Among the many, widely distributed secondary metabolites in plants that are crucial to their growth and reproduction are phenolic compounds. This broad class is comprised of approximately 8000 organic compounds, ranging from simple phenolics like phenolic acids to complex compounds like tannins [1, 2]. Phenolic compounds can be further classified into multiple groups, one of which is the flavonoids. These compounds can only be produced by plants. They perform numerous tasks connected to the physiology of growth in addition to characterizing plants’ flavors and colors. The composition of these substances allows flavonoids to be classified into six primary groups: anthocyanidins, isoflavones, flavones, flavonols, and flavanones [3, 4]. The flavonols are among the most well-known flavonoids, and occur naturally in fruits and vegetables [5]. This subgroup includes quercetin (3,5,7,3^′,4^′-pentahydroxyfavone), which can be found in apples, red grape, kales, cherries, onions, broccoli, berries, edible seeds, and tea, among others [6]. One of the most widely used crops for both food and medicine, onion (Allium cepa) is among the most abundant source of quercetin. Fig. 1 shows the chemical formula of quercetin, which has the molecular formula C₁₅H₁₀O₇. It is a yellow-tinted compound, and its name derives from the Latin word “quercetum”. Quercetin dissolves readily in lipids and alcohol, but is insoluble in cold water and has low solubility in hot water.

Free radicals interact with other substances very rapidly in order to entrap their electron and stabilize. The molecule under attack loses an electron and transforms into a free radical, starting a domino effect that damages biological cells [7]. According to the literature, the hydroxyl groups at the A and B rings 3, 5, 7, 3^′, and 4^′, the double bond spanning the third and second carbons, and the carbonyl group on the fourth carbon play major roles in quercetin’s antioxidant characteristics [8]. Several researchers have explored quercetin’s antibacterial properties in depth and have proposed it as a potential treatment against a variety of harmful microbes [9]. Moreover, because bacterial diseases are commonly treated with antibiotics, multidrug resistance (MDR) in bacteria has grown to be a pressing issue on a global scale. The pharmaceutical industry has faced substantial difficulties in treating MDR strains [10].

The suppression of $\beta$-ketoacyl carrier protein synthesis, which contributes to the synthesis of bacterial fatty acids, is assumed to be the mechanism of quercetin’s antibacterial effect, although eradication of the biofilm was mentioned as another potential method of action [11]. Flavonoids have also been found to have antifungal effects; by lowering cell adhesion and affecting the genes involved in the production of biofilms, quercetin works in conjunction with medications like fluconazole and amphotericin B to fight fungal growth [12]. Furthermore, flavonoids also hinder the synthesis of cell walls and interfere with the plasma membrane, cell proliferation, the efflux system, and the synthesis of RNA and protein, as well as causing mitochondrial dysfunction [13]. They have also been found to suppress a number of DNA and RNA viruses through several different destruction methods [14]. Quercetin in particular has demonstrated antiviral effects at various times during the pathogenesis of viruses, such as during virus entry, replication, translation, and protein synthesis. The use of quercetin in combination with other supplements, such as vitamin C, has also been demonstrated to enhance antiviral activities while minimizing negative effects [15].

With severely acute and chronic effects, diabetes—the prevalence of which is rising daily—has emerged as a serious global issue. Among its long-term consequences are retinopathy, neuropathy, nephropathy, and podiatric ailments. Furthermore, hypoglycemia, hyperglycemia, and diabetic ketoacidosis are acute effects that require immediate medical attention [16]. Quercetin has been shown to suppress apoptosis and cell growth by blocking enzymes such as protein kinases and cyclooxygenases. Moreover, it was reported that quercetin enhances insulin release, normalizes blood sugar, and encourages beta cell regeneration in pancreatic islets [17].

In cancerous cells, such as those found in breast, lung, ovarian, colorectal, gastric, and hepatic malignancies, quercetin has demonstrated strong inhibitory actions [18]. Its anticancer properties have been shown to occur through a number of mechanisms, including cell death, angiogenesis inhibition, P-gp channel inhibition, reduced oncogene expression, and signaling pathway regulation [19]. Furthermore, inflammation worsens the disease profile in several conditions, such as rheumatoid arthritis, ulcers, and so forth, because it releases inflammatory mediators. Quercetin’s ability to reduce inflammation was found to be mediated by blocking ATP, proinflammatory cytokine, and the binding sites of nuclear factor kappa B (IkBa) [20]. Another key therapeutic characteristic is quercetin’s capacity to bind with various metal ions, such as Fe²⁺, Fe³⁺, Cu²⁺, and Ni²⁺. The resulting quercetin metal complexes have displayed good activity against inflammation, cancer, ulcer, microbes, and Alzheimer’s disease [21].

Due to the numerous demonstrated benefits of quercetin, it is already being employed in biomedicine for its pharmacological qualities. However, it also has several drawbacks, including low bioavailability, a hydrophobic nature, minimal solubility, and minimal permeability, which make it difficult to be absorbed. To increase quercetin bioavailability and solubility, it is commonly complexed with biodegradable polymers employing chitosan [22]. Recently, the United States Food and Drug Administration (FDA) granted quercetin Generally Recognized as Safe (GRAS) certification [23]. We have outlined the antibacterial, antifungal, antiviral, and antioxidant properties of quercetin in this review, paying particular attention to the underlying molecular concepts. In order to better understand how quercetin prevents microbial infections and how it might be used as a clinically useful antimicrobial drug, future researchers will benefit from reading this review.

Quercetin is present in vegetables and fruits such as red and white onions (22 mg/100 g), elderberries (26.77 mg/100 g), cranberries (14 mg/100 g), green hot peppers (2 mg/100 g), kale (22.58 mg/100 g), blueberries (14 mg/100 g), red apples (5 mg/100 g), lettuce (31 mg/100 g), pears (4.24 mg/100 g), spinach (27.2 mg/100 g), tea (2.63 mg/100 g), cabbage (0.28 mg/100 g), and cauliflower (0.54 mg/100 g) [24]; Table 1 (Ref. [25]) shows other plant sources of quercetin. The compound is frequently utilized as a dietary supplement due to its diverse range of pharmacological properties. From the intake of fruit, vegetables, and tea, varying between 50 to 800 mg/day in several nations, varying daily dietary intakes were observed. According to reports, the average daily intake of quercetin was 18, 16.2, 18.48, and 9.75 mg in China, Japan, Spain, and the USA, respectively [24]. Fig. 2 illustrates the various sources and biological properties of quercetin.

Reactive oxygen species (ROS) and pro-inflammatory cytokines lead to oxidative stress, one of the earliest processes connected to gout and its comorbidities [55]. At the two last steps of the purine metabolic pathway, xanthine oxidoreductase (XOR), particularly the xanthine oxidase (XO) form, oxidizes hypoxanthine to yield xanthine, which is then transformed into urate, releasing H₂O₂ and O₂.

Quercetin is well known as a strong antioxidant substance. Studies have shown strong in vitro antioxidant activity in a variety of tests, including those using OH radicals, 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and Ferric Reducing Antioxidant Power (FRAP) [56, 57]. The existence of a 30, 40-catechol configuration in B-ring, a 4-carbonyl group conjugated to a double bond between C-2 and C-3 in the C-ring and a free OH group at C-3 are some of the structural components of quercetin that are thought to support its antioxidant effects [58]. Furthermore, there are indications that quercetin improves the antioxidant system of defense. In both normal and hyperuricemic rats, using quercetin at 5 mg/kg substantially elevated the total antioxidant capacity of the serum (FRAP value) and greatly decreased the increased levels of malondialdehyde in hyperuricemic rats. This was accomplished by its ability to inhibit the liver enzymes XO and XDH, which produce uric acid, and thus significantly decrease the serum uric acid levels of hyperuricemic rats [59]. In mice with galactose-induced oxidative stress, the serum total antioxidant capacity increased after treatment with 0.3 mmol/kg quercetin, superoxide dismutase, catalase, and glutathione peroxidase levels along with the increase in the mRNA expression levels of these antioxidant enzymes. In addition, the quercetin also reduced serum levels of malondialdehyde and nitric oxide [57]. Another investigation into the inflammation caused by monosodium urate crystals in rats found that quercetin at 200 and 400 mg/kg doses reduced malondialdehyde levels while increasing the activity of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase [60].

Nanotechnology has made it feasible to handle substances that are smaller than 100 nm, which helps them be absorbed by cells and work well in small amounts. Applications of nanotechnology in different fields have grown recently [61, 62], particularly in aquaculture [63, 64, 65], including in health management via nutrient and vaccine supply, fish breeding, pollution cleanup, and water purification [63, 66]. Despite its many beneficial effects, the volatility and limited absorption of quercetin limit its use. To overcome these limitations, the beneficial properties and increased bioavailability of quercetin nanoparticles have been explored [67].

The drawbacks of quercetin include its low solubility in water (about 60 mg/L), poor intestinal permeability, and physiological instability [68, 69, 70]. Several studies have made an effort to overcome these restrictions, as doing so is essential to providing safe and efficient solutions to the evaluated formulations. Consequently, a variety of nanostructures have been created, such as liposomes, cyclodextrin, mesoporous silica nanoparticles, chitosan nanoparticles, PLGA polymer nanoparticles [71], biogenic nanomaterials [72], and other technologies. The size and shape of the nanoparticles affect the solubility of bioactive compounds; for example, particles of smaller size with larger surface area lead to improved dissolution rates [72, 73, 74].

Aghapour et al. [75] used a wet impregnation technique with ultrasonic assistance to create quercetin-conjugated silica nanoparticles. Their objective was to assess the impact on the induction of apoptosis and growth inhibition in MCF-7 cells, a cell line used to treat breast cancer. The authors found that the system contained 45% quantifiable quercetin and that the spherical nanoparticles had an average size of 84 nm. Their subsequent biological experiments showed that 100 µM quercetin and 10 µM quercetin nanoparticles were efficient against breast cancer cells; by causing apoptosis at lower doses than the isolated drug, the method prevented cell division. Similarly, to test quercetin chitosan nanoparticles’ efficacy in cancer treatment, Baksi et al. [76] employed an ionic gelling technique and conducted controlled-release research, finding that the system was highly successful in raising the bioavailability of compounds that were poorly soluble.

Studies conducted both in vitro and in vivo were used to investigate the potential of free material and nanoparticles. These found that the release of flavonoids occurred over a 12-hour period at pH 7.4 (67.28%), and that the IC₅₀ of the nanoparticles was substantially lower than that of quercetin alone (p 0.05) in in vitro cytotoxicity tests. Furthermore, administration of A549 and MDA MB 468 cells to mice resulted in appreciable tumor volume reductions. Sarkar et al. [63] investigated the effects of MDA-MB 231 and MCF 7 human breast cancer cell lines on mesoporous silica quercetin nanoparticles tagged with folic acid, showing that the nanoparticles triggered apoptosis and reduced cell proliferation without causing any harm to normal cells. The authors concluded that the beneficial activity they had observed was caused by quercetin being delivered to the precise region of action with improved bioavailability. Aiming for the synergy between quercetin and vincristine, Wong et al. [51] created liposomal formulations that had an impact on JIMT-1 breast cancer xenografts, a subtype of the disease for which there are presently no viable therapy alternatives. According to the authors, the medications’ optimal synergistic ratio was 2:1 (Inhibitory Concentration (IC): 0.0900), and in Severe Combined Immunodeficient (SCID) mice, good anticancer activity was observed at two-thirds of the highest tolerable dose of vincristine. The animals did not significantly lose weight. This finding suggested that because the medications were more persistent in the bloodstream, there was lower toxicity and higher exposure to the pharmaceuticals inside the tumor.

Tumor growth is largely influenced by the processes of mitosis and cell proliferation; this is why two successful cancer treatments involve blocking cell proliferation and stopping the cell cycle. When quercetin was applied to PC-3 human prostate cancer cells for 24 and 48 hours at different concentrations (50–200 µM), it was observed that the vitality of the cells gradually declined. Additionally, in a dose-dependent manner, quercetin therapy boosted the G2/M phase population in PC-3 and LNCaP cells as well as the S phase population in PC-3 cells [77].

Quercetin derivatives have been identified in several patents as a viable candidate for a variety of medicinal uses, including as anti-aging, anti-inflammatory, anticoagulant, and antioxidant agents [78]. A quercetin patent was filed based on new quercetin derivatives that were proposed as anticancer agents and could be used to make medications that reduce the chance of getting cancer. Quercetin derivatives with hydrogen, benzyl, or substituted benzyl structures have demonstrated cytotoxic effects on cancer cell lines, including those from prostate, ovary, and lung cancers [79]. Furthermore, a derivative of quercetin was produced from sinapinic acid, and metal salt and quercetin showed anticancer activity against human myeloid leukemia cells and human promyelocytic leukemia HL-60 cells [80]. Another chemical was created when quercetin and p-coumaric acid reacted; when tested on SCC-4 human tongue squamous cell carcinoma cells, the substance demonstrated anticancer activity [81, 82].

In a randomized, double-blind, 10-week clinical experiment, 72 women received an individual daily dosage of 500 mg quercetin. Their high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), interleukin-6 (IL-6), and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) levels were all significantly lowered by quercetin, whereas their TG, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) were not. The findings demonstrated that supplementing with quercetin had no effect on cardiovascular risk factors [83]. Recently, a thorough analysis of quercetin’s potential benefits for cardiovascular disorders revealed favorable effects on lipid and glycemic indices [84].

Another randomized, double-blind, placebo-controlled clinical trial explored quercetin’s effect on 50 women with rheumatoid arthritis. For eight weeks, they were divided into two groups: one received a placebo and the other received quercetin (500 mg/day). It was shown that quercetin substantially lowered high-sensitivity tumor necrosis factor-$\alpha$ (hs-TNF-$\alpha$), which in turn decreased morning discomfort, after-activity pain, and early morning stiffness. However, there were no appreciable differences in the tender joint counts, swelling, or erythrocyte sedimentation rate [85].

The effects of quercetin (500 and 1000 mg/day) in comparison to placebo were assessed in 1002 patients with upper respiratory tract infection (URTI) during the course of a 12-week randomized, double-blind, placebo-controlled experiment. The study demonstrated that quercetin had no discernible impact on URTI rates when compared to the placebo [86]. Additionally, a randomized controlled clinical study with an open-label design was carried out to assess the efficacy of quercetin and curcumin at daily doses of 260 mg and 168 mg, respectively, against COVID-19. Twenty-five patients with early to mid-stage COVID-19 received the medication twice a day at home. The results showed that the treated patients’ problems resolved rapidly [87]. Furthermore, due to their multi-target binding capabilities with many SARS-CoV-2 viral proteins, quercetin and some quercetin derivatives are essential for disrupting viral replication. To boost therapeutic efficacy, quercetin and its derivatives can be employed alone or in conjunction with other treatments to target the aforementioned target proteins and impede viral replication and transcription [88].

To elucidate how quercetin affects patients with Type 2 diabetes mellitus postprandial hyperglycemia, a randomized, blind, cross-over study was conducted. It found that patients with type 2 diabetes might successfully lower their postprandial hyperglycemia when taking 400 mg of quercetin [89]. A different randomized, double-blind, placebo-controlled trial recruited overweight participants, who were divided into two groups—the placebo group, which consisted of six men and 30 women, and the 100 mg quercetin group, which consisted of five men and 30 women—for a period of 12 weeks. Both the control and treatment groups had a reduction in blood glucose and leptin levels, and quercetin significantly lowered the participants’ weight and body fat percentage [90].

Nineteen participants with prehypertension and 22 participants with hypertension participated in a double-blind, placebo-controlled, cross-over trial to investigate the effects of 730 mg quercetin over a 28-day period. It was demonstrated that while oxidative stress was not affected, there was a significant drop in both the systolic and diastolic blood pressures in the hypertension participants following quercetin supplementation [91]. In contrast, blood pressure did not alter in the prehypertensive subjects.

The use of natural antimicrobials for food preservation is a recent trend followed by both consumers and food manufacturers. Despite great efforts to improve production and distribution techniques, hygiene standards, and consumer education, food-borne pathogenic and spoilage-causing microorganisms continue to cause huge economic losses and human costs. The increase in consumption of fresh, ready-to-eat, and processed foods to ensure its microbial safety has encouraged the development of innovative food preservation concepts that are primarily based on the use of natural antimicrobial substances rather than synthetic preservatives. This increasing demand and concern about food are leading to increased interest in natural antimicrobials that exhibit effective antagonistic activity against a wide range of undesirable microorganisms in foods. Recent studies have shown that the growth of pathogenic and spoilage-causing microorganisms may be significantly reduced or inhibited by many plant extracts, and their effective antimicrobial activities make them an interesting alternative to synthetic preservatives [92].

Phenolic compounds are considered natural functional components that can be used as antimicrobial food preservatives. These work according to different antimicrobial mechanisms, with at least three mechanisms agreed upon by many authors: (1) Modification of the permeability of cell membranes and rupture of the cytoplasmic membrane; (2) changes in various intracellular functions caused by hydrogen bonding of phenolic compounds with enzymes through their OH groups; and (3) modification of cell morphology (cell wall rigidity and loss of integrity) caused by various interactions with cell membranes [93]. As one of the most powerful antioxidants among phenolic compounds, in addition to possessing other properties such as antibacterial, antiviral, and antifungal activity, quercetin has the ability to act as a biologically active additive in food products [94]. Quercetin works according to various antibacterial mechanisms. These mechanisms involve destroying bacterial cell walls, changing the permeability of the bacterial cell, inhibiting the synthesis of nucleic acids—which affects the synthesis and expression of protein—and reducing enzyme activity [95].

The human diet includes large levels of flavonoids, as this family of polyphenolic chemicals is widely dispersed in the plant kingdom. Numerous studies have demonstrated the potential advantages of flavonoids as antibacterial agents when included in a healthy diet. These include apigenin (40,5,7,-trihydroxyflavone), myricetin (3,5,7,3^′,4^′,5^′-hexa-hydroxyflavone), luteolin (30,40,5,7-tet-rahydoxyflavone), morin (2-(2, 4-dihydroxiphenyl)-3,5,7-trihydroxychromen-4-one), quercetin (3,5,7,3^′,4^′-pentahydroxyfavone), kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one), and many others [96, 97]. Their beneficial bioactive properties include antiviral, antibacterial, antifungal, anti-inflammatory, and cardio-protective qualities, leading to their increasing importance in research.

For example, pharmaceutical studies have shown quercetin and kaempferol to be potential antibacterial drugs inhibiting a variety of harmful microorganisms. The antibacterial mechanisms of these compounds is well documented in literature based on microbial research, and includes bacterial membrane rupture. It has been suggested that flavonoids may prevent bacterial growth in a number of ways, including by rupturing and permeabilizing membranes, directly interacting with membrane proteins, preventing unchecked production of ROS, and preventing the formation of membranes and cell walls [98, 99].

One investigation found several flavonoids, including rutin, myricetin, naringin, catechin, luteolin, and aparin, to have antibacterial and antifungal properties. The study employed nine strains found in dental plaque—Streptococcus oralis, Streptococcus sanguinis, Lactobacillus casei, Escherichia coli, Enterococcus faecalis, Aggregatibacter actinomycetemcomitans, Actinomyces naeslundii, Actinomyces viscosus, Staphylococcus aureus—and the fungal strain Candida albicans. The findings showed that rutin, luteolin, morin, naringin, and quercetin all successfully slowed the growth of bacteria and fungi, with the most potent of these being morin [96].

The effects of flavonoids on sheep erythrocyte membrane structure and on the diameter, zeta-potential, and membrane organization of viable S. aureus cells were compared by Veiko et al. [100]. According to flavonoid lipophilicity, fluorescence tests showed that naringenin and catechin had substantially lower access to the membrane interior than quercetin. Depending on their ability to alter the bacterial membrane structure, naringenin, catechin, and quercetin (100–200 µM) all suppressed the development of S. aureus cells. S. aureus-produced, $\alpha$HL toxin-induced sheep erythrocyte hemolysis was only prevented by lipophilic quercetin at doses of 10–80 µM, not by catechin or naringenin [100].

For decades, flavonoids have been extracted using traditional techniques like Soxhlet, maceration, heat-reflux extraction, and hydro distillation. Unfortunately, the methods require prolonged treatment durations, high temperatures, and more solvents; in addition, the apparatus must be used by qualified persons, the methods are not eco-friendly, and the systems are not cost-effective. These techniques include enzyme-aided extraction (EAE), supercritical fluid extraction (SFE), microwave-assisted extraction (MWAE), and ultrasound-assisted extraction (UAE). Every technique has different processing principles, parameters, and approaches to improving extraction. The new extraction methods are less time-consuming, use less organic solvents, and are safe for the environment [101]. The table below (Table 2, Ref. [102, 103, 104, 105, 106, 107, 108]) shows some methods of extracting quercetin from plant sources in general.

Quercetin is a natural flavonoid found in many fruits, vegetables, and grains, such as apples, onions, broccoli, berries, and green tea. Quercetin has attracted the attention of researchers for its potential health benefits, including its antioxidant, anti-inflammatory, antiviral, and anti-cancer properties. The mode of action of quercetin involves multiple mechanisms and different levels of action on cells and molecules, making it a promising compound in the prevention and treatment of many diseases.

The antioxidant activities of quercetin come mainly from its ability to neutralize free radicals and chelate metal ions that can catalyze the formation of reactive oxygen species (ROS). Free radicals are unstable molecules that contain unpaired electrons and can cause cell damage by reacting with proteins, lipids and nucleic acids. By neutralizing these reactive species, quercetin contributes to protecting cells from oxidative stress that is associated with aging and many chronic diseases such as cardiovascular disease and cancer [124]. This antioxidant property is largely attributed to the hydroxyl groups in its chemical structure, which can provide hydrogen atoms to neutralize free radicals.

In addition to its direct antioxidant effects, quercetin modulates the expression of antioxidant enzymes through activation of the Nrf2 transcription factor pathway. Nrf2 is a transcription factor involved in regulating the expression of antioxidant genes. When Nrf2 is activated, it translocates to the nucleus and binds to the antioxidant moiety in the promoter regions of a variety of genes encoding antioxidant proteins such as superoxide dismutase (SOD), catalase, and glutathione peroxidase [125]. This enhances the cells’ antioxidant defense system, providing additional protection against oxidative damage.

Quercetin also exhibits anti-inflammatory effects by modulating key signaling pathways associated with inflammation. One of the main mechanisms is inhibition of the NF-$\kappa$B transcription factor pathway which plays a crucial role in regulating the expression of cytokines, chemokines and adhesion molecules. Cytokines are small proteins secreted by immune cells and play a key role in regulating the immune and inflammatory response. NF-$\kappa$B is a transcription factor that regulates the expression of many genes involved in the inflammatory response [126]. Quercetin inhibits the phosphorylation and dissociation of I$\kappa$B$\alpha$, an inhibitory protein that binds to NF-$\kappa$B, preventing its activation and translocation to the nucleus. This suppresses genes involved in the inflammatory response, reducing inflammation [127].

Furthermore, quercetin inhibits the MAPK pathway, which is involved in cell proliferation, differentiation, and stress responses. The MAPK pathway involves several protein kinases that are activated in response to external signals, and plays a critical role in the regulation of many cellular processes. By inhibiting the MAPK pathway, quercetin reduces the production of inflammatory mediators and reduces the expression of enzymes such as Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS), which are involved in the inflammatory process [128]. COX-2 is an enzyme that catalyzes the formation of prostaglandins, which play a key role in promoting inflammation and pain. iNOS is an enzyme that catalyzes the production of nitric oxide, a molecule that plays a dual role in inflammation and vascular regulation.

The antiviral properties of quercetin also deserve attention. It interferes with different stages of viral replication and can inhibit the activity of viral enzymes. For example, quercetin has been shown to inhibit the protease activity of hepatitis C virus, preventing viral replication [129]. In addition, quercetin modulates signaling pathways in host cells, enhancing the antiviral response of the immune system. It can increase the production of interferons, which are cytokines that play a crucial role in antiviral defense by activating immune cells and preventing virus replication [130]. Interferons are proteins secreted by virus-infected cells that activate immune cells such as natural killer cells and cytotoxic T cells, enhancing the ability to fight viruses.

The anticancer effects of quercetin are attributed to its ability to induce apoptosis, inhibit cell proliferation, and suppress proliferation. Apoptosis is a programmed process that leads to the death of unwanted or damaged cells, and is essential for maintaining tissue health and preventing cancer. Quercetin induces apoptosis in cancer cells through activation of both mitochondrial (intrinsic) and death receptor (extrinsic) pathways of apoptosis.

It increases the expression of cell death-inducing proteins such as Bax and reduces the expression of anti-apoptotic proteins such as Bcl-2, leading to the release of cytochrome c from mitochondria and the activation of caspases, which are enzymes that carry out the process of apoptosis [131]. In addition, quercetin inhibits the PI3K/Akt pathway, which is often dysregulated in cancer, leading to reduced cell survival and proliferation [132]. The PI3K/Akt pathway is a cellular signaling pathway that plays a key role in regulating cell growth, survival, and metabolism.

Quercetin also affects the tumor environment by inhibiting angiogenesis, the process of creating new blood vessels to supply nutrients to tumors. It reduces the expression of vascular endothelial growth factor (VEGF) and other angiogenesis-stimulating factors, starving the tumor of its blood supply and thus inhibiting its growth and metastasis [133]. VEGF is a protein secreted by cancer cells to promote the growth of new blood vessels, and is essential for tumor nutrition and growth.

Furthermore, quercetin has the ability to modulate gene expression in cancer cells. It can reduce the expression of genes related to cell proliferation and invasion, while increasing the expression of genes inducing apoptosis. This balance between inducing cell death and inhibiting cell proliferation is one of the key factors that makes quercetin a promising ingredient in anti-cancer therapies [134].

Besides its antioxidant, anti-inflammatory, antiviral and anti-cancer properties, quercetin also has beneficial effects on neurological health. Studies show that quercetin can cross the blood-brain barrier and exert protective effects on neurons. By reducing oxidative stress and inflammation in the central nervous system, quercetin can contribute to the prevention of neurodegenerative diseases such as Alzheimer’s and Parkinson’s [135]. Research suggests that quercetin can inhibit the buildup of beta-amyloid protein, which is linked to the development of Alzheimer’s disease, and reduce nerve cell damage caused by oxidative stress [136].

Furthermore, research shows that quercetin can improve cardiovascular health. It can improve vascular endothelial function, reduce blood pressure, and improve blood flow. By inhibiting low-density lipoprotein (LDL) oxidation and reducing inflammation, quercetin may contribute to the prevention of atherosclerosis, a disease characterized by the accumulation of fats and plaques on the walls of arteries [137]. In addition, quercetin can improve blood vessel elasticity and reduce the risk of clot formation, promoting overall cardiovascular health.

Regarding the effects of quercetin in foods, it plays an important role as a natural preservative due to its antioxidant and antimicrobial properties. Quercetin helps extend the shelf life of foods by preventing oxidation and spoilage caused by microorganisms. Quercetin’s antioxidant effects enhance the stability of fats and oils in foods, preventing decomposition and oxidation that lead to rancidity. In addition, quercetin can be used as an antimicrobial agent in foods, contributing to reducing the growth of harmful microorganisms such as bacteria and fungi [27].

Quercetin exhibits antibacterial and antifungal effects, making it a promising candidate for use in combating infections. Its mechanism of action against bacteria is thought to involve inhibiting enzymes necessary for bacterial reproduction and growth.

For example, quercetin inhibits the activity of enzymes such as DNA gyrase and topoisomerase IV, which play a crucial role in bacterial DNA replication [138]. For fungi, quercetin is thought to weaken the fungal cell wall and disrupt membrane functions, leading to fungal death [139].

Quercetin also shows anti-type 2 diabetes effects. Research suggests that quercetin can improve insulin sensitivity and reduce blood glucose levels. It does this by modulating insulin-related signaling pathways and enhancing glucose uptake into cells [140].

Numerous phytochemicals, derived from a large number of natural sources, have demonstrated therapeutic efficacy against a variety of pathogenic species in multiple notable research projects carried out in recent years. Among them is quercetin, one of the most well-known and biologically active antioxidants. Quercetin has been shown to possess strong antagonistic properties against a range of bacteria, fungi, and viruses. This review examined quercetin’s safety as a nutritional supplement and its range of biological effects in both humans and animals. The majority of published studies demonstrated the safety profile of its antibacterial, antifungal, antiviral, and antioxidant activity in animals. However, more thorough analyses in this regard, with reliable results, is urgently required. A key issue with the usage of quercetin is its poor oral bioavailability and solubility. Because of its synergistic actions with other substances, quercetin is a promising chemical for creating modern, more effective, and less harmful treatment modalities for both acute and chronic human disorders. The available research reveals quercetin to have broad-spectrum antimicrobial properties, making it a potential nutraceutical for fighting bacteria, fungi, and viruses. Unfortunately, its low oral absorption and bioavailability in the human body hampers its usage as an efficient antibacterial agent. To fully utilize its medicinal potential, additional study is needed to improve its bioavailability. It is also important to understand the potential future role of quercetin, as subsequent research may reveal it to have greater potential in the treatment of chronic diseases such as diabetes, cancer, and heart disease, and new treatments may be developed based on our increasing understanding of this important protein. Thus, investing in research on quercetin and understanding its underlying role may be key to improving overall health and increasing quality of life in the future.

SGA-S, SHB, and ZKA-Y performed the literature search and wrote the manuscript. SHB contributed to the figure design. SGA-S provided oversight and direction for the manuscript. All authors have participated sufficiently in the work to take public responsibility for appropriate portions of the content and agreed to be accountable for all aspects of the work in ensuring that questions related to its accuracy or integrity. All authors read and approved the final manuscript. All authors contributed to editorial changes in the manuscript.

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This research received no external funding.

The authors declare no conflict of interest.