Search Results (11)

Three types of fermented tea (lightly fermented tea, LFT; semi-fermented tea, SFT; and highly fermented tea, HFT) processed from the same tea variety were subjected to submerged fermentation (SmF) using pure Eurotium cristatum. Chemical analysis and untargeted metabolomics showed that the major chemical components of the three tea infusions underwent significant changes, each exhibiting distinct metabolic profiles, with LFT showing the most upregulated metabolites. Antioxidant assays revealed that all three fermented tea infusions exhibited significantly enhanced antioxidant capacity, with 17 bioactive metabolites (e.g., Phloretin, Epicatechin gallate) showing strong correlations with activity. These distinct variations were correlated with the initial chemical composition of the tea infusions, suggesting that the initial chemical profile served as an important influencing factor in the metabolic process of E. cristatum, yet microbial mediation played a dominant role in guiding the direction of fermentation and shaping the final quality characteristics, despite the presence of spontaneous chemical changes in the tea infusion. Further network pharmacology and molecular docking analyses identified 15 potential health-beneficial antioxidant metabolites, most of which were more abundant in LFT. Combined with sensory evaluation results, our results indicated that LFT was most suitable for making functional antioxidant beverages fermented by E. cristatum. Full article

Exposure to ultraviolet (UV) radiation causes harmful effects on the skin, such as inflammatory states and photoaging, which depend strictly on the form, amount, and intensity of UV radiation and the type of individual exposed. Fortunately, the skin is endowed with a number of endogenous antioxidants and enzymes crucial in its response to UV radiation damage. However, the aging process and environmental stress can deprive the epidermis of its endogenous antioxidants. Therefore, natural exogenous antioxidants may be able to reduce the severity of UV-induced skin damage and aging. Several plant foods constitute a natural source of various antioxidants. These include gallic acid and phloretin, used in this work. Specifically, polymeric microspheres, useful for the delivery of phloretin, were made from gallic acid, a molecule that has a singular chemical structure with two different functional groups, carboxylic and hydroxyl, capable of providing polymerizable derivatives after esterification. Phloretin is a dihydrochalcone that possesses many biological and pharmacological properties, such as potent antioxidant activity in free radical removal, inhibition of lipid peroxidation, and antiproliferative effects. The obtained particles were characterized by Fourier transform infrared spectroscopy. Antioxidant activity, swelling behavior, phloretin loading efficiency, and transdermal release were also evaluated. The results obtained indicate that the micrometer-sized particles effectively swell, and release the phloretin encapsulated in them within 24 h, and possess antioxidant efficacy comparable to that of free phloretin solution. Therefore, such microspheres could be a viable strategy for the transdermal release of phloretin and subsequent protection from UV-induced skin damage. Full article

Neuroinflammation is a hallmark of traumatic brain injury (TBI)’s acute and chronic phases. Despite the medical and scientific advances in recent years, there is still no effective treatment that mitigates the oxidative and inflammatory damage that affects neurons and glial cells. Therefore, searching for compounds with a broader spectrum of action that can regulate various inflammatory signaling pathways is of clinical interest. In this study, we determined not only the in vitro antioxidant capacity of apple pomace phenolics, namely, phlorizin and its metabolite, phloretin, but we also hypothesize that the use of these bioactive molecules may have potential use in TBI. We explored the antioxidant effects of both compounds in vitro (DPPH, iron-reducing capacity (IRC), and Folin–Ciocalteu reducing capacity (FCRC)), and using network pharmacology, we investigated the proteins involved in their protective effects in TBI. Our results showed that the antioxidant properties of phloretin were superior to those of phlorizin in the DPPH (12.95 vs. 3.52 mg ascorbic acid equivalent (AAE)/L), FCRC (86.73 vs. 73.69 mg gallic acid equivalent (GAE)/L), and iron-reducing capacity (1.15 vs. 0.88 mg GAE/L) assays. Next, we examined the molecular signature of both compounds and found 11 proteins in common to be regulated by them and involved in TBI. Meta-analysis and GO functional enrichment demonstrated their implication in matrix metalloproteinases, p53 signaling, and cell secretion/transport. Using MCODE and Pearson’s correlation analysis, a subcluster was generated. We identified ESR1 (estrogen receptor alpha) as a critical cellular hub being regulated by both compounds and with potential therapeutic use in TBI. In conclusion, our study suggests that because of their vast antioxidant effects, probably acting on estrogen receptors, phloretin and phlorizin may be repurposed for TBI treatment due to their ease of obtaining and low cost. Full article

The isolation of phlorizin from the bark of an apple tree in 1835 led to a flurry of research on its inhibitory effect on glucose transporters in the intestine and kidney. Using phlorizin as a prototype drug, antidiabetic agents with more selective inhibitory activity towards glucose transport at the kidney have subsequently been developed. In contrast, its hydrolysis product in the body, phloretin, which is also found in the apple plant, has weak antidiabetic properties. Phloretin, however, displays a range of pharmacological effects including antibacterial, anticancer, and cellular and organ protective properties both in vitro and in vivo. In this communication, the molecular basis of its anti-inflammatory mechanisms that attribute to its pharmacological effects is scrutinised. These include inhibiting the signalling pathways of inflammatory mediators’ expression that support its suppressive effect in immune cells overactivation, obesity-induced inflammation, arthritis, endothelial, myocardial, hepatic, renal and lung injury, and inflammation in the gut, skin, and nervous system, among others. Full article

Phloretin is a flavonoid of the dihydrogen chalcone class, present abundantly in apples and strawberries. The beneficial effects of phloretin are mainly associated with its potent antioxidant properties. Phloretin modulates several signaling pathways and molecular mechanisms to exhibit therapeutic benefits against various diseases including cancers, diabetes, liver injury, kidney injury, encephalomyelitis, ulcerative colitis, asthma, arthritis, and cognitive impairment. It ameliorates the complications associated with diabetes such as cardiomyopathy, hypertension, depression, memory impairment, delayed wound healing, and peripheral neuropathy. It is effective against various microbial infections including Salmonella typhimurium, Listeria monocytogenes, Mycobacterium tuberculosis, Escherichia coli, Candida albicans and methicillin-resistant Staphylococcus aureus. Considering the therapeutic benefits, it generated interest for the pharmaceutical development. However, poor oral bioavailability is the major drawback. Therefore, efforts have been undertaken to enhance its bioavailability by modifying physicochemical properties and molecular structure, and developing nanoformulations. In the present review, we discussed the pharmacological actions, underlying mechanisms and molecular targets of phloretin. Moreover, the review provides insights into physicochemical and pharmacokinetic characteristics, and approaches to promote the pharmaceutical development of phloretin for its therapeutic applications in the future. Although convincing experimental data are reported, human studies are not available. In order to ascertain its safety, further preclinical studies are needed to encourage its pharmaceutical and clinical development. Full article

Currently, medication for benign prostate hyperplasia (BPH) and prostate cancer (PCa) are mainly based on modulating the hormone and nervous systems. However, side effects often affect patients, and might decrease their commitment to continuing the medication and lower their quality of life. Some studies have indicated that chronic inflammation might be the cause of BPH and PCa. Based on this hypothesis, the effect of phloretin, a potent anti-inflammatory and anti-oxidative flavonoid, has been researched since 2010. Results from animal and in-vitro studies, obtained from databases, also indicate that the use of phloretin in treating BPH and PCa is promising. Due to its effect on inflammatory cytokines, apoptosis or anti-apoptosis, reactive oxygen species, anti-oxidant enzymes and oxidative stress, phloretin is worthy of further study in human clinical trials regarding safety and effective dosages. Full article

Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential neuroprotective strategy for stroke, in which the temperature is decreased safely. The present study determined whether neuroprotective PH with chlorpromazine and promethazine (C + P), plus dihydrocapsaicin (DHC) improved glucose metabolism in acute ischemic stroke. A total of 208 adult male Sprague Dawley rats were randomly divided into the following groups: sham, stroke, and stroke with various treatments including C + P, DHC, C + P + DHC, phloretin (glucose transporter (GLUT)-1 inhibitor), cytochalasin B (GLUT-3 inhibitor), TZD (thiazolidinedione, phosphoenolpyruvate carboxykinase (PCK) inhibitor), and apocynin (nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor). Stroke was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 6 or 24 h of reperfusion. Rectal temperature was monitored before, during, and after PH. Infarct volume and neurological deficits were measured to assess the neuroprotective effects. Reactive oxygen species (ROS), NOX activity, lactate, apoptotic cell death, glucose, and ATP levels were measured. Protein expression of GLUT-1, GLUT-3, phosphofructokinase (PFK), lactate dehydrogenase (LDH), PCK1, PCK2, and NOX subunit gp91 was measured with Western blotting. PH with a combination of C + P and DHC induced faster, longer, and deeper hypothermia, as compared to each alone. PH significantly improved every measured outcome as compared to stroke and monotherapy. PH reduced brain infarction, neurological deficits, protein levels of glycolytic enzymes (GLUT-1, GLUT-3, PFK and LDH), gluconeogenic enzymes (PCK1 and PCK2), NOX activity and its subunit gp91, ROS, apoptotic cell death, glucose, and lactate, while raising ATP levels. In conclusion, stroke impaired glucose metabolism by enhancing hyperglycolysis and gluconeogenesis, which led to ischemic injury, all of which were reversed by PH induced by a combination of C + P and DHC. Full article

Omicron is an emerging SARS-CoV-2 variant, evolved from the Indian delta variant B.1.617.2, which is currently infecting worldwide. The spike glycoprotein, an important molecule in the pathogenesis and transmissions of SARS-CoV-2 variants, especially omicron B.1.1.529, shows 37 mutations distributed over the trimeric protein domains. Notably, fifteen of these mutations reside in the receptor-binding domain of the spike glycoprotein, which may alter transmissibility and infectivity. Additionally, the omicron spike evades neutralization more efficiently than the delta spike. Most of the therapeutic antibodies are ineffective against the omicron variant, and double immunization with BioNTech-Pfizer (BNT162b2) might not adequately protect against severe disease induced by omicron B.1.1.529. So far, no efficient antiviral drugs are available against omicron. The present study identified the promising inhibitors from seaweed’s bioactive compounds to inhibit the omicron variant B.1.1.529. We have also compared the seaweed’s compounds with the standard drugs ceftriaxone and cefuroxime, which were suggested as beneficial antiviral drugs in COVID-19 treatment. Our molecular docking analysis revealed that caffeic acid hexoside (−6.4 kcal/mol; RMSD = 2.382 Å) and phloretin (−6.3 kcal/mol; RMSD = 0.061 Å) from Sargassum wightii (S. wightii) showed the inhibitory effect against the crucial residues ASN417, SER496, TYR501, and HIS505, which are supported for the inviolable omicron and angiotensin-converting enzyme II (ACE2) receptor interaction. Cholestan-3-ol, 2-methylene-, (3beta, 5 alpha) (CMBA) (−6.0 kcal/mol; RMSD = 3.074 Å) from Corallina officinalis (C. officinalis) manifested the strong inhibitory effect against the omicron RBD mutated residues LEU452 and ALA484, was magnificently observed as the essential residues in Indian delta variant B.1.617.2 previously. The standard drugs (ceftriaxone and cefuroxime) showed no or less inhibitory effect against RBD of omicron B.1.1.529. The present study also emphasized the pharmacological properties of the considered chemical compounds. The results could be used to develop potent seaweed-based antiviral drugs and/or dietary supplements to treat omicron B.1.1529-infected patients. Full article

Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG/RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide. Full article

Anthocyanins have multiple biological activities of benefit to human health. While a few studies have been conducted to evaluate the bioavailability of anthocyanins, the mechanisms of their absorption mechanism remain ill-defined. In the present study, we investigated the absorption mechanism of cyanidin-3-O-β-glucoside (Cy-3-G) in human intestinal epithelial (Caco-2) cells. Cy-3-G transport was assessed by measuring the absorptive and efflux direction. Inhibition studies were conducted using the pharmacological agents, phloridzin, an inhibitor of sodium-dependent glucose transporter 1 (SGLT1), or phloretin, an inhibitor of glucose transporter 2 (GLUT2). The results showed that phloridzin and phloretin significantly inhibited the absorption of Cy-3-G. In addition, Caco-2 cells transfected with small interfering RNA (siRNA) specific for SGLT1 or GLUT2 showed significantly decreased Cy-3-G absorption. These siRNA transfected cells also showed a significantly decreased rate of transport of Cy-3-G compared with the control group. These findings suggest that Cy-3-G absorption is dependent on the activities of SGLT1 and GLUT2 in the small intestine and that SGLT1 and GLUT2 could be a limiting step for the bioavailability of Cy-3-G. Full article

Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic swelling activates two types of macroscopic anion conductance with different voltage-dependence and pharmacology. At the single-channel level, we identified two types of events: one corresponded to the maxi-anion channel, and the other one had characteristics of the volume-sensitive outwardly rectifying (VSOR) chloride channel of intermediate conductance. A VSOR inhibitor, phloretin, significantly suppressed both macroscopic VSOR-type conductance and single-channel activity of intermediate amplitude. The maxi-anion channel activity was largely suppressed by Gd³⁺ ions but not by phloretin. Surprisingly, [(dihydroindenyl)oxy] alkanoic acid (DIOA), a known antagonist of K-Cl cotransporter, was found to significantly suppress the activity of the VSOR-type single-channel events with no effect on the maxi-anion channels at 10 μM. The regulatory volume decrease (RVD) phase of cellular response to hypotonicity was mildly suppressed by Gd³⁺ ions and was completely abolished by phloretin suggesting a major impact of the VSOR chloride channel and modulatory role of the maxi-anion channel. The inhibitory effect of DIOA was also strong, and, most likely, it occurred via blocking the VSOR Cl⁻ channels. Full article