Class Of Polyphenols Research Articles

Punica granatum Bioactive Compounds-Loaded Chitosan Nanoparticles Exhibit Potent Antihyperglycemic Effect in Alloxan-Induced Diabetic Mice

In the current study, alloxan-induced diabetic mice model was used to assess the antihyperglycemic effects of Chitosan Nanoparticles (CSNP) loaded with (Punica granatum methanol extract-PG) bioactive compounds. Analysis of P. granatum extract revealed significant concentrations of various classes of polyphenols. In particular, the total polyphenols content is noted at 289.6 ± 5.1 mg/g, while flavonoids and anthocyanins exhibited concentrations of 53.7 ± 0.8 mg/g and 34.8 ± 0.4 mg/g, respectively. Chitosan nanoparticles were prepared by ionic gelation technique using TPP as crosslinking agent. Their spectroscopic characterization showed a good stability, high encapsulation efficiency and the bioactive molecule-loaded CNPs were well-dispersed with homogeneous distribution in the nanosolutions. In vivo experiments showed that when compared to the diabetic control group, diabetic mice treated with CSPG-CNP (100 mg/kg bw) displayed a significant decrease in their mean fasting blood glucose levels. Moreover, hepatic and kidneys histopathological examination showed clear improvements in hepatic alterations in animals treated with CSPG-CNP compared to diabetic control group. Indeed, hepatic cells regained normal size, hepatic steatosis decreased, and the number of inflammatory cells was drastically reduced, suggesting effectiveness of this combination in improving diabetes-induced hepatic lesions. Moreover, mice of CSPG-CNP group showed significant improvements in renal alterations with signs of renal tissue repair. Indeed, damage to Bowman's capsule, glomeruli, and renal tubules were improved, returning to normal renal histology.

In Vitro Evaluation of Purple Sweet Potato Leaf Extract (Ipomoea batatas) as a Tyrosinase Inhibitor and Malondialdehyde Formation Inhibitor

The study purple sweet potato is known to contain flavonoids, a class of natural polyphenols with the capability to mitigate skin pigmentation. The research aims to assess the antioxidant and tyrosinase inhibitory activities of purple sweet potato extracts obtained through hexane, ethyl acetate, ethanol, and water solvents. The results of phytochemical identification show that the extract contains various secondary metabolites which have the potential to act as antioxidants. The DPPH method IC50 values of 6948.12ppm for n-hexane, 3015.19ppm for ethyl acetate, 128.05ppm for ethanol, and 791.77ppm for water extract. The MDA inhibitor test IC50 values of 2067.02ppm for n-hexane, 1968.13ppm for ethyl acetate, 116.14ppm for ethanol, and 921.14ppm for water extract. In the tyrosinase inhibitor assay, IC50 values were 1328.29ppm for n-hexane, 1245.13ppm for ethyl acetate, 217.35ppm for ethanol, and 391.21ppm for water extract. Tuckey test statistics, ethanol extract was not significantly different from the positive control in the DPPH test, MDA inhibitor and tyrosinase test. These findings suggest that purple sweet potato extracts, particularly the ethanol extract, hold promise as natural ingredients with antioxidant and tyrosinase inhibitory properties, making them potential candidates for safe and effective skin brightening formulations.

Metabolites from Aerial Parts of Glycyrrhiza foetida as Modulators of Targets Related to Metabolic Syndrome.

A detailed phytochemical investigation has been carried out on the aerial parts of G. foetida leading to the isolation of 29 pure compounds, mainly belonging to the amorfrutin and polyphenol classes. Among them, the new amorfrutin N (5) and exiguaflavone L (21) were isolated and their structures elucidated by means of HR-ESIMS and NMR. All the isolated compounds were investigated for modulation of mitochondrial activity and stimulation of glucose uptake via GLUT transporters, two metabolic processes involved in intracellular glucose homeostasis, which, therefore, correlate with the incidence of metabolic syndrome. These experiments revealed that amorfrutins were active on both targets, with amorfrutin M (17) and decarboxyamorfrutin A (2) emerging as mitochondrial stimulators, and amorfrutin 2 (12) as a glucose uptake promoter. However, members of the rich chalcone/flavonoid fraction also proved to contribute to this activity.

Interactions between Salivary Proteins and Apple Polyphenols and the Fate of Complexes during Gastric Digestion.

Beneficial polyphenols in apples can reach the stomach as complexes formed with salivary proteins. The present study aimed at documenting the interactions between salivary proteins and cider apple polyphenols and the fate of complexes during gastric digestion. A polyphenolic extract was mixed with human saliva, and interactions were characterized by analyzing proteins and polyphenols in the insoluble and soluble fractions of the mixtures, before and after in vitro gastric digestion. Results confirmed that proline-rich proteins can efficiently precipitate polyphenols and suggested that two zinc-binding proteins can also form insoluble complexes with polyphenols. The classes of polyphenols involved in such complexes depended on the polyphenol-to-protein ratio. In vitro gastric digestion led to extensive proteolysis of salivary proteins, and we formulate the hypothesis that the resulting peptides can interact with and precipitate some procyanidins. Saliva may therefore partly modulate the bioaccessibility of at least procyanidins in the gastric compartment.

Comprehensive polyphenolic profiling of nine distinct plants and edible mushrooms by targeted and untargeted LC-(HR)MS(/MS)

Polyphenols are a broad molecular family whose occurence patterns in an organism are often only partially known. They are secondary metabolites exhibiting antioxidant properties and are involved in a wide range of biological actions. Moreover, polyphenol oxidases, metalloenzymes present in various plants and fungi, play a role in metabolic pathways by catalyzing the hydroxylation and oxidation of polyphenols. Functional studies on these enzymes are greatly hampered by the lack of information on the polyphenols present in a specific organisms, meaning the physiological substrate is unknown for most polyphenol oxidases. Therefore, seven commercially available fungal and two plant species were examined in detail for the presence of polyphenols using an LC-HRMS-based suspect screening workflow. A total of 401 features were annotated, composed of 221 flavonoids and 180 non-flavonoids. As 64% of the flavonoids were conjugated with a glycone, (semi-)quantification was applied when a reference standard of the aglycone was available. Isomers of hesperetin-O-glucoside were ubiquitous in all investigated samples. The samples were then additionally investigated by a quantitative, targeted LC-MS/MS assay that covers 90 polyphenols from 13 distinct polyphenol classes. The targeted assay showed phenolic acids as prevalent analytes. Overall, this pilot study provides new insights into the complex polyphenol profiles of nine mushroom and plant species.

Polyphenol contents in meal recommendations from the Brazilian dietary guidelines

Research has demonstrated that consuming polyphenols is linked to a lower risk of non-communicable chronic diseases. The objective of this study was to quantify the polyphenol content in the meal recommendations provided by the Food Guide for the Brazilian Population (2014). This quantitative and descriptive analysis was conducted on the data from photographic documentation in the national food guide, focusing on the food items, their preparation methods, and the suggested quantities for breakfast, lunch, and dinner. The polyphenol contents of the foods and meals were estimated using the Phenol-Explorer database, which allowed determining the contribution of foods and polyphenol classes to the total polyphenol content. The mean total polyphenol content for breakfast patterns was found to be 242.67 ± 161.09 mg, with coffee being the primary contributor to this amount. Phenolic acids were the most significant contributors, accounting for ≥95% of the total. For lunch and dinner patterns, the average polyphenol contents were 311.97 ± 208.15 mg and 337.14 ± 220.17 mg, respectively. Contrary to breakfast, flavonoids emerged as the predominant class in these meals (p < 0.005), with legumes making a notable contribution to the total polyphenol content in both lunch and dinner. No significant difference was observed between the polyphenol contents of the different breakfast, lunch, and dinner patterns (p = 0.71). Therefore, the inclusion of different meals throughout the day is important for the intake of different polyphenol classes. Staple items in the national diet, particularly coffee and beans, were identified as key contributors to the polyphenol content in the meals suggested by the national food guide. Furthermore, in natura and minimally processed foods are highlighted as significant sources of polyphenols in the Brazilian diet.

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases.

Mast cells (MCs) are immune cells that reside in tissues; particularly in the skin, and in the gastrointestinal and respiratory tracts. In recent years, there has been considerable interest in the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2), which is present on the surface of MCs and can be targeted by multiple exogenous and endogenous ligands. It is potentially implicated in non-IgE-mediated pseudoallergic reactions and inflammatory conditions such as asthma or atopic dermatitis. In this paper, we review natural products and herbal medicines that may potentially interact with MRGPRX2. They mainly belong to the classes of polyphenols, flavonoids, coumarins, and alkaloids. Representative compounds include rosmarinic acid, liquiritin from licorice extract, osthole, and sinomenine, respectively. While evidence-based medicine studies are still required, these compounds have shown diverse effects, such as antioxidant, analgesic, anti-inflammatory, or neuroprotective. However, despite potential beneficial effects, their use is also burdened with risks of fatal reactions such as anaphylaxis. The role of MRGPRX2 in these reactions is a subject of debate. This review explores the literature on xenobiotic compounds from herbal medicines that have been shown to act as MRGPRX2 ligands, and their potential clinical significance.

Flavonoids as Insecticides in Crop Protection-A Review of Current Research and Future Prospects.

Pesticide overuse in agricultural systems has resulted in the development of pest resistance, the impoverishment of soil microbiota, water pollution, and several human health issues. Nonetheless, farmers still depend heavily on these agrochemicals for economically viable production, given the high frequency at which crops are affected by pests. Phytopathogenic insects are considered the most destructive pests on crops. Botanical pesticides have gained attention as potential biopesticides and complements to traditional pesticides, owing to their biodegradability and low toxicity. Plant-based extracts are abundant in a wide variety of bioactive compounds, such as flavonoids, a class of polyphenols that have been extensively studied for this purpose because of their involvement in plant defense responses. The present review offers a comprehensive review of current research on the potential of flavonoids as insecticides for crop protection, addressing the modes and possible mechanisms of action underlying their bioactivity. The structure-activity relationship is also discussed. It also addresses challenges associated with their application in pest and disease management and suggests alternatives to overcome these issues.

Polyphenol exposure of mothers and infants assessed by LC–MS/MS based biomonitoring in breast milk

Exposure to polyphenols is relevant throughout critical windows of infant development, including the breastfeeding phase. However, the quantitative assessment of polyphenols in human breast milk has received limited attention so far, though polyphenols may positively influence infant health. Therefore, a targeted LC–MS/MS assay was developed to investigate 86 analytes representing different polyphenol classes in human breast milk. The sample preparation consisted of liquid extraction, salting out, freeze-out, and a dilution step. Overall, nearly 70% of the chemically diverse polyphenols fulfilled all strict validation criteria for full quantitative assessment. The remaining analytes did not fulfill all criteria at every concentration level, but can still provide useful semi-quantitative insights into nutritional and biomedical research questions. The limits of detection for all analyzed polyphenols were in the range of 0.0041–87 ng*mL−1, with a median of 0.17 ng*mL−1. Moreover, the mean recovery was determined to be 82% and the mean signal suppression and enhancement effect was 117%. The developed assay was applied in a proof-of-principle study to investigate polyphenols in breast milk samples provided by twelve Nigerian mothers at three distinct time points post-delivery. In total, 50 polyphenol analytes were detected with almost half being phenolic acids. Phase II metabolites, including genistein-7-β-D-glucuronide, genistein-7-sulfate, and daidzein-7-β-D-glucuronide, were also detected in several samples. In conclusion, the developed method was demonstrated to be fit-for-purpose to simultaneously (semi-) quantify a wide variety of polyphenols in breast milk. It also demonstrated that various polyphenols including their biotransformation products were present in breast milk and therefore likely transferred to infants where they might impact microbiome development and infant health.Graphical abstract

Nutrological aspects of polyphenols and gut microbiota in sports performance: a systematic review

Introduction: In the context of nutrology and sports performance, the focus for intake in athletes and physically active individuals has been directed to the main class of polyphenols. Interest in a personalized approach is increasing in sports to maximize each individual's athletic ability in endurance and strength sports. Polyphenols represent a heterogeneous class of compounds with marked antioxidant and anti-inflammatory properties. The impact of the gut microbiota on the bioavailability and activity of polyphenols is highlighted. Objective: It was to carry out a systematic review to highlight the main relationships between polyphenols, gut microbiota, and sports performance. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from May to July 2023 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 115 articles were found, and 81 articles were evaluated in full and 76 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 6 studies with a high risk of bias and 10 studies that did not meet GRADE. As a result and conclusion, it was shown that the metabolic mechanisms favored by polyphenols improve sports performance, improve cardiometabolic functions, reduce recovery times and post-exercise pain, maintain a low degree of oxidative stress, and avoid unregulated inflammatory processes. Thus, polyphenols are able, through their interaction with the gut microbiota, to favor the proliferation of bacterial genera of great importance for metabolic and cognitive functions, such as Akkermansia, Lactobacilli, and Bifidobacteria. Gut microbiota metabolizes polyphenols in the colon to produce small bioactive molecules that exert epigenetic mechanisms on biochemical pathways modulating gene expression. Polyphenols have multiple biological effects, and future exercise studies should be appropriately and specifically designed to determine the physiological interactions between exercise and the selected supplement, rather than just considering performance.

A Comprehensive Review on Polyphenols Based Nanovesicular System for Topical Delivery.

Polyphenols are naturally occurring compounds having more than one hydroxy functional group. They are ubiquitous secondary plant metabolites possessing a wide range of pharmacological activity. Brightly colored fruits and vegetables are the natural source of polyphenols. Majorly, they possess antioxidant, anti-inflammatory and antimicrobial properties which make them suitable candidates to target skin related disorders. This study is focused to explore the potential of polyphenols loaded nanovesicles for skin related disorders. The aim of the study is to review the applicability and efficacy of different vesicular systems encapsulated with various classes of polyphenols for skin related disorders, thus opening the opportunity for future studies based on these drug delivery systems. Web of Science, PubMed, Scopus database, and the search engine Google Scholar were accessed for the literature search. The results were then filtered based on the titles, abstracts, and accessibility of the complete texts. The expository evaluation of the literature revealed that various nanovesicles like liposomes, niosomes, ethosomes and transferosomes incorporating polyphenol have been formulated to address issues pertaining to delivery across the skin. These developed nano vesicular systems have shown improvement in the physicochemical properties and pharmacological action. Polyphenol based nano-vesicular formulations have proved to be an effective system for topical delivery and henceforth, they might curtail the use of other skin therapies having limited applicability.

Synthesis and structural confirmation of selaginpulvilin X.

We report the first total synthesis of the natural product selaginpulvilin X, a selaginellaceae polyphenol class of compounds. Our synthetic strategy employs cross-coupling reactions and an organolithium addition to construct the carbon framework. Subsequently, the functional group modifications and deprotection yield the natural product. Spectral analysis confirms the proposed structure by comparing natural and synthetic samples.

Efektivitas Aktivitas Antibakteri Ekstrak Etanol 70% Daun Mimba (Azadirachta indica A. Juss) Dari Praya Lombok Tengah Dan Seyegan Sleman Yogyakarta Terhadap Staphylococcus aureus Dan Escherichia coli Secara In Vitro Serta Skrining Fitokimia

Nimba (Azadirachta indica A. Juss) is a plant that is widely used as traditional medicine and contains a class of flavonoid compounds, saponins, tannins and polyphenols. This study aims to determine the differences in the class of antibacterial compounds contained in plants and the activity of 70% ethanol extract of nimba leaves (Azadirachta indica A. Juss) from Seyegan, Sleman, Yogyakarta and Praya, Central Lombok, Lombok against Escherichia coli and Staphylococcus aureus. Extraction of nimba leaves (Azadirachta indica A. Juss) using 70% ethanol as a solvent. The extract was tested on Escherichia coli and Staphylococcus aureus bacteria. Minimum Inhibitory Concentration (MIC) was tested using the liquid dilution method, variations in the concentration of sample solution 50% w/v, 25% w/v, 12.5% w/v, 6.25% w/v, 3.125% w/v and 1.56% w/v , the minimum kill concentration (MBC) was determined from the lowest observed concentrations on McConkey's medium for Escherichia coli and Blood Agar for Staphylococcus aureus. Phytochemical screening of the 70% ethanol extract of nimba leaves (Azadirachta indica A. Juss ) was carried out with a tube to determine the class of active compounds in the 70% ethanol test of neem leaves (Azadirachta indica A. Juss ) from different growing sites. The results of 70% ethanol extract of nimba leaves (Azadirachta indica A. Juss) could not be determined because the test solution looked cloudy. Meanwhile, the KBM of 70% ethanolic extract of nimba (Azadirachta indica A. Juss ) on Escherichia coli bacteria was 25% w/v of 70% ethanol extract of nimba (Azadirachta indica A. Juss ) leaves from Seyegan, Sleman, Yogyakarta and 70% ethanol extract of nimba leaves (Azadirachta indica A. Juss ) from Praya, Central Lombok, Lombok is 25%w/v. Minimum kill concentration against Staphylococcus aureus was 6.25% w/v 70% ethanol extract of nimba leaves (Azadirachta indica A. Juss) from Seyegan, Sleman, Yogyakarta and 70% ethanol extract of nimba leaves (Azadirachta indica A. Juss) from Praya, Central Lombok, Lombok is 6.25% b/. The test results of the 70% ethanol extract of nimba leaves (Azadirachta indica A. Juss) from Seyegan, Sleman, Yogyakarta and Praya, Central Lombok, Lombok contained flavonoid compounds, saponins, tannins, and polyphenols. Keyword : Antibacteria, Nimba (Azadirachta indica A.Juss), Escherichia coli, Staphylococcus aureus.

Unraveling Biotic and Abiotic Factors Shaping Sugarcane Straw Polyphenolic Richness: A Gateway to Artificial Intelligence-Driven Crop Management.

Sugarcane straw (Saccharum officinarum) is a valuable coproduct renowned for its abundant polyphenolic content. However, extracting these polyphenols for natural ingredients faces challenges due to their inherent variability, influenced by biotic stress factors and plant characteristics. We explored the impact of five crucial factors on sugarcane straw polyphenolic diversity: (i) production area (Guariba, Valparaíso), (ii) borer insect (Diatraea saccharalis) infestation, (iii) plant age (first to seventh harvest), (iv) harvest season, and (v) plant variety. Response surface methodology (RSM) and artificial neural networks (ANN) were used to optimize polyphenol extraction conditions. A second-order polynomial model guided us to predict ideal sugarcane straw harvesting conditions for polyphenol-rich extracts. The analysis identified CU0618-variety straw, harvested in Guariba during the dry season (October 2020), at the seventh harvest stage, with 13.81% borer insect infection, as the prime source for high hydroxybenzoic acid (1010 µg/g), hydroxycinnamic acid (3119 µg/g), and flavone (573 µg/g) content and consequently high antioxidant capacity. The ANN model surpasses the RSM model, demonstrating superior predictive capabilities with higher coefficients of determination and reduced mean absolute deviations for each polyphenol class. This underscores the potential of artificial neural networks in forecasting and enhancing polyphenol extraction conditions, setting the stage for AI-driven advancements in crop management.

Phytochemical-loaded Nanoparticles in COVID-19 Management

A phytochemical-loaded nanoparticle is an important therapeutic agent that aids in enhancing the bioavailability of phytochemicals of lower water solubility and delivering the phytochemicals to the site of infection in a targeted manner. This strategy has also been developed for the management of COVID-19. They can be used as antiviral medication carriers, causing the direct death of viral particles and imitating the host in order to neutralize viral processes. In the formulation of phytochemical-loaded nanoparticles against SARS-CoV-2, different categories of nanoparticles, including inorganic, lipid-based, and polymeric nanoparticles, are used. Numerous phytochemicals belonging to the classes of alkaloids, flavonoids, terpenes, terpenoids, saponins, glycosides, polyphenols, and lignans, that demonstrate effective antiviral properties are utilized for the phytochemical-loaded nanoparticles. This approach results in increased solubility and stability of the phytochemicals with lower systemic toxicity, in addition to site-specific delivery. The combination therapy delivers multiple therapeutic agents at the site of infection. It can also be administered directly to the respiratory system by inhalation delivery. Therefore, this approach can potentially inhibit the application of phytochemical-loaded nanoparticles for the treatment of COVID-19, which is still in its replication of the SARS-CoV-2 virus and reduces the severity of the disease. The infancy and a number of obstacles must be overcome prior to their widespread use.

Research progress on the effects of proanthochanidins in reshaping microbiota and suppressing inflammation

Proanthocyanidins (PCs) are a class of polyphenols that are composed of flavanate monomers and their polymers, which have antibacterial and anti-inflammatory properties with very few side effects. This article reviews the mechanism by which PCs differentially regulate microbiota, reshape microflora diversity and play a role in suppressing inflammation, providing a reference for the basic research of PCs in improving female vaginal health, and is expected to provide a new idea and breakthrough for the combined use of PCs with other antibacterial drugs in the treatment of vaginitis.

Sericin “hairpin structure”-based multifunctional anthocyanin nanoencapsulation for remodeling ROS-dependent cutaneous wound healing

Anthocyanins, a class of polyphenols possessing potent antioxidant properties, are limited in their applicability in biomedical industries owing to their low stability. This study harnessed the bioactive silk sericin to encapsulate anthocyanins and thereby conferred enhanced stability and multifunctional bioactivity. Meanwhile, experimental and computational methods were used to systematically probe the interaction between silk sericin and anthocyanins. The hydrogel formulation of silk sericin displayed higher encapsulation efficiency and concomitant improvements in stability under diverse conditions such as pH, metals, and temperature. Molecular simulations revealed that the amino acids, phenylalanine and tyrosine, with a hairpin structure were pivotal in the interaction between the two components, culminating in the formation of nanocomposites, a finding corroborated by the experimental results using various spectroscopic techniques. Significantly, the encapsulated anthocyanins exhibited enhanced bioactivity, particularly in their reactive oxygen species (ROS) scavenging ability. Leveraging the potent antioxidant properties of silk sericin and anthocyanins, the formulation evinced ROS-triggered wound healing functions by modulating factors such as TGF-β, IL-1β, TNF-α, IL-10, and VEGF. This study highlights the potential of utilizing two bioactive components derived from the same sericultural system to enhance stability and regulate bioactivity in tissue engineering applications.

Exploring the Impact of In Vitro Gastrointestinal Digestion in the Bioaccessibility of Phenolic-Rich Chestnut Shells: A Preliminary Study

Chestnut shells (CS), the principal by-product of the chestnut processing industry, contain high concentrations of flavonoids and other polyphenols with huge interest for the nutraceuticals field. Nonetheless, the bioaccessibility and bioactivity of phytochemicals can be influenced by their digestibility, making it imperative to evaluate these activities prior to application of CS as a nutraceutical ingredient. This work aims to appraise the effects of in vitro simulated gastrointestinal digestion on the bioaccessibility, bioactivity, and metabolic profiling of CS. An increase in the total phenolic and flavonoid contents, antioxidant/antiradical properties, radical scavenging capacity, and inhibition on acetylcholinesterase activity was evidenced during in vitro simulated digestion. Metabolomic profiling by LC-ESI-LTQ-Orbitrap-MS revealed changes during the simulated digestion, particularly in phenolic compounds (46% of total compounds annotated), lipids (22%), phenylpropanoids (9%), organic acids (7%), carbohydrates (5%), nucleosides (5%), amino acids (4%), and alcohols (1%). Phenolic acids (gallic acid, syringic acid, and hydroxyphenylacetic acid) and flavonoids (epicatechin) were the major polyphenolic classes identified. The heatmap-positive correlations highlighted that the bioactivity of CS is closely related to the phenolic compounds and their bioaccessibility. These findings suggest the reuse of CS as a potential nutraceutical ingredient with antioxidant and neuroprotective effects, encouraging the use of appropriate extraction and/or encapsulation techniques to enhance the bioaccessibility of phenolic compounds.

A sulfonamide chalcone AMPK activator ameliorates hyperglycemia and diabetic nephropathy in db/db mice

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which currently lacks effective treatments. AMP-activated protein kinase (AMPK) stimulation by chalcones, a class of polyphenols abundantly found in plants, is proposed as a promising therapeutic approach for DM. This study aimed to identify novel chalcone derivatives with improved AMPK-stimulating activity in human podocytes and evaluate their mechanisms of action as well as in vivo efficacy in a mouse model of DN. Among 133 chalcone derivatives tested, the sulfonamide chalcone derivative IP-004 was identified as the most potent AMPK activator in human podocytes. Western blot analyses, intracellular calcium measurements and molecular docking simulation indicated that IP-004 activated AMPK by mechanisms involving direct binding at allosteric site of calcium-dependent protein kinase kinase β (CaMKKβ) without affecting intracellular calcium levels. Interestingly, eight weeks of intraperitoneal administration of IP-004 (20 mg/kg/day) significantly decreased fasting blood glucose level, activated AMPK in the livers, muscles and glomeruli, and ameliorated albuminuria in db/db type II diabetic mice. Collectively, this study identifies a novel chalcone derivative capable of activating AMPK in vitro and in vivo and exhibiting efficacy against hyperglycemia and DN in mice. Further development of AMPK activators based on chalcone derivatives may provide an effective treatment of DN.

Natural Compounds and Glutathione: Beyond Mere Antioxidants.

The tripeptide glutathione plays important roles in many cell processes, including differentiation, proliferation, and apoptosis; in fact, disorders in glutathione homeostasis are involved both in the etiology and in the progression of several human diseases, including cancer. Natural compounds have been found to modulate glutathione levels and function beyond their role as mere antioxidants. For example, certain compounds can upregulate the expression of glutathione-related enzymes, increase the availability of cysteine, the limiting amino acid for glutathione synthesis, or directly interact with glutathione and modulate its function. These compounds may have therapeutic potential in a variety of disease states where glutathione dysregulation is a contributing factor. On the other hand, flavonoids' potential to deplete glutathione levels could be significant for cancer treatment. Overall, while natural compounds may have potential therapeutic and/or preventive properties and may be able to increase glutathione levels, more research is needed to fully understand their mechanisms of action and their potential benefits for the prevention and treatment of several diseases. In this review, particular emphasis will be placed on phytochemical compounds belonging to the class of polyphenols, terpenoids, and glucosinolates that have an impact on glutathione-related processes, both in physiological and pathological conditions. These classes of secondary metabolites represent the most food-derived bioactive compounds that have been intensively explored and studied in the last few decades.