Synergistic Antioxidant Effect Research Articles

Recent Advances in the Synthesis of Commercially Available Phosphite Antioxidants.

Phosphite antioxidants exhibit superior anti-aging and color-stabilizing properties when incorporated into polymer materials. Their synergistic antioxidative effects are particularly noteworthy when used in combination with hindered phenol antioxidants and other primary antioxidants, serving as effective secondary antioxidants, displaying noteworthy synergistic antioxidation effects. This review systematically classifies the synthetic methods for phosphite antioxidants into three distinct categories based on the types of starting materials: synthesis from phosphorus trichloride, phosphorus-containing esters, and white phosphorus. Additionally, it delineates the reaction mechanisms associated with these approaches and provides an overview of future potential research directions and applications for organophosphorus antioxidants.

Evaluation and prediction of synergistic antioxidant effects of green walnut hulls, potato peel, and date pulp extracts on the stability of sunflower oil by deep neural networks

Evaluation and prediction of synergistic antioxidant effects of green walnut hulls, potato peel, and date pulp extracts on the stability of sunflower oil by deep neural networks

Mechanistic Insights into the Antioxidant Potential of Sugarcane Vinegar Polyphenols: A Combined Approach of DPPH-UPLC-MS, Network Pharmacology and Molecular Docking.

This study investigated the antioxidant potential of sugarcane vinegar, an emerging functional food, by analyzing its polyphenols and underlying molecular mechanisms that intervene in oxidative stress. Using a 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) assay combined with UPLC-MS analysis, six key polyphenols were identified: chlorogenic acid, caffeic acid, ferulic acid, luteolin, protocatechuic acid, and syringic acid. These compounds showed a positive correlation with antioxidant capacity. In a simulated sugarcane vinegar environment, these polyphenols exhibited synergistic antioxidant effects, while in methanol, antagonistic interactions were predominant. Network pharmacology revealed five key polyphenols targeting 10 critical proteins involved in oxidative stress, including the PI3K-Akt and IL-17 signaling pathways. Molecular docking confirmed strong binding affinities between these polyphenols and core targets like PTGS2, STAT3, and GSK3B. This study establishes a reference for the antioxidant mechanisms of sugarcane vinegar and highlights its potential for developing functional products.

Therapeutic Effects of Althaea officinalis L. and Metformin on Estradiol-Induced Polycystic Ovary Syndrome in Rats: Insights into The PI3K/AKT Pathway, Inflammation, and Oxidative Stress.

Polycystic ovary syndrome (PCOS) is one of the most important causes of infertility, irregular menstrual cycles, and anovulation in women. The current study aimed to investigate the therapeutic effects of Althaea officinalis L. (A. officinale) extract on PCOS in rats. In this experimental study, 70 rats in 7 groups (n=10/group) were studied for three weeks as follows; healthy control (HC), patient (PCOS), metformin (PCOS+MET), A. officinale treatment (PCOS+250 and 500 mg/kg A. officinale) and synergistic (PCOS+MET+250 and 500 mg/kg A. officinale) groups. Luteinizing hormone (LH), folliclestimulating hormone (FSH), progesterone (P) and testosterone (T) levels as well as inflammatory cytokines were measured. Total antioxidant capacity and lipid peroxidation levels were analyzed in ovarian tissue. The expression of GLUT-4, AKT, PI3K, PTEN genes and Ki-67 was assessed by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. A. officinale alone and especially in combination with MET moderated inflammatory and antioxidant parameters compared to the PCOS and MET groups. A. officinale in synergistic groups increased the apoptosis of granulosa cells by activating the PI3K/AKT pathway, resulting in a rise in the number of Ki-67 positive cells (P<0.05). Furthermore, following A. officinale treatment the LH/FSH rate decreased and FSH and P increased (P<0.05). Also, A. officinale extract could effectively normalize estrus cycle duration close to the normal group. The extract of A. officinale, in combination with metformin, can enhance the hypothalamic-pituitaryovary (HPO) axis with synergistic anti-inflammatory and antioxidant effects. Additionally, the extract showed apoptotic effect on cystic granulosa cells.

Cromolyn sodium and masitinib combination inhibits fibroblast-myofibroblast transition and exerts additive cell-protective and antioxidant effects on a bleomycin-induced invitro fibrosis model.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease. While recent studies have suggested the potential efficacy of tyrosine kinase inhibitors in managing IPF, masitinib, a clinically used tyrosine kinase inhibitor, has not yet been investigated for its efficacy in fibrotic lung diseases. In a previous study on an invitro neurodegenerative model, we demonstrated the synergistic antitoxic and antioxidant effects of masitinib combined with cromolyn sodium, an FDA-approved mast cell stabilizer. This study aims to investigate the anti-fibrotic and antioxidant effects of the masitinib-cromolyn sodium combination in an invitro model of pulmonary fibrosis. Fibroblast cell cultures treated with bleomycin and/or hydrogen peroxide (H2O2) were subjected to masitinib and/or cromolyn sodium, followed by assessments of cell viability, morphological and apoptotic nuclear changes, triple-immunofluorescence labeling, and total oxidant/antioxidant capacities, besides ratio of Bax and Bcl-2 mRNA expressions as an indication of apoptosis. The combined treatment of masitinib and cromolyn sodium effectively prevented the fibroblast myofibroblast transition, a hallmark of fibrosis, and significantly reduced bleomycin / H2O2-induced apoptosis and oxidative stress. This study is the first to demonstrate the additive anti-fibrotic, cell-protective, and antioxidant effects of the masitinib-cromolyn sodium combination in an invitro fibrosis model, suggesting its potential as an innovative therapeutic approach for pulmonary fibrosis. Combination therapy may be more advantageous in that both drugs could be administered in lower doses, exerting less side effects, and at the same time providing diverse mechanisms of action simultaneously.

Co‐encapsulation of ω‐3 LC‐PUFAs and carotenoids for enhanced synergistic antioxidant effects

AbstractThis work aimed to study the co‐encapsulation of ω‐3 Long‐Chain Polyunsaturated Fatty Acids (LC‐PUFAs) with β‐carotene, lutein and zeaxanthin and the cellular uptake of carotenoids. Monodisperse microcapsules with good properties, including particle surface morphology, water activity, microencapsulation efficiency, and glass transition temperature, were successfully prepared using a microfluidic‐jet spray drier with OSA‐modified starch as a wall matrix. The presence of carotenoids enhanced the oxidative stability of ω‐3 LC‐PUFAs. Caco‐2 cell uptakes of the carotenoids from the spray‐dried microcapsules were studied and compared to those encapsulated in the methylcellulose (MC) or xanthan gum (XG) delivery systems. The microcapsules encapsulated by OSA‐modified starch showed higher cellular uptakes of carotenoids (i.e., β‐carotene, 0.31 μg/mg protein; lutein, 0.52 μg/mg protein; zeaxanthin, 0.54 μg/mg protein) than those in the MC or XG delivery systems. The Caco‐2 cell uptake depended on carotenoid type, where hydrocarbon carotenoids (i.e., β‐carotene) had lower uptake than oxygenated carotenoids (i.e., lutein or zeaxanthin).

Selenomethionine and Allicin Synergistically Mitigate Intestinal Oxidative Injury by Activating the Nrf2 Pathway.

Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a H2O2-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that H2O2 induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice.

Multiple Enzyme-Mimicking CuMOF-Driven Self-Cascading Antioxidant Reaction for Synergistic Electrochemiluminescence Modulation in Ultrasensitive Biosensing.

Developing nanozyme-based free radical scavenging is a promising signal modulation approach for ECL sensing. Nevertheless, the relatively low antioxidant activity and inherent pro-oxidant activity of numerous nanozymes have significantly hindered the development of this strategy. Here a biofunctional copper-based metal-organic framework (CuMOF) with multiple enzyme-mimicking activities was employed for the modulation of the ECL immunosensor, guided by the self-cascade antioxidant reaction. The inherent SOD, CAT, and the capacity to eliminate ·OH endow CuMOF with powerful synergistic antioxidant effects while little pro-oxidant activities were displayed, enabling efficient scavenging of the O2·- produced during the electrochemical oxidation of H2O2. Subsequently, the nanoconfinement effect of the layered double hydroxide was introduced to ensure a steady ECL signal. The suggested ECL immunosensor, using aflatoxin B1 as a proof-of-concept target, demonstrated a detection range spanning from 0.001 pg/mL to 10 ng/mL, with the detection limit calculated to be 0.18 fg/mL. This exceptional achievement greatly broadens the range of possible uses for nanozyme-based radical scavenging modulated ECL analysis.

Multifunctional bio-nanocomposite films integrated with essential oils@metal−phenolic network nanocapsules for durable fruit preservation

Food spoilage exacerbates global hunger and poverty, necessitating urgent advancements in food shelf life extension methodologies. However, balancing antibacterial efficacy for food preservation with human and environmental safety remains a significant challenge. Natural essential oils (EOs), known for their potent antibacterial and antioxidant properties, offer eco-friendly alternatives, yet their high volatility and instability limit practical applications. Herein, we conducted the encapsulation of EOs within biocompatible metal phenolic networks (MPNs) to create EOs@MPN nanocapsules. Subsequently, these nanocapsules were integrated into bio-nanocomposite films composed of natural soy protein isolate (SPI) and carboxymethyl cellulose (CMC). The resulting films exhibited robust mechanical properties (Tensile Strength >10 MPa) and significantly enhanced antioxidant activity (7-fold higher than pure films). Importantly, the synergistic combination of EOs and MPNs conferred enhanced antibacterial efficacy. Safety assessments confirmed the bio-nanocomposite films' high biodegradability (> 90 %) and negligible cytotoxicity, ensuring environmental sustainability and human health safety. In practical applications, the bio-nanocomposite films effectively delayed the surface browning of fresh-cut fruits for up to 48 h, demonstrating a pronounced synergistic antioxidative effect against oxidation. Moreover, tomatoes and blueberries packaged with the bio-nanocomposite films still maintained freshness for up to 12 days, offering promising strategies for extending the shelf life of perishable fruits. These findings underscore the potential of EOs@MPN-based bio-nanocomposite films as sustainable solutions for food preservation and highlight their practical viability in mitigating food spoilage and enhancing food security globally.

Unlocking Antioxidant-Anticancer Synergy: An Exploration of Therapeutic Bioactives from Methanolic Extracts of Rubus ellipticus and Boerhavia diffusa Using HeLa Cell Line.

This study aimed to assess the synergistic antioxidant and anticancer effects of methanolic extracts derived from Rubus ellipticus and Boerhavia diffusa fruits against the HeLa cell line. The methanolic extracts were prepared from the fruits of R. ellipticus and B. diffusa, and their antioxidant potential was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity assay and the ferric reducing antioxidant power (FRAP) assay. The anticancer effects of benzoic acid and rutin extracted from the aforementioned fruits were also investigated against the HeLa cell line using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay to measure the cell metabolic activity. Using Synergy Finder plus software, the bioactive compounds were tested to explore any synergistic effects. R. ellipticus exhibited higher antioxidant potential as revealed by higher DPPH scavenging activity and FRAP value compared with B. diffusa. The benzoic acid extracted from R. ellipticus demonstrated potent anticancer activity against the HeLa cell line, with an IC50 of 1.07 µg/mL. Similarly, rutin extracted from B. diffusa displayed moderate anticancer activity with an IC50 of 1.4 µg/mL while exhibiting minimal impact on normal cell lines. The combination studies of the extracted bioactive compounds revealed a synergistic effect. These findings suggest the therapeutic potential of R. ellipticus and B. diffusa in combating the oxidative stress and cancer. Their bioactive compounds like benzoic acid and rutin were observed to act synergistically. Further investigations are warranted to elucidate the underlying mechanisms and evaluate their applicability in clinical settings.

Preparation and characterization of agarose-sodium alginate hydrogel beads for the co-encapsulation of lycopene and resveratrol nanoemulsion

In the study, lycopene and resveratrol nanoemulsion hydrogel beads were prepared by using agarose‑sodium alginate as a carrier and the semi-interpenetrating polymer network technique, characteristics and morphologies were evaluated by scanning electron microscopy, fluorescence microscopy, rheological measurement. The synergistic antioxidant effect of lycopene and resveratrol was confirmed, the best synergistic antioxidant performance is achieved when the ratio of 1:1. To increase the solubility and improve the stability, the lycopene was prepared as solid dispersion added to the nanoemulsion. The encapsulation rate of lycopene and resveratrol reached 93.60 ± 2.94 % and 89.30 ± 1.75 %, respectively, and the cumulative release showed that the addition of agarose slowed down the release rate of the compound, which improves the applicability of lycopene and resveratrol and development of carriers for the delivery of different bioactive ingredients.

Exploration on the synergistic effect of antioxidants for coal-to-liquid base oil: From the perspective of oxidation resistance and thermal stability

Coal-to-liquid (CTL) base oil is a high-quality lubricant base oil made from coal. However, its poor oxidation stability and short service life limit its application. Pressurized differential scanning calorimetry and Rotary bomb oxidation test are utilized for the evaluation of oxidation stability. Thermogravimetric analysis is performed for the thermal stability assessment. The results showed the reasonable combination of commercial antioxidants can significantly improve the oxidative and thermal stability of two typical CTL base oils, CTL3 and CTL6. The synergistic mechanism of antioxidants in CTL base oil was studied from the perspective of pyrolysis kinetics and pyrolysis mechanism. For CTL3, adding the compound antioxidant 2,6-di-tert-butyl-4-methylphenol (T501) and n-phenyl-1-naphthylamine (T531) results in an almost eightfold increase in oxidation induction time (OIT) and a 33.4 % increase in activation energy compared to pure CTL3. For CTL6, adding the compound antioxidant dialkyl dithiophosphate (T203) and diphenylamine (L57) results in an almost tenfold increase in OIT and a 10.9 % increase in activation energy compared to pure CTL6. The designed commercial antioxidant compound systems had excellent synergistic effects and the synergistic mechanisms were illustrated.

Synergistic Antioxidant Effects of Cysteine Derivative and Sm-Cluster for Food Applications.

The incorporation of antioxidants in food products is essential to prevent or delay deterioration, thereby addressing food spoilage. Thiol compounds, recognized for their natural antioxidant properties, are widely used in various foods; however, their antioxidant capacity is often limited. This study investigates the potential enhancement of thiol antioxidant capacity through the addition of a soluble, low-toxic inorganic Sm-cluster. Our findings demonstrate that the Sm-cluster significantly bolsters the antioxidant efficacy of thiol compounds. We explored, for the first time, the in vitro antioxidant activities of an Sm-oxo/hydroxy cluster combined with a cysteine derivative for potential food applications. The composition exhibited a robust inhibition of aromatic aldehyde flavor compound oxidation and displayed strong, dose-dependent DPPH (2,2-diphenyl-1-picrylhydrazine) radical scavenging activity. Notably, the antioxidant activity of the Sm-cluster/cysteine derivative was further enhanced under strong visible light conditions, which typically increased the likelihood of oxidation. These results suggest that the combination of inorganic cluster and thiol compounds presents a promising natural alternative to traditional antioxidants in the food industry.

Characterization of free and encapsulated cinnamon and clove essential oils for enhancing fresh sausage quality: A natural substitute for synthetic preservatives

This study aims to evaluate the properties of essential oils (EOs) from cinnamon (Cinnamomum cassia) and clove (Eugenia caryophyllus). Mixtures of cinnamon and clove EOs at ratios of 75:25, 50:50, and 25:75 were encapsulated and applied in fresh sausage. The research includes a kinetic examination of active component release and preservation parameter monitoring. Clove EO showed superior antioxidant activity (0.039 mg/mL), while cinamon oil exhibited promising bacterial inhibition (minimum inhibitory concentration lower 1.5). Combinations of cinnamon and clove EOs demonstrated synergistic antioxidant and antimicrobial effects. Encapsulation efficiency for the 25:75 cinnamon and clove oil mixture reached 89.4%, with 80.9% EO retention. The microencapsulated mixture displayed commendable antimicrobial and antioxidant activities, slowing compound release (>50% after 15 days). The encapsulated EOs (25:75) showed comparable results in lipid oxidation (0.194 mg malonaldehyde/kg) and microbial control to traditional curing salt, suggesting substitution potential. By encapsulating cinnamon and clove essential oils and evaluating their efficacy in fresh sausages, this research demonstrates their potential to enhance the safety and quality of meat products while addressing consumer demand for healthier and more natural food options.

Nonswellable Hydrogel Patch with Tissue-Mimetic Mechanical Characteristics Remodeling In Vivo Microenvironment for Effective Adhesion Prevention.

Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol-gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.

Modeling and analysis of synergistic phenolic antioxidants in edible oil: Integrating molecular simulation and artificial neural network approach

Oxidation causes edible oil deterioration affecting nutrition and safety. Antioxidants delay aging, but selecting compounds experimentally is time-consuming and arbitrary. Thus, a rapid and rational screening method for synergistic antioxidants is essential. This study evaluates the antioxidant effects and mechanisms of four phenolic antioxidants on the oil matrix using multiscale simulation. Tert-butylhydroquinone (TBHQ) exhibited the lowest dissociation energy (226.92 kJ/mol), followed by flavanol (TP) (233.00 kJ/mol). Syringic acid (CA) showed the smallest mean square displacement value. An artificial neural network (ANN) was established to analyze the synergistic and antagonistic interactions between TBHQ and TP, predicting optimal synergy at 3.6 mg TP and 1.8 mg TBHQ. The relative prediction deviation (RPD) value of the validation set was 3.91, and the relative error production (RER) value was 1.87 %. Fourier transform infrared spectroscopy experiments validated this synergy. This research establishes a screening system for compound antioxidants and models the synergistic effects of phenolic antioxidants in edible oil, offering theoretical and technical support for their application in the food industry.

Preparation of chitosan‐based macromolecular synergistic antioxidants containing hindered phenolic and secondary amine structures and its effects on thermo‐oxidative aging of styrene‐butadiene rubber/silica composites

AbstractIn this study, chitosan (CS)‐based macromolecular synergistic antioxidant CS‐UC‐TDAA containing carbon–carbon double bond, hindered phenol, and aromatic secondary amine was prepared by using CS,10‐undecenoyl chloride (UC), p‐aminobenzoic acid (AA), 3,5‐di‐tert‐butyl‐2‐hydroxybenzaldehyde (TD) via esterification, Schiff base reaction, and acylation reaction. The molecular structure of CS‐UC‐TDAA was characterized by fourier transform infrared, 1H NMR, and elemental analysis. The effects of macromolecular synergistic antioxidant CS‐UC‐TDAA, small molecular antioxidant TDAA, commercial antioxidant 4020, and butylated hydroxytoluene (BHT) on the antiaging properties of styrene‐butadiene rubber (SBR)/SiO2 composites were systematically studied by accelerated thermo‐oxidative aging test, thermogravimetric (TG) analysis, and methanol Soxhlet extraction experiment. The experimental results show that CS‐UC‐TDAA has more outstanding thermo‐oxidative aging resistance, thermal stability, and solvent extraction resistance in SBR/SiO2 composites than TDAA, 4020, and BHT. The macromolecular synergistic antioxidant CS‐UC‐TDAA endows SBR/SiO2 composites with more durable antiaging performance, which is attributed to the synergistic antioxidant effect of its hindered phenol and aromatic secondary amine groups. Additionally, its resistance to migration and extraction is facilitated by the crosslinking of the carbon–carbon double bond with the rubber and its substantial molecular weight.

Synergistic rosemary extract with TBHQ and citric acid improves oxidative stability and shelf life of peanut.

Lipid oxidation often accompanies the processing and storage of peanuts, which causes a serious waste of peanut resources. To solve the problem of being prone to oxidation in peanut processing, a ternary complex antioxidant based on rosemary extract (RE) was constructed to investigate its effect on the oxidative and thermal stability of peanuts, and the inhibition of peanut oxidation by compound antioxidants was revealed by dynamic Arrhenius formula and complexation theory. The results showed that there was a synergistic effect between RE and Tert-butyl hydroquinone (TBHQ), and the antioxidant effects of RE and TBHQ were 4.86 and 1.45 times higher when used in combination than when used alone, respectively. In addition, RE-TBHQ-CA (citric acid) effectively inhibited primary and secondary oxidation of peanuts with a shelf life 8.7 times longer than that of control peanuts. This study provides a novel antioxidant compounding idea, which has a positive effect on improving the quality of peanut and other nut products, prolonging the shelf life and reducing the waste of resources. PRACTICAL APPLICATION: Compounding a complex antioxidant that permits its use in peanuts. It was found that rosemary and TBHQ might have synergistic antioxidant effects. Meanwhile, this combination of RE-TBHQ-CA effectively inhibited the oxidation of peanut oils and prolonged the shelf life of peanuts. RE-TBHQ-CA is a highly efficient complex antioxidant that can reduce the amounts of antioxidants added while maintaining high antioxidant efficiency, which may be useful for the future preservation and storage of nut products as it positively affects the quality and shelf life of the product.

Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by excessive proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and accumulation of inflammatory cytokines. Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) dual-model imaging-guided multi-treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin-nanoparticles (MNPs), hydrogen gas (H2), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT.

A synergistic mechanism of Liquiritin and Licochalcone B from Glycyrrhiza uralensis against COPD

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a refractory respiratory disease mainly attributed to multiple pathological factors such as oxidative stress, infectious inflammation, and idiopathic fibrosis for decades. The medicinal plant Glycyrrhiza uralensis extract (ULE) was widely used to control respiratory diseases in China. However, the regulatory mechanism of scientific evidence to support the therapeutic benefits of ULE in the management of COPD is greatly limited. PurposeThis study aims to discover the potential protection mechanism of ULE on COPD via a muti-targets strategy. Study design and methodsThe present study set out to determine the potential protective effects of ULE on COPD through a multi-target strategy. In vivo and in vitro models of COPD were established using cigarette smoke and lipopolysaccharide to assess the protective effects of ULE. It was evaluated by measuring inflammatory cytokines and assessing pulmonary pathological changes. HPLC was used to verify the active compounds of the potential compounds that were collected and screened using HERB, works of literature, and ADME tools. The mechanisms of ULE in the treatment of COPD were explored using transcriptomics, connectivity-map, and network pharmacology approaches. The relevant targets were further investigated using RT-PCR, western blot, and immunohistochemistry. The HCK inhibitor (iHCK-37) was used to evaluate the potential mechanism of ULE's active compounds in the prevention of COPD. ResultsULE effectively protected the lungs of COPD mice from oxidative stress, inflammation, and fibrosis damage. After screening and verification using ADME properties and HPLC, 4 active compounds were identified in ULE: liquiritin (LQ), licochalcone B (LCB), licochalcone A (LCA), and echinatin (ET). Network pharmacology integrated with transcriptomics analysis showed that ULE mitigated oxidative stress, inflammation, and fibrosis in COPD by suppressing HCK. The combination of LCB and LQ was optimized for anti-inflammation, antioxidation, and anti-fibrosis activities. The iHCK-37 further validated the preventive treatment of LCB and LQ on COPD by inhibiting HCK to exert antioxidant, anti-inflammatory, and anti-fibrotic effects. The combination of LCB and LQ, in a 1:1 ratio, exerted synergistic antioxidative, anti-inflammatory, and anti-fibrotic effects in the treatment of COPD by downregulating HCK. ConclusionThe combination of LCB and LQ performed a significant anti-COPD effect via downregulating HCK.