Enhanced permeability of ferulic acid loaded nanoemulsion based gel through skin against UVA mediated oxidative stress

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

BackgroundApproximately 90%~99% of ultraviolet A (UVA) ray reaches the Earth's surface. The deeply penetrating UVA rays induce the formation of reactive oxygen species (ROS), which results in oxidative stress such as photoproducts, senescence, and cell death. Thus, UVA is considered a primary factor that promotes skin aging.ObjectiveResearchers investigated whether pretreatment with ferulic acid protects human dermal fibroblasts (HDFs) against UVA-induced cell damages.MethodsHDF proliferation was analyzed using the water-soluble tetrazolium salt assay. Cell cycle distribution and intracellular ROS levels were assessed by flow cytometric analysis. Senescence was evaluated using a senescence-associated β-galactosidase assay, while Gadd45α promoter activity was analyzed through a luciferase assay. The expression levels of superoxide dismutase 1 (SOD1), catalase (CAT), xeroderma pigmentosum complementation group A and C, matrix metalloproteinase 1 and 3, as well as p21 and p16 were measured using quantitative real-time polymerase chain reaction.ResultsInhibition of proliferation and cell cycle arrest were detected in cells that were irradiated with UVA only. Pretreatment with ferulic acid significantly increased the proliferation and cell cycle progression in HDFs. Moreover, ferulic acid pretreatment produced antioxidant effects such as reduced DCF intensity, and affected SOD1 and CAT mRNA expression. These effects were also demonstrated in the analysis of cell senescence, promoter activity, expression of senescent markers, and DNA repair.ConclusionThese results demonstrate that ferulic acid exerts protective effects on UVA-induced cell damages via anti-oxidant and stress-inducible cellular mechanisms in HDFs.

Enhancement of photoprotection potential of catechin loaded nanoemulsion gel against UVA induced oxidative stress

Ferulic Acid Stabilizes a Solution of Vitamins C and E and Doubles its Photoprotection of Skin

Solar radiation, especially ultraviolet A (UVA) and ultraviolet B (UVB), can cause damage to the human body, and exposure to the radiation may vary according to the geographical location, time of year and other factors. The effects of UVA and UVB radiation on organisms range from erythema formation, through tanning and reduced synthesis of macromolecules such as collagen and elastin, to carcinogenic DNA mutations. Some studies suggest that, in addition to the radiation emitted by the sun, artificial sources of radiation, such as commercial lamps, can also generate small amounts of UVA and UVB radiation. Depending on the source intensity and on the distance from the source, this radiation can be harmful to photosensitive individuals. In healthy subjects, the evidence on the danger of this radiation is still far from conclusive.

Ferulic acid-loaded aspasomes: A new approach to enhance the skin permeation, anti-aging and antioxidant effects

Human skin undergoes aging and degenerative processes, like other body tissues. Skin aging is characterized by various structural and functional changes, such as decreased skin elasticity, degradation of elastic fibers, thinning of the epidermis, reduced collagen content, the appearance of wrinkles, and increased skin dryness. One effort to inhibit this process is the use of natural phytochemical compounds with antioxidant and skin-protective activity, such as ferulic acid. Ferulic acid is known to scavenge free radicals and absorb ultraviolet (UV) light. Furthermore, this compound can protect the structure of collagen, elastin, and fibroblast cells from damage, and inhibit the enzymes collagenase and tyrosinase, which play a role in collagen degradation and the formation of hyperpigmentation. This literature review aims to examine the anti-aging activity of ferulic acid based on the results of in vitro and in vivo studies published in the past ten years. The search was conducted through a systematic literature review of relevant scientific articles. The results indicate that ferulic acid has a promising mechanism of action in preventing and slowing skin aging. This compound can improve skin elasticity, suppress melanin production, reduce dark spots, and exhibit anti-inflammatory properties that help reduce redness and inflammation caused by acne. Its antioxidant effects also contribute to slowing the appearance of wrinkles, thus helping maintain a more youthful appearance. Despite its significant potential, further research is needed to better understand its mechanism of action and long-term safety for use on human skin.

UltravioletA (UVA) rays with an intensity of 95% can induce skin cancer due to the activation of reactive oxygen species (ROS). The 3,4-dimethoxychalcone (3,4-DMC) chalcone derivative has a wide wavelength, antioxidant activity, presumed has activity as sunscreen (UVA rays). Topical delivery of water-insoluble 3,4-DMC with log P 3.84 required capable, cream formulation was chosen because it was suitable for application this chemical sunscreen. This study aims to obtain the optimal formulation of 3,4-DMC in a sunscreen cream dosage form as a UVA-protection factor (UVA-PF). This study involves experimental design. The cream 3,4-DMC was evaluated physically for 4 weeks by measuring pH, viscosity, spreadability, adhesion, centrifugation, freeze–thaw, photostability, UVA-PF used TranporeTM tape, and skin irritation test on animals. The result obtained was evaluated statistically using ANOVA (SPSS version 24). The ratio UVA/UVB value of 3,4 DMC sunscreen cream having 5 stars (*****) for all concentrations, shows the product in this study can be used as an anti-UVA agent in sunscreen cream cosmetic products. The stability of the cream has pH 4.0–4.2; spreadability 5–6 cm; viscosity 4.470–5.763; and adhesion <1 s. Freeze-thaw and centrifugation were known did not affect the stability due to the absence of separation. There was no wavelength shift in the photostability test and no skin irritation due to in vivo examination using New Zealand rabbits. The 3,4-DMC as a new agent in conventional sunscreen cream dosage form has good properties as a protection against UVA rays.

The sun is here! What will you recommend?

Disc degeneration is strongly associated with back pain and herniation that increase the costs of health care. The degeneration of intervertebral disc (IVD) could be divided into 5 stages. In the first and second stages, there are no significant symptoms but could be traced by magnetic resonance imaging or computed tomography-scan. Generally, no aggressive treatment would be processed in the clinics. Recent studies indicated that overproduction of reactive oxygen species (ROS) may accelerate the degenerative process of IVD and associate with apoptosis of nucleus pulposus (NP) cells and degradation of extracellular matrix. Ferulic acid (FA) is an excellent antioxidant and relatively stable in air. FA has been proven to have ability to prevent ROS-induced diseases. The object of the study was aimed to evaluate the possible therapeutic effect of FA on hydrogen peroxide (H2O2)-induced oxidative stress NP cells and the feasibility of use the thermosensitive chitosan/gelatin/glycerophosphate (C/G/GP) hydrogel as a sustained release system of FA for early treatment in IVD degeneration. In the study, NP cells were harvested from the IVD of New Zealand rabbits. The results showed that 500 μM of FA might be the threshold to treat NP cells without cytotoxicity. Post-treatment of FA on H2O2-induced oxidative stress NP cells significantly up regulated the expression of aggrecan, type II collagen and BMP-7 and down regulated the expression of MMP-3 in mRNA level. Post-treatment of FA on H2O2-induced oxidative stress NP cells could restore the production of sulfated glycosaminoglycans (GAGs) and inhibit the apoptosis caused by H2O2. The results showed that the release of FA from C/G/GP hydrogel could decrease the H2O2-induced oxidative stress. Post-treatment of FA-incorporated C/G/GP hydrogel on H2O2-induced oxidative stress NP cells showed up-regulation of aggrecan and type II collagen and down-regulation of MMP-3 in mRNA level. The results of sulfated GAGs to DNA ratio and alcian blue staining revealed that the GAGs production of H2O2-induced oxidative stress NP cells could reach to normal level. The results of caspase-3 activity and TUNEL staining indicated that FA-incorporated C/G/GP hydrogel decreased the apoptosis of H2O2-induced oxidative stress NP cells. The results showed that FA was successfully immobilized on C/G/GP hydrogel by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) crosslinking method. The gelation temperature of the FA-immobilized C/G/GP hydrogel was 31.80 degree celsius under neutral pH. Post-treatment of FA-immobilized C/G/GP hydrogel on H2O2-induced oxidative stress NP cells showed down-regulation of MMP-3 and up-regulation aggrecan and type II collagen in mRNA level. The sulfated GAGs production of H2O2-induced oxidative stress NP cells could be increased to the normal level in the post-treatment of FA-immobilized C/G/GP hydrogel group. The results of caspase-3 activity and TUNEL staining showed that the apoptosis of H2O2-induced oxidative stress NP cells could be inhibited by post-treatment of FA-immobilized C/G/GP hydrogel. From the results of the study, FA could be used as a therapeutic molecule for NP regeneration and FA-incorporated C/G/GP hydrogel might be potentially applied as a long-term release system. The immobilization of FA on C/G/GP hydrogel could significantly prolong the release period of FA. These results suggest that combination of FA and thermosensitive C/G/GP hydrogel can treat NP cells from the damage caused by oxidative stress and may apply in minimally invasive surgery for NP regeneration in the future.

Ferulic acid in Chaihu Shugan San modulates depression-like behavior, endothelial and gastrointestinal dysfunction in rats via the Ghrl-Edn1/Mecp2/P-mTOR/VEGFA pathway: A multi-omics study.

The present study aimed to develop nanostructured lipid carriers (NLCs) and evaluate their effectiveness in enhancing the delivery and stability of vanillic and ferulic acid in the aqueous enzymatic extract of glutinous rice husk using a 0.5% w/w cellulase solution (CE0.5). NLCs were developed using a high-pressure homogenization technique and characterized for their particle size, polydispersity index, and zeta potential. The entrapment efficiency, physical and chemical stability, release profile, skin permeation, and skin retention of the NLCs loaded with CE0.5 were evaluated. It was observed that NLCs with high entrapment efficiencies efficiently encapsulate and protect both vanillic and ferulic acid, in contrast to a solution. The controlled and sustained release profile of vanillic acid and ferulic acid from NLCs suggests their potential for prolonged and targeted delivery. The findings also demonstrate the superior skin retention capabilities of NLCs without permeation compared to the solution. Notably, NLC2 exhibited the highest delivery into the skin layer, which can be attributed to its smaller particle size (107.3 ± 1.3 nm), enabling enhanced skin penetration. This research highlights the promising application of NLCs in enhancing the delivery and stability of bioactive compounds in cosmetic formulations and related fields.

Plants have been one of the important sources of medicine even since the-dawn of human civilization. Curcumin has been found to possess tremendous therapeutic potency as antiinflammatory, antioxidant and antimicrobial agent. The present study was designed to examine possible potential therapeutic and protective effect of curcumin from oxidative stress and on total antioxidant capacity in liver damage. The study was conducted using H2O2 as inducing agent of oxidative stress in vivo. Rats were randomly divided into five groups, where n = 20 for each group. Group 1 (G1) rats served as control group. Group 2 (G2) rats subjected to experimentally induced oxidative stress by the ad libitum supply of drinking water containing 0.5% H2O2(v/v) was prepared daily over entire 60 days. Group 3 (G3) rats received H2O2 for sixty days followed by giving 200 mg kg(-1) of curcumin for 30 days. Group 4 (G4) was simultaneously given curcumin (200 mg kg(-1)) for 15 days then followed by receiving H2O2 with curcumin for sixty days. Group 5 (G5) rats was received H2O2 for sixty days followed by giving 200 mg kg(-1) of N-acetyl 1-cystine as standard drug for 30 days. Levels of marker enzymes (ALT, AST and ALP), uric acid, Total Protein (TP) and tumor necrosis factor (α-TNF) were assessed in serum for all studied groups. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguinosine, Total Antioxidant Capacity (TAC), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) were assayed in liver homogenates for all studied groups. The results revealed significant increase (p < 0.05) in levels of ALT, AST, ALP, uric acid and α-TNF while there are significant decrease (p < 0.05) in levels of TP in G2 comparing to G1. Also there are significant differences (p < 0.05) between G3 and G4 comparing to G2 and between G3, G4 and G5 which curcumin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation. The results also revealed a significant increase (p < 0.05) in levels of MDA and 8-H-2-deoxy guinosine while there was significant reduction (p < 0.05) in TAC, GSH, SOD and catalase in G2 comparing to G1. Also there are significant differences (p < 0.05) between G3 and G4 comparing to G2 and between G3, G4 and G5. The conclusion could be drown from this study that the ability of curcumin as therapeutic agent and hepatoprotective against liver damage from oxidative damage and on TAC more than N-acetyl 1-cystine related to its antioxidant and free radical scavenger activity.

Dear Sir, Heme oxygenase (HO) is a microsomal enzyme that catalyzes the first, rate-limiting step in the degradation of heme, and plays an important role in its recycling (Maines, 1997). It cleaves the a-meso carbon bridge of heme, yielding equimolar quantities of carbon monoxide, Fe, and biliverdin (Tenhunen et al., 1968). The enzymatic activity of HO results in decreased oxidative stress, an attenuated inflammatory response, and a lower rate of apoptosis. Three distinct mammalian HO isoforms (HO-1, HO-2, and HO-3) have been identified. They are the products of three different genes (Maines, 1988). Heme oxygenase-1, the inducible 32-kDa isoform, also known as heat shock protein 32, is highly expressed in liver and spleen, but can also be detected in many other tissues. It can be induced strongly in response to cellular stress and diverse oxidative stimuli, including its heme substrate, heat shock, ultraviolet (UV) irradiation, reactive oxygen species (ROS), nitric oxide (NO), inflammatory cytokines, prostaglandins, ethanol, heavy metals, and hypoxia (Applegate et al., 1991; Choi and Alam, 1996). Most of the known HO-1 inducers stimulate the production of ROS or lead to the depletion of glutathione levels, suggesting the involvement of HO-1 activity in cellular protection against oxidative stress (Ryter and Choi, 2002). Heme oxygenase-1 is known to play an important role in resistance to apoptosis and in the rapid growth of several solid tumors. It is often up-regulated in tumor tissues, and its expression can be further increased in response to therapy (Jozkowicz et al., 2007). Induction of HO-1 has been recognized as one of the most promising targets for chemoprevention and chemoprotection research (Prawan et al., 2005). Few studies of HO-1 expression in melanoma have been reported. Okamoto et al. (2006) suggested that HO-1 is an important candidate gene in the pathogenesis and growth of melanomas. Was et al. (2006) found that overexpression of HO-1 increased the viability, proliferation, and angiogenic potential of melanoma cells, augmented metastasis, and decreased survival of melanoma-bearing mice. In this study, we examined the expression of HO-1 in melanocytic nevi and melanomas by immunohistochemical staining, and in cultured normal human melanocytes and melanoma cell lines. We enrolled 38 patients, 20 with melanocytic nevi and 18 with melanomas. Patient characteristics are shown in Table S1. The mean age of the patients was 42 ± 23 yr (range 6–80). The diagnoses of the 20 melanocytic nevi were as follows: compound nevi (12; 60%), junctional nevi (4; 20%), intradermal nevus (1; 5%), and Spitz nevi (3; 15%). The histopathological types of the 18 melanomas were superficial spreading type (7; 39%), acral lentiginous type (7; 39%), lentigo maligna type (3; 17%), and metastatic melanoma (1; 6%). Immunohistochemical staining was performed using formalin-fixed, paraffin-embedded tissue specimens from 20 patients with melanocytic nevi and 18 with melanomas, using the LSAB2 System-HRP (DakoCytomation, Carpenteria, CA, USA). The intensity of HO-1 immunoreactivity was graded using the following scale: 0 = negative (no staining of melanocytic cells, but staining of the epidermis); 1 = weakly positive (staining intensity was markedly weaker than that of the epidermis); 2 = moderately positive (staining intensity was mildly weaker than that of the epidermis); and 3 = strongly positive (staining intensity was at least equal to that of the epidermis). The Mann–Whitney test (performed using SPSS version 12.0; SPSS Inc., Chicago, IL, USA) was used to analyze differences in HO-1 staining intensity between melanocytic nevi and melanomas. Additionally, HO-1 expression in melanocytic nevi and melanomas from sun-exposed and sun-protected areas was compared. Expression of HO-1 was detected in 19 of 20 melanocytic nevi (95%) and in 11 of 18 melanomas (61%). Of melanomas, one superficial spreading type, four acral lentiginous type, one lentigo maligna type, and one metastatic type did not express HO-1. Note that the intensity of HO-1 expression was markedly different between melanocytic nevi and melanomas (Figure 1). The mean intensity in melanocytic nevi was 1.82 ± 0.86. There was no difference in staining intensity among the types of melanocytic nevi. The intensity of HO-1 expression in the nearby epidermis in melanocytic nevi was 2.30 ± 0.64 (Figure S1). Only 13 of 20

This study aimed to optimize nanoemulsions loading with Mangifera indica L. kernel extract using response surface methodology for enhancing the stability and skin permeation of the extract. Central composite design was employed for optimization and evaluation of three influencing factors including hydrophile-lipophile balance (HLB), % co-surfactant (PEG-7 glyceryl cocoate), and surfactant-to-oil ratio (SOR) on physical properties of the nanoemulsions. The desired nanoemulsions were then incorporated with the extract and characterized. Physicochemical properties of the extract-loaded nanoemulsions and their antibacterial effects against Propionibacterium acnes were also evaluated after storage at various conditions and compared to those of the initial. Ex vivo skin permeation was also investigated. The factors significantly (p < 0.05) influenced on droplet size, polydispersity index (PDI), and zeta potential, especially HLB of the surfactant and its combined effects with co-surfactant and SOR. The extract-loaded nanoemulsions revealed a very small spherical droplets (size of 26.14 ± 0.22 nm) with narrow size distribution (PDI of 0.16 ± 0.02). The formulation also presented an excellent stability profile and successfully enhanced antibacterial stability of the extract comparing with the extract solution. Ex vivo skin permeation study illustrated that the extract in nanoemulsions could be delivered through a primary skin barrier to reach viable epidermis dermis layers. In conclusion, the affinity of surfactant and hydrophilicity of the system play a crucial role in nanoemulsions’ characteristics. Such results might provide promising anti-acne nanoemulsions with the notable capacities of extract stabilization and permeation enhancing which will be further clinically evaluated.