Possible Side Effects of Polyphenols and Their Interactions with Medicines

Duda-Chodak, Aleksandra; Tarko, Tomasz

doi:10.3390/molecules28062536

Cited by 63 publications

(42 citation statements)

References 415 publications

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“…Oral administration of anti-invasion phenolic compounds faces similar challenges, in addition to potential problems with absorption and modification by metabolic processes and microbes within the gut (53,69,(133)(134)(135). Furthermore, the intake of very high amounts of plant-derived phenolics might have detrimental effects, such as iron depletion, liver and kidney toxicity, and irritation of the gastrointestinal tract (10,12,(136)(137)(138). Despite these limitations, the work presented here highlights the potential therapeutic utility of plant-derived phenolic compounds as a means to inhibit host cell invasion by UPEC which, if optimized, could help disrupt cycles of rUTIs in some individuals.…”

Section: Discussionmentioning

confidence: 99%

Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by UropathogenicEscherichia coli

Lewis,

Richards,

Mendez

et al. 2023

Preprint

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Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic and polyphenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here we tested a panel of four well-studied phenolic compounds – caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate – for effects on host cell adherence and invasion by uropathogenicEscherichia coli(UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses, and likely contribute to the development of chronic and recurrent infections. Using cell culture-based assays, we found that only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK, or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model, and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenicEscherichia coli(UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds (resveratrol) effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds can be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues, and help explain some of the benefits attributed to traditional plant-based medicines.

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Section: Discussionmentioning

confidence: 99%

Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by UropathogenicEscherichia coli

Lewis,

Richards,

Mendez

et al. 2023

Preprint

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“…Flavonols have also been shown to inhibit the production of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-) and interleukin-6 (IL-6) [ 162 ]. These cytokines are important in the development of chronic inflammation, and inhibiting them with flavonols can help reduce inflammation [ 37 , 98 ]. Flavonols have been proved to influence the activity of inflammatory immune cells such as macrophages and T lymphocytes [ 109 ].…”

Section: Main Textmentioning

confidence: 99%

Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases

Mahmud

Ema

Siddiquee

et al. 2023

Beni-Suef Univ J Basic Appl Sci

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Background Flavonols are phytoconstituents of biological and medicinal importance. In addition to functioning as antioxidants, flavonols may play a role in antagonizing diabetes, cancer, cardiovascular disease, and viral and bacterial diseases. Quercetin, myricetin, kaempferol, and fisetin are the major dietary flavonols. Quercetin is a potent scavenger of free radicals, providing protection from free radical damage and oxidation-associated diseases. Main body of the abstract An extensive literature review of specific databases (e.g., Pubmed, google scholar, science direct) were conducted using the keywords “flavonol,” “quercetin,” “antidiabetic,” “antiviral,” “anticancer,” and “myricetin.” Some studies concluded that quercetin is a promising antioxidant agent while kaempferol could be effective against human gastric cancer. In addition, kaempferol prevents apoptosis of pancreatic beta-cells via boosting the function and survival rate of the beta-cells, leading to increased insulin secretion. Flavonols also show potential as alternatives to conventional antibiotics, restricting viral infection by antagonizing the envelope proteins to block viral entry. Short conclusion There is substantial scientific evidence that high consumption of flavonols is associated with reduced risk of cancer and coronary diseases, free radical damage alleviation, tumor growth prevention, and insulin secretion improvement, among other diverse health benefits. Nevertheless, more studies are required to determine the appropriate dietary concentration, dose, and type of flavonol for a particular condition to prevent any adverse side effects.

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“…Flavonoids (e.g., catechins, epigallocatechin-3-gallate, quercetin) act as iron chelators with antioxidant properties, which can adversely affect iron deficiency and homeostasis depending upon their dose [ 113 ]. Furthermore, flavonoids (e.g., hesperidin, quercetin, catechins) can inhibit the function of enzymes, particularly digestive enzymes, which may be unfavorable for athletes, older individuals, or those with enzyme problems [ 113 , 114 ]. More importantly, some flavonoids (e.g., myricetin, apigenin, kaempferol, and isoquercitrin) can influence intestinal microbiota–an antimicrobial effect–in a dose-dependent manner [ 113 , 115 ].…”

Section: Autophagy and Metastasis Dynamicmentioning

confidence: 99%

“…Furthermore, flavonoids (e.g., hesperidin, quercetin, catechins) can inhibit the function of enzymes, particularly digestive enzymes, which may be unfavorable for athletes, older individuals, or those with enzyme problems [ 113 , 114 ]. More importantly, some flavonoids (e.g., myricetin, apigenin, kaempferol, and isoquercitrin) can influence intestinal microbiota–an antimicrobial effect–in a dose-dependent manner [ 113 , 115 ]. However, there were also some controversial findings.…”

Section: Autophagy and Metastasis Dynamicmentioning

confidence: 99%

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Flavonoids target different molecules of autophagic and metastatic pathways in cancer cells

et al. 2023

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Despite the success of cancer therapy, it has encountered a major obstacle due to the complicated nature of cancer, namely resistance. The recurrence and metastasis of cancer occur when anti-cancer therapeutic agents fail to eradicate all cancer cells. Cancer therapy aims to find the best agent that targets all cancer cells, including those sensitive or resistant to treatment. Flavonoids, natural products from our diet, show anti-cancer effects in different studies. They can inhibit metastasis and the recurrence of cancers. This review discusses metastasis, autophagy, anoikis in cancer cells, and their dynamic relationship. We present evidence that flavonoids can block metastasis and induce cell death in cancer cells. Our research suggests that flavonoids can serve as potential therapeutic agents in cancer therapy.

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Possible Side Effects of Polyphenols and Their Interactions with Medicines

Cited by 63 publications

References 415 publications

Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by UropathogenicEscherichia coli

Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by UropathogenicEscherichia coli

Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases

Flavonoids target different molecules of autophagic and metastatic pathways in cancer cells

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