Quercetin: Comparison
Please note this is a comparison between Version 3 by Camila Xu and Version 5 by Camila Xu.

Quercetin (QRC) is a flavonoid belonging to a group of plant-derived nonsteroidal compounds called phytoestrogens. It is a polyphenol-based molecule and it is widely distributed in many vegetables, fruits, seed, grains, and also in tea and wine.

  • Quercetin
  • antibacterial effect
  • nanocomposite
  • tissue regeneration
  • natural compound
  • polyphenol

1. The Antibacterial Effect of Quercetin

Oral bacterial infections are strongly associated with the most common oral diseases, such as periodontitis and gingivitis. The kinds of bacteria involved are both Gram-positive, including Streptococcus and Actinomyces, and Gram-negative (Figure 2) [1]. On the one hand, the increase in bacterial number is related to a reduction of innate and adaptative immunity; on the other hand, the growth of drug-resistant bacterial strains makes the treatment of these diseases a challenge. In light of this, the usage of flavonoids, such as QRC, has been proposed as an alternative to common antibacterial treatments [2].

Figure 2. Bacterial strains involved in periodontal disease.

Some studies have investigated the role of flavonoids in the management of dental plaque bacterial infection. Notably, Gutierrez-Venegas et al. have demonstrated that QRC and other flavonoids possessed bacteriostatic activity on almost all microorganisms affecting the oral cavity, including Candida albicans. The latter is well known to cause candidiasis, which could manifest in different clinical forms and involves one or more mouth sites [3].

The properties of some microorganism to produce biofilm as well as the drug resistance are contemplated as global public health problems. In particular, biofilm promotes the growth of microorganisms, protecting them from the surrounding environment, acting as an important factor of virulence, and increasing bacterial resistance to antibiotics and the host’s immune system [4]. In a study proposed by Dias da Costa Júnior et al., the antibacterial and antibiofilm activity of QRC against Staphylococcus aureus and Staphylococcus saprophyticus, both vancomycin and methicillin resistant, was evaluated. QRC displayed the MIC values, ranging between 250 to 1000 µg/mL and 62.5 to 1000 µg/mL for Staphylococcus aureus and Staphylococcus saprophyticus, respectively. The best inhibitory effect of QRC was observed against the methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate Staphylococcus aureus (VISA) strains (MIC = 250, 500 and 125 µg/mL, respectively), while the lowest inhibitory effect was against the vancomycin-resistant Staphylococcus aureus (VRSA) strain (MIC = 1000 µg/mL). Regarding the antibiofilm activity, QRC was able to reduce 50% of the biofilm production, even when it was analysed in sub inhibitory concentrations [5].

An antibacterial mechanism of QRC has been proposed by Wang et al. Firstly, in this study they found that the MICs of QRC for Escherichia coli and Staphylococcus aureus were 0.0082 and 0.0068 µmol/mL, respectively. After that, both bacterial strains were treated with concentrations of QRC up to 500-fold higher than their respective MICs for 24 h and then analysed by transmission electron microscopy (TEM) and in term of alkaline phosphatase (ALP) extracellular activity, to investigate the morphology and the permeability of the bacteria. The TEM images displayed that the cell wall and membrane were already damaged using concentrations 50-fold higher than the MIC for Escherichia coli, and 10-fold higher for Staphylococcus aureus. At the same conditions, the researchers found that the ALP activity in Staphylococcus aureus was significantly higher than Escherichia coli, confirming the previous results. In conclusion, according to this study, the bacteriostatic effect of QRC is greater for Gram-positive than Gram-negative bacteria, probably related to the difference in peptidoglycan concentration in the cell wall [6].

Since Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) are both strongly associated with the onset of periodontitis, Geoghegan et al. have studied the effect of QRC against these bacteria. Both the in vitro cultures of these periodontal pathogens were treated with an aqueous QRC solution of 0.1, 0.05, and 0.025 g/mL, using chlorhexidine and sodium chloride as a positive and negative control, respectively. All the results were carried out after 1, 3, 6, and 24 h of incubation. They found that QRC was able to reduce significantly the growth of Pg at 1 h and no difference with the positive control after 6 h was detected, while the growth of Aa was inhibited in a time-dependent manner when compared with the negative control. Finally, in another study they showed that QRC possesses an antibacterial activity of 0.0125 g/mL and 0.1 g/mL MIC for Pg and Aa, respectively [7].

2. Effect of Quercetin on Bone Tissue Regeneration

Phytoestrogens are plant-derived dietary chemicals found in a lot of vegetables and fruits consisting of isoflavonoids, lignans, stilbenes, and the flavonoid QRC

[8]

. Some studies have displayed their role in prevention and treatment of cardiovascular diseases, osteoporosis, diabetes, obesity, and menopausal symptoms

[9][10]

. They are chemically characterized by structural similarity to 17-β-oestradiol (E2), which enables them to modulate the osteogenic mechanism by interaction with ERa and ERb, subtypes of the oestrogen receptors (ERs), both present on the surface of osteoblasts cells

[11]

. The effect of QRC on osteogenesis has been confirmed by several studies 

[12][13]

and it is considered the most potent osteogenic chemical ever discovered, although the real mechanism involved is still unclear.

Pang et al. have investigated the effect of QRC in the proliferation and osteoblastic differentiation on the in vitro cultures of mice-derived bone marrow mesenchymal stem cells (BMSCs). The latter are multipotent stromal cells able to differentiate into various cell types, including the osteoblasts, and therefore play an important role in the induction of osteogenesis [14]. After treatment with increasing concentrations of QRC (0.1 μM–5 μM), they observed a significant rise in BMSC proliferation and ALP activity, which meant an enhanced osteoblast formation in a dose-dependent manner. They also displayed that QRC stimulated osteogenic differentiation, interacting with the oestrogen-signalling pathway, which led to the up-regulation of the osteogenic genes runt-related transcription factor 2 (RUNX2) and Osterix (OXS) [15].

The stimulatory effect of QRC on ALP activity was evaluated by Prouillet et al. In one study, they worked on human osteoblastic cell MG-63 incubated with QRC at 1, 10, and 50 μM for 24 and 48 h in Dulbecco’s modified eagle medium (DMEM), observing that QRC was able to rapidly increase the ALP activity in time and dose-dependent manners. They also found that the extracellular signal-regulated kinase (ERK) pathway was involved in the mechanism, highlighted by the reduction in QRC’s effect when the cells were treated with the MEK inhibitor PD 98059. They evidenced that ICI 182780, an antagonist of the oestrogen receptors (ERs), was also able to reduce the quercetin-mediated ALP activity, confirming the role of these receptors in the phenomenon [16].

Since is well known that the mitogen-activated protein kinase (MAPK) pathway was involved in the osteogenic differentiation of mesenchymal stem cells (MSCs), Li et al. have evaluated the role of QRC in this phenomenon. The MCSs obtained by mice were treated with QRC at 0.01, 0.1, 1, 10, and 100 μM for 72 h. After incubation, the authors found that QRC stimulated the ALP activity in a dose-dependent manner and increased the levels of osteocalcin (BGP) and type 1 collagen (COL I), two bone marker proteins. Moreover, the MAPK and ERK pathways were also stimulated by the treatment with QRC; these results were confirmed, incubating the cells simultaneously with QRC and antagonists of these pathways. The authors highlighted that all the above-mentioned markers were downregulated, confirming the role of QRC in the osteogenesis of MAPK [17].

QRC seems to influence also the osteoclastogenesis phenomenon. In a study carried out by Wattel et al., the in vitro role of QRC on osteoclastic differentiation was evaluated using two major models of osteoclastic-like cells, RAW 264.7 and PBMC, treated with various concentrations of this flavonoid up to 10 μM. They found that QRC showed a strong inhibitory effect in osteoclast differentiation at concentrations as low as 1 μM. Their investigations highlighted that QRC inhibits two transcription factors, the nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and the activator protein 1 (AP-1), which are well known to modulate the differentiation and proliferation of osteoclasts [18].

A summary of QRC’s antibacterial activity and bone tissue regeneration properties is provided in Table 1.

Table 1. Summary of in vitro QRC antibacterial activity and bone tissue regeneration properties.

References

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