SkinCeuticals Phloretin CF Serum

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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. The nonalcoholic fatty liver disease (NAFLD) experimental model is routinely used for the evaluation of therapeutic agents targeting the various components of metabolic dysfunction associated with lipids. By using Huh7 cells exposed to high doses of free fatty acids, Chhimwal et al. [ 68] have shown that phloretin encouraged autophagy-mediated hepatic lipid clearance and restored mitochondrial membrane potential and redox homeostasis. In the in vivo model of NAFLD using mice subjected to a western diet, a reduction in hepatic histological injury, hepatic lipogenesis, and enhanced fatty acid oxidation were observed in phloretin (50, 100, and 200 mg/kg, p.o.)-treated animals. While improving body weight, oral glucose tolerance, and antioxidant status in the liver (increased levels of SOD, CAT, and decreased lipid peroxidation products, malondialdehyde (MDA) status, a reduction in inflammation was evident as demonstrated by diminished levels of TNF-α and IL-6 in the liver. Beyond the anti-inflammatory effect, phloretin restored the AMPK activity (induction of phosphorylation of AMPK) in the liver of NAFLD and fatty acids-loaded hepatocyte cell lines. The activity of PPARα and its target genes carnitine palmitoyltransferase 1 (CPT1) and CPT2, as well as fatty acids metabolism in the liver, was also augmented by phloretin supplementation in the diet. The in vitro LPS-stimulated macrophages assay model is the standard experimental model to demonstrate the anti-inflammatory properties of potential therapeutic agents. Indeed, both phloretin and phlorizin have been tried out in this model for their potential to suppress the release of inflammatory mediators from LPS-activated cells. When tested at the concentration of 3–100 μM, phlorizin did not suppress the inflammatory response in LPS-stimulated RAW 264.7 cells, while phloretin (10 μM) was able to decrease the level of nitric oxide (NO), prostaglandin E 2 (PGE 2), IL-6, TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [ 36]. The NO release in LPS-stimulated macrophages is a function of the activation of iNOS, an enzyme that cleaves l-arginine into l-citrulline and NO. Activation of induction of COX-2 in macrophages leads to the release of various lipid mediators including PGE 2, which is a potent inflammatory mediator and pain stimulus. Hence, the compound inhibits the inflammation-associated expression of both cytokine and non-cytokine mediators. This data was also consistent with others where phloretin was shown to suppress the LPS-induced myeloperoxidase (MPO) and iNOS activity in RAW 264.7 cells [ 37]. In one experiment [ 38], the IC 50 value of 5.2 μM was reported as an inhibitory effect of phloretin in NO production by RAW 264.7 cells which was associated with the inhibition of the LPS-induced iNOS. The effect of phloretin in this assay model for NO release ranged from potent (less than 10 μM) to moderate with IC 50 values between 10–100 μM [ 36]. The release of proinflammatory cytokines (IL-1α, IL-1β, IL-6, and IFN-γ) and chemokines (C-C motif chemokine Ligand 2 (CCL2), CCL5, macrophage inflammatory protein-1α (MIP-1α), and C-X-C motif Chemokine ligand 5 (CXCL5)) from cultured human peripheral blood mononuclear cells stimulated with LPS was also suppressed by phloretin and other natural antioxidants (e.g., silymarin, hesperetin, or resveratrol) when tested at the concentration of 100 µM [ 39]. SkinCeuticals C E Ferulic Antioxidant Serum has received countless awards and accolades (in addition to garnering a cult following) since its debut in 2005, but we don’t like to play favorites when it comes to the brand’s vitamin C topical antioxidant serums! C E Ferulic’s younger sibling, Phloretin CF Antioxidant Serum, has made a name for itself since its introduction in 2008, and this vitamin C serum offers all the advanced antioxidant protection SkinCeuticals is known for while providing a unique set of benefits. Should I use Phloretin CF or C E Ferulic?

Evidence is now emerging in support of the PI3K/Akt pathway of NF-κB activation which is targeted by phloretin. Readers should bear in mind that this pathway is far too complex and in some cases, inhibition of the pathway displays protective effects while in others, it worsens the inflammation (see review, [ 121]). More research is thus needed to ascertain the significance of either enhancing or suppressing the PI3K/Akt pathway by phloretin. Another way that ascorbic acid helps to reduce signs of aging is through collagen synthesis. Specifically, ascorbic acid serves as a cofactor for prolysyl and lysyl hydroxylase, the enzymes that are responsible for stabilizing and cross-linking the collagen molecules. Thus, SkinCeuticals Phloretin CF may be able to help reduce the appearance of fine lines and wrinkles while promoting firmer, more youthful skin. One of the main benefits of ascorbic acid is its potent antioxidant activity. Ascorbic acid donates electrons to neutralize free radicals from environmental factors such as UVA/UVB radiation, infrared radiation (IRA), and ozone pollution (O3). This is important because the harmful effects of free radicals occur as direct chemical alterations of the cellular DNA, the cell membrane, and cellular proteins, including collagen. Damaged collagen manifests as signs of premature skin aging, including wrinkles, lines, and sagging skin. By protecting collagen and other skin components, ascorbic acid helps to prevent signs of aging. This is one way that SkinCeuticals Phloretin CF provides advanced environmental protection.

What Products should I Pair with C E Ferulic and Phloretin CF to Address Discoloration?

Due to air and light exposure, vitamin C products can darken after opening. The formula will remain effective. Pure vitamin C (l-ascorbic acid): Lauded for its superior antioxidant benefits, this highly potent form of pure vitamin C neutralizes damaging free radicals and protects against oxidative stress while providing visible anti-aging benefits Helps prevent free radical damage, diminishes the appearance of discolouration and improves skin tone and texture.

The hepatoprotective effect of phloretin has been demonstrated under various in vivo experimental models including overdose intake of acetaminophen [ 28], choline [ 93], D-galactosamine (D-GalN) [ 30], and arsenate [ 94]. These effects which are also shown in renal protection by toxic agents (e.g., by Singh et al. [ 94]) mostly demonstrated the antioxidant mechanism of therapeutic potential of phloretin. The focus herein is to highlight the inflammatory mechanisms of hepato- and renoprotective effects. 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. But what does alcohol do here? It’s a volatile carrier that helps the active ingredients penetrate skin, so they can work better and faster. In the various sections of this review ( Section 2, Section 3, Section 4, Section 5, Section 6, Section 7, Section 8, Section 9, Section 10 and Section 11), the anti-inflammatory potential of phloretin that has been established through studies both in vitro and in vivo are outlined. Indeed, phloretin does also possess various other pharmacological effects including anticancer properties. Readers should bear in mind that carcinogenesis and the process of cancer metastasis including angiogenesis share some aspects of inflammation biology. Hence, the reported anti-inflammatory mechanism of phloretin could also be relevant to its anticancer properties. The focus of this section is however to summarise the anti-inflammatory mechanism of phloretin that accounts for its diverse other effects in vitro and in vivo.

KEY INGREDIENTS & BENEFITS: Ferulic Acid (neutralizes free radicals, helps inhibits UV-induced skin discolorations, and has anti-inflammatory properties) 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].