicillin-resistant Staphylococcus aureus, tannic acid showed a MIC of 64 μg/mL [46]. TA penetrates bacterial cell walls, disturbing bacterial metabolism, and potentially causing DNA leakage. Moreover, TA limits bacterial growth by hindering sugar and amino acids absorption [47]. TA demonstrates cytotoxic abilities against various cancer cell lines (S2 Table). TA induces cytotoxicity by caspase-mediated apoptosis, suppresses fatty acid synthase and inhibits epidermal growth factor receptor pathway. It reduces viability, metastatic potential and stemness of cancer cells [48–50].

In this study, we will evaluate the antimicrobial activity of these six natural phenolic acids against a bacterial strains living in the digestive system, i.e. Escherichia coli and Lactobacillus rhamnosus based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Studies of antimicrobial activity aim to determine the suitability of the tested compounds as potential preservatives with antimicrobial properties against selected food pathogens (E.coli). Moreover, the studies on the effect of the analysed compounds on L. rhamnosus were conducted, which are part of the human intestinal microflora to exclude any negative effects on beneficial probiotic bacteria. We will also investigate those phenolic acids cytotoxic effects of on two colorectal adenocarcinoma cell lines: Caco-2 and DLD-1 cell lines in order to analyze potential anticancer activity of studied compounds. Additionally, some structural parameters of the phenolic acids such as lipophilicity coefficient (logP) and reactivity of molecules on the basis of parameters calculated in Gaussian 09W program such aslike ionization potential, electron affinity, electronegativity, chemical hardness, chemical softness, dipole moment and electrophilicity index. The six natural phenolic compounds were chosen on purpose. They have proven biological properties such as antioxidant, antimicrobial or chemopreventive evaluated in different model systems of bacteria or cell lines (S1 and S2 Tables). The chosen ligands are derivatives of two important aromatic acids, i.e. benzoic and cinnamic acids which differ in the presence of vinyl moiety between the aromatic ring and carboxylic group. Moreover they differ in the number of hydroxyl substituents in the ring (i.e. p-coumaric, caffeic and gallic acid), some of them are caffeic acid esters (i.e. rosmarinic and chlorogenic acids) or gallic acid ester (i.e. tannic acid). All this structural difference influence on the solubility, lipophilicity and reactivity of molecules. Therefore the following questions may arise: (1) does the number of -OH substituents in the aromatic ring is the main factor that affect the antimicrobial and cytotoxic activity of compounds (toward selected bacteria and cell lines), (2) does the conjugation of caffeic and gallic acid with other molecules influence on the physico-chemical and biological properties of molecules, (c) do the selected experimental (logP) and theoretical (e.g. energy of HOMO or LUMO orbitals) correlates with the biological activity of molecules?

Materials and methods

Reagents

Dulbecco’s modified Eagle’s medium (DMEM) with 4.5 mg/mL (25 mM) of glucose with Glutamax, penicillin, streptomycin, trypsin–EDTA, FBS (Fetal Bovine Serum) Gold, and PBS (Phosphate Buffer Saline) (without Ca and Mg) were provided by Gibco (San Diego, CA, USA). MTT reagent was purchased from Sigma-Aldrich.

Quantum-chemical calculations

The density functional theory (DFT) calculations were performed in the gas phase with approximation of the isolated molecules using the Gaussian 09 [51] program running on PC computer and Gauss View [52] molecular visualization program. To calculate the geometrical structure of the compounds the B3LYP method with 6–311++G(d,p) basis set was used. The exception was represented by a molecule of tannic acid, where the HF631/3-21G method was employed. The optimized structures were possessed the minimum in the energy with no imaginary infrared wavenumbers.

Bacterial strains

Escherichia coli (ATCC 25922) and Lactobacillus rhamnosus (ATCC 53103) were obtained from the American Type Culture Collection (Manassas, VA, USA). E. coli (Gram-negative bacteria) and L. rhamnosus (Gram-positive bacteria) were grown overnight in Mueller Hinton II Broth at 37°C. The next day, the overnight cultures were diluted in fresh MH II Broth to obtain 10⁸ CFU/mL (CFU–colony forming units). For the antimicrobial activity was used the inoculum where the suspension of E. coli and L. rhamnosus cells was 10⁶ CFU/mL.

Determining antimicrobial activity assay.

Antimicrobial activity of tested p-coumaric acid (p-CA), caffeic acid (CA), gallic acid (GA), chlorogenic acid (5-CQA), rosmarinic acid (RA) and tannic acid (TA) against of E. coli and L. rhamnosus were calculated based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The MTT assay was conducted according to Jablonska-Trypuc et al (2019) [53]. The final concentrations of tested compounds in each well were: 500 μM, 250 μM, 125 μM, 62.5 μM, 31.25 μM, 15.63 μM, 7.81 μM, 3.91 μM and 0.98 μM. The selected concentrations correspond to the levels of detected tested compounds in the human body as a result of the consumption of products rich in phenolic compounds.

Cytotoxicity assay.

The cytotoxicity assay was performed according to the method of Carmichael et al using MTT reagent [54]. Activity of 5-CQA, CA, p-CA, GA, TA and RA in the concentration range from 0.5μM to 500μM, was studied in colorectal adenocarcinoma Caco-2 cell line and Dukes’ type C colorectal adenocarcinoma DLD-1 cell line obtained from ATCC. 5-CQA, CA, p-CA, RA, GA and TA were stored at temperature 4°C and the stock solution was prepared by dissolving it in TrisHCl buffer prior analysis. GloMax®-Multi Microplate Multimode Reader was used in order to measure the absorbance (570 nm). The viability of DLD-1 cells and Caco-2 cells was calculated as a percentage of control non—treated cells [54].

Statistical analysis

All data are given as me an values ±SD (standard deviation). Differences between treatments and untreated control human cells were analyzed by one-way ANOVA, followed by Dunnett’s procedure for multiple comparisons. Significant effects are represented by p ≤ 0.05 (*), p ≤ 0.01 (**), p ≤ 0.001 (***).

Results and discussion

The theoretical electronic parameters and lipophilicity

The calculated dipole moment, the energy of the HOMO and LUMO orbitals and the electronic parameters (such as ionization potential (I), electron affinity (A), electronegativity (χ), chemical hardness (η), softness (S), chemical potential (μ) and electrophilicity (ω) indexes calculated on the basis of the HOMO and LUMO orbital’s energy) [55] were obtained for the studied compounds (Fig 1). The parameters are used to predicting the electronic charge transfer within the molecule, reactivity, and stability of the compounds (S3 Table and Table 1) [55]. Because for tannic acid the electronic parameters were obtained at different theoretical level than for the other ligands, they can’t be directly compared within the whole series of the compounds.

Download:

Fig 1. HOMO and LUMO orbitals for p-coumaric acid (p-CA), caffeic acid (CA), gallic acid (GA), chlorogenic acid (5-CQA), rosmarinic acid (RA) and tannic acid (TA).

https://doi.org/10.1371/journal.pone.0299372.g001

Download:

Table 1. Energy of HOMO/LUMO orbitals and other reactivity descriptors.

https://doi.org/10.1371/journal.pone.0299372.t001

The HOMO-LUMO gap values increase in the following order: RA < 5-CQA < CA < p-CA < GA, indicating the decrease in the bioreactivity of studied molecules in above series (Table 1). As a result, it can be inferred that among the studied compounds, rosmarinic acid is the most chemically active, while gallic acid is the least active. The ionization potential decreases and the value of the energy of HOMO orbital increases in same the series: p-CA → GA → 5-CQA → CA → RA what means the rise in the electron donating properties in the above series of ligands in the redox reactions.

The presented MEP surface (Fig 2) describes the overall molecular charge distribution and allows to predict the sites for electrophilic and nucleophilic attack. The red region in the MEP plot shows an electron-rich site with electrophilic reactivity that covers the oxygen atoms in carbonyl group and phenolic OH groups. Whereas the blue color indicates an electron-deficient region which is the site of the nucleophilic attack and it is mainly located in the region of the hydrogen atom of the phenolic OH groups.

Download:

Fig 2. Calculated electrostatic potential surfaces on the molecules for p-coumaric acid (p-CA), caffeic acid (CA), gallic acid (GA), chlorogenic acid (5-CQA), rosmarinic acid (RA) and tannic acid (TA).

https://doi.org/10.1371/journal.pone.0299372.g002

Lipophilicity

The logarithmic coefficient of substance distribution (log P) in the water-n-octanol system is a crucial parameter used to assess the hydrophilicity/lipophilicity of chemicals. Factors like bioaccumulation and toxicity are largely correlated with logP. Regarding most of the analyzed phenolic acids, the collected experimental data and calculated log P values are consistent with each other (Table 2). Based on the experimental logP values, the compounds can be arranged in order of increasing lipophilicity as follows: 5-CQA< GA< CA< RA< p-CA< TA. GA and 5-CQA logP experimental values of 0.70 and 0.30 respectively indicates their low lipophilicity (Table 2). LogP experimental values for RA, CA and p-CA are in the range of 1–2 this means that these compounds possess moderately lipophilic properties. The experimental logP value of 4.84 for TA indicates it’s high lipophilic properties. pKa is a measure of the acidity or basicity of a compound. In the context of lipophilicity, pKa can provide information about the ionization state of a compound at different pH values. Compounds with lower pKa values are more likely to be ionized at physiological pH (around 7.4), while compounds with higher pKa values are more likely to be in their neutral, non-ionized form. Therefore, based on experimental data and calculated values, it can be deduced that the molecular and monodeprotonated forms of GA, RA, 5-CQA, p-CA and CF are predominant within the range of physiological pH. Among those phenolic compounds 5-CQA and RA possessed lowest pKa experimental value (3.42 and 3.57 respectively), this is due to high number of the hydroxyl groups they possess. The presence of functional groups that can act as hydrogen bond donors or acceptors enhances the hydrophilicity of a compound. Compounds containing hydroxyl and carboxylic groups have the ability to form hydrogen bonds with water molecules in an aqueous environment, influencing their solubility in water. However tannic acid possesses multiple hydroxyl groups and exhibits a pKa value of 8.5. As a result, tannic acid is significantly less acidic and highly lipophilic compared to the other studied phenolic compounds. This heightened hydrophobicity and low acidity can primarily be attributed to its strong propensity to form hydrogen bonds with itself.

Download:

Table 2. Theoretical (calculated in ACD/labs or percepta: LogP classic, logP galas, pKa classic) and experimental logP and pKa values.

https://doi.org/10.1371/journal.pone.0299372.t002

Antimicrobial activity

Fig 3 shows the influence of p-CA, CA, GA, 5-CQA, RA and TA on the concentration range 0.98–500 μM on tested E. coli and L. rhamnosus strains. The obtained results are in agreement with S1 Table. In the case of E. coli, it was observed that CA, p-CA and 5-CQA caused an insignificant increase of the bacteria growth with rising concentration of tested acids and the highest value did not exceed 16% (Fig 3). For GA the average relative viability of E. coli was approximately of 1 to 10% compared to untreated cells. After the application of TA at the concentrations from 62.5 to 500 μM one can observe a relative decrease in the cell viability approximately of 1 to 10% compared to the control cells. In the studied range of concentration the selected phenolic acid showed no effect on E. coli [44].

Download:

Fig 3. Relative cell viability after GA, 5-CQA, CA, p-CA, RA and TA acids treatment after 24 h depending on the concentration of the tested compounds (*- p<0.05, **- p<0.01, ***- p<0.001 represent significant effects between treated and untreated bacteria followed by a Dunnett’s test and error bars represent the standard deviation ±SD).

https://doi.org/10.1371/journal.pone.0299372.g003

On the other hand, the studied phenolic compounds had differentiated effects on L. rhamnosus viability. In the studied range of concentration 0.98–500 μM GA, 5-CQA, CA, RA significantly stimulated the tested bacteria strain (only in case of RA at the highest concentration 500 μM no stimulation was observed). Especially for CA, 5-CQA and RA a significant increase of L. rhamnosus viability with increasing concentration of the tested acids was observed and the highest value for the bacteria did not exceed 180%. These phenolic compounds possessed the lowest logP among the tested compounds which increase in the order GA→5-CQA→CA→RA (0.70–1.60). The values of the energy of the HOMO orbitals (EHOMO) calculated for these compounds increase in the same order as well. In turn, after the application of TA on L. rhamnosus at the lowest concentrations from 0.98 to 15.63 μM, an increase in relative cell viability of 40 to 60% was observed, while at TA concentrations from 31.25 to 500 μM there was a decrease in the relative cell viability of 20 to 80% compared to the control untreated cells. For p-CA the inhibitory effect on L. rhamnosus viability was observed only in the case of the concentration 500 μM. The observation correlates with the value of logP and EHOMO which are respectively the highest and which is the lowest for these two phenolic acids (comparing the rest of studied phenolic acids), i.e. for TA: logP = 4.86, -EHOMO = -8,554 eV and p-CA: logP = 1.69; EHOMO = -6.431 eV. The obtained results suggest that the phenolic compounds in the studied concentration range did not significantly influence the viability of E. coli, which indicates that these compounds do not stimulate the growth of a potentially pathogenic bacterium naturally present in the human microbiome. On the other hand GA, CA, 5-CQA, p-CA, RA possess prebiotic properties toward L. rhamnosus in the concentration range 0.98–250 μM. For TA this stimulatory effect was observed in the concentration range 0.98–15.63 μM.

Cytotoxic activity

As it was shown in Figs 4 and 5, studied compounds did not exert significant cytotoxic effect on Caco-2 cells. 5-CQA caused increases in relative Caco-2 cell viability even in 200μM concentration. After 48h treatment decreases in studied parameter were observed in lower concentrations (from 0.5μM to 10μM). In case of p-CA no significant decreases in cell viability as compared to control untreated cells were noticed. Relatively more significant effect was observed in case of p-CA after 48h treatment, when decreases below control level were observed in all analyzed concentrations.

Download:

Fig 4. Relative cell viability results for Caco-2 cells exposed to the range of 5-CQA, CA, p-CA, RA, GA and TA concentrations for 24h and 48h calculated as a percentage of control, untreated cells.

Each value on the graph is the mean of three independent experiments and error bars show the standard deviation (SD). * p < 0.05, ** p < 0.01 and *** p < 0.001 represent significant effects between treatments and control followed by a Dunnett’s test.

https://doi.org/10.1371/journal.pone.0299372.g004

Download:

Fig 5. Relative cell viability results for DLD-1 cells exposed to the range of 5-CQA, CA, p-CA and RA concentrations for 24h and 48h calculated as a percentage of control, untreated cells.

Each value on the graph is the mean of three independent experiments and error bars show the standard deviation (SD). * p < 0.05, ** p < 0.01 and *** p < 0.001 represent significant effects between treatments and control followed by a Dunnett’s test.

https://doi.org/10.1371/journal.pone.0299372.g005

It should be underline that studied compounds were more effective against DLD-1 cells that towards Caco-2 cells (Figs 4 and 5). Statistically significant decreases in relative cell viability were observed under the influence of p-CA already in 0.5μM concentration. After 48h incubation 26% decline in cells viability as compared to control untreated cells was noticed. DLD-1 cells treated with RA showed decrease in cell viability already in 5μM concentration.

As shown in Figs 4 and 5, in Caco-2 cell line cytotoxic effect was observed rather after 48h incubation with both studied compounds. In DLD-1 cell line incubation with especially TA in all analyzed concentrations leads to statistically significant decreases in cell viability. However, 5μM of GA in Caco-2 cell line caused an increase in relative cell viability. Similar effect was observed in case of TA treatment after 48h incubation time in the lowest tested concentration. TA in 200 μM concentration caused almost 50% decline in Caco-2 cell viability after 48h incubation. More significant inhibitory effect of studied compounds was observed in DLD-1 cell line than in Caco-2 cell line. Decrease by about 50% was noticed in DLD-1 cells in the concentration of 200μM for both compounds. It should be also mentioned that in case of DLD-1 cell line we did not observe any increases as compared to control untreated cells. From the group of studied compounds TA, GA and RA were especially active inDLD-1 cell line. Obtained results are in accordance with literature data indicating anticancer properties of phenolic compounds [12]. Differences between the individual tested compounds may result from their chemical structure and thus their ability to penetrate cell membranes. The research results presented in the literature, similarly to our results, indicate differences between the tested cell lines, which are partly due to differences in the genetic and metabolic profile of cancer cells [12, 18, 19]. The main difference between the Caco-2 and DLD-1 lines is their origin. Caco-2 cells represent Dukes’ stage B, which means that the cancer has grown into the muscular layer of the intestine, while DLD-1 cells represent Dukes’ stage C, which means that the cancer has metastasized to at least one lymph node in the intestinal area. By considering gene expression in both lines, differences between both lines were identified, which translate into their response to pro-apoptotic factors [66].

Conclusions

In the study it was observed that the tested compounds did not affect the viability of E.coli in the tested concentration range (0.98–500 μM), which means that they do not stimulate the growth of a potentially pathogenic bacterium naturally present in human microbiome. Additionally, GA, CA, 5-CQA, p-CA, RA possessed prebiotic properties toward L. rhamnosus in the concentration range 0.98–500 μM. For TA the prebiotic effect was observed at the lower concentration range 0.98–15.63 μM. The lipophilicity (described by the logP parameter) of the phenolic compounds was correlated with their antibacterial activity toward L. rhamnosus. The compounds (i.e. TA, p-CA) with the highest values of logP exhibited an inhibitory effect on microbial growth at lower concentration levels than the phenolic compounds with the higher logP. What is interesting the calculated energy of HOMO orbital reflected changes in the lipophilicity of these compounds and may be used as a additional parameter to describe the biological activity of phenolic compounds toward L. rhamnosus. The cytotoxic activity of the phenolic acids was tested in the same concentration range as the antimicrobial. Based on the obtained results, it can be concluded that a significantly better response to the applied treatments was obtained in the case of the DLD-1 line than Caco-2, and the most effective in relation to both cell lines was TA. On the other hand, CA showed the lowest biological activity, especially in the Caco-2 line. The highest cytotoxic properties of TA toward DLD-1 cell line correspond with the highest lipophilicity and stability of the molecule compared to other tested phenolic compounds. Although these two parameters are important factors determining the biological activity of chemicals, the explanation of the high activity of TA is more complicated and is related to other mechanisms involved in induction of cell apoptosis like generation of reactive oxygen species, regulation of apoptotic and anti-apoptotic proteins, suppression and promotion of oncogenes or inhibition of matrix metalloproteinases. The aspect of possible induction of apoptosis is one of the most important elements of modern therapy from the point of view of eliminating cancer cells. The vast majority of the tested compounds seem to be promising potential anticancer agents, but they require further analysis at the molecular level to understand the mechanisms of their action.

Supporting information

S1 Fig. Co-occurrence of selected keywords in articles in 2014–2023 (search terms: “Phenolic compounds”, “cytotoxicity”, “antimicrobial activity”), created with VOSviewer [3].

https://doi.org/10.1371/journal.pone.0299372.s001

(TIFF)

S2 Fig.

Structures of p-coumaric acid (A), caffeic acid (B), rosmarinic acid (C), chlorogenic acid (D), gallic acid (E) and tannic acid (F).

https://doi.org/10.1371/journal.pone.0299372.s002

(TIF)

S1 Table. Antimicrobial effects of phenolic acids on microbial strains (minimal inhibitory concentration (MIC) and inhibition zone (IZ) *MIC–minimal inhibitory concentration, IZ–inhibition zone, MBC–minimum bactericidal concentration, MQIC–minimal quorum inhibitory concentration, mm–milimeter, mM–milimolar concentration, %–percentage.

https://doi.org/10.1371/journal.pone.0299372.s003

(PDF)

S2 Table. Effects of phenolic acids on cell lines in in vitro assays.

https://doi.org/10.1371/journal.pone.0299372.s004

(PDF)

S3 Table. Values of dipole moment and energy calculated for p-coumaric acid (p-CA), caffeic acid (CA), gallic acid (GA), chlorogenic acid (5-CQA), rosmarinic acid (RA) and tannic acid (TA).

https://doi.org/10.1371/journal.pone.0299372.s005

(DOCX)

References

1. Heleno S. A., Martins A., Queiroz M. J. R. P., and Ferreira I. C. F. R., “Bioactivity of phenolic acids: Metabolites versus parent compounds: A review,” Food Chem, vol. 173, pp. 501–513, Apr. 2015, pmid:25466052
- View Article
- PubMed/NCBI
- Google Scholar
2. Wahle K. W. J., Brown I., Rotondo D., and Heys S. D., “Plant Phenolics in the Prevention and Treatment of Cancer,” 2010, pp. 36–51. pmid:21520702
- View Article
- PubMed/NCBI
- Google Scholar
3. van Eck N. and Waltman L., “Software Survey: VOSviewer, a Computer Program for Bibliometric Mapping,” Scientometrics, vol. 84, pp. 523–538, 2010. pmid:20585380
- View Article
- PubMed/NCBI
- Google Scholar
4. Padmanabhan P., Correa-Betanzo J., and Paliyath G., “Berries and Related Fruits,” in Encyclopedia of Food and Health, Elsevier, 2016, pp. 364–371. https://doi.org/10.1016/B978-0-12-384947-2.00060-X
5. Kalinowska M. et al., “Fe(III) and Cu(II) Complexes of Chlorogenic Acid: Spectroscopic, Thermal, Anti-/Pro-Oxidant, and Cytotoxic Studies,” Materials, vol. 15, no. 19, p. 6832, Oct. 2022, pmid:36234176
- View Article
- PubMed/NCBI
- Google Scholar
6. Gagliardini E., Benigni A., and Perico N., “Pharmacological Induction of Kidney Regeneration,” in Kidney Transplantation, Bioengineering and Regeneration, Elsevier, 2017, pp. 1025–1037. https://doi.org/10.1016/B978-0-12-801734-0.00074–6
7. Veljkovic E. et al., “Other Compounds From Tobacco With Potential Impact on Neurodegenerative Diseases,” in Nicotine and Other Tobacco Compounds in Neurodegenerative and Psychiatric Diseases, Elsevier, 2018, pp. 83–97. https://doi.org/10.1016/B978-0-12-812922-7.00010-X
8. Kalinowska M., Bajko E., Matejczyk M., Kaczyński P., Łozowicka B., and Lewandowski W., “The Study of Anti-/Pro-Oxidant, Lipophilic, Microbial and Spectroscopic Properties of New Alkali Metal Salts of 5-O-Caffeoylquinic Acid,” Int J Mol Sci, vol. 19, no. 2, p. 463, Feb. 2018, pmid:29401704
- View Article
- PubMed/NCBI
- Google Scholar
9. Cai R. et al., “Antibacterial activity and mechanism of cinnamic acid and chlorogenic acid against Alicyclobacillus acidoterrestris vegetative cells in apple juice,” Int J Food Sci Technol, vol. 54, no. 5, pp. 1697–1705, May 2019,
- View Article
- Google Scholar
10. Yun J. and Lee D. G., “Role of potassium channels in chlorogenic acid-induced apoptotic volume decrease and cell cycle arrest in Candida albicans,” Biochimica et Biophysica Acta (BBA)—General Subjects, vol. 1861, no. 3, pp. 585–592, Mar. 2017, pmid:28040564
- View Article
- PubMed/NCBI
- Google Scholar
11. Lou Z., Wang H., Zhu S., Ma C., and Wang Z., “Antibacterial Activity and Mechanism of Action of Chlorogenic Acid,” J Food Sci, vol. 76, no. 6, pp. M398–M403, Aug. 2011, pmid:22417510
- View Article
- PubMed/NCBI
- Google Scholar
12. Hernandes L. C. et al., “Caffeic acid and chlorogenic acid cytotoxicity, genotoxicity and impact on global DNA methylation in human leukemic cell lines,” Genet Mol Biol, vol. 43, no. 3, 2020, pmid:32644097
- View Article
- PubMed/NCBI
- Google Scholar
13. Meinhart A. D. et al., “Chlorogenic and caffeic acids in 64 fruits consumed in Brazil,” Food Chem, vol. 286, pp. 51–63, Jul. 2019, pmid:30827640
- View Article
- PubMed/NCBI
- Google Scholar
14. Arciszewska Ż. et al., “Caffeic Acid/Eu(III) Complexes: Solution Equilibrium Studies, Structure Characterization and Biological Activity,” Int J Mol Sci, vol. 23, no. 2, p. 888, Jan. 2022, pmid:35055074
- View Article
- PubMed/NCBI
- Google Scholar
15. Kyselka J. et al., “Antioxidant and antimicrobial activity of linseed lignans and phenolic acids,” European Food Research and Technology, vol. 243, no. 9, pp. 1633–1644, Sep. 2017,
- View Article
- Google Scholar
16. Perumal S., Mahmud R., and Ismail S., “Mechanism of action of isolated caffeic acid and epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa,” Pharmacogn Mag, vol. 13, no. 50, p. 311, 2017, pmid:28808398
- View Article
- PubMed/NCBI
- Google Scholar
17. Sevimli-Gur C. and Yesil-Celiktas O., “Cytotoxicity screening of supercritical fluid extracted seaweeds and phenylpropanoids,” Mol Biol Rep, vol. 46, no. 4, pp. 3691–3699, Aug. 2019, pmid:31004301
- View Article
- PubMed/NCBI
- Google Scholar
18. Rezaei-Seresht H., Cheshomi H., Falanji F., Movahedi-Motlagh F., Hashemian M., and Mireskandari E., “Cytotoxic activity of caffeic acid and gallic acid against MCF-7 human breast cancer cells: An in silico and in vitro study.,” Avicenna J Phytomed, vol. 9, no. 6, pp. 574–586, 2019, pmid:31763216
- View Article
- PubMed/NCBI
- Google Scholar
19. Matejczyk M., Świsłocka R., Golonko A., Lewandowski W., and Hawrylik E., “Cytotoxic, genotoxic and antimicrobial activity of caffeic and rosmarinic acids and their lithium, sodium and potassium salts as potential anticancer compounds,” Adv Med Sci, vol. 63, no. 1, pp. 14–21, Mar. 2018, pmid:28818744
- View Article
- PubMed/NCBI
- Google Scholar
20. Taofiq O., González-Paramás A., Barreiro M., and Ferreira I., “Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review,” Molecules, vol. 22, no. 2, p. 281, Feb. 2017, pmid:28208818
- View Article
- PubMed/NCBI
- Google Scholar
21. Nasr G., Banaszak Holl M. M., Greige-Gerges H., Hamade A., Daakour S., and atallah C., “P-Coumaric Acid in Poly(Amidoamine) G4 Dendrimer: Characterization and Toxicity Evaluation,” SSRN Electronic Journal, 2022,
- View Article
- Google Scholar
22. Bag A. and Chattopadhyay R. R., “Synergistic antibacterial and antibiofilm efficacy of nisin in combination with p-coumaric acid against food-borne bacteria Bacillus cereus and Salmonella typhimurium,” Lett Appl Microbiol, vol. 65, no. 5, 2017, pmid:28815637
- View Article
- PubMed/NCBI
- Google Scholar
23. Abdel-Wareth M. and Ghareeb M., “Bioprospecting certain freshwater-derived fungi for phenolic compounds with special emphasis on antimicrobial and larvicidal activity of methyl gallate and p-coumaric Acid,” Egypt J Chem, vol. 0, no. 0, pp. 0–0, Jun. 2018,
- View Article
- Google Scholar
24. Lou Z., Wang H., Rao S., Sun J., Ma C., and Li J., “p-Coumaric acid kills bacteria through dual damage mechanisms,” Food Control, vol. 25, no. 2, pp. 550–554, Jun. 2012,
- View Article
- Google Scholar
25. Karakurt S., Abuşoğlu G., and Arituluk Z. C., “Comparison of anticarcinogenic properties of viburnum opulus and its active compound P-coumaric acid on human colorectal carcinoma,” Turkish Journal of Biology, vol. 44, no. 5, 2020, pmid:33110363
- View Article
- PubMed/NCBI
- Google Scholar
26. Ramos-Hryb A. B., Cunha M. P., Kaster M. P., and Rodrigues A. L. S., “Natural Polyphenols and Terpenoids for Depression Treatment: Current Status,” 2018, pp. 181–221.
- View Article
- Google Scholar
27. Wang S.-J. et al., “Regulation effects of rosemary (Rosmarinus officinalis Linn.) on hepatic lipid metabolism in OA induced NAFLD rats,” Food Funct, vol. 10, no. 11, pp. 7356–7365, 2019, pmid:31650134
- View Article
- PubMed/NCBI
- Google Scholar
28. Fadel O., El Kirat K., and Morandat S., “The natural antioxidant rosmarinic acid spontaneously penetrates membranes to inhibit lipid peroxidation in situ,” Biochimica et Biophysica Acta (BBA)—Biomembranes, vol. 1808, no. 12, pp. 2973–2980, Dec. 2011, pmid:21864504
- View Article
- PubMed/NCBI
- Google Scholar
29. Budzianowski J. et al., “Rosmarinic acid 4′-O-β-glucoside–A compound with prospective medicinal and cosmetological applications—its isolation from callus and root cultures of Eryngium species and biological activity,” Ind Crops Prod, vol. 193, 2023,
- View Article
- Google Scholar
30. Wang Q. et al., “Salviachinensines A-F, Antiproliferative Phenolic Derivatives from the Chinese Medicinal Plant Salvia chinensis,” J Nat Prod, vol. 81, no. 11, pp. 2531–2538, Nov. 2018, pmid:30370766
- View Article
- PubMed/NCBI
- Google Scholar
31. Jang Y.-G., Hwang K.-A., and Choi K.-C., “Rosmarinic Acid, a Component of Rosemary Tea, Induced the Cell Cycle Arrest and Apoptosis through Modulation of HDAC2 Expression in Prostate Cancer Cell Lines,” Nutrients, vol. 10, no. 11, p. 1784, Nov. 2018, pmid:30453545
- View Article
- PubMed/NCBI
- Google Scholar
32. Wu C.-F., Hong C., Klauck S. M., Lin Y.-L., and Efferth T., “Molecular mechanisms of rosmarinic acid from Salvia miltiorrhiza in acute lymphoblastic leukemia cells,” J Ethnopharmacol, vol. 176, pp. 55–68, Dec. 2015, pmid:26476154
- View Article
- PubMed/NCBI
- Google Scholar
33. Erukainure O. L., Sanni O., and Md S. Islam , “Clerodendrum volubile: Phenolics and Applications to Health,” in Polyphenols: Mechanisms of Action in Human Health and Disease, Elsevier, 2018, pp. 53–68. https://doi.org/10.1016/B978-0-12-813006-3.00006–4
34. Kalinowska M. et al., “Plant-Derived and Dietary Hydroxybenzoic Acids—A Comprehensive Study of Structural, Anti-/Pro-Oxidant, Lipophilic, Antimicrobial, and Cytotoxic Activity in MDA-MB-231 and MCF-7 Cell Lines,” Nutrients, vol. 13, no. 9, p. 3107, Sep. 2021, pmid:34578985
- View Article
- PubMed/NCBI
- Google Scholar
35. Sorrentino E. et al., “Antimicrobial activity of gallic acid against food-related Pseudomonas strains and its use as biocontrol tool to improve the shelf life of fresh black truffles,” Int J Food Microbiol, vol. 266, pp. 183–189, Feb. 2018, pmid:29227905
- View Article
- PubMed/NCBI
- Google Scholar
36. Osamudiamen P. M., Oluremi B. B., Oderinlo O. O., and Aiyelaagbe O. O., “Trans-resveratrol, piceatannol and gallic acid: Potent polyphenols isolated from Mezoneuron benthamianum effective as anticaries, antioxidant and cytotoxic agents,” Sci Afr, vol. 7, p. e00244, Mar. 2020,
- View Article
- Google Scholar
37. Rajamanickam K., Yang J., and Sakharkar M. K., “Gallic Acid Potentiates the Antimicrobial Activity of Tulathromycin Against Two Key Bovine Respiratory Disease (BRD) Causing-Pathogens,” Front Pharmacol, vol. 9, Jan. 2019, pmid:30662404
- View Article
- PubMed/NCBI
- Google Scholar
38. Sarjit A., Wang Y., and Dykes G. A., “Antimicrobial activity of gallic acid against thermophilic Campylobacter is strain specific and associated with a loss of calcium ions,” Food Microbiol, vol. 46, pp. 227–233, Apr. 2015, pmid:25475290
- View Article
- PubMed/NCBI
- Google Scholar
39. Nohynek L. J. et al., “Berry Phenolics: Antimicrobial Properties and Mechanisms of Action Against Severe Human Pathogens,” Nutr Cancer, vol. 54, no. 1, pp. 18–32, Jan. 2006, pmid:16800770
- View Article
- PubMed/NCBI
- Google Scholar
40. Pham H. N. T., Sakoff J. A., Van Vuong Q., Bowyer M. C., and Scarlett C. J., “Comparative cytotoxic activity between kaempferol and gallic acid against various cancer cell lines,” Data Brief, vol. 21, pp. 1033–1036, Dec. 2018, pmid:30450396
- View Article
- PubMed/NCBI
- Google Scholar
41. Khan S., Sahar A., Tariq T., Sameen A., and Tariq F., “Essential oils in plants: Plant physiology, the chemical composition of the oil, and natural variation of the oils (chemotaxonomy and environmental effects, etc.),” in Essential Oils, Elsevier, 2023, pp. 1–36. https://doi.org/10.1016/B978-0-323-91740-7.00016–5
42. Aelenei N., Popa M. I., Novac O., Lisa G., and Balaita L., “Tannic acid incorporation in chitosan-based microparticles and in vitro controlled release,” J Mater Sci Mater Med, vol. 20, no. 5, pp. 1095–1102, May 2009, pmid:19160025
- View Article
- PubMed/NCBI
- Google Scholar
43. Choi J. et al., “Antimicrobial and immunomodulatory effects of tannic acid supplementation in broilers infected with Salmonella Typhimurium,” Poult Sci, vol. 101, no. 11, p. 102111, Nov. 2022, pmid:36081234
- View Article
- PubMed/NCBI
- Google Scholar
44. Sahiner N., Sagbas S., Sahiner M., Silan C., Aktas N., and Turk M., “Biocompatible and biodegradable poly(Tannic Acid) hydrogel with antimicrobial and antioxidant properties,” Int J Biol Macromol, vol. 82, pp. 150–159, Jan. 2016, pmid:26526171
- View Article
- PubMed/NCBI
- Google Scholar
45. Sethulekshmi A. S. et al., “Multifunctional role of tannic acid in improving the mechanical, thermal and antimicrobial properties of natural rubber-molybdenum disulfide nanocomposites,” Int J Biol Macromol, vol. 225, pp. 351–360, Jan. 2023, pmid:36427617
- View Article
- PubMed/NCBI
- Google Scholar
46. Dong G. et al., “Antimicrobial and anti-biofilm activity of tannic acid against Staphylococcus aureus,” Nat Prod Res, vol. 32, no. 18, pp. 2225–2228, Sep. 2018, pmid:28826250
- View Article
- PubMed/NCBI
- Google Scholar
47. Pandey A. and Negi P. S., “Phytochemical composition, in vitro antioxidant activity and antibacterial mechanisms of Neolamarckia cadamba fruits extracts,” Nat Prod Res, vol. 32, no. 10, pp. 1189–1192, May 2018, pmid:28475362
- View Article
- PubMed/NCBI
- Google Scholar
48. Nie F. et al., “Apoptotic effect of tannic acid on fatty acid synthase over-expressed human breast cancer cells,” Tumor Biology, vol. 37, no. 2, pp. 2137–2143, Feb. 2016, pmid:26349913
- View Article
- PubMed/NCBI
- Google Scholar
49. Darvin P. et al., “Tannic acid inhibits EGFR / STAT 1/3 and enhances p38/ STAT 1 signalling axis in breast cancer cells,” J Cell Mol Med, vol. 21, no. 4, pp. 720–734, Apr. 2017, pmid:27862996
- View Article
- PubMed/NCBI
- Google Scholar
50. SP N. et al., “Tannic Acid Inhibits Non-small Cell Lung Cancer (NSCLC) Stemness by Inducing G ₀ /G ₁ Cell Cycle Arrest and Intrinsic Apoptosis,” Anticancer Res, vol. 40, no. 6, pp. 3209–3220, Jun. 2020, pmid:32487615
- View Article
- PubMed/NCBI
- Google Scholar
51. M.; T. G. W.; S. H. B.; S. G. E.; R. M. A.; C. J. R.; et al. Frisch, “Gaussian 09.” Gaussian, Inc.: Wallingford, CT, USA, 2009.
52. Dennington Roy, Keith Todd A., and Millam John M., “GaussView.” Semichem Inc, 2016.
- View Article
- Google Scholar
53. Jabłońska-Trypuć A., Wydro U., Serra-Majem L., Wołejko E., and Butarewicz A., “The Analysis of Bifenox and Dichlobenil Toxicity in Selected Microorganisms and Human Cancer Cells,” Int J Environ Res Public Health, vol. 16, no. 21, p. 4137, Oct. 2019, pmid:31717849
- View Article
- PubMed/NCBI
- Google Scholar
54. Carmichael J., DeGraff W. G., Gazdar A. F., Minna J. D., and Mitchell J. B., “Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing.,” Cancer Res, vol. 47, no. 4, pp. 936–42, Feb. 1987, Accessed: Jan. 09, 2018. [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/3802100 pmid:3802100
- View Article
- PubMed/NCBI
- Google Scholar
55. Litwinienko G. and Ingold K. U., “Solvent Effects on the Rates and Mechanisms of Reaction of Phenols with Free Radicals,” Acc Chem Res, vol. 40, no. 3, pp. 222–230, Mar. 2007, pmid:17370994
- View Article
- PubMed/NCBI
- Google Scholar
56. “ILO-WHO International Chemical Safety Cards (ICSCs).”
57. Settimo L., Bellman K., and Knegtel R. M. A., “Comparison of the Accuracy of Experimental and Predicted pKa Values of Basic and Acidic Compounds,” Pharm Res, vol. 31, no. 4, pp. 1082–1095, Apr. 2014, pmid:24249037
- View Article
- PubMed/NCBI
- Google Scholar
58. Hanai T. and Hubert J., “Hydrophobicity and chromatographic behaviour of aromatic acids found in urine,” J Chromatogr A, vol. 239, pp. 527–536, Apr. 1982,
- View Article
- Google Scholar
59. Linder P. W. and Voyé A., “Potentiometric investigations of the equilibria between caffeic acid and copper(II), zinc(II), iron(II) and hydrogen ions in aqueous solution,” Polyhedron, vol. 6, no. 1, pp. 53–60, Jan. 1987,
- View Article
- Google Scholar
60. Barvinchenko V. N., Lipkovskaya N. A., Kulik T. V., and Kartel N. T.’, “Adsorption of Natural 3-Phenylpropenic Acids on Cerium Dioxide Surface,” Colloid Journal, vol. 81, no. 1, pp. 1–7, Jan. 2019,
- View Article
- Google Scholar
61. Naseem S. et al., “Photo-isomerization upshifts the pKa of the Photoactive Yellow Protein chromophore to contribute to photocycle propagation,” J Photochem Photobiol A Chem, vol. 270, pp. 43–52, Oct. 2013,
- View Article
- Google Scholar
62. Alam A. et al., “Pharmacokinetic and Molecular Docking Studies of Plant-Derived Natural Compounds to Exploring Potential Anti-Alzheimer Activity,” in In Silico Approach for Sustainable Agriculture, Singapore: Springer Singapore, 2018, pp. 217–238. https://doi.org/10.1007/978-981-13-0347-0_13
63. Sik B., Kapcsándi V., Székelyhidi R., Hanczné E. L., and Ajtony Z., “Recent Advances in the Analysis of Rosmarinic Acid From Herbs in the Lamiaceae Family,” Nat Prod Commun, vol. 14, no. 7, p. 1934578X1986421, Jul. 2019,
- View Article
- Google Scholar
64. Chen W., Shi X., Xu W., McClements D. J., Liu X., and Liu F., “Effects of different polyphenols on the structure and properties of sodium caseinate films mediated by tyrosinase,” J Agric Food Res, vol. 10, p. 100395, Dec. 2022,
- View Article
- Google Scholar
65. Adatoz E. B., Hendessi S., Ow-Yang C. W., and Demirel A. L., “Restructuring of poly(2-ethyl-2-oxazoline)/tannic acid multilayers into fibers,” Soft Matter, vol. 14, no. 19, pp. 3849–3857, 2018, pmid:29718054
- View Article
- PubMed/NCBI
- Google Scholar
66. Abrahamse H. and Houreld N. N., “Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells,” Int J Mol Sci, vol. 20, no. 13, p. 3254, Jul. 2019, pmid:31269724
- View Article
- PubMed/NCBI
- Google Scholar

[ref1] 1. Heleno S. A., Martins A., Queiroz M. J. R. P., and Ferreira I. C. F. R., “Bioactivity of phenolic acids: Metabolites versus parent compounds: A review,” Food Chem, vol. 173, pp. 501–513, Apr. 2015, pmid:25466052
View Article
PubMed/NCBI
Google Scholar

[2] View Article

[3] PubMed/NCBI

[4] Google Scholar

[ref2] 2. Wahle K. W. J., Brown I., Rotondo D., and Heys S. D., “Plant Phenolics in the Prevention and Treatment of Cancer,” 2010, pp. 36–51. pmid:21520702
View Article
PubMed/NCBI
Google Scholar

[6] View Article

[7] PubMed/NCBI

[8] Google Scholar

[ref3] 3. van Eck N. and Waltman L., “Software Survey: VOSviewer, a Computer Program for Bibliometric Mapping,” Scientometrics, vol. 84, pp. 523–538, 2010. pmid:20585380
View Article
PubMed/NCBI
Google Scholar

[10] View Article

[11] PubMed/NCBI

[12] Google Scholar

[ref4] 4. Padmanabhan P., Correa-Betanzo J., and Paliyath G., “Berries and Related Fruits,” in Encyclopedia of Food and Health, Elsevier, 2016, pp. 364–371. https://doi.org/10.1016/B978-0-12-384947-2.00060-X

[ref5] 5. Kalinowska M. et al., “Fe(III) and Cu(II) Complexes of Chlorogenic Acid: Spectroscopic, Thermal, Anti-/Pro-Oxidant, and Cytotoxic Studies,” Materials, vol. 15, no. 19, p. 6832, Oct. 2022, pmid:36234176
View Article
PubMed/NCBI
Google Scholar

[15] View Article

[16] PubMed/NCBI

[17] Google Scholar

[ref6] 6. Gagliardini E., Benigni A., and Perico N., “Pharmacological Induction of Kidney Regeneration,” in Kidney Transplantation, Bioengineering and Regeneration, Elsevier, 2017, pp. 1025–1037. https://doi.org/10.1016/B978-0-12-801734-0.00074–6

[ref7] 7. Veljkovic E. et al., “Other Compounds From Tobacco With Potential Impact on Neurodegenerative Diseases,” in Nicotine and Other Tobacco Compounds in Neurodegenerative and Psychiatric Diseases, Elsevier, 2018, pp. 83–97. https://doi.org/10.1016/B978-0-12-812922-7.00010-X

[ref8] 8. Kalinowska M., Bajko E., Matejczyk M., Kaczyński P., Łozowicka B., and Lewandowski W., “The Study of Anti-/Pro-Oxidant, Lipophilic, Microbial and Spectroscopic Properties of New Alkali Metal Salts of 5-O-Caffeoylquinic Acid,” Int J Mol Sci, vol. 19, no. 2, p. 463, Feb. 2018, pmid:29401704
View Article
PubMed/NCBI
Google Scholar

[21] View Article

[22] PubMed/NCBI

[23] Google Scholar

[ref9] 9. Cai R. et al., “Antibacterial activity and mechanism of cinnamic acid and chlorogenic acid against Alicyclobacillus acidoterrestris vegetative cells in apple juice,” Int J Food Sci Technol, vol. 54, no. 5, pp. 1697–1705, May 2019,
View Article
Google Scholar

[25] View Article

[26] Google Scholar

[ref10] 10. Yun J. and Lee D. G., “Role of potassium channels in chlorogenic acid-induced apoptotic volume decrease and cell cycle arrest in Candida albicans,” Biochimica et Biophysica Acta (BBA)—General Subjects, vol. 1861, no. 3, pp. 585–592, Mar. 2017, pmid:28040564
View Article
PubMed/NCBI
Google Scholar

[28] View Article

[29] PubMed/NCBI

[30] Google Scholar

[ref11] 11. Lou Z., Wang H., Zhu S., Ma C., and Wang Z., “Antibacterial Activity and Mechanism of Action of Chlorogenic Acid,” J Food Sci, vol. 76, no. 6, pp. M398–M403, Aug. 2011, pmid:22417510
View Article
PubMed/NCBI
Google Scholar

[32] View Article

[33] PubMed/NCBI

[34] Google Scholar

[ref12] 12. Hernandes L. C. et al., “Caffeic acid and chlorogenic acid cytotoxicity, genotoxicity and impact on global DNA methylation in human leukemic cell lines,” Genet Mol Biol, vol. 43, no. 3, 2020, pmid:32644097
View Article
PubMed/NCBI
Google Scholar

[36] View Article

[37] PubMed/NCBI

[38] Google Scholar

[ref13] 13. Meinhart A. D. et al., “Chlorogenic and caffeic acids in 64 fruits consumed in Brazil,” Food Chem, vol. 286, pp. 51–63, Jul. 2019, pmid:30827640
View Article
PubMed/NCBI
Google Scholar

[40] View Article

[41] PubMed/NCBI

[42] Google Scholar

[ref14] 14. Arciszewska Ż. et al., “Caffeic Acid/Eu(III) Complexes: Solution Equilibrium Studies, Structure Characterization and Biological Activity,” Int J Mol Sci, vol. 23, no. 2, p. 888, Jan. 2022, pmid:35055074
View Article
PubMed/NCBI
Google Scholar

[44] View Article

[45] PubMed/NCBI

[46] Google Scholar

[ref15] 15. Kyselka J. et al., “Antioxidant and antimicrobial activity of linseed lignans and phenolic acids,” European Food Research and Technology, vol. 243, no. 9, pp. 1633–1644, Sep. 2017,
View Article
Google Scholar

[48] View Article

[49] Google Scholar

[ref16] 16. Perumal S., Mahmud R., and Ismail S., “Mechanism of action of isolated caffeic acid and epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa,” Pharmacogn Mag, vol. 13, no. 50, p. 311, 2017, pmid:28808398
View Article
PubMed/NCBI
Google Scholar

[51] View Article

[52] PubMed/NCBI

[53] Google Scholar

[ref17] 17. Sevimli-Gur C. and Yesil-Celiktas O., “Cytotoxicity screening of supercritical fluid extracted seaweeds and phenylpropanoids,” Mol Biol Rep, vol. 46, no. 4, pp. 3691–3699, Aug. 2019, pmid:31004301
View Article
PubMed/NCBI
Google Scholar

[55] View Article

[56] PubMed/NCBI

[57] Google Scholar

[ref18] 18. Rezaei-Seresht H., Cheshomi H., Falanji F., Movahedi-Motlagh F., Hashemian M., and Mireskandari E., “Cytotoxic activity of caffeic acid and gallic acid against MCF-7 human breast cancer cells: An in silico and in vitro study.,” Avicenna J Phytomed, vol. 9, no. 6, pp. 574–586, 2019, pmid:31763216
View Article
PubMed/NCBI
Google Scholar

[59] View Article

[60] PubMed/NCBI

[61] Google Scholar

[ref19] 19. Matejczyk M., Świsłocka R., Golonko A., Lewandowski W., and Hawrylik E., “Cytotoxic, genotoxic and antimicrobial activity of caffeic and rosmarinic acids and their lithium, sodium and potassium salts as potential anticancer compounds,” Adv Med Sci, vol. 63, no. 1, pp. 14–21, Mar. 2018, pmid:28818744
View Article
PubMed/NCBI
Google Scholar

[63] View Article

[64] PubMed/NCBI

[65] Google Scholar

[ref20] 20. Taofiq O., González-Paramás A., Barreiro M., and Ferreira I., “Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review,” Molecules, vol. 22, no. 2, p. 281, Feb. 2017, pmid:28208818
View Article
PubMed/NCBI
Google Scholar

[67] View Article

[68] PubMed/NCBI

[69] Google Scholar

[ref21] 21. Nasr G., Banaszak Holl M. M., Greige-Gerges H., Hamade A., Daakour S., and atallah C., “P-Coumaric Acid in Poly(Amidoamine) G4 Dendrimer: Characterization and Toxicity Evaluation,” SSRN Electronic Journal, 2022,
View Article
Google Scholar

[71] View Article

[72] Google Scholar

[ref22] 22. Bag A. and Chattopadhyay R. R., “Synergistic antibacterial and antibiofilm efficacy of nisin in combination with p-coumaric acid against food-borne bacteria Bacillus cereus and Salmonella typhimurium,” Lett Appl Microbiol, vol. 65, no. 5, 2017, pmid:28815637
View Article
PubMed/NCBI
Google Scholar

[74] View Article

[75] PubMed/NCBI

[76] Google Scholar

[ref23] 23. Abdel-Wareth M. and Ghareeb M., “Bioprospecting certain freshwater-derived fungi for phenolic compounds with special emphasis on antimicrobial and larvicidal activity of methyl gallate and p-coumaric Acid,” Egypt J Chem, vol. 0, no. 0, pp. 0–0, Jun. 2018,
View Article
Google Scholar

[78] View Article

[79] Google Scholar

[ref24] 24. Lou Z., Wang H., Rao S., Sun J., Ma C., and Li J., “p-Coumaric acid kills bacteria through dual damage mechanisms,” Food Control, vol. 25, no. 2, pp. 550–554, Jun. 2012,
View Article
Google Scholar

[81] View Article

[82] Google Scholar

[ref25] 25. Karakurt S., Abuşoğlu G., and Arituluk Z. C., “Comparison of anticarcinogenic properties of viburnum opulus and its active compound P-coumaric acid on human colorectal carcinoma,” Turkish Journal of Biology, vol. 44, no. 5, 2020, pmid:33110363
View Article
PubMed/NCBI
Google Scholar

[84] View Article

[85] PubMed/NCBI

[86] Google Scholar

[ref26] 26. Ramos-Hryb A. B., Cunha M. P., Kaster M. P., and Rodrigues A. L. S., “Natural Polyphenols and Terpenoids for Depression Treatment: Current Status,” 2018, pp. 181–221.
View Article
Google Scholar

[88] View Article

[89] Google Scholar

[ref27] 27. Wang S.-J. et al., “Regulation effects of rosemary (Rosmarinus officinalis Linn.) on hepatic lipid metabolism in OA induced NAFLD rats,” Food Funct, vol. 10, no. 11, pp. 7356–7365, 2019, pmid:31650134
View Article
PubMed/NCBI
Google Scholar

[91] View Article

[92] PubMed/NCBI

[93] Google Scholar

[ref28] 28. Fadel O., El Kirat K., and Morandat S., “The natural antioxidant rosmarinic acid spontaneously penetrates membranes to inhibit lipid peroxidation in situ,” Biochimica et Biophysica Acta (BBA)—Biomembranes, vol. 1808, no. 12, pp. 2973–2980, Dec. 2011, pmid:21864504
View Article
PubMed/NCBI
Google Scholar

[95] View Article

[96] PubMed/NCBI

[97] Google Scholar

[ref29] 29. Budzianowski J. et al., “Rosmarinic acid 4′-O-β-glucoside–A compound with prospective medicinal and cosmetological applications—its isolation from callus and root cultures of Eryngium species and biological activity,” Ind Crops Prod, vol. 193, 2023,
View Article
Google Scholar

[99] View Article

[100] Google Scholar

[ref30] 30. Wang Q. et al., “Salviachinensines A-F, Antiproliferative Phenolic Derivatives from the Chinese Medicinal Plant Salvia chinensis,” J Nat Prod, vol. 81, no. 11, pp. 2531–2538, Nov. 2018, pmid:30370766
View Article
PubMed/NCBI
Google Scholar

[102] View Article

[103] PubMed/NCBI

[104] Google Scholar

[ref31] 31. Jang Y.-G., Hwang K.-A., and Choi K.-C., “Rosmarinic Acid, a Component of Rosemary Tea, Induced the Cell Cycle Arrest and Apoptosis through Modulation of HDAC2 Expression in Prostate Cancer Cell Lines,” Nutrients, vol. 10, no. 11, p. 1784, Nov. 2018, pmid:30453545
View Article
PubMed/NCBI
Google Scholar

[106] View Article

[107] PubMed/NCBI

[108] Google Scholar

[ref32] 32. Wu C.-F., Hong C., Klauck S. M., Lin Y.-L., and Efferth T., “Molecular mechanisms of rosmarinic acid from Salvia miltiorrhiza in acute lymphoblastic leukemia cells,” J Ethnopharmacol, vol. 176, pp. 55–68, Dec. 2015, pmid:26476154
View Article
PubMed/NCBI
Google Scholar

[110] View Article

[111] PubMed/NCBI

[112] Google Scholar

[ref33] 33. Erukainure O. L., Sanni O., and Md S. Islam , “Clerodendrum volubile: Phenolics and Applications to Health,” in Polyphenols: Mechanisms of Action in Human Health and Disease, Elsevier, 2018, pp. 53–68. https://doi.org/10.1016/B978-0-12-813006-3.00006–4

[ref34] 34. Kalinowska M. et al., “Plant-Derived and Dietary Hydroxybenzoic Acids—A Comprehensive Study of Structural, Anti-/Pro-Oxidant, Lipophilic, Antimicrobial, and Cytotoxic Activity in MDA-MB-231 and MCF-7 Cell Lines,” Nutrients, vol. 13, no. 9, p. 3107, Sep. 2021, pmid:34578985
View Article
PubMed/NCBI
Google Scholar

[115] View Article

[116] PubMed/NCBI

[117] Google Scholar

[ref35] 35. Sorrentino E. et al., “Antimicrobial activity of gallic acid against food-related Pseudomonas strains and its use as biocontrol tool to improve the shelf life of fresh black truffles,” Int J Food Microbiol, vol. 266, pp. 183–189, Feb. 2018, pmid:29227905
View Article
PubMed/NCBI
Google Scholar

[119] View Article

[120] PubMed/NCBI

[121] Google Scholar

[ref36] 36. Osamudiamen P. M., Oluremi B. B., Oderinlo O. O., and Aiyelaagbe O. O., “Trans-resveratrol, piceatannol and gallic acid: Potent polyphenols isolated from Mezoneuron benthamianum effective as anticaries, antioxidant and cytotoxic agents,” Sci Afr, vol. 7, p. e00244, Mar. 2020,
View Article
Google Scholar

[123] View Article

[124] Google Scholar

[ref37] 37. Rajamanickam K., Yang J., and Sakharkar M. K., “Gallic Acid Potentiates the Antimicrobial Activity of Tulathromycin Against Two Key Bovine Respiratory Disease (BRD) Causing-Pathogens,” Front Pharmacol, vol. 9, Jan. 2019, pmid:30662404
View Article
PubMed/NCBI
Google Scholar

[126] View Article

[127] PubMed/NCBI

[128] Google Scholar

[ref38] 38. Sarjit A., Wang Y., and Dykes G. A., “Antimicrobial activity of gallic acid against thermophilic Campylobacter is strain specific and associated with a loss of calcium ions,” Food Microbiol, vol. 46, pp. 227–233, Apr. 2015, pmid:25475290
View Article
PubMed/NCBI
Google Scholar

[130] View Article

[131] PubMed/NCBI

[132] Google Scholar

[ref39] 39. Nohynek L. J. et al., “Berry Phenolics: Antimicrobial Properties and Mechanisms of Action Against Severe Human Pathogens,” Nutr Cancer, vol. 54, no. 1, pp. 18–32, Jan. 2006, pmid:16800770
View Article
PubMed/NCBI
Google Scholar

[134] View Article

[135] PubMed/NCBI

[136] Google Scholar

[ref40] 40. Pham H. N. T., Sakoff J. A., Van Vuong Q., Bowyer M. C., and Scarlett C. J., “Comparative cytotoxic activity between kaempferol and gallic acid against various cancer cell lines,” Data Brief, vol. 21, pp. 1033–1036, Dec. 2018, pmid:30450396
View Article
PubMed/NCBI
Google Scholar

[138] View Article

[139] PubMed/NCBI

[140] Google Scholar

[ref41] 41. Khan S., Sahar A., Tariq T., Sameen A., and Tariq F., “Essential oils in plants: Plant physiology, the chemical composition of the oil, and natural variation of the oils (chemotaxonomy and environmental effects, etc.),” in Essential Oils, Elsevier, 2023, pp. 1–36. https://doi.org/10.1016/B978-0-323-91740-7.00016–5

[ref42] 42. Aelenei N., Popa M. I., Novac O., Lisa G., and Balaita L., “Tannic acid incorporation in chitosan-based microparticles and in vitro controlled release,” J Mater Sci Mater Med, vol. 20, no. 5, pp. 1095–1102, May 2009, pmid:19160025
View Article
PubMed/NCBI
Google Scholar

[143] View Article

[144] PubMed/NCBI

[145] Google Scholar

[ref43] 43. Choi J. et al., “Antimicrobial and immunomodulatory effects of tannic acid supplementation in broilers infected with Salmonella Typhimurium,” Poult Sci, vol. 101, no. 11, p. 102111, Nov. 2022, pmid:36081234
View Article
PubMed/NCBI
Google Scholar

[147] View Article

[148] PubMed/NCBI

[149] Google Scholar

[ref44] 44. Sahiner N., Sagbas S., Sahiner M., Silan C., Aktas N., and Turk M., “Biocompatible and biodegradable poly(Tannic Acid) hydrogel with antimicrobial and antioxidant properties,” Int J Biol Macromol, vol. 82, pp. 150–159, Jan. 2016, pmid:26526171
View Article
PubMed/NCBI
Google Scholar

[151] View Article

[152] PubMed/NCBI

[153] Google Scholar

[ref45] 45. Sethulekshmi A. S. et al., “Multifunctional role of tannic acid in improving the mechanical, thermal and antimicrobial properties of natural rubber-molybdenum disulfide nanocomposites,” Int J Biol Macromol, vol. 225, pp. 351–360, Jan. 2023, pmid:36427617
View Article
PubMed/NCBI
Google Scholar

[155] View Article

[156] PubMed/NCBI

[157] Google Scholar

[ref46] 46. Dong G. et al., “Antimicrobial and anti-biofilm activity of tannic acid against Staphylococcus aureus,” Nat Prod Res, vol. 32, no. 18, pp. 2225–2228, Sep. 2018, pmid:28826250
View Article
PubMed/NCBI
Google Scholar

[159] View Article

[160] PubMed/NCBI

[161] Google Scholar

[ref47] 47. Pandey A. and Negi P. S., “Phytochemical composition, in vitro antioxidant activity and antibacterial mechanisms of Neolamarckia cadamba fruits extracts,” Nat Prod Res, vol. 32, no. 10, pp. 1189–1192, May 2018, pmid:28475362
View Article
PubMed/NCBI
Google Scholar

[163] View Article

[164] PubMed/NCBI

[165] Google Scholar

[ref48] 48. Nie F. et al., “Apoptotic effect of tannic acid on fatty acid synthase over-expressed human breast cancer cells,” Tumor Biology, vol. 37, no. 2, pp. 2137–2143, Feb. 2016, pmid:26349913
View Article
PubMed/NCBI
Google Scholar

[167] View Article

[168] PubMed/NCBI

[169] Google Scholar

[ref49] 49. Darvin P. et al., “Tannic acid inhibits EGFR / STAT 1/3 and enhances p38/ STAT 1 signalling axis in breast cancer cells,” J Cell Mol Med, vol. 21, no. 4, pp. 720–734, Apr. 2017, pmid:27862996
View Article
PubMed/NCBI
Google Scholar

[171] View Article

[172] PubMed/NCBI

[173] Google Scholar

[ref50] 50. SP N. et al., “Tannic Acid Inhibits Non-small Cell Lung Cancer (NSCLC) Stemness by Inducing G ₀ /G ₁ Cell Cycle Arrest and Intrinsic Apoptosis,” Anticancer Res, vol. 40, no. 6, pp. 3209–3220, Jun. 2020, pmid:32487615
View Article
PubMed/NCBI
Google Scholar

[175] View Article

[176] PubMed/NCBI

[177] Google Scholar

[ref51] 51. M.; T. G. W.; S. H. B.; S. G. E.; R. M. A.; C. J. R.; et al. Frisch, “Gaussian 09.” Gaussian, Inc.: Wallingford, CT, USA, 2009.

[ref52] 52. Dennington Roy, Keith Todd A., and Millam John M., “GaussView.” Semichem Inc, 2016.
View Article
Google Scholar

[180] View Article

[181] Google Scholar

[ref53] 53. Jabłońska-Trypuć A., Wydro U., Serra-Majem L., Wołejko E., and Butarewicz A., “The Analysis of Bifenox and Dichlobenil Toxicity in Selected Microorganisms and Human Cancer Cells,” Int J Environ Res Public Health, vol. 16, no. 21, p. 4137, Oct. 2019, pmid:31717849
View Article
PubMed/NCBI
Google Scholar

[183] View Article

[184] PubMed/NCBI

[185] Google Scholar

[ref54] 54. Carmichael J., DeGraff W. G., Gazdar A. F., Minna J. D., and Mitchell J. B., “Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing.,” Cancer Res, vol. 47, no. 4, pp. 936–42, Feb. 1987, Accessed: Jan. 09, 2018. [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/3802100 pmid:3802100
View Article
PubMed/NCBI
Google Scholar

[187] View Article

[188] PubMed/NCBI

[189] Google Scholar

[ref55] 55. Litwinienko G. and Ingold K. U., “Solvent Effects on the Rates and Mechanisms of Reaction of Phenols with Free Radicals,” Acc Chem Res, vol. 40, no. 3, pp. 222–230, Mar. 2007, pmid:17370994
View Article
PubMed/NCBI
Google Scholar

[191] View Article

[192] PubMed/NCBI

[193] Google Scholar

[ref56] 56. “ILO-WHO International Chemical Safety Cards (ICSCs).”

[ref57] 57. Settimo L., Bellman K., and Knegtel R. M. A., “Comparison of the Accuracy of Experimental and Predicted pKa Values of Basic and Acidic Compounds,” Pharm Res, vol. 31, no. 4, pp. 1082–1095, Apr. 2014, pmid:24249037
View Article
PubMed/NCBI
Google Scholar

[196] View Article

[197] PubMed/NCBI

[198] Google Scholar

[ref58] 58. Hanai T. and Hubert J., “Hydrophobicity and chromatographic behaviour of aromatic acids found in urine,” J Chromatogr A, vol. 239, pp. 527–536, Apr. 1982,
View Article
Google Scholar

[200] View Article

[201] Google Scholar

[ref59] 59. Linder P. W. and Voyé A., “Potentiometric investigations of the equilibria between caffeic acid and copper(II), zinc(II), iron(II) and hydrogen ions in aqueous solution,” Polyhedron, vol. 6, no. 1, pp. 53–60, Jan. 1987,
View Article
Google Scholar

[203] View Article

[204] Google Scholar

[ref60] 60. Barvinchenko V. N., Lipkovskaya N. A., Kulik T. V., and Kartel N. T.’, “Adsorption of Natural 3-Phenylpropenic Acids on Cerium Dioxide Surface,” Colloid Journal, vol. 81, no. 1, pp. 1–7, Jan. 2019,
View Article
Google Scholar

[206] View Article

[207] Google Scholar

[ref61] 61. Naseem S. et al., “Photo-isomerization upshifts the pKa of the Photoactive Yellow Protein chromophore to contribute to photocycle propagation,” J Photochem Photobiol A Chem, vol. 270, pp. 43–52, Oct. 2013,
View Article
Google Scholar

[209] View Article

[210] Google Scholar

[ref62] 62. Alam A. et al., “Pharmacokinetic and Molecular Docking Studies of Plant-Derived Natural Compounds to Exploring Potential Anti-Alzheimer Activity,” in In Silico Approach for Sustainable Agriculture, Singapore: Springer Singapore, 2018, pp. 217–238. https://doi.org/10.1007/978-981-13-0347-0_13

[ref63] 63. Sik B., Kapcsándi V., Székelyhidi R., Hanczné E. L., and Ajtony Z., “Recent Advances in the Analysis of Rosmarinic Acid From Herbs in the Lamiaceae Family,” Nat Prod Commun, vol. 14, no. 7, p. 1934578X1986421, Jul. 2019,
View Article
Google Scholar

[213] View Article

[214] Google Scholar

[ref64] 64. Chen W., Shi X., Xu W., McClements D. J., Liu X., and Liu F., “Effects of different polyphenols on the structure and properties of sodium caseinate films mediated by tyrosinase,” J Agric Food Res, vol. 10, p. 100395, Dec. 2022,
View Article
Google Scholar

[216] View Article

[217] Google Scholar

[ref65] 65. Adatoz E. B., Hendessi S., Ow-Yang C. W., and Demirel A. L., “Restructuring of poly(2-ethyl-2-oxazoline)/tannic acid multilayers into fibers,” Soft Matter, vol. 14, no. 19, pp. 3849–3857, 2018, pmid:29718054
View Article
PubMed/NCBI
Google Scholar

[219] View Article

[220] PubMed/NCBI

[221] Google Scholar

[ref66] 66. Abrahamse H. and Houreld N. N., “Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells,” Int J Mol Sci, vol. 20, no. 13, p. 3254, Jul. 2019, pmid:31269724
View Article
PubMed/NCBI
Google Scholar

[223] View Article

[224] PubMed/NCBI

[225] Google Scholar

Figures

Abstract

Introduction

Materials and methods

Reagents

Quantum-chemical calculations

Bacterial strains

Determining antimicrobial activity assay.

Cytotoxicity assay.

Statistical analysis

Results and discussion

The theoretical electronic parameters and lipophilicity

Lipophilicity

Antimicrobial activity

Cytotoxic activity

Conclusions

Supporting information

S1 Fig. Co-occurrence of selected keywords in articles in 2014–2023 (search terms: “Phenolic compounds”, “cytotoxicity”, “antimicrobial activity”), created with VOSviewer [3].

S2 Fig.

S2 Table. Effects of phenolic acids on cell lines in in vitro assays.

S3 Table. Values of dipole moment and energy calculated for p-coumaric acid (p-CA), caffeic acid (CA), gallic acid (GA), chlorogenic acid (5-CQA), rosmarinic acid (RA) and tannic acid (TA).

References