Studies on pharmacokinetic properties and absorption mechanism of phloretin: In vivo and in vitro

Zhao, Yuan; Fan, Yu; Wang, Mei; Wang, Jing; Cheng, Jiang; Zou, Jun bo; Zhang, Xiao Fei; Shi, Ya jun; Guo, Dong yan

doi:10.1016/j.biopha.2020.110809

Cited by 34 publications

(30 citation statements)

References 33 publications

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“…Such adipogenic inhibition was mediated, in part, by the ability of phloretin to both increase β-catenin, as well as induce apoptosis of adipocytes in the late stages of their differentiation. Although the pharmacological use of phloretin is complicated, due to its low solubility [87], these results show that consumption of phloretin-enriched products may have positive effects for prevention and treatment of different pathologies, such as obesity. Likewise, it may have effects for decreasing bone-marrow adiposity associated with aging.…”

Section: Discussionmentioning

confidence: 91%

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 91%

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

et al. 2021

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“…Among the natural dihydrochalcone found in apple, phloretin is one of the main active ingredients. Some evidence suggests that phloretin can treat cardiovascular disease, cancer, chemical perfusion injury, neurodegeneration, diabetes and ameliorates colon in ammation [13][14][15]. The four hydroxyl groups in the phloretin structure can inhibit the transmembrane transport of sugars in cells, block energy transport, and induce cancer cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Phloretin Combined With Radiotherapy on Lung Cancer

Juan

Gong²

2021

Preprint

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OBJECTIVE: The purpose of this study was to investigate the synergistic anti-tumor effects of phloretin (Ph) and radiotherapy (RT) on Lewis lung cancer (LLC), and the mechanisms involved. METHODS：The proliferative rate of Lewis cells treated with phloretin was detected by MTT assay; Clone formation experiments were used to demonstrate the synergistic effect of phloretin and radiotherapy; Mice engrafted with the LLC cells were given intraperitoneal injections of saline, phloretin with or without RT. Tumor models were established by laterally transplanting LLC cells in the right thigh of C57BL/J mice. They were randomly divided into four groups, namely saline group, phloretin group, radiotherapy group, phloretin combined with radiotherapy group. 10Gy radiotherapy was performed during the administration. PET-CT was used to detect 18F-FDG uptake in tumor tissue; immunohistochemistry was used to detect Ki67 expression in tumor tissue; cell apoptosis was detected by flow cytometry. RESULTS: Different concentrations of phloretin inhibited the proliferation of Lewis cells in a time and dose-dependent manner (P<0.05). The radiotherapy sensitization ratio (SER) of 50μg Phloretin was 1.645 in the LLC cells. The combination of Phloretin and RT increased survival compared to free Phloretin and RT (p<0.05), and prolonged tumor growth delay (TGD). Furthermore, the RT + Phloretin combination therapy significantly reduced 18F-FDG uptake, increased apoptosis and decreased the proliferation index (Ki67) in tumor cells compared to either monotherapy. CONCLUSION: phloretin combined with radiotherapy has a synergistic anti-tumor effect, possibly by promoting apoptosis, as well as inhibiting proliferation rate and glucose transport.

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“…In another study on rats, phloretin appeared in the plasma 10 min after oral administration (100 mg/kg BW), taking at least 5.49 h to eliminate 63.2%. Its oral bioavailability was 8.68% [ 62 ]. Crespy et al [ 63 ] reported that when phloridzin is fed to rats in a supplemented diet, it took longer for phloretin to be detected in the plasma than when the diet contained phloretin, but after 10 h, the phloretin concentration was the same, irrespective of the compound ingested.…”

Section: Aspalathin and Related Compounds—structures Sources Stability Bioaccessibility And Bioavailabilitymentioning

confidence: 99%

“…Wang et al [ 64 ] postulated that changes in the intestinal tract permeability may be due to up-regulation of lipopolysaccharides (LPS) and down-regulation of P-gp. Zhao et al In addition, [ 62 ] showed that phloretin is a substrate of P-gp and multidrug resistance protein 2 (MRP2).…”

Section: Aspalathin and Related Compounds—structures Sources Stability Bioaccessibility And Bioavailabilitymentioning

confidence: 99%

New Insights into the Efficacy of Aspalathin and Other Related Phytochemicals in Type 2 Diabetes—A Review

Muller

Joubert

Chellan

et al. 2021

IJMS

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In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D.

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Studies on pharmacokinetic properties and absorption mechanism of phloretin: In vivo and in vitro

Cited by 34 publications

References 33 publications

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

Synergistic Effect of Phloretin Combined With Radiotherapy on Lung Cancer

New Insights into the Efficacy of Aspalathin and Other Related Phytochemicals in Type 2 Diabetes—A Review

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