Exploring the Anticancer Potential of Premna resinosa (Hochst.) Leaf Surface Extract: Discovering New Diterpenes as Heat Shock Protein 70 (Hsp70) Binding Agents.

Premna, a genus consisting of approximately 200 species, predominantly thrives in tropical and subtropical areas. Many of these species have been utilized in ethnopharmacology for diverse medicinal applications. In Saudi Arabia, Premna resinosa (Hochst.) Schauer (Lamiaceae) grows wildly, and its slightly viscid leaves are attributed to the production of leaf accession. In this study, we aimed to extract the surface accession from fresh leaves using dichloromethane to evaluate the anticancer potential. The plant exudate yielded two previously unknown labdane diterpenes, Premnaresone A and B, in addition to three already described congeners and four known flavonoids. The isolation process was accomplished using a combination of silica gel column chromatography and semi-preparative HPLC, the structures of which were identified by NMR and HRESIMS analyses and a comparison with the literature data of associated compounds. Furthermore, we employed a density functional theory (DFT)/NMR approach to suggest the relative configuration of different compounds. Consequently, we investigated the possibility of developing new chaperone inhibitors by subjecting diterpenes 1-5 to a Surface Plasmon Resonance-screening, based on the knowledge that oridonin, a diterpene, interacts with Heat Shock Protein 70 (Hsp70) 1A in cancer cells. Additionally, we studied the anti-proliferative activity of compounds 1-5 on human Jurkat (human T-cell lymphoma) and HeLa (epithelial carcinoma) cell lines, where diterpene 3 exhibited activity in Jurkat cell lines after 48 h, with an IC50 of 15.21 ± 1.0 µM. Molecular docking and dynamic simulations revealed a robust interaction between compound 3 and Hsp70 key residues.

An Insight into Citrus medica Linn.: A Systematic Review on Phytochemical Profile and Biological Activities.

Plant species are a reservoir of natural compounds that can potentially be used to treat different diseases. Citrus medica Linn. belonging to the Rutaceae family, has been used for centuries in medicine for its antioxidant, anti-inflammatory, antimicrobial, antiviral, and antihyperglycemic properties. These activities are ascribable not only to the presence of health-promoting macronutrients and micronutrients, such as carbohydrates, minerals, amino acids, and vitamins, but also to specialized metabolites, such as flavonoids (apigenin, hesperetin, hesperidin, naringin, naringenin, rutin, quercetin, and diosmin), coumarins (citropten, scoparone, and bergapten), terpenes (limonene, γ-terpinene, limonin, and nomilin), and phenolic acids (p-coumaric acid, trans-ferulic acid, and chlorogenic acid). In recent years, particular attention has been focused on the antioxidant, anti-inflammatory, antimicrobial activity, antidiabetic, anticancer, and neuroprotective activity of C. medica. However, although many studies have reported this species' chemical and biological properties, the literature has never been analyzed via a systematic approach. For this reason, using PubMed and Scopus as databases, we performed a systematic review of C. medica's chemical composition and biological properties to inspire new research approaches and increase its curative application.

Neurotensin(8-13) analogs as dual NTS1 and NTS2 receptor ligands with enhanced effects on a mouse model of Parkinson's disease.

The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders.

The healing bitterness of Gentiana lutea L., phytochemistry and biological activities: A systematic review.

Over many years, natural products have been a source of healing agents and have exhibited beneficial uses for treating human diseases. The Gentiana genus is the biggest genus in the Gentianaceae, with over 400 species distributed mainly in alpine zones of temperate countries around the world. Plants in the Gentiana genus have historically been used to treat a wide range of diseases. Still, only in the last years has particular attention been paid to the biological activities of Gentiana lutea Linn., also known as yellow Gentian or bitterwort. Several in vitro/vivo investigations and human interventional trials have demonstrated the promising activity of G. lutea extracts against oxidative stress, microbial infections, inflammation, obesity, atherosclerosis, etc.. A systematic approach was performed using Pubmed and Scopus databases to update G. lutea chemistry and activity. Specifically, this systematic review synthesized the major specialized bitter metabolites and the biological activity data obtained from different cell lines, animal models, and human interventional trials. This review aims to the exaltation of G. lutea as a source of bioactive compounds that can prevent and treat several human illnesses.

Antimicrobial and antioxidant properties and quantitative screening of phytochemicals of Fraxinus excelsior L. and Eschscholtzia californica Cham. mother tinctures.

The antioxidant and antimicrobial activities of Fraxinus excelsior L. and Eschscholtzia californica Cham. mother tinctures against a range of foodborne bacteria were investigated to determine the major components and to analyse the action spectrum and antimicrobial effectiveness of the extracts. Results demonstrated a significant antioxidant activity of Fraxinus excelsior L. and a lower activity of Eschscholtzia californica Cham. and a good chemical phenolic composition with the highest content of flavonoids. The Fraxinus excelsior L. and Eschscholtzia californica Cham. mother tinctures demonstrated a middle-high antimicrobial activity against, respectively, 66.67% and 43.33% of all tested bacteria. The inhibitory activity showed a moderate effect on the growth of the sensitive strains in presence of extracts minimum inhibitory concentration. The synergistic actions of bioactive compounds detected in the extracts might be on the basis of antioxidant and biological activities observed and should be used in pharmaceutical, food preservation, alternative medicine and natural therapies fields.

The Production of γ-Aminobutyric Acid from Free and Immobilized Cells of Levilactobacillus brevis Cultivated in Anaerobic and Aerobic Conditions.

γ-aminobutyric acid (GABA) has several beneficial effects on human health. GABA may be produced via chemical synthesis or through microbial metabolism, and Levilactobacillus brevis is recognized as a GABA-producing species. In this study, 11 Lvb. brevis strains were screened for GABA production, and the best producers were selected to verify the effect of aerobic (AE) and respiratory (RS) cultivations on growth parameters, biomass, and GABA accumulation. Lvb. brevis LB12 was then used to evaluate the combined effect of the incubation atmosphere (anaerobiosis vs. aerobiosis), cell protection (free vs. immobilized cells), and cell recycling (fresh vs. starved cells) on GABA production. Glutamate (GLU) consumption and GABA accumulation were detected by Thin-layer Chromatography (TLC) and RP-HPLC analyses. The ability to produce GABA was widespread among the strains. AE and RS growth improved biomass production, but oxygen availability impaired GLU to GABA conversion, and the anaerobically growing cells had the highest GABA productivity. Immobilized strains had lower efficiency in both GLU uptake and conversion compared to free cells, probably due to the poor diffusion in alginate beads. The use of resting cells allowed further GABA production without the cultivation step, but cell activity was exhausted after three cycles of reutilization. Lvb. brevis LB12 is an excellent GABA producer, and AE cultivation can be exploited to improve the final cell density; however, the conditions for boosting GLU to GABA conversion and cell regeneration need to be further investigated.

Nanotechnological exploitation of the antioxidant potential of Humulus lupulus L. extract.

The present study investigated the potential antioxidant applications of Humulus lupulus L. as raw extract and nanoformulated in liposomes. H. lupulus is commonly used as a food ingredient, but it is also a promising source of specialized metabolites with health-promoting effects. In the extract obtained by hydroalcoholic maceration, 24 compounds were characterized using liquid chromatography-mass spectrometry analyses. The extract exhibited an interesting antioxidant activity in in vitro spectrophotometric and cell assays. The extract was nanoformulated into liposomes to exploit and improve its beneficial proprieties. The in vitro assays revealed that, after incorporation into liposomes, the extract's antioxidant activity was preserved and even improved. Moreover, a lower dose of the extract was required to prevent reactive oxygen species overproduction when included in the nanoformulation. These results confirm the advantages of nanoformulating herbal extract to maximize its health-promoting effects for a potential pharmaceutical application.

New Insight on the Bioactivity of Solanum aethiopicum Linn. Growing in Basilicata Region (Italy): Phytochemical Characterization, Liposomal Incorporation, and Antioxidant Effects.

Food extract's biological effect and its improvement using nanotechnologies is one of the challenges of the last and the future decades; for this reason, the antioxidant effect of scarlet eggplant extract liposomal incorporation was investigated. Scarlet eggplant (Solanum aethiopicum L.) is a member of the Solanaceae family, and it is one of the most consumed vegetables in tropical Africa and south of Italy. This study investigated the antioxidant activity and the phytochemical composition of S. aethiopicum grown in the Basilicata Region for the first time. The whole fruit, peel, and pulp were subjected to ethanolic exhaustive maceration extraction, and all extracts were investigated. The HPLC-DAD analysis revealed the presence of ten phenolic compounds, including hydroxycinnamic acids, flavanones, flavanols, and four carotenoids (one xanthophyll and three carotenes). The peel extract was the most promising, active, and the richest in specialized metabolites; hence, it was tested on HepG2 cell lines and incorporated into liposomes. The nanoincorporation enhanced the peel extract's antioxidant activity, resulting in a reduction of the concentration used. Furthermore, the extract improved the expression of endogenous antioxidants, such as ABCG2, CAT, and NQO1, presumably through the Nrf2 pathway.

Insights into the leaves of Ceriscoides campanulata: Natural proanthocyanidins alleviate diabetes, inflammation, and esophageal squamous cell cancer via in vitro and in silico models.

Fourteen flavones (1-14) including twelve polymethoxylated flavones, two A-type proanthocyanidins (oligomeric flavonoids) (15, 16), one benzoyl glucoside (17), one triterpenoid (18), and one phenylpropanoid (19) were isolated from the leaves of the South Asian medicinal plant Ceriscoides campanulata (Roxb.) Tirveng (Rubiaceae). The structures of the compounds were identified based on their spectroscopic and spectrometric data and in comparison with literature data. Isolated compounds were tested in vitro against inflammatory enzymes (COX-2, iNOS), pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α), esophageal squamous carcinoma cell line (TE13), and carbohydrate digestion enzymes (α-amylase, α-glucosidase). Proanthocyanidins 15 and 16 significantly attenuated the LPS-induced inflammatory response of COX-2, iNOS, IL-1ß, IL-6, TNF-α in RAW 264.7 cells. Proanthocyanidins also satisfactorily inhibited the regrowth (64%), migration (51%), and formation of tumor-spheres (48%) in ESCC cell line TE13 at 50% toxic concentration. Compounds 15 and 16 showed the most potent effect against mammalian α-amylase (IC50 8.4 ± 0.3 µM and 3.5 ± 0.0 µM, respectively) compared to reference standard acarbose (IC50 5.9 ± 0.1 µM). As yeast α-glucosidase inhibitors, compounds 15 and 16 also displayed significant activities (IC50 6.2 ± 0.3 and 4.7 ± 0.1 µM, respectively), while compounds 1-6 displayed weaker α-glucosidase inhibitory activities, ranging from 49 to 142 µM, compared to acarbose (IC50 665 ± 42 µM). In an anticholinesterase assay, compounds 1, 2, 6 (IC50 51 ± 2, 53 ± 7, 64 ± 5 µM, respectively), and 4 (IC50 44 ± 1 µM) showed moderate inhibitory activities against acetylcholinesterase and butyrylcholinesterase, respectively. Furthermore, molecular docking and molecular dynamic simulation analyses of compounds 15 and 16 were performed against human pancreatic α-amylase and human lysosomal acid α-glucosidase to elucidate the interactions of these compounds in the respective enzymes' active sites.

Dittrichia graveolens (L.) Greuter, a Rapidly Spreading Invasive Plant: Chemistry and Bioactivity.

Dittrichia graveolens L. Greuter belonging to the Asteraceae family, is an aromatic herbaceous plant native to the Mediterranean region. This plant species has been extensively studied for its biological activities, including antioxidant, antitumor, antimicrobial, antifungal, anti-inflammatory, anticholinesterase, and antityrosinase, and for its peculiar metabolic profile. In particular, bioactivities are related to terpenes and flavonoids metabolites, such as borneol (40), tomentosin (189), inuviscolide (204). However, D. graveolens is also well known for causing health problems both in animals and humans. Moreover, the species is currently undergoing a dramatic northward expansion of its native range related to climate change, now including North Europe, California, and Australia. This review represents an updated overview of the 52 literature papers published in Scopus and PubMed dealing with expansion, chemistry (262 different compounds), pharmacological effects, and toxicology of D. graveolens up to October 2021. The review is intended to boost further studies to determine the molecular pathways involved in the observed activities, bioavailability, and clinical studies to explore new potential applications.

Olive Trees By-Products as Sources of Bioactive and Other Industrially Useful Compounds: A Systematic Review.

The need to produce an ever-increasing quantity of material products and food resulting from the planet globalization process has contributed to the spread of modern agriculture based on a linear production resulting in the generation of tons of waste. This huge amount of waste is generally accumulated in landfills, causing different environmental problems. Hence, researchers moved on to study the processes used to recover agro-industrial by-products within a circular and sustainable bio-economy concept. A systematic quest on Scopus and PubMed databases was performed to identify the data available to date on recycling agro-industrial by-products of Olea europaea L. This systematic review summarizes the knowledge regarding the use of olive trees by-products for producing animal feed, biocomposites, bioethanol, cellulose pulp, activated carbon, and as a fuel source for energy production. Furthermore, the data regarding the potential biological activity of extracts from olive roots, wood, bark, and pruning were analyzed. Olive trees by-products are, indeed, rich in molecules with antioxidant, antimicrobial, cardioprotective, and anticancer activity, representing a promising candidate for treat several human diseases.

Screening of in vitro and in silico α-amylase, α-glucosidase, and lipase inhibitory activity of oxyprenylated natural compounds and semisynthetic derivatives.

Metabolic syndrome has several characteristic manifestations, including insulin resistance and dyslipidaemia, that demand therapeutic approaches, such as the inhibition of enzymes involved in nutrient absorption and digestion.This study aimed to evaluate the potential pharmacological use of natural compounds widespread in the plant kingdom and their semisynthetic compounds against target enzymes. Twenty-three oxyprenylated natural compoundswere investigated for their ability to inhibit α-amylase, α-glucosidase, and pancreatic lipase enzymes by in vitro assays. Moreover, in silico molecular docking was performed to analyse their binding capabilities into 3D structures. Farnesyloxyferulic acid, geranyloxyvanillic acid, nelumal A, and geranyloxyferulic acid showed the highest inhibition activity in all three in vitro enzyme assays. Moreover, in silico molecular docking of these four compounds was used to analyse their possible binding in 3D structures of the investigated enzymes. The results indicate that these compounds have considerable therapeutic potential for the treatment of metabolic syndrome, and further studies are warranted for their pharmacological development.

Preserving Biodiversity as Source of Health Promoting Compounds: Phenolic Profile and Biological Activity of Four Varieties of Solanum lycopersicum L.

Tomato (Solanum lycopersicum L.) is a precious source of specialized metabolites with a great role in human health. Many varieties of tomatoes characterize the south of Italy's agronomic production and biodiversity, thanks to its warm temperatures and favorable weather. The preservation of biodiversity is a major goal of recent years, as each variety shows a peculiar phytochemical profile and provides a wide variety of metabolites with health-beneficial properties. Among the wide range of tomato varieties, literature focused on the most commercially-known types, including San Marzano and Datterino, while this study considered typical South Italy varieties for the first time, as well as Crovarese and Arsicolo. The aim of our work is to enrich the current knowledge about the tomato by evaluating the carotenoid content, the phytochemical profile by HPLC-DAD, and the biological activity of the different parts (peel, fruit, pulp, and seeds) of niche cultivars compared with commercial ones. Radical scavenging activity, assessed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) method, was higher in Crovarese peel extract, while Arsicolo possessed the highest lycopene content, underlying the importance of local ecotypes as a precious source of health promoting compounds. However, out of all of the varieties considered, peel extract was the most active one, opening new insights on their valorization in light of the circular economy.

The Promising Ability of Humulus lupulus L. Iso-α-acids vs. Diabetes, Inflammation, and Metabolic Syndrome: A Systematic Review.

For centuries, natural medicines have represented the only option for treating human diseases and, nowadays, plant phytochemicals are considered as promising compounds to treat or prevent chronic conditions. Among them, hop flowers (Humulus lupulus L.), typically used in brewing industries to give the typical aroma and flavor to beer, have attracted particular attention for their health promoting properties. Several in vivo/vitro studies and human interventional trials have demonstrated the beneficial effects of these molecules on weight gain, lipid metabolism, glucose homeostasis, insulin sensitivities, and inflammation by acting on different targets. All these activities suggest a possible role of bitter hop acid in preventing metabolic syndrome and its related diseases. A systematic quest on PubMed and Scopus databases was performed to identify pre-clinical and clinical studies focusing on this topic. This systematic review summarizes the results obtained by different cell lines, animal models, and human interventional trials to propose iso-α-acids as medical nutrition therapy to treat or prevent metabolic syndrome and its related disorders as diabetes, dislipidemia inflammation, etc.

The Beneficial Effects of Red Sun-Dried Capsicum annuum L. Cv Senise Extract with Antioxidant Properties in Experimental Obesity are Associated with Modulation of the Intestinal Microbiota.

SCOPE: Capsicum annuum L. cv Senise is a sweet pepper containing health promoting compounds that can be modified by ripening and drying. This study focuses on finding the peppers with the best antioxidant properties, which are evaluated on an experimental model of obesity. METHODS AND RESULTS: Phytochemical profile and antioxidant activity are evaluated on several peppers obtained from the same cultivar at different ripening stages. Red sweet peppers show the highest content in polyphenols, ß-carotene, lycopene, and capsinoids, and demonstrate the best antioxidant activity in vitro. Mice fed a high fat diet are orally treated with an extract from these peppers (Capsicum annuum extract [CAE]) (1, 10, and 25 mg/kg/day). It promotes weight loss and improves plasma markers related to glucose and lipid metabolisms. CAE also ameliorates obesity-associated systemic inflammation reducing the expression of pro-inflammatory cytokines in adipose and hepatic tissues and improving the expression of different markers involved in the gut epithelial barrier function. These effects are associated with a modulation of the intestinal microbiome, which appears altered. CONCLUSIONS: The extract can be considered a new potential approach for the treatment of obesity, complementary to dietary restrictions.

Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review.

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.

Advances in Azorella glabra Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization.

Azorella glabra Wedd. (AG) is traditionally used to treat gonorrhea or kidney's problems. The antioxidant, antidiabetic, anticholinesterase and in vitro antitumor activities of AG extracts were recently reported. The aim of this work was to investigate anti-leukemic properties of AG chloroform fraction (AG CHCl3) and of its ten sub-fractions (I-X) and to identify their possible bioactive compounds. We determined their in vitro antioxidant activity using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO) and superoxide anion (SO) assays, and their phytochemical profile by spectrophotometric and LC-MS/MS techniques. I-X action on two acute myeloid leukemia (AML) cell lines viability, apoptosis and cell cycle were evaluated by MTS, western blotting and cytofluorimetric assays. Different polyphenol, flavonoid and terpenoid amount, and antioxidant activity were found among all samples. Most of I-X induced a dose/time dependent reduction of cell viability higher than parent extract. IV and VI sub-fractions showed highest cytotoxic activity and, of note, a negligible reduction of healthy cell viability. They activated intrinsic apoptotic pathway, induced a G0/G1 block in leukemic cells and, interestingly, led to apoptosis in patient AML cells. These activities could be due to mulinic acid or azorellane terpenoids and their derivatives, tentatively identified in both IV and VI. In conclusion, our data suggest AG plant as a source of potential anti-AML agents.

New Insights into the Exploitation of Vitis vinifera L. cv. Aglianico Leaf Extracts for Nutraceutical Purposes.

The leaves of Vitis vinifera L. have been used for a long time in traditional medicine for the treatment of many ailments. Grape polyphenols, indeed, have been demonstrated to be able to defend against oxidative stress, responsible for various disorders such as cancer, diabetes and neurodegenerative diseases. The effects of different extraction techniques, Soxhlet (SOX), Accelerated Solvent (ASE 40, ASE 50) and Ultrasound Assisted Extraction (UAE) were studied in this work to evaluate their impact on the chemical profile and bioactive potential of Vitis vinifera L. (cv. Aglianico) leaf extracts. The phytochemical profile was investigated by HPLC-DAD and 9 phenolic compounds were identified and quantified in the extract. Moreover, the antioxidant, anticholinesterase and antityrosinase activities were evaluated. In detail, the total polyphenol content and antioxidant activity (2,2-diphenyl-1-picrylhydrazyl, Oxygen Radical Absorbance Capacities and ß-Carotene Bleaching assays) were evaluated and compared to assess the Relative Antioxidant Capacity Index (RACI). To test the inhibitory activity of extracts towards cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assays were performed. SOX and ASE 50 have shown the highest value of RACI, 0.76 and 0.65, respectively. Regarding enzymatic inhibitory activity, ASE 50 (IC50 = 107.16 ± 8.12 µg/mL) and SOX (IC50 = 171.34 ± 12.12 µg/mL) extracts exhibited the highest AChE and BChE inhibitory activity, respectively, while UAE (IC50 = 293.2 ± 25.6 µg/mL, followed by SOX (IC50 = 302.5 ± 38.3 µg/mL) showed the highest tyrosinase inhibition value. Our results demonstrated for the first time that Aglianico leaves are important sources of phenols that could be used to prevent oxidative stress and be potentially helpful in diseases treatable with tyrosinase and cholinesterase inhibitors, like myasthenia gravis or Alzheimer's.

Hura crepitans L. Extract: Phytochemical Characterization, Antioxidant Activity, and Nanoformulation.

The purpose of this study was to improve the knowledge on Hura crepitans L., a plant belonging to the Euphorbiaceae family that, on the one hand, is known to be toxic, but on the other, is a source of polyphenols with health-promoting effects. Different green extraction methods were applied, varying solvent, temperature, and duration of extraction, which can influence the phytochemical profile and biological activity of plant extracts, and the extracts were fully characterized. Aqueous extracts exhibited a superior antioxidant activity, as indicated by different spectrophotometric tests, and were cytoprotective to HepG2 cells used as model cells. Liquid chromatography-mass spectrometry analyses were performed to identify the secondary metabolites involved in these effects and demonstrated that solvent, duration, and temperature indeed influenced the extraction of polyphenols. Furthermore, the most promising extract, in terms of antioxidant potential, was incorporated into liposomes with the aim of promoting cell interaction and enhancing the antioxidant activity.

Phytochemical Profile of Capsicum annuum L. cv Senise, Incorporation into Liposomes, and Evaluation of Cellular Antioxidant Activity.

Overproduction of oxidants in the human body is responsible for oxidative stress, which is associated with several diseases. High intake of vegetables and fruits can reduce the risk of chronic diseases, as they are sources of bioactive compounds capable of contrasting the free radical effects involved in cancer, obesity, diabetes, and neurodegenerative and cardiovascular diseases. Capsicum annuum L. cv Senise is a sweet pepper that is grown in the Basilicata region (Italy). It is an important source of polyphenols, carotenoids, and capsinoids and can play a key role in human health. In this study, an ethanol extract was obtained from C. annuum dried peppers and the analysis of the phytochemical composition was performed by LC-ESI/LTQ Orbitrap/MS. The extract was incorporated into liposomes, which showed small size (~80 nm), good homogeneity, negative surface charge, and good stability in storage. The biological activity of the extract was evaluated in the human hepatoma (HepG2) cell line, used as model cells. The extract showed no cytotoxic activity and reduced the intracellular reactive oxygen species (ROS) level in stressed cells. The antioxidant activity was further improved when the extract was loaded into liposomes. Moreover, the extract promoted the expression of endogenous antioxidants, such as catalase, superoxide dismutase, and glutathione peroxidase through the Nrf-2 pathway evaluated by RT-PCR.