Synergistic effects of phosphorylation modification and protocatechuic acid copolymerization improve the physical and oxidation stability of high internal phase emulsion stabilized by perilla protein isolate.

A compact antioxidant interfacial layer was fabricated by combining phosphorylation treatment with protocatechuic acid (PA) copolymerization to enhance the physical and oxidative stability of high internal phase emulsions (HIPEs) prepared using perilla protein isolate (PPI). The covalent binding between PPI and phosphate groups induced conformational changes, facilitating the interaction between PPI and PA. The formed phosphorylated PPI-PA conjugates (LPPI-PA) exhibited a reduced particle size of 196.75 nm, promoting their adsorption at the interface. HIPEs prepared by LPPI-PA conjugates showed higher storage stability due to decreased droplet size, increased interfacial protein adsorption content (90.48%), and the formation of an interconnected network within the system. Additionally, the combination of LPPI and PA anchored PA to the interface, significantly inhibiting lipid oxidation in HIPEs as evidenced by low levels of lipid hydroperoxide (30.33 µmol/g oil) and malondialdehyde (379.34 nmol/g oil). This study holds significant implications for improving the stability of HIPEs.

Inhibitory effects of compounds isolated from Geranium wilfordii on IL-4 production and ß-hexosaminidase release in RBL-2H3 cells.

This study aimed to investigate the anti-allergic activity of compounds isolated from Geranium wilfordii Maxim. and to suggest potential therapeutic agents for allergies. Nine compounds were isolated from an ethanolic G. wilfordii extract using chromatographic methods and identified chemically and by spectroscopic analysis. These compounds were identified using reported literature data as brevifolin carboxylic acid (1), chlorogenic acid (2), corilagin (3), ellagic acid (4), geraniol (5), kaempferol 3-O-dirhamnoside (6), kaempferol 3-O-neohesperidoside (7), protocatechuic acid (8), and gallic acid (9). All nine identified compounds were assessed for including IL-4 mRNA expression and ß-hexosaminidase release in RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA. IL-4 gene expression assay showed that corilagin (3) potently inhibited IL-4 production, and ß-hexosaminidase release assay showed that protocatechuic acid (8) markedly reduced histamine release. The study shows that of the nine compounds isolated from G. wilfordii, corilagin (3), and protocatechuic acid (8) are potential treatments for allergy-related diseases.

Protocatechuic acid enhanced the selective degradation of sulfonamide antibiotics in Fe(III)/peracetic acid process under actually neutral pH conditions.

The practical application of the Fe-catalyzed peracetic acid (PAA) processes is seriously restricted due to the need for narrow pH working range and poor anti-interference capacity. This study demonstrates that protocatechuic acid (PCA), a natural and eco-environmental phenolic acid, significantly enhanced the removal of sulfonamide antibiotics in Fe(III)/PAA process under actually neutral pH conditions (6.0-8.0) by complexing Fe(III). With sulfamethoxazole (SMX) as the model contaminant, the pseudo-first-order rate constant of SMX elimination in PCA/Fe(III)/PAA process was 63.5 times higher than that in Fe(III)/PAA process at pH 7.0, surpassing most of the previously reported strategies-enhanced Fe-catalyzed PAA processes (i.e., picolinic acid and hydroxylamine etc.). Excluding the primary contribution of reactive species commonly found in Fe-catalyzed PAA processes (e.g., •OH, R-O•, Fe(IV)/Fe(V) and 1O2) to SMX removal, the Fe(III)-peroxy complex intermediate (CH3C(O)OO-Fe(III)-PCA) was proposed as the primary reactive species in PCA/Fe(III)/PAA process. DFT theoretical calculations indicate that CH3C(O)OO-Fe(III)-PCA exhibited stronger oxidation potential than CH3C(O)OO-Fe(III), thereby enhancing SMX removal. Four potential removal pathways of SMX were proposed and the toxicity of reaction solution decreased with the removal of SMX. Furthermore, PCA/Fe(III)/PAA process exhibited strong anti-interference capacity to common natural anions (HCO3-, Cl-and NO3-) and humic acid. More importantly, the PCA/Fe(III)/PAA process demonstrated high efficiency for SMX elimination in actual samples, even at a trace Fe(III) dosage (i.e., 5 µM). Overall, this study provided a highly-efficient and eco-environmental strategy to remove sulfonamide antibiotics in Fe(III)/PAA process under actually neutral pH conditions and to strengthen its anti-interference capacity, underscoring its potential application in water treatment.

Biodegradation of DEP, DIBP, and BBP by a psychrotolerant Sphingobium yanoikuyae strain P4: Degradation potentiality and mechanism study.

Phthalic acid esters (PAEs) are human made chemicals widely used as plasticizers to enhance the flexibility of plastic products. Due to the lack of chemical bonding between phthalates and plastics, these materials can easily enter the environment. Deleterious effects caused by this chemo-pollutant have drawn the attention of the scientific community to remediate them from different ecosystem. In this context, many bacterial strains have been reported across different habitats and Sphingobium yanoikuyae strain P4 is among the few psychrotolerant bacterial species reported to biodegrade simple and complex phthalates. In the present study, biodegradation of three structurally different PAEs viz., diethyl phthalate (DEP), di-isobutyl phthalate (DIBP), and butyl benzyl phthalate (BBP) have been investigated by the strain P4. Quantitative analyses through High-performance liquid chromatography (HPLC) revealed that the bacterium completely degraded 1 g/L of DEP, DIBP, and BBP supplemented individually in minimal media pH 7.0 within 72, 54, and 120 h of incubation, respectively, at 28 °C and under shake culture condition (180 rpm). In addition, the strain could grow in minimal media supplemented individually with up to 3 g/L of DEP and 10.0 g/L of DIBP and BBP at 28 °C and pH 7.0. The strain also could grow in metabolites resulting from biodegradation of DEP, DIBP, and BBP, viz. n-butanol, isobutanol, butyric acid, ethanol, benzyl alcohol, benzoic acid, phthalic acid, and protocatechuic acid. Furthermore, phthalic acid and protocatechuic acid were also detected as degradation pathway metabolites of DEP and DIBP by HPLC, which gave an initial idea about the biodegradation pathway(s) of these phthalates.

Selective Degradation of Technically Relevant Lignin to Vanillic Acid and Protocatechuic Acid.

A new and practical method for the thermal degradation of technically relevant bio-based lignin is presented. By heating a solution of lignin in highly concentrated caustic potash, vanillic acid is almost exclusively obtained in yields up to 10.6 wt %. By altering the reaction parameters, the selectivity of the reaction can be shifted towards the demethylation product, protocatechuic acid, which is obtained in a yield of 6.9 wt %. Furthermore, the procedure was applicable to different types of Kraft and organosolv lignin. To create an economically feasible process, ion exchange resins were used for the work-up of the highly caustic reaction media without neutralizing the complete mixture. By the selective removal of the desired vanillic acid from the caustic potash, this alkaline media could directly be reused for at least 5 further lignin degradations without significant loss of yield.

Exploring the Efficacy of Hydroxybenzoic Acid Derivatives in Mitigating Jellyfish Toxin-Induced Skin Damage: Insights into Protective and Reparative Mechanisms.

The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the potential of hydroxybenzoic acid derivatives, specifically protocatechuic acid (PCA) and gentisic acid (DHB), for alleviating Nemopilema nomurai Nematocyst Venom (NnNV)-induced injuries. By employing an in vivo mouse model, the study delves into the therapeutic efficacy of these compounds. Through a combination of ELISA and Western blot analyses, histological examinations, and molecular assays, the study scrutinizes the inflammatory response, assesses skin damage and repair mechanisms, and investigates the compounds' ability to counteract venom effects. Our findings indicate that PCA and DHB significantly mitigate inflammation by modulating critical cytokines and pathways, altering collagen ratios through topical application, and enhancing VEGF and bFGF levels. Furthermore, both compounds demonstrate potential in neutralizing NnNV toxicity by inhibiting metalloproteinases and phospholipase-A2, showcasing the viability of small-molecule compounds in managing toxin-induced injuries.

Patterns of alteration in boar semen quality from 9 to 37 months old and improvement by protocatechuic acid.

BACKGROUND: Comprehending the patterns of alteration in boar semen quality and identifying effective nutritional interventions are crucial for enhancing the productivity of commercial pig systems. This study aimed to examine the alteration in semen quality in boars, and assess the impact of protocatechuic acid (PCA) on semen quality during the phase of declining semen quality. METHODS: In Exp. 1, a total of 38 Pig Improvement Company (PIC) boars were selected and their semen quality data were recorded from the age of 9 to 37 months. In Exp. 2, 18 PIC boars (28 months old) were randomly assigned into three groups (n = 6) and fed a basal diet, a basal diet containing 500 or 1,000 mg/kg PCA, respectively. The experiment lasted for 12 weeks. RESULTS: The semen volume, concentration, and total number of spermatozoa in boars exhibited an increase from 9 to 19 months old and showed a significant linear decreased trend in 28, 24, and 22 months old. Sperm motility displayed an upward trajectory, reaching its peak at 20 months of age, and showed a significant linear decreased trend at 20 months old. Dietary supplementation of PCA demonstrated an effect to mitigate the decrease in semen volume, concentration of spermatozoa, total number of spermatozoa (P > 0.05), and significantly increased the sperm motility (P < 0.05). Moreover, supplementation of 1,000 mg/kg PCA significantly increased the sperm viability (P < 0.05). Analysis on cellular signaling pathways revealed that PCA restored serum testosterone levels and alleviated oxidative damage by upregulating the expression of HO-1, SOD2, and NQO1 in testicular stromal cells. Notably, PCA can enhance phosphorylation by selectively binding to AMP-activated protein kinase (AMPK) protein, thereby improving sperm mitochondrial function and augmenting sperm motility via PGC-1/Nrf1. CONCLUSIONS: These data elucidated the pattern of semen quality variation in boars within the age range of 9 to 37 months old, and PCA has the potential to be a natural antioxidant to enhance sperm quality through modulation of the AMPK/PGC-1/Nrf1 signaling pathway.

The Cancer-Protective Potential of Protocatechuic Acid: A Narrative Review.

Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from natural sources, such as certain vegetables containing a variety of secondary metabolites with beneficial effects on the body and that play a crucial role in the fight against cancer, is essential. Among the compounds with the greatest efficacy in controlling this disease, those with antioxidant activity, particularly phenolic com-pounds, stand out. A remarkable example of this group is protocatechuic acid (PCA), which has been the subject of various revealing research on its activities in different areas. These studies sustain that protocatechuic acid has anti-inflammatory, antimutagenic, antidiabetic, antiulcer, antiviral, antifibrogenic, antiallergic, neuroprotective, antibacterial, anticancer, antiosteoporotic, anti-aging, and analgesic properties, in addition to offering protection against metabolic syndrome and con-tributing to the preservation of hepatic, renal, and reproductive functionality. Therefore, this paper aims to review the biological activities of PCA, focusing on its anticancer potential and its in-volvement in the control of various molecular pathways involved in tumor development, sup-porting its option as a promising alternative for cancer treatment.

Biological Valorization of Lignin-Derived Aromatics in Hydrolysate to Protocatechuic Acid by Engineered Pseudomonas putida KT2440.

Alongside fermentable sugars, weak acids, and furan derivatives, lignocellulosic hydrolysates contain non-negligible amounts of lignin-derived aromatic compounds. The biological funnel of lignin offers a new strategy for the "natural" production of protocatechuic acid (PCA). Herein, Pseudomonas putida KT2440 was engineered to produce PCA from lignin-derived monomers in hydrolysates by knocking out protocatechuate 3,4-dioxygenase and overexpressing vanillate-O-demethylase endogenously, while acetic acid was used for cell growth. The sugar catabolism was further blocked to prevent the loss of fermentable sugar. Using the engineered strain, a total of 253.88 mg/L of PCA was obtained with a yield of 70.85% from corncob hydrolysate 1. The highest titer of 433.72 mg/L of PCA was achieved using corncob hydrolysate 2 without any additional nutrients. This study highlights the potential ability of engineered strains to address the challenges of PCA production from lignocellulosic hydrolysate, providing novel insights into the utilization of hydrolysates.

Protocatechuic acid as an inhibitor of lipid oxidation in meat.

Lipid oxidation is the principal driver of meat and meat product deterioration during shelf life, causing the loss of fresh meat color, flavor, and aroma. Currently, synthetic antioxidants are used to prevent oxidation, but increasing consumer demand for natural ones leaves the industry with few alternatives. In this study, protocatechuic acid (PCA), known to have high antioxidant activity, was evaluated as a potential inhibitor of meat lipid oxidation. For this purpose, the antioxidant capacity and lipoxygenase (LOX) inhibitory activity of PCA were evaluated in vitro, and a set of four experiments was conducted, treating minced meat with water (control), lactic acid (LA), rosmarinic acid (RA) and PCA, at different concentrations (1-12 mg mL-1), depending on the experiment. The potential antioxidant effect of PCA when applied to meat cubes was also evaluated, as well as the potential of carboxymethyl cellulose (CMC) as a delivery system for PCA. The in vitro results showed that PCA is a potent antioxidant and an effective LOX inhibitor at 1 mg mL-1. PCA effect on meat lipid oxidation prevention was dose-dependent, and at 2 mg mL-1, it inhibited color change by 50% and lipid peroxidation by up to 70% when compared to water-treated samples, performing better than RA at 0.25 mg mL-1. These results suggest that PCA is a promising molecule to the meat industry as a natural preservative for meat and meat products directly or in a formulation.

The Potential of Roselle (Hibiscus sabdariffa) Plant in Industrial Applications: A Promising Source of Functional Compounds.

Roselle is an annual botanical plant that widely planted in different countries worldwide. Its different parts, including seeds, leaves, and calyces, can offer multi-purpose applications with economic importance. The present review discusses the detailed profile of bioactive compounds present in roselle seeds, leaves, and calyces, as well as their extraction and processing, to explore their potential application in pharmaceutical, cosmetic, nutraceutical, food and other industries. Roselle seeds with high phenolics, fiber, and protein contents, which are suitable to use in functional food product development. Besides, roselle seeds can yield 17-20% of roselle seed oil with high content of linoleic acid (35.0-45.3%) and oleic acid (27.1- 36.9%). This unique fatty acid composition of roselle seed oil makes it suitable to use as edible oil to offer the health benefits of essential fatty acid. Moreover, high contents of tocopherols, phenolics, and phytosterols were detected in roselle seed oil to provide nutritional, pharmaceutical, and therapeutic properties. On the other hand, roselle leaves with valuable contents of phenols, flavonoids, organic acid, and tocopherols can be applied in silver nanoparticles, food product development, and the pharmaceutical industry. Roselle calyces with high content of anthocyanins, protocatechuic acids, and organic acids are widely applied in food and colorant industries.

Plant-Derived Phenolic Acids Limit the Pathogenesis of Salmonella Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions.

The incidence of gastrointestinal illness attributable to Salmonella enterica serovar Typhimurium (ST) remains a concern for public health worldwide, as it can progress into systemic infections mediated by the type-three secretion system (T3SS), which allows for adherence and invasion to intestinal epithelial cells. The current study evaluates the ability of gallic acid (GA), protocatechuic acid (PA), and vanillic acid (VA) to impair the adhesion and invasion abilities of ST to a human epithelial (INT-407) cell monolayer while also assessing their cytotoxicity. GA, PA, and VA inhibited detectable ST growth at specific concentrations but showed cytotoxicity against INT-407 cells (>20% reduction in viability) after 3 h of treatments. Adjusting the pH of the solutions had a neutralizing effect on cytotoxicity, though it did reduce their antimicrobial potency. Adhesion of ST was reduced significantly when the cells were treated with 4.0 mg/mL of VA, whereas invasion was reduced in all treatments, with GA requiring the lowest concentration (0.5 mg/mL). Relative gene expression of virulence genes after treatment with GA showed downregulation in the T3SS regulator and effector hilA and sipA, respectively. These findings suggest further use of phenolic acids in reducing the activity of key virulence factors critical during ST infection.

Efficient production of protocatechuic acid using systems engineering of Escherichia coli.

Protocatechuic acid (3, 4-dihydroxybenzoic acid, PCA) is widely used in the pharmaceuticals, health food, and cosmetics industries owing to its diverse biological activities. However, the inhibition of 3-dehydroshikimate dehydratase (AroZ) by PCA and its toxicity to cells limit the efficient production of PCA in Escherichia coli. In this study, a high-level strain of 3-dehydroshikimate, E. coli DHS01, was developed by blocking the carbon flow from the shikimate-overproducing strain E. coli SA09. Additionally, the PCA biosynthetic pathway was established in DHS01 by introducing the high-activity ApAroZ. Subsequently, the protein structure and catalytic mechanism of 3-dehydroshikimate dehydratase from Acinetobacter pittii PHEA-2 (ApAroZ) were clarified. The variant ApAroZR363A, achieved by modulating the conformational dynamics of ApAroZ, effectively relieved product inhibition. Additionally, the tolerance of the strain E. coli PCA04 to PCA was enhanced by adaptive laboratory evolution, and a biosensor-assisted high-throughput screening method was designed and implemented to expedite the identification of high-performance PCA-producing strains. Finally, in a 5 L bioreactor, the final strain PCA05 achieved the highest PCA titer of 46.65 g/L, a yield of 0.23 g/g, and a productivity of 1.46 g/L/h for PCA synthesis from glucose using normal fed-batch fermentation. The strategies described herein serve as valuable guidelines for the production of other high-value and toxic products.

Inhibition of Photoaging by Anthocyanin Metabolites Derived from Rose Petal Extract.

SCOPE: Rose petal extract (RPE) shows a significant antioxidant effect through its anthocyanin content. However, the mechanism underlying the anti-aging effects of orally administered RPE remains unclear. This study aims to describe the anti-aging effect and mechanism of action of orally administered RPE in ultraviolet (UV)B-induced skin aging. METHODS AND RESULTS: This study evaluates the protein expression of collagen type I alpha 1 (COL1A1) and matrix metalloproteinase 1 (MMP-1) and the mRNA expression of hyaluronic synthase 2 (HAS2) in human dermal fibroblasts. In addition, the hyaluronidase and collagenase inhibitory activities of RPE are confirmed. To evaluate the anti-aging effects of RPE, SKH-1 hairless mice are administered RPE daily for 12 weeks. Wrinkle formation, transepidermal water loss (TEWL), and skin moisture loss induced by UVB irradiation are suppressed in the dorsal skin of SKH-1 hairless mice orally administered RPE. Oral administration of RPE suppresses UVB irradiation-induced collagen disruption and reduction of hyaluronic acid. To find the bioactive compound in the RPE, serum protocatechuic acid (PCA), an anthocyanin metabolite, is analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CONCLUSION: Anthocyanins in RPE are metabolized to PCA in the body and circulated through the bloodstream to exhibit anti-aging effects on the skin.

Protective Effect of Protocatechuic Acid on Oxidative Damage and Cognitive Impairment in Pb-Induced Rats.

Protocatechuic acid (PCA), a class of water-soluble phenolic acid abundant in the human diet, has been shown to be of great nutritional interest and to have medicinal value. However, the protective effects against lead (Pb)-induced body injury have not been elucidated. In this study, we explored the protective effect of PCA on Pb-induced oxidative damage and cognitive impairment in rats. The results showed that PCA could reduce the Pb content in rat bodies (blood, bone, brain, liver, and kidney) after Pb exposure. Moreover, PCA may inhibit Pb-induced oxidative damage by increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreasing the level of malondialdehyde (MDA) in the brain, liver, and kidney. In addition, PCA may alleviate Pb-induced learning and memory impairment by upregulating neurotransmitter levels; maintaining the normal function of N-methyl-D-aspartate receptors (NMDARs); and promoting Ca2+ influx, thus activating signaling molecules, related protein kinases, and transcription factors in the cAMP-PKA-CREB pathway. In general, PCA could reduce oxidative stress and ameliorate the learning and memory deficits in Pb-treated rats, indicating that PCA may be an effective preventive agent and treatment or plumbism.

Elucidation of 4-Hydroxybenzoic Acid Catabolic Pathways in Pseudarthrobacter phenanthrenivorans Sphe3.

4-hydroxybenzoic acid (4-HBA) is an aromatic compound with high chemical stability, being extensively used in food, pharmaceutical and cosmetic industries and therefore widely distributed in various environments. Bioremediation constitutes the most sustainable approach for the removal of 4-hydroxybenzoate and its derivatives (parabens) from polluted environments. Pseudarthrobacter phenanthrenivorans Sphe3, a strain capable of degrading several aromatic compounds, is able to grow on 4-HBA as the sole carbon and energy source. Here, an attempt is made to clarify the catabolic pathways that are involved in the biodegradation of 4-hydroxybenzoate by Sphe3, applying a metabolomic and transcriptomic analysis of cells grown on 4-HBA. It seems that in Sphe3, 4-hydroxybenzoate is hydroxylated to form protocatechuate, which subsequently is either cleaved in ortho- and/or meta-positions or decarboxylated to form catechol. Protocatechuate and catechol are funneled into the TCA cycle following either the ß-ketoadipate or protocatechuate meta-cleavage branches. Our results also suggest the involvement of the oxidative decarboxylation of the protocatechuate peripheral pathway to form hydroxyquinol. As a conclusion, P. phenanthrenivorans Sphe3 seems to be a rather versatile strain considering the 4-hydroxybenzoate biodegradation, as it has the advantage to carry it out effectively following different catabolic pathways concurrently.

The Sustainable Approach of Process Intensification in Biorefinery Through Reactive Extraction Coupled with Regeneration for Recovery of Protocatechuic Acid.

In the current scenario, where environmental degradation, global climate change, and the depletion of petroleum feedstock pose significant challenges, the chemical industry seeks sustainable alternatives for manufacturing chemicals, fuels, and bioplastics. Biorefining processes that integrate biomass conversion and microbial fermentation have emerged as preferred approaches to create value-added compounds. However, commercializing biorefinery products is hindered by dilute concentrations of final products and the demand for high purity goods. To address these challenges, effective separation and recovery procedures are essential to minimize costs and equipment size. This article proposes a biorefinery route for the production of protocatechuic acid (PCA) by focusing on in situ PCA separation and purification from fermentation broth. PCA is a significant phenolic molecule with numerous applications in the pharmaceutical sector for its anti-inflammatory, antiapoptotic, and antioxidant properties, as well as in the food, polymer, and other chemical industries. The chemical approach is predominantly used to produce PCA due to the cost-prohibitive nature of natural extraction techniques. Reactive extraction, a promising technique known for its enhanced extraction efficiency, is identified as a viable strategy for recovering carboxylic acids compared to conventional methods. The extraction of PCA has been explored using various solvents, including natural and conventional solvents, such as aminic and organophosphorous extractants, as well as the potential utilization of ionic liquids as green solvents. Additionally, back extraction techniques like temperature swing and diluent composition swing can be employed for reactive extraction product recovery, facilitating the regeneration of the extractant from the organic phase. By addressing the challenges associated with PCA production and usage, particularly through reactive extraction, this proposed biorefinery route aims to contribute to a more sustainable and environmentally friendly chemical industry. The incorporation of PCA in the biorefinery process allows for the utilization of this valuable compound with diverse industrial applications, thus providing an additional incentive for the development and optimization of efficient separation techniques.

Dextran coated iron oxide nanoparticles loaded with protocatechuic acid as multifunctional therapeutic agents.

Nowadays, there is a growing interest in multifunctional therapeutic agents as valuable tools to improve and expand the applicability field of traditional bioactive compounds. In this context, the synthesis and main characteristics of dextran-coated iron oxide nanoparticles (IONP-Dex) loaded with both an antioxidant, protocatechuic acid (PCA), and an antibiotic, ceftazidime (CAZ) or levofloxacin (LEV) are herein reported for the first time, with emphasis on the potentiation effect of PCA on drugs activity. All nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, vibrating sample magnetometry, differential scanning calorimetry and dynamic light scattering. As evidenced by DPPH method, IONP-Dex loaded with PCA and LEV had similar antioxidant activity like those with PCA only, but higher than PCA and CAZ loaded ones. A synergy of action between PCA and each antibiotic co-loaded on IONP-Dex has been highlighted by an enhanced activity against reference bacterial strains, such as S. aureus and E. coli after 40 min of incubation. It was concluded that PCA, which is the main cause of the antioxidative properties of loaded nanoparticles, further improves the antimicrobial activity of IONP-Dex nanoparticles when was co-loaded with CAZ or LEV antibiotics. All constructs also showed a good biocompatibility with normal human dermal fibroblasts.

Dietary Achievable Dose of Protocatechuic Acid, a Metabolite of Flavonoids, Inhibits High-Fat Diet-Induced Obesity in Mice.

SCOPE: Protocatechuic acid (PCA), a gut microbiota metabolite of flavonoids, inhibits dietary obesity and increases uncoupling protein 1 (UCP1), a critical regulator responsible for adipose thermogenesis; however, these effects are achieved at dietary unachievable (pharmacological) dose. It evaluates whether dietary achievable dose of PCA inhibits adiposity by activating adipose thermogenesis. METHODS AND RESULTS: Six-week-old male C57BL/6J mice are fed a high-fat diet (HFD) alone (control) or supplemented with 0.003% PCA w/w for 16 weeks. PCA consumption does not affect food intake but appreciably reduces body weight gain, improves insulin sensitivity, and attenuates hepatic steatosis. These effects are associated with no significant changes in the abundance of UCP1 in adipose tissues. Instead, PCA consumption increases the abundance and enzymatic activity of carnitine palmitoyltransferase 1 (the first rate-limiting enzyme in fatty acid oxidation) in the livers, inguinal white, and brown adipose tissues. Surprisingly, PCA at physiologically achievable dose does not affect the abundance and enzymatic activity of carnitine acyltransferase-1 expression and the capacity of fatty acid oxidation in 3T3-L1-derived white or brown adipocytes and human hepatoma HepG2 cells. CONCLUSIONS: Dietary achievable dose of PCA attenuates HFD-induced adiposity, which is likely achieved by increasing fatty acid oxidation other than activating adipose thermogenesis.

Menadione and protocatechuic acid: A drug combination with antitumor effects in murine osteosarcoma cells.

Osteosarcoma (OS) is a primary malignant bone tumor that has an abnormal expression of oncogenesis and tumor suppressors and causes dysregulation of various signaling pathways. Thus, novel therapeutic strategies for OS are needed to overcome the resistance of traditional treatments. This study evaluated the cytotoxic and anticancer effects of the association between menadione (MEN) and protocatechuic acid (PCA) in murine OS cells (UMR-106). The concentrations were 3.12 µM of isolated MEN, 500 µM of isolated PCA, and their associations. We performed cell viability assays, morphology modification analysis, cell migration by the wound-healing method, apoptosis by flow cytometry, reactive oxygen species (ROS) production, gene expression of NOX by RT-qPCR, and degradation of MMP-2 and 9 by zymography. Our results showed that the association of MEN+PCA was more effective in OS cells than the compounds alone. The association decreased cell viability, delayed cell migration, and decreased the expression of NOX-2 and ROS. In addition, the MEN+PCA association induced a slight increase in the apoptotic process. In summary, the association can enhance the compound's antitumor effects and establish a higher selectivity for tumor cells, possibly caused by significant mitochondrial damage and antioxidant properties.