SkinCeuticals Phloretin CF Serum

Product Information

The crosstalk between AMPK, Nrf2, and SIRT1 pathways in the anti-inflammatory effect of phloretin. The activation of AMPK and SIRT1 are closely related in the regulation of metabolism and pathologies such as oxidative stress and inflammation. Activation of AMPK by phloretin via its phosphorylation as well as increased expression of SERT1 have been associated with its anti-inflammatory effect and modulation of lipid metabolism such as inhibition of lipid accumulation. This activity was further shown to be related to the induction of Nrf2 that suppresses both the oxidative stress and inflammatory pathways induced by a variety of agents including LPS. Increased SERT3 activity by phloretin is also reported. The red line shows the inhibitory response. Inhibits the proliferation of T lymphocytes; inhibits the expression of CD69 and CD25; induces cell cycle arrest at G0/G1 phase; reduces NO production of LPS-stimulated macrophages; reduces phagocytosis rate of macrophages. To study the anti-inflammatory effect of phloretin in vivo, Huang et al. [ 55] employed the LPS-induced lung injury model in mice where phloretin (20 mg/kg, intraperitoneal (i.p.)) was shown to suppress the upregulated neutrophil infiltration in lung tissue and reduce the levels of IL-6 and TNF-α in serum and bronchoalveolar lavage fluid. In the lung tissues, phloretin also suppressed the level of activity of MPO and superoxide dismutase (SOD) activity and decreased the gene expression levels of chemokines and proinflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1, and CCL5), intercellular adhesion molecule-1 (ICAM-1), iNOS, and COX-2 in inflamed lung tissues. The serum level of IL-6 and TNF-α were also suppressed in LPS-treated animals. As with the in vitro data, phloretin also reduced the phosphorylation of NF-κB and MAPK, while promoting the expression of haeme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) [ 55]. In the lung model of inflammation induced by Mycobacteria tuberculosis, phloretin (2.5 or 5 mg/kg, i.p.) effectively suppressed the levels of TNF-α, IL-1β, and IL-6 in lung tissue [ 45]. Always put the serum in the fridge for 12 hours before you first use it to restabilise the ingredients. Do not shake the bottle before use. Due to air and light exposure, vitamin C products can darken after opening. The formula will remain effective.

SkinCeuticals Phloretin CF is an advanced daytime antioxidant serum that provides superior environmental protection that is a pigment regulator helping to reduce dullness and discolouration of the skin, it retextures and evens skin tone for a brighter more radiant complexion. Suitable for normal, combination skin with ageing and hyperpigmentation. The effect of phloretin on LPS-induced stimulation of macrophages could be a result of a direct effect on TLRs. Kim et al. [ 49] assessed TLR2/1 heterodimerization and signalling in RAW 264.7 cells by using a selective agonist, Pam 3CSK 4. They have shown that phloretin displays molecular interactions with TLR2/1 and modulates the TLR2 signalling pathway leading to suppressed NF-κB phosphorylation and TNF-α production. Cheon et al. [ 50] used the Propionibacterium acnes-induced skin infection model to examine the effect of phloretin on the TLR-2-mediated inflammatory signalling in human keratinocytes. By measuring secreted embryonic alkaline phosphatase (SEAP) activity induced by either Pam 3CSK 4 or by P. acnes in HEK-Blue TM-hTLR2 cells, which are designed for studying the stimulation of TLR-2 via activation of NF-κB, they were able to confirm the signalling pathway associated with the inhibitory effect of phloretin (5–50 µM). In a similar manor, the P. acnes-stimulated levels of TNF-α, IL-1β, and IL-12 as well as phosphorylated c-Jun N-terminal kinase (JNK) in HaCaT cells was inhibited by phloretin through inhibition of the TLR-2 signalling pathway. While the study by Chang et al. [ 36] (see above) demonstrated phlorizin displays weak or no effect when applied directly on LPS-stimulated RAW 264.7 macrophage, positive results were reported for phlorizin metabolites. When tested at low concentrations (1–5 μg/mL), phloretin 4- O-β-D-glucuronide, 6-methoxyl-phloretin-2- O-β-D-glucuronide, and phloretin-2- O-β-D-glucuronide inhibited NO production and iNOS protein expression [ 51]. Their effect on cytokine expression could however vary and hence a more comprehensive in vivo analysis is needed to assess the potential of phlorizin metabolites as anti-inflammatory agents. Prevent, SkinCeuticals, cosmeceutical, Vitamin C, protect, protection, free radicals, Phloretin, stronger skin, youthful skin, radiant skin, natural, normal skin, oily skin, firmer skin But if you use alcohol together with moisturizing ingredients, they’ll counteract its drying effects. Science confirms this. Recent studies show that alcohol isn’t as drying as we once thought.

Should I use Phloretin CF or C E Ferulic?

One common link to the release of the above-mentioned proinflammatory mediators from activated macrophages is the nuclear transcription factor κ-B (NF-κB) which regulates the expression of several genes (e.g., chemokines, cytokines, and adhesion molecules) involved in inflammation. For details of NF-κB signalling, readers can refer to the numerous review articles in the field (e.g., [ 40, 41]). The NF-κB represents a family of protein transcription factors such as NF-κB1 (also named p50), NF-κB2 (also named p52), RelA (also named p65), RelB, and c-Rel. The expression of target genes happens when these transcription factors translocate from the cytoplasm to the nucleus and bind (through their transcriptional transactivation domain at their C-terminus) to the κB enhancer region of the DNA. Since the NF-κB proteins are sequestered in the cytoplasm by binding to inhibitory proteins, including inhibitors of κB (IκB) family members (most important is IκBα, others include IκBβ, IκBε, and their precursors), releasing the NF-κB from the complex is a key cell signalling step in inflammatory genes activation. Many agents that activate the inflammatory pathway such as LPS stimulate the degradation of IκBα via the multi-subunit IκB kinase (IKK)-induced phosphorylation. This further triggers ubiquitin-dependent IκBα degradation in the proteasome, thereby allowing the nuclear translocation of NF-κB. The IKK itself is a complex of two kinases (IKKα and IKKβ) and other proteins and constitutes the classic example of the canonical NF-κB pathway of activation which is common to various immunostimulant-based macrophage activation: i.e., the IκBα degradation-execute the canonical activation pathway of NF-κB. A variety of inflammatory stimuli activate the canonical pathway in macrophages, and these include proinflammatory cytokines, pattern-associated molecular patterns (PAMPs), or damage-associated molecular patterns (DAMPs) binding to cognate receptors. The LPS is recognised in macrophages by Toll-like receptors (e.g., TLR4) and its stimulatory effect is orchestrated through the canonical pathway. Other pathways or the noncanonical NF-κB pathway of activation are, however, also known. Activation of macrophages to a phenotypically M1 state leads to the induction of inflammatory mediators (e.g., IL-1, IL-6, IL-12, TNF-α, and chemokines) which promotes the process of inflammation while the M2 phenotype leads to the production of anti-inflammatory cytokines (e.g., IL-10 and IL-13) which promote resolution of inflammation (e.g., during the wound healing stage) [ 42]. Most of the anti-inflammatory mechanisms of phloretin discussed in the following sections are associated with modulation of the above-mentioned signalling pathway of NF-κB including macrophage polarisation. Dr. Webster’s Recommendation: SkinCeuticals Phloretin CF is an extremely popular antioxidant for daytime use as it helps to reduce and prevent dark marks on the skin. In more recent studies it has shown a 20% improvement in more even skin tone. It is important for everyone to use an antioxidant together with sunscreen during the day but even more so for people who spend a great deal of time outdoors, especially in more urban or industrial areas. One: it removes everything that’s not absolutely necessary, like fragrance and fancy plant extracts that look good in the marketing copy but do absolutely nothing for your skin. By using the standard ulcerative colitis experimental model in mice induced by dextran sulfate sodium (DSS), Wu et al. [ 87] demonstrated the anti-inflammatory effect of phloretin (60 mg/kg p.o. daily for 7 days) in vivo. The novel feature of this study was faecal microbiota transplantation (FMT) or transferring faecal microbes (10 9 CFU/mL) from phloretin-treated diseased mice by gavage to non-phloretin-treated diseased mice. This FMT, as well as phloretin treatment, ameliorated ulcerative colitis by improving pathological markers (e.g., reversing the shortening of colon length and increased Muc2 mRNA and Claudin-1, zonula occludens-1 (ZO-1) protein expressions) and colon inflammation (suppression of cytokines including TNF-α, IL-6 and IL-1β, NF-κB and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation) and oxidative stress (increase the levels of SOD and GSH and decreasing MDA) markers in colonic tissues. This study which also demonstrated the reversal of the change in the gut microflora population induced by ulcerative colitis supports the hypothesis that some of the phloretin’s effects as an anti-inflammatory agent may be associated with modulation of the gut microbiota structure/population. Further evidence substantiating the link between gut microbiota dysbiosis and ulcerative colitis and the reversal of the disease’s pathology by phloretin came from the study by Liu et al. [ 88]. In DSS-induced ulcerative colitis in mice, treatment with phloretin (100 mg/kg, p.o. for three weeks) was shown to reverse the disease score, inflammatory markers (NF-κB activation), and reverse the change in microbiota population of the gut. In an experiment using a lower dose of phloretin (60 mg/kg, p.o.), the DSS-induced ulcerative colitis score in mice was shown to be correlated with normalising the composition of microbes and their metabolites [ 89].

Hi, I'm Gio! I’m a tell-it-like-it-is skin coach and author on a mission to help you achieve your best skin day ever - every day.At an effective dose of 10 μM, phloretin inhibits the levels of NO, PGE 2, IL-6, TNF-α, iNOS, and COX-2; suppresses the nuclear translocation of NF-κB subunit p65 proteins; decreases phosphorylation in MAPK pathway; no effect observed for phlorizin up to 100 μM. Delays the deposition of sugar deposits in your skin (sugar hardens collagen, resulting in wrinkles). The best vitamin C serums have the power to promote the skin’s collagen and elastin production, neutralise free radicals from environmental stress, and brighten the complexion – helping to fade and prevent hyperpigmentation. Vitamin C – the ingredient also known as ascorbic acid or l-ascorbic acid – really is an anti-ageing powerhouse, but not all skincare formulas centred on the antioxidant are made equal. This broad-spectrum treatment provides advanced environmental protection to defend skin against the reactive molecules (including free radicals) that are known to cause cellular damage. In addition to its superior antioxidant capabilities, it has been proven to correct existing damage from the inside out.

Increasing the uptake of phloretin in biological systems to improve its efficacy received some attention in recent years. This has also been tried out in inflammation research [ 156] but most of the studies are related to absorption from the skin given the wide application of the compound in skin products. Thus, polymeric nanocapsules loaded with phloretin [ 157], hydrophilic, and other lipophilic formulations [ 158], and absorption from skin lotions [ 159] have been studied. By using mixed polymeric-modified self-nanoemulsions, Wang et al. [ 160] have shown that the water solubility of phloretin can be enhanced 3000-fold, its bioavailability by 7.9-fold, and it is in vivo anti-inflammatory effect by 6.8-fold. The application of fast-dissolving nanofibers [ 161] and nanoparticles [ 162] including chitosan nanoparticles [ 163] for drug-resistant cells in cancer therapy using phloretin formulation has also been explored. Moreover, various other approaches are now adopted to formulate phloretin for a better therapeutic efficacy outcome and more research in this field will solve its limitation in bioavailability. I’ve already told you how Skinceuticals Phloretin CF compares to Skinceuticals CE Ferulic. To me, the latter is the BEST Vitamin C serum on the market (and yes, it makes me cry, it’s so expensive!), so I don’t see the need for more Vitamin C serums. Skinceuticals obviously disagrees with me as they have quite a few options available. Let’s take a look at how Skinceuticals Phloretin CF compares to them: Phloretin 4- O-β-D-glucuronide, 6-methoxyl-phloretin-2- O-β-D-glucuronide, and phloretin-2- O-β-D-glucuronide inhibi NO production and iNOS protein expression. No, Skinceuticals isn’t cruelty-free. They may test on animals or outsource the process. Their parent company, L’Oreal, surely does. Price & Availability Phloretin is a natural antioxidant derived from apples, pears and other plants. In addition to neutralizing free radicals generated by UV rays, infrared radiation (IRA) and ozone pollution, phloretin enhances the action of other antioxidants, improves the appearance of uneven skin tone and helps minimize the look of sun damage.Text, 16% improvement in skin tone evenness in 24 weeks. 24% improvement in skin firmness in 24 weeks. Phloretin (at concentrations less than 100 µM) is known to inhibit adipogenesis and promote apoptosis in adipocytes in vitro [ 62, 63, 64]. In oleic acid-treated HepG2 cells, it also prevented excessive lipid accumulation and decreased the sterol regulatory element-binding protein 1c (SREBP-1c), inhibiting the expression of fatty acid synthase (FAS), while it increased the sirtuin 1 (SIRT1), and phosphorylation of AMPK to suppress acetyl-CoA carboxylase expression thereby suppressing the synthesis of fatty acids [ 65]. In high-fat-diet (HFD)-fed obese mice, phloretin reduced body weight and fat weight, liver weight and liver lipid accumulation, and improved hepatocyte steatosis. In liver tissue of obese mice, phloretin further suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. In addition, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice [ 65]. The role of phloretin in lipid metabolism is, however, complex as it also promotes adipocyte differentiation in vitro and improves glucose homeostasis in vivo by increasing the expression of adipose-related genes or adipogenic markers (peroxisome proliferator-activated receptor-γ (PPARγ), CAAT enhancer binding protein-α (C/EBPα), fatty acid synthase, fatty acid-binding protein 4, and adiponectin such as fatty acids translocase and fatty acid synthase [ 64]. In this connection, phloretin is known to enhance adipocyte differentiation and adiponectin expression by mechanisms including PPARγ activation as well as modulation of gene expression with the implication of reducing insulin resistance [ 66]. When RAW 264.7 macrophages were co-cultured with 3T3-L1 cells during adipocytes differentiation, phloretin (and to a very less extent phlorizin) inhibited the adipogenesis-related transcription factors. The phosphorylation of AMPK and the activity of adipose triglyceride lipase and hormone-sensitive lipase were augmented. As an anti-inflammatory compound, phloretin also suppressed the NF-κB and MAPK pathways [ 67]. Its effects on obesity-associated inflammation are further scrutinised below. SkinCeuticals’ maximum strength Retinol 1.0 is best for skin that has been preconditioned with Retinol 0.5 or has a higher retinol tolerance, as well as those switching from a prescription-based retinol product. A considerable level of research has been done in the past few years to show that the antioxidant and anti-inflammatory effects of several compounds are mediated through the expression of the Nrf2, which derives macrophage to anti-inflammatory phenotype (M2). The Nrf2 is another master transcription factorthat regulates the cellular response to inflammationand oxidative stress. The Nrf2 binds to the regulatory regions (antioxidant response element (ARE)) of target genes to upregulate the expression of cytoprotective or antioxidant enzymes such as phase II detoxification enzymes and stress proteins. By far the most characterised genes/proteins under the regulatory control of Nrf2 are haeme oxygenase-1 (HMOX1, HO-1), glutamate-cysteine ligase, glutathione peroxidase 1 (GPX1), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1), glutathione- S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), peroxiredoxin (PRDX1), and ferritin. The Nrf2 activity depends on the negative regulator, Kelch-like ECH-associated protein 1 (Keap1, also called electrophile response element), which binds to it and presents it for ubiquitination and subsequent degradation by proteosomes. External stimuli such as ROS-based electrophilic reaction with Keap1 lead to the inactivation of Keap1 and leave the Nrf2 stable or available for nuclear translocation, and transcriptional induction of Nrf2-target genes. Alternative mechanisms of Nrf2 regulation are also known but not discussed herein. For details of Nrf2 regulation in inflammation/oxidative stress, readers should refer to review articles on this topic [ 56, 57, 58, 59]. In this line, phloretin (50 μM) treatment of mouse bone marrow-derived macrophages have been shown to reduce the inflammatory phenotype of macrophages through the upregulation of the Nrf2-signalling pathway [ 33]. In macrophages stimulated with phorbol 12-myristate 13-acetate, the levels of ROS and mRNA of proinflammatory genes NOS2, IL-6, COX2,and IL-12 were all shown to be reduced by phloretin, while Nrf2-response genes, HO-1and NQO1were activated. Interestingly, Keap1 degradation in macrophages was enhanced by phloretin. Furthermore, phloretin treatment led to the AMP-activated protein kinase (AMPK) phosphorylation and activation in macrophages which was shown to be associated with cell autophagy (see details in Section 12). In an in vivo model, a macrophage-driven experimental autoimmune encephalomyelitis (EAE) was reported to be suppressed by phloretin (50 mg/kg, i.p.). This was evidenced by increased expression of anti-inflammatory and neurotrophic factors, i.e., IL-4, ciliary neurotrophic factor, and insulin-like growth factor-1 in the spinal cord of EAE animals, elevated Nrf2 signalling in the CNS and increased mRNA expression of Nrf2 and its downstream targets, NQO1 and GPX1.

This antioxidant combination isn’t as well-researched as Vitamin C + Vitamin E + ferulic acid, so it may be less effective.

Vitamin C Serums

Did you know that SkinCeuticals Founding Scientist Sheldon Pinnell, M.D. filed the first vitamin C patent in 1992? This discovery paved the way for an entirely new skin care category: topical vitamin C. Thus, it makes sense that vitamin C is included in many SkinCeuticals skincare products, with SkinCeuticals Phloretin CF being no exception. This antioxidant serum features a patented synergistic combination of 10% pure vitamin C (L-ascorbic acid), 2% phloretin, and 0.5% ferulic acid. We’ll discuss each of these ingredients in detail below so you’ll know exactly how they affect your skin.