Synergistic Antioxidant Research Articles

A Review on Sustainable Alternatives of Post Harvest Treatments in Fruits

The fruit farming industry faces spoilage and disease after harvest, with Colletotrichum being the most common cause. Safer, more effective, biorational, and sustainable disease management are suggested. Plant-based essential oils (Eos) have synergistic antimicrobial, herbicide, insecticide, antioxidant, and fungicide properties that can fight agricultural fungi. Due to their negative effects on agroecosystems and public health, the OECD recommends a switch to sustainable food systems and synthetic fungicides. Essential oils are complex lipids from plants' secondary metabolism that are allelopathic, herbivorous, and phytopathogenic microorganism-protective. Their effects on bacteria and fungi include cell wall degradation, cytoplasmic and lipid membrane synthesis interference, lysis, cell death, and mitochondrial dysfunction. Essential oils were shown to treat postharvest diseases in apple cultivars and Penicillium spp., B. cinerea in strawberries and apples. Combining essential oils and non-toxic additives can control fruit postharvest fungal infections. Immersion, spraying, fumigation, and volatilization can be applied to fruit. Researchers suggest adding essential oils to edible or biodegradable films and coatings to extend fruit shelf life and reduce microorganism spoilage. Agriculture is promising with nanobiotechnologies that improve volatile compound stability, pesticide residual effects and Aedes aegypti adhesion and repellency. Further research is needed to determine nanomaterials' toxicity and environmental impact.

Study on the Properties and Synergistic Antioxidant Effects of Novel Bifunctional Fusion Proteins Expressed Using the UTuT6 System.

Important antioxidant enzymes, glutathione peroxidase (GPx) and superoxide dismutase (SOD), are involved in maintaining redox balance. They can protect each other and result in more efficiently removing excessive reactive oxygen species (ROS), protecting cells against injury, and maintaining the normal metabolism of ROS. In this study, human cytosolic GPx (hGPx1) and human phospholipid hydroperoxide GPx (hGPx4) genes were integrated into the same open reading frame with human extracellular SOD active site (SOD3-72P) genes, respectively, and several novel fusion proteins were obtained by using the UTuT6 expression system for the first time. Among them, Se-hGPx1UAG-L4-SOD3-72P is the bifunctional fusion protein with the highest GPx activity and the best anti-hydrogen peroxide inactivation ability thus far. The Se-hGPx4UAG-L3-SOD3-72P fusion protein exhibits the strongest alkali and high temperature resistance and a greater protective effect against lipoprotein peroxidation damage. Se-hGPx1UAG-L4-SOD3-72P and Se-hGPx4UAG-L3-SOD3-72P fusion proteins both have good synergistic and antioxidant abilities in H2O2-induced RBCs and liver damage models. We believe that this research will help with the development of novel bifunctional fusion proteins and the investigation of the synergistic and catalytic mechanisms of GPx and SOD, which are important in creating novel protein therapeutics.

Potential of UV-Vis Spectroscopy for Determining the Mechanism of the Synergistic Antioxidant Process of Kaempferol with Three Other Flavonoids and β-Carotene

Potential of UV-Vis Spectroscopy for Determining the Mechanism of the Synergistic Antioxidant Process of Kaempferol with Three Other Flavonoids and β-Carotene

Phycocyanin/tannic acid complex nanoparticles as Pickering stabilizer with synergistic interfacial antioxidant properties

This study reported a type of phycocyanin (PC)-tannic acid (TA) complex nanoparticles (NPs) fabricated by simply mixing PC with TA at appropriate mass ratios. The assembly of PC-TA NPs was driven by secondary forces involving hydrophobic interactions and hydrogen bonding. PC-TA NPs promoted formations of Pickering emulsions with an oil volume fraction (φ) of 0.1–0.8. The interfacial antioxidant ability of PC-TA NPs was evaluated by comparing the contents of hydroperoxides, malonaldehyde, and hexanal due to lipid oxidation. The results showed that PC-TA NPs retarded lipid oxidation more efficiently than did PC, TA, tween 20, or tween 80, which suggested the synergistic antioxidant action of PC and TA. Besides, the PC-TA NPs stabilized high internal phase emulsion facilitated a higher retention of β-carotene under UV irradiation. Altogether, our findings demonstrate that the modification of PC by TA represents a strategy to fabricate PC-TA NPs with enhanced emulsification and antioxidant efficiency.

Exploring The in vitro Efficacy of Psidium Guajava Leaf Oil Against Cutibacterium Granulosum

One potential approach to treat acne vulgaris is by utilizing Cutibacterium granulosum (C. granulosum) to break down the biofilm formed by Cutibacterium acnes (C. acnes). When using cosmeceutical products containing certain essential oils, as they may have the unintended effect of eliminating C. granulosum, leading to the potential development of more severe acne vulgaris in the long term. No data for Psidium guajava (guava) leaves oil against C. granulosum has been reported. Therefore, this study aimed to investigate in vitro antimicrobial activity of guava leaves oil against C. granulosum. This oil was extracted from the guava leaves by hydrodistillation using a clevenger-type apparatus. Then, the chemical compositions of this crude oil were identified by gas chromatography-mass spectrometry. The percentage yield of this essential oil was 0.13 ± 0.2% (w/w) on fresh weight basis. The major compounds were β-caryophyllene (25.50%), limonene (11.58%), caryophyllene oxide (3.43%),a-copaene (2.92%), 1,8-cineole (2.08%), and a-pinene (1.28%). This essential oil exerted a potent antioxidant capacity with the half maximal inhibitory concentration of 32.7 ± 0.3 mg/ml from 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Additionally, the essential oil of guava leaves showed the susceptibility of C. granulosum by agar disc diffusion method with 22 ± 0.2 mm of clear inhibition zone. This essential oil also possessed against C. granulosum with the minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) of 3.125 µg/ml and 6.25 µg/ml from the broth microdilution susceptibility test. From these findings, this essential oil exhibited notable synergistic antioxidant and antimicrobial activities against C. granulosum.

Effects of Processing Conditions and Simulated Digestion In Vitro on the Antioxidant Activity, Inhibition of Xanthine Oxidase and Bioaccessibility of Epicatechin Gallate.

The bioactivity and gastrointestinal stability of epicatechin gallate (ECG) may be affected by processing conditions. Results showed that the antioxidant ability and inhibitory activity on xanthine oxidase (XO) of ECG were higher at low pH values. Appropriate microwave and heating treatments improved the antioxidant (the scavenging rate increased from 71.75% to 92.71% and 80.88% under the microwave and heating treatments) and XO inhibitory activity (the inhibitory rate increased from 47.11% to 56.89% and 51.85% at the microwave and heating treatments) of ECG. The treated ECG led to a more compact structure of XO. Moreover, there may be synergistic antioxidant and inhibitory effects between ECG and its degradation products. The bioaccessibility of ECG after simulated digestion was untreated > microwave > heating, and the microwave-treated ECG still had good XO inhibitory activity after digestion. These findings may provide some significant information for the development of functional foods enriched in catechins.

Characterization of the Synergistic Antioxidant Activity of Epigallocatechin Gallate (EGCG) and Kaempferol.

Epigallocatechin gallate (EGCG) and kaempferol exhibit cellular antioxidant activity; however, their interactive effects in terms of antioxidant actions and underlying mechanisms remain unclear. In this study, their cytoprotective effects were examined against 2,2-azobis (2-amidinopropane) dihydrochloride solution (ABAP)-induced oxidative stress in HepG2 cells. The results showed that the median effective dose (EC50) of the EGCG and kaempferol (6:1.5, c/c) combination was 3.4 ± 0.1 μg/mL, with a combination index (CIavg) value of 0.54, which represented a significant synergistic effect. Further experiments proved that the combined pretreatment with EGCG and kaempferol exerted protective effects by suppressing reactive oxygen species (ROS) generation, upregulating cellular antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)) in a dose-dependent manner. The mechanism of synergistic antioxidant effects of EGCG combined with kaempferol may be due to the up-regulation of higher antioxidant enzyme activities that improve the antioxidant capacities and balance the cell oxidative stress. The synergistic antioxidant effect of EGCG and kaempferol can provide a theoretical basis for the development of formulas of functional food ingredients.

Edaravone Dexborneol Alleviates Neuroinflammation by Reducing Neuroglial Cell Proliferation and Suppresses Neuronal Apoptosis/Autophagy in Vascular Dementia Rats.

More and more evidence shows that the pathological mechanism of vascular dementia (VD) is closely related to oxidative stress injury, cell apoptosis, autophagy, inflammatory response, excitatory amino acid toxicity, synaptic plasticity change, calcium overload, and other processes. Edaravone dexborneol (EDB) is a new type of neuroprotective agent that can improve the neurological damage caused by an ischemic stroke. Previous studies showed that EDB has effects on synergistic antioxidants and induces anti-apoptotic responses. However, it remains unclear whether EDB can affect apoptosis and autophagy by activating the PI3K/Akt/mTOR signaling pathway and its impact on the neuroglial cells. In this study, we established the VD model of rats by bilateral carotid artery occlusion to explore the neuroprotective effect of EDB and its mechanism. Morris Water Maze test was applied to assess the cognitive function of rats. H&E and TUNEL staining were applied to observe the cellular structure of the hippocampus. Immunofluorescence labeling was used to observe the proliferation of astrocytes and microglia. ELISA was applied to examine the levels of TNF-α, IL-1β and IL-6, and RT-PCR was applied to examine their mRNA expression levels. Western blotting was applied to examine apoptosis-related proteins (Bax, Bcl-2, Caspase-3), autophagy-related proteins (Beclin-1, P62, LC3B), PI3K/Akt/mTOR signaling pathway proteins and their phosphorylation levels. The results indicated that EDB ameliorates learning and memory in rats subjected to the VD model, alleviates neuroinflammatory response by reducing the proliferation of the neuroglial cell and inhibits apoptosis and autophagy, which may be mediated by the PI3K/Akt/mTOR signaling pathway.

Structural Design of Oleogel‐Hydrogel Bigels for Co‐Delivery of Curcumin and Epigallocatechin Gallate with Synergistic Stability and Bioactivity

AbstractBigels are novel biphasic systems containing hydrogel and oleogel structures, which are designed to deliver multiple bioactives for synergistic activity. The current study develops bigels based on a carrageenan hydrogel and a monoglyceride (GMS) oleogel. Results show that the microstructures of bigels are facilely modified by two surface active ingredients (Tween 20 and polyglycerol polyricinoleate), which then influence the microstructures of the bigels. When curcumin and epigallocatechin gallate (EGCG) are delivered simultaneously, the bioactives work synergistically to slow thermal degradation. Simulated digestion tests indicate that the bigel structures can delay the release of the two bioactives in artificial saliva and simulated gastric fluid (SGF), and allow fast release in simulated intestinal fluid (SIF). DPPH and ABTS tests show the digested Tween 20 bigels containing EGCG and curcumin present synergistic antioxidant activity. Anticancer activity is evaluated in human colon adenocarcinoma HCT116, and the two bioactives work cooperatively to lower cell viability. The bioactives released from Tween 20 bigels have higher cytotoxicity than those from polyglycerol polyricinoleate bigels. The results reveal that facile structural design of bigels has the potential to achieve synergistic stability and bioactivity of co‐delivered bioactives, which is meaningful for the development of functional pharmaceutical, cosmetic, and food products.

Scalable fabrication of uniform nanoparticles for the efficient co-encapsulation of curcumin and procyanidins driven by multiple interactions

The co-delivery of curcumin (CUR) with other polyphenol bioactives often has synergistic benefits. However, conventional co-encapsulation carriers formed by precipitation frequently exhibit limited loading properties, particularly for bioactives with different solubilities. In this study, we designed a highly efficient vehicle for the co-delivery of hydrophobic CUR and hydrophilic procyanidins (PCs), adopting a multiple interactions–based strategy via a two-step flash nanoprecipitation (FNP) process. The optimal nanoparticles (NP), composed of a FeII crosslinked PCs/CUR nanocore (NC) and a soy protein isolates (SPI) shell, showed high individual encapsulation efficiency (∼95%) and a total loading content of ∼38%. Compared with the conventional production process, FNP endowed our NP with a small size (133 nm) and good uniformity (polydispersity index = 0.267). Ultraviolet–visible and Fourier transform infrared spectra revealed multiple interactions (coordination and hydrogen bonding) among the carrier materials and bioactives, which played a central role in achieving excellent loading properties for both PCs and CUR. The core–shell structure of the NP greatly enhanced the thermal–light stability of the encapsulated PCs and CUR. Synergistic antioxidation effect was found between PCs and CUR, and the nano-formulation further increased the antioxidation efficiency. In vitro release experiments showed the favorable pH responsiveness of our NP in the vast gastrointestinal pH gradient effectively preventing the leakage of wrapped bioactives in the stomach pH environment, which benefits the intestinal delivery of the bioactives. Our nanoparticulate co-delivery system fabricated using the FNP process provides new insights into the formulation strategy of multiple bioactives and shows great potential for application in the fields of functional foods and dietary supplements.

Effects of combined binding of chlorogenic acid/caffeic acid and gallic acid to trypsin on their synergistic antioxidant activity, enzyme activity and stability.

The combined application of multiple natural polyphenols in functional foods may provide better health benefits. The binding of polyphenols with different structures to proteins will affect their respective functions. Spectroscopy and molecular docking were used to investigate the competitive binding of chlorogenic acid (CGA)/caffeic acid (CA) and gallic acid (GA) to trypsin. The effects of different molecular structures and the order of adding the three phenolic acids on the binding were assessed. The stability of trypsin and its docked complexes with CGA/CA/GA was evaluated by molecular dynamics simulation. The effects of the binding process on the activity and thermal stability of trypsin, as well as on the antioxidant activity and stability of CGA/CA/GA were explored. The competitive binding of CGA/CA and GA to trypsin affected their synergistic antioxidant effects. The results may provide a reference for the combined application of CGA/CA and GA in food and pharmaceutical fields.

Ceria Nanoparticles as Copper Chaperones that Activate SOD1 for Synergistic Antioxidant Therapy to Treat Ischemic Vascular Diseases (Adv. Mater. 16/2023)

Therapeutic Antioxidants In article number 2208989, Gwang-Bum Im, Young Geon Kim, Tae Yong Yoo, Taeghwan Hyeon, Suk Ho Bhang, and co-workers report the therapeutic effect of copper-deposited ceria nanoparticles (CuCe NPs) on ischemic vascular diseases. They exhibit enhanced antioxidant effects over pristine ceria nanoparticles as the released copper buffers the depletion of glutathione while providing the bioavailable copper as a cofactor for the antioxidant enzyme, superoxide dismutase 1.

Evaluation of phytochemicals and antioxidant potential of a new polyherbal formulation TC-16: additive, synergistic or antagonistic?

BackgroundScientific literature has demonstrated the association of free radicals in the aetiology of various chronic diseases. Hence, the identification of potent antioxidants remains a useful task. The combination of multiple herbs in polyherbal formulations (PHF) is often associated with greater therapeutic efficacy due to synergistic interactions. However, antagonism can occur in natural product mixtures and the resultant antioxidant potential might not always be the additive value of the antioxidant properties of each component. In this study, we aimed to evaluate the phytochemicals, antioxidative potential and interaction among the herbs in TC-16, a new PHF comprising Curcuma longa L., Zingiber officinale var. Bentong, Piper nigrum L., Citrofortunella microcarpa (Bunge) Wijnands and Apis dorsata honey.MethodsTC-16 was screened for phytochemicals. Phenolic and flavonoid contents of TC-16 and its individual ingredients were determined, followed by assessment of antioxidant properties using in vitro assays including 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and β-carotene bleaching (BCB) assays. Interactions among the herbs were also investigated by calculating the difference in antioxidant activity and combination index.ResultsAlkaloids, flavonoids, terpenoids, saponins and glycosides were present in TC-16. TC-16 possessed the highest phenolic (46.14 ± 1.40 mg GAE/g) and flavonoid (132.69 ± 1.43 mg CE/g) contents following C. longa. Synergistic antioxidant activity among the herbs was evident in ORAC and BCB assays which uses mainly hydrogen atom transfer-based antioxidant mechanisms.ConclusionsTC-16 demonstrated roles in combating free radicals. In a PHF, synergistic interaction among the herbs is observed in some but not all mechanisms. Mechanisms showing synergistic interactions should be highlighted to maximise the beneficial property of the PHF.

Ceria Nanoparticles as Copper Chaperones that Activate SOD1 for Synergistic Antioxidant Therapy to Treat Ischemic Vascular Diseases.

All exogenous nanomaterials undergo rapid biotransformation once injected into the body and fall short of executing the intended purpose. Here,it is reported that copper-deposited ceria nanoparticles (CuCe NPs) exhibit enhanced antioxidant effects overpristine ceria nanoparticles, as the released copper buffers the depletion of glutathione while providing the bioavailable copper as a cofactor for the antioxidant enzyme, superoxide dismutase 1. The upregulated intracellular antioxidants along with the ceria nanoparticles synergistically scavenge reactive oxygen species and promote anti-inflammation and M2 polarization of macrophages by modulating signal transducer and activator of transcription 1 and 6 (STAT1 and STAT6). The therapeutic effect of CuCe NPs is demonstrated in ischemic vascular diseases (i.e., murine models of hindlimb ischemia and myocardial infarction) in which the copper-deposition affords increased perfusion and alleviation in tissue damage. The results provide rationale that metal oxide nanomaterials can be designed in a way to induce the upregulation of specific biological factors for optimal therapeutic performance.

Carissa carandas L. fruit mediated in vitro synthesis of silver nanoparticles and their antioxidant and antibacterial activities

Currently, we synthesized silver nanoparticles (AgNPs) from the aqueous fruit extract of Carissa carandas L. and evaluated their antioxidant and antibacterial properties. The UV-visible spectra showed a characteristic absorption peak at 412 nm. The Fourier transform infrared (FTIR) spectroscopy exhibits intense peaks at 3430.23cm-1 and 1625.67cm-1 which indicates the involvement of flavonoids and other functional groups in the biosynthesis, capping, and stabilization of AgNPs. From XRD analysis, the average size of AgNPs was estimated to be 45nm. The biogenic AgNPs were spherical in shape and average size range between 10 to 95nm confirmed by HR-TEM analysis. The fabricated AgNPs by fruit extract were monitored for antioxidant activity using DPPH method. The fruit extract of AgNPs (IC50= 946.22μg/ml) had the highest antioxidant activity against standard ascorbic acid. The antibacterial activity was done using Staphylococcus aureus and Escherichia coli bacterial strains. It was found from the results that the bacterial strain S. aureus had the highest antibacterial activity when compared to E. coli and aqueous fruit extract. Thus, the present study exhibits synergistic antioxidant and antibacterial activity which may explore in future clinical treatment.

Synergistic Antioxidant Activity of Four—Component Mixture of Essential Oils: Basil, Cedarwood, Citronella and Thyme for the Use as Medicinal and Food Ingredient

Mixture design is a statistical tool used to obtain the maximum desired effect using the minimum number of experiments. The aim of the presented work was the optimization of the composition of a mixture of essential oils from basil, citronella, cedarwood and thyme using simplex-lattice mixture design method. The optimized parameter was an antioxidant activity measured in DPPH assay and expressed as effective concentration (EC50). The test results showed an interesting synergy between the components of essential oils. The prepared binary and quaternary mixtures were characterized by higher activity than simple average activity. The designed mixture with approximated highest antioxidant activity was composed of: 54.4% citronella essential oil, 33.0% thyme essential oil, 9.2% cedarwood essential oil and 3.4% basil essential oil and its approximated activity was in agreement with experimental values. This work confirmed that it is possible to approximate the best antioxidant composition of four essential oils used as a potential medicinal and food ingredient.

The hepatoprotective candidates by synergistic formula of marine and terrestrial against Acetaminophen toxicity using in-vitro, in-vivo, and in silico screening approach

BackgroundOne of the most regularly used hepatotoxic medicines is paracetamol (acetaminophen, N-acetyl-p-aminophenol; APAP). It causes liver failure in overdoses but is safe at therapeutic dosages. Combination therapy combining many natural compounds with a synergistic impact as hepatoprotective agents has become an essential therapeutic method against various disorders. ObjectiveDue to the lack of literature on paracetamol's effects on hematological and hepatic status parameters in male albino mice, the main goal of this study was to compare the hepatoprotective activities of a mixture of three marine-derived polyphenolics and polysaccharides (Sargassum vulgare Bacillus oceanisediminis, and alginic acids) to Chrysanthemum extract and the mixture of them. MethodsSargassumvulgare, Bacillus Oceanisediminis, and alginate, as well as Chrysanthemum ethanol extracts, were tested for APAP-induced liver damage. Group 1 received saline solution subcutaneously, while Group 2 received 500 mg/kg body weight/day APAP intraperitoneal. Group 3 got 200 mg/day algal extract i.p. As in group 3, group 4 got an i.p. dose of 200 mg of algal extract before the APAP dose. This group was protected by Sargassum vulgare extract. Group 5: Received 200 mg/100 g/body of Bacillus oceanisediminis extracts i.p. for one week. Group 6: Received 200 mg/body of Bacillus oceanisediminis extract i.p. for one week before APAP treatment. Alginate (p200 mg/body weight/day) was given to Group 7. As in group 7, group 8 received 200 mg/body weight/day alginate extract i.p. before APAP. Group 9: Chrysanthemum extracts 200 mg/day for a week. Group 10: got an i.p. dose of Chrysanthemum extracts for one week before the APAP dose. Group 11: Four mixed extracts (Bacillus Oceanisediminis, Sargassum vulgare, Chrysanthemum, and alginate) were i.p200 mg/day for one week as a positive (+ve) control group. Group 12: Received i.p200 mg/kg combination extract for one week before APAP. ResultsDue to their synergistic antioxidant and anti-inflammatory actions, marine extracts and combinations of marine-derived extracts demonstrated a great effect against APAP toxicity, demonstrating hepatoprotective potential against APAP-induced liver damage. ConclusionThe synergy of the three marine-derived combinations may lead to novel liver toxicity prevention agents.

Study on the Synergistic Antioxidant Effect of Coal Inhibitors and the DFT Calculation

ABSTRACT In order to improve efficiency when preventing and controlling spontaneous combustion of coal, a type of compound inhibitor with tea polyphenol and vitamin E as the chemical inhibitor, grafted on a copolymer hydrogel, was prepared. The oxidation resistance of the compound inhibitor to coal was analyzed by thermogravimetric test, Fourier infrared spectroscopy, and quantum chemistry theory. The experiment results showed that: The optimum ratio of tea polyphenols and vitamin E was 1:0.05; tea polyphenols and vitamin E inhibited the oxidation of coal by capturing the decomposition products of hydroperoxides and finally forming stable ether structures, and slowing down the hydrogen supply reaction between aliphatic hydrocarbons and carboxyl groups; the antioxidant properties of vitamin E (VE) and tea polyphenols (EGCG) were mainly due to the presence of active hydroxyl groups in the ring; H22 of VE and H38 of EGCG were able to inhibit the chain reaction of coal effectively. This study provides a new technical method for development of comprehensive fire prevention technology to address spontaneous combustion of coal, and provides a reference for the research into the inhibition mechanism of spontaneous combustion of coal.

LC-ESI-MS phenolic contents assessment, antioxidant, and protective ability of Punica granatum root bark extract against ethanol-induced gastric ulcer in rats: in silico H+, K+-ATPase inhibitory pathway study.

The objectives of the current study were to evaluate the Punica granatum root bark extract's (PGE) antioxidant and gastroprotective activities against ethanol-induced gastric ulcers in Wistar rats and to elucidate the putative mechanism of action using in silico analysis. The PGE phytochemical study shows high levels of phenolics, flavonoids, tannins, and polysaccharides. In vitro, the PGE was more effective at scavenging hydroxyl radicals than quercetin and had lower ferric reducing activity than catechin. In vivo, it was revealed that pretreatment of ethanol-ulcerated rats with PGE at oral doses of 100, 200, and 400mg/kg b.w. offered a dose-dependent shield against ethanol-induced ulcers when compared to Omeprazole (20mg/kg b.w.) by preventing the development of deep ulcer lesions, lowering gastric juice output and pH rises, boosting gastric mucus production and antioxidant enzyme levels, and attenuating malondialdehyde and myeloperoxidase contents. Moreover, the liquid chromatography-mass spectrometry analysis of PGE identified 5 phenolic acids and 4 flavonoids, which revealed an in silico high oral bioavailability, drug-likenesses, and good binding affinities and thus inhibitory effects on the gastric H+, K+-ATPase enzyme. PGE may have synergistic antioxidant, anti-inflammatory, and H+, K+-proton pump inhibitory actions that contribute to its antiulcer efficacy.

Novel Caffeic Acid - Zinc Acetate Complex: Studies on Promising Antidiabetic and Antioxidative Synergism Through Complexation.

The role of Zn(II) in storage, insulin secretion and function has been documented, while plant phenolics have antioxidant and other pharmacological credence. The study aimed at synthesizing a novel medicinal Zn(II) complex. The medicinal properties of zinc(II) and caffeic acid were considered in synthesizing a novel complex with promising and improved antioxidant and anti-hyperglycaemic attributes. Complex synthesis was done using a 1:2 molar ratio of zinc acetate and caffeic acid and structurally characterized using NMR, FT-IR, high resolution-mass spectroscopy and HPLC. Its cellular toxicity was assessed in Chang liver cells and L-myotubes. In vitro, cellular, and isolated tissue models were used to evaluate the antioxidant and anti-hyperglycaemic properties of the complex relative to its precursors. Molecular docking was used to investigate the interaction with insulin signalling target proteins: GLUT-4 and protein kinase B (Akt/PKB). Zinc(II) and caffeic acid interacted via Zn:O4 coordination, with the complex having one moiety of Zn(II) and 2 moieties of caffeic acid. The complex showed in vitro radical scavenging, α- glucosidase and α-amylase inhibitory activity up to 2.6 folds stronger than caffeic acid. The ability to inhibit lipid peroxidation (IC50 = 26.4 μM) and GSH depletion (IC50 = 16.8 μM) in hepatocytes was comparable to that of ascorbic acid (IC50 = 24.5 and 29.2 μM) and about 2 folds stronger than caffeic acid. Complexation improved glucose uptake activity of caffeic acid in L-6 myotubes (EC50 = 23.4 versus 169 μM) and isolated rat muscle tissues (EC50 = 339 versus 603 μM). Molecular docking showed better interaction with insulin signalling target proteins (GLUT-4 and Akt/PKB) than caffeic acid. The complex was not hepatotoxic or myotoxic. Data suggest a synergistic antioxidant and anti-hyperglycaemic potential between zinc and caffeic acid, which could be attributed to the Zn:O4 coordination. Thus, it may be of medicinal relevance.