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Background Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Black pepper, the fruits of Piper nigrum L., is well known as “the king of spices” and used as seasoning and condiments globally. In addition to being an important food additive, black pepper is also used as a traditional medicine to treat vomiting, abdominal pain, and diarrhea, among others. Piperine is a major pungent alkaloid identified in the fruits of P. nigrum (black pepper), whose content is at a range of ~5–13%. Black pepper and piperine have shown protective effect on CVDs. Scope and approach Literature search was conducted to systematically review the cardiovascular protective effect of both black pepper and its major bioactive constituent piperine. Key findings and conclusions Black pepper was reported to regulate lipid metabolism, inflammation, and oxidation status in CVDs. Piperine exhibited beneficial effect by targeting many processes associated with atherosclerosis. Piperine is able to prevent lipid peroxidation, oxidized low-density lipoprotein uptake in macrophages, lipid droplet formation, and adhesion of inflammatory cells to endothelial monolayer, promote cholesterol efflux from macrophages, as well as improve lipid profile. Besides, piperine may ameliorate myocardial ischemia, cardiac injury, and cardiac fibrosis, exhibit antihypertensive and antithrombosis effect, as well as prevent arterial stenosis by inhibiting vascular smooth muscle cell proliferation. The summarized information could provide the basis to develop black pepper or piperine as a food additive to prevent or treat CVDs.

Ginger (Zingiber officinale Roscoe) is a common and widely used spice. It is rich in various chemical constituents, including phenolic compounds, terpenes, polysaccharides, lipids, organic acids, and raw fibers. Herein, we reviewed its effects on the vascular system. Studies utilizing cell cultures or animal models showed that ginger constituents alleviate oxidative stress and inflammation, increase nitric oxide synthesis, suppress vascular smooth muscle cell proliferation, promote cholesterol efflux from macrophages, inhibit angiogenesis, block voltage-dependent Ca2+ channels, and induce autophagy. In clinical trials, ginger was shown to have a favorable effect on serum lipids, inflammatory cytokines, blood pressure, and platelet aggregation. Taken together, these studies point to the potential benefits of ginger and its constituents in the treatment of hypertension, coronary artery disease, peripheral arterial diseases, and other vascular diseases.

Elastase is a proteolytic enzyme belonging to the family of hydrolases produced by human neutrophils, monocytes, macrophages, and endothelial cells. Human neutrophil elastase is known to play multiple roles in the human body, but an increase in its activity may cause a variety of diseases. Elastase inhibitors may prevent the development of psoriasis, chronic kidney disease, respiratory disorders (including COVID-19), immune disorders, and even cancers. Among polyphenolic compounds, some flavonoids and their derivatives, which are mostly found in herbal plants, have been revealed to influence elastase release and its action on human cells. This review focuses on elastase inhibitors that have been discovered from natural sources and are biochemically characterised as flavonoids. The inhibitory activity on elastase is a characteristic of flavonoid aglycones and their glycoside and methylated, acetylated and hydroxylated derivatives. The presented analysis of structure–activity relationship (SAR) enables the determination of the chemical groups responsible for evoking an inhibitory effect on elastase. Further study especially of the in vivo efficacy and safety of the described natural compounds is of interest in order to gain better understanding of their health-promoting potential.

Scavenger receptor class B type I (SR-BI) protein is an integral membrane glycoprotein. SR-BI is emerging as a multifunctional protein, which regulates autophagy, efferocytosis, cell survival and inflammation. It is well known that SR-BI plays a critical role in lipoprotein metabolism by mediating cholesteryl esters selective uptake and the bi-directional flux of free cholesterol. Recently, SR-BI has also been identified as a potential marker for cancer diagnosis, prognosis, or even a treatment target. Natural products are a promising source for the discovery of new drug leads. Multiple natural products were identified to regulate SR-BI protein expression. There are still a number of challenges in modulating SR-BI expression in cancer and in using natural products for modulation of such protein expression. In this review, our purpose is to discuss the relationship between SR-BI protein and cancer, and the molecular mechanisms regulating SR-BI expression, as well as to provide an overview of natural products that regulate SR-BI expression.

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

Four diets, formulated with and without stevia and with and without exogenous xylanase, following a 2 × 2 factorial design, were prepared. Each diet was fed ad libitum to birds in eight pens (three birds in each pen) in a randomised block design. It was found that birds fed xylanase grew faster, used the feed more efficiently and had an increased concentration of hepatic α-tocopherol and vitamin E concentrations (P < 0.05). Feeding stevia did not affect growth performance (P > 0.05), but increased hepatic CoQ10 (P = 0.05), lutein, zeaxanthin and total carotenoids (P < 0.001) concentrations. There were no dietary stevia by xylanase interactions (P > 0.05) for any of the studied variables. The results showed that alone, dietary stevia and dietary xylanase can improve the antioxidative status of birds through enhancing dietary antioxidant availability.

The aim of the study was to investigate the changes in the activity of antioxidant enzymes, i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity in ostrich meat, as influenced by various packaging systems and storage time under refrigeration. Three packaging methods were used: vacuum packaging (VP) and modified atmosphere packaging (MAP) in two combinations of gases, MAP1 (40% O2/40% CO2/20% N2) and MAP2 (60% O2/30% CO2/10% N2). Meat samples were taken from the M. ilifibularis (IF) muscles of eight ostriches in each treatment group. The meat samples were stored in a refrigerator in 2 °C and analyzed at days 0, 4, 8, 12 and 16. The lowest level of SOD activity during storage was observed in ostrich muscles packed in vacuum, as compared to MAP1 and MAP2. In turn, the highest increase in GPx activity was recorded in VP, especially up to day 8 of storage, when this parameter reached maximum value (54.37). GR increased up to the eighth day of storage in MAP1 and VP. Between the 12th and 16th days of storage, stabilization of the GR activity level was observed only in VP, while under MAP1, it further decreased. DPPH remained relatively stable until the eighth day of storage and after this period, a decrease in this parameter was recorded, reaching the lowest value on day 12 for all types of packaging systems.

BackgroundThe banana (Musa spp.) plant produces elongated and edible fruit. The two main parthenocarpic species of banana are Musa accuminata Colla and Musa balbisiana Colla. There are several health-promoting and disease-preventing effects of Musa accuminata Colla, which are attributed to its important bioactive compounds, including phenolics, carotenoids, biogenic amines, phytosterols, and volatile oils, found in the stem, fruit, pseudostem, leaf, flower, sap, inner trunk, root, and inner core. Banana possesses numerous pharmacological activities, such as antioxidant, immunomodulatory, antimicrobial, antiulcerogenic, hypolipidemic, hypoglycemic, leishmanicidal, anthelmintic, and anticancer properties. Various individual studies have reported anticancer effects of different components of the banana plant. However, according to our understanding, an up-to-date, systematic, and critical analysis of existing scientific results has not yet been carried out.ObjectivesThis review aims to include a thorough assessment of banana and its phytochemicals for cancer prevention and therapy with a focus on cellular and molecular mechanisms of action.MethodsThe available research studies on anticancer activities of banana extracts, fractions and pure compounds were collected using various scholarly databases, such as PubMed, ScienceDirect, and Scopus, based on predetermined selection criteria.ResultsVarious banana extracts, fractions, and phytoconstituents, including ferulic acid, protocatechualdehyde, 2-pentanone, 4-epicyclomusalenone, cycloeucalenol acetate, and chlorogenic acid, have been shown to exhibit cancer preventative and anticancer activities in breast, cervical, colorectal, esophageal, hepatic, oral, prostate, and skin cancers. Bioactive components present in bananas have exhibited antiproliferative, cell cycle arrest-inducing, apoptotic, anti-adhesive, anti-invasive, and antiangiogenic effects through modulation of diverse, dysregulated oncogenic signaling pathways.ConclusionBased on the critical analysis of available literature, banana products and phytoconstituents show enormous potential for future development of drugs for cancer prevention and therapy. However, more mechanistic studies and well-designed clinical trials should be performed to establish its efficacy.

Background Black pepper, the briefly cooked and dried unripe fruits of Piper nigrum L. has broad culinary applications around the world and has been considered as the “king of spices”. In recent years, studies have shown that a diet supplemented with black pepper not only improves digestion but also has anti-oxidant and anti-inflammatory effects as well as the ability to regulate levels of serum lipids. Purpose The objective of this study was to investigate the effects of dietary supplementation with milled black pepper on serum lipoproteins, three anti-oxidant status-related parameters (serum vitamin C, polyphenols, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging capacity), average daily growth, and food intake in growing and fattening pigs. Study design/Methods Two groups of randomly assigned piglets with a body weight of each 30 kg (17 animals per group, 34 animals overall) of Bulgarian Danube White breed were subject to feeding a diet supplemented with or without black pepper. As feed additive, milled black pepper at a dose of 3 g/kg food weight was mixed into standardized food to continuously feed the animals gaining weight to 100 kg. The changes in lipoproteins and anti-oxidant index were examined both in the growing and fatting periods. Results The results of the measured serum profile in the black pepper diet group showed i) a significant increase of high-density lipoprotein (HDL), and ii) a significant increase of vitamin C in comparison with the group fed a normal diet. Supplementation with black pepper also showed a tendency to improve daily food intake and decrease average daily growth of pigs (both without reaching statistical significance) during both the growing period and the fattening period. Conclusion Dietary intake of black pepper might lead to positive effects on blood lipid regulation and anti-oxidant capacity. Overall the gained data in our study suggest that black pepper can be used as a natural food additive to support animal health. Moreover, the results obtained from this porcine model might hint for potential beneficial effects on lipid metabolism in humans and thus warrant further exploratory studies.

Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of atherosclerotic lesions. Targeting foam cell formation in the atherosclerotic lesions can be a promising approach to treat and prevent atherosclerosis. The formation of foam cells is determined by the balanced effects of three major interrelated biologic processes, including lipid uptake, cholesterol esterification, and cholesterol efflux. Natural products are a promising source for new lead structures. Multiple natural products and pharmaceutical agents can inhibit foam cell formation and thus exhibit antiatherosclerotic capacity by suppressing lipid uptake, cholesterol esterification, and/or promoting cholesterol ester hydrolysis and cholesterol efflux. This review summarizes recent findings on these three biologic processes and natural products with demonstrated potential to target such processes. Discussed also are potential future directions for studying the mechanisms of foam cell formation and the development of foam cell-targeted therapeutic strategies.

Recently, a natural compound leoligin, a furan-type lignan, was discovered as an interesting hit compound with an anti-inflammatory pharmacological activity profile. We developed a modular and stereoselective approach for the synthesis of the edelweiss-derived lignan leoligin and used the synthetic route to rapidly prepare leoligin analogs even on the gram scale. Proof of concept of this approach together with cell-based bio-assays gained structural analogs with increased selectivity towards vascular smooth muscle versus endothelial cell proliferation inhibition, a major benefit in fighting vascular neointima formation. In addition, we identified the structural features of leoligin analogs that define their ability to inhibit the pro-inflammatory NF-κB pathway. Results are discussed in the context of structural modification of these novel synthetic lignans.

Intrinsic or acquired drug resistance, adverse drug reactions and tumor heterogeneity between and within cancer patients limit the efficacy of clinical management of advanced cancers. To overcome these barriers, predictive biomarkers have recently emerged to guide medical oncologists in the selection of cancer patients who will respond to various anticancer treatments and to improve the toxicity to benefit ratio. Notably, targeted therapy has significantly benefited from these advances, but the application of predictive biomarkers have been a bit slower with some drugs derived from natural sources such as trabectedin, cabazitaxel and alvocidib. In this paper, we discuss some recent advances regarding the use of cancer biomarkers to predict efficacy of some selected natural compounds with a focus on human clinical studies.

Dihydroquercetin (DHQ), also known as taxifolin, is a natural antioxidant that can be commercially obtained by extraction from Siberian Larch (Larix sibirica). Four wheat-soy based diets, formulated to contain 0, 0.5, 1.5 and 4.5 g/kg of supplementary DHQ were prepared. Each diet was fed ad libitum to birds in seven pens (three birds in each pen) in a randomised block design from 7 to 21 days of age. The effect of DHQ on weight gain was not significant overall (P 0.05), although there was an indication of a linear increase (L 0.05). The blood glutathione peroxidase responded (P 0.001) in a curvilinear manner (L 0.001 and Q 0.05) to increased dietary DHQ. The results from this study indicate that dietary DHQ supplementation may be beneficial at levels greater than 1.5 g/kg feed, due to improved bird antioxidant status. Further research to define an upper inclusion level and optimal timing for phase feeding programmes is warranted.

Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7β-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholesterol and 7β-hydroxycholesterol cause a specific form of cytotoxic activity defined as oxiapoptophagy, including oxidative stress and induction of death by apoptosis associated with autophagic criteria. Oxiaptophagy is associated with organelle dysfunction and in particular with mitochondrial and peroxisomal alterations involved in the induction of cell death and in the rupture of redox balance. As the criteria characterizing 7-ketocholesterol- and 7β-hydroxycholesterol-induced cytotoxicity are often simultaneously observed in major age-related diseases (cardiovascular diseases, age-related macular degeneration, Alzheimer's disease) the involvement of these oxysterols in the pathophysiology of the latter seems increasingly likely. It is therefore important to better understand the signalling pathways associated with the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol in order to identify pharmacological targets, nutrients and synthetic molecules attenuating or inhibiting the cytotoxic activities of these oxysterols. Numerous natural cytoprotective compounds have been identified: vitamins, fatty acids, polyphenols, terpenes, vegetal pigments, antioxidants, mixtures of compounds (oils, plant extracts) and bacterial enzymes. However, few synthetic molecules are able to prevent 7-ketocholesterol- and/or 7β-hydroxycholesterol-induced cytotoxicity: dimethyl fumarate, monomethyl fumarate, the tyrosine kinase inhibitor AG126, memantine, simvastatine, Trolox, dimethylsufoxide, mangafodipir and mitochondrial permeability transition pore (MPTP) inhibitors. The effectiveness of these compounds, several of which are already in use in humans, makes it possible to consider using them for the treatment of certain age-related diseases associated with increased plasma and/or tissue levels of 7-ketocholesterol and/or 7β-hydroxycholesterol.

Aging is associated with a drastic decline in fertility/fecundity and with an increased risk of pregnancy complications. Resveratrol (RES), a natural polyphenolic compound, has shown anti-oxidant and anti-inflammatory activities in both human and animal models, thus representing a potential therapeutic and prophylactic anti-aging supplement. Here, we investigated whether preconceptional resveratrol supplementation improved reproductive outcomes in mid-aged (8-month-old) and old (12-month-old) C57BL/6J female mice. Female siblings were cohoused and assigned to either RES or vehicle supplementation to drinking water for 10 consecutive weeks. Subsequently, females were mated with non-supplemented males and their pregnancy outcomes were monitored. RES improved mating success in old, but not in mid-aged females, and prevented the occurrence of delivery complications in the latter. These results indicate that preconceptional RES supplementation could partially improve age-related reproductive complications, but it was not sufficient to restore fecundity in female mice at a very advanced age.

Cardiovascular diseases are overall the leading cause of mortality and morbidity worldwide. Therefore, treating and preventing coronary heart disease are of high scientific interest. Among several percutaneous coronary intervention procedures, coronary artery stenting displayed potent activity against restenosis, often observed using other invasive therapies. Nowadays, drug eluting stents’ superiority over bare metal stents is increasingly recognizable, since drug eluting stents are able to overcome problems encountered with bare metal stent technology. Within this study, we developed a novel method for performing drug-releasing experiments utilizing an affordable stent model made from a readily available silver-coated copper wire, which was further coated with poly(n-butyl methacrylate). Leoligin, previously reported to inhibit intimal hyperplasia and the regrowth of endothelial cells, was exploited along with several structural analogs in drug-releasing experiments. It was found that compounds exhibiting similar biological activity can have significantly different releasing properties, a crucial parameter to know for the selection of compounds for in vivo studies.

The use of natural antioxidants, in particular polyphenols such as dihydroquercetin (DHQ), in animal nutrition have recently increased in popularity. This may partly be due to the risk of increased incidences of heat stress associated with raising livestock in warmer ambient temperatures, facilitated by global warming, reducing antioxidant capacity. The current research demonstrates the effect of dietary DHQ, vitamin E and standard or high ambient temperatures on growth performance, energy and nutrient metabolism, gastrointestinal tract development (GIT), jejunal villus morphometry and antioxidant status in broiler chickens. Each of the four experimental diets were fed to 16 pens of five birds, which were allocated to four rooms (four pens in each room). The temperature in two rooms was maintained at a constant 35 °C (high temperature; HT), and the temperature in the other two rooms was gradually reduced from 27 °C at 7d of age to 22 °C at 20d of age (standard temperature; ST). Rearing birds at HT reduced: feed intake, weight gain, weight of small intestine, total GIT, liver, spleen, heart, villus height, villus surface area and lowered blood glutationperoxidase (GSH-Px). Dietary DHQ increased blood GSH-Px and total antioxidant status, increased heart weight and reduced caecal size. When fed separately, DHQ and vitamin E improved hepatic vitamin E concentration. Feeding vitamin E increased spleen and liver weights. When fed together, DHQ and vitamin E reduced villus height, villus height to crypt depth ratio and villus surface area. Temperature and antioxidants did not affect energy and nutrient metabolism. There were no effects of dietary antioxidants on growth performance of broiler chickens and there were no mortalities. At present it is unclear if feeding antioxidants (in particular DHQ) at different levels, using different dietary formulations, and rearing birds under a range of environmental conditions may be effective at enhancing production performance and bird health in hot ambient climates.

The ligand-activated farnesoid X receptor is an emerging therapeutic target for the development of drugs against metabolic syndrome-related diseases. In this context, selective bile acid receptor modulators represent a novel concept for drug development. Selective bile acid receptor modulators act in a target gene- or tissue-specific way and are therefore considered less likely to elicit unwanted side effects. Based on leoligin, a lignan-type secondary plant metabolite from the alpine plant Leontopodium nivale ssp. alpinum, 168 synthesized structural analogs were screened in a farnesoid X receptor in silico pharmacophore-model. Fifty-six virtual hits were generated. These hits were tested in a cell-based farnesoid X receptor transactivation assay and yielded 7 farnesoid X receptor-activating compounds. The most active one being LT-141A, with an EC50 of 6 µM and an Emax of 4.1-fold. This analog did not activate the G protein-coupled bile acid receptor, TGR5, and the metabolic nuclear receptors retinoid X receptor α, liver X receptors α/β, and peroxisome proliferator-activated receptors β/γ. Investigation of different farnesoid X receptor target genes characterized LT-141A as selective bile acid receptor modulators. Functional studies revealed that LT-141A increased cholesterol efflux from THP-1-derived macrophages via enhanced ATP-binding cassette transporter 1 expression. Moreover, cholesterol uptake in differentiated Caco-2 cells was significantly decreased upon LT-141A treatment. In conclusion, the leoligin analog LT-141A selectively activates the nuclear receptor farnesoid X receptor and has an influence on cholesterol transport in 2 model systems.

Increased cholesterol efflux from macrophage foam cells in the subendothelial space confers protection against atherosclerosis. Soraphen A, a myxobacterial macrolactone, is an inhibitor of acetyl coenzyme A carboxylases (ACC), which control fatty acid synthesis and oxidation. To assess a potential direct link between macrophage cholesterol efflux and ACC inhibition, we examined [3H]-cholesterol efflux from human THP-1-derived foam cells in the presence of soraphen A. We dissected underlying molecular events by western blot analyses, RT-qPCR, reporter gene and coactivator recruitment assays as well as relative quantification of free and total cholesterol. Soraphen A increased cholesterol efflux from macrophage foam cells via upregulation of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1). Soraphen A enhanced transcription of ABCA1 in an LXR-dependent manner, however, without direct binding to the ligand-binding domain of this nuclear receptor. Soraphen A elevated the cellular level of free cholesterol, and failed to activate LXR upon exogenous supplementation with fatty acids or inhibition of cholesterol synthesis. Thus, impeded conversion from acetyl- to malonyl-CoA by soraphen A may lead to more unesterified cholesterol and thus potential LXR agonists. The present study reveals ACC inhibition as a previously unrecognized mechanism to regulate macrophage cholesterol efflux via indirect LXR activation and ABCA1 upregulation.

Eudragit S100-coated chitosan microspheres (S100Ch) are proposed as a new oral delivery system for green tea polyphenon-60 (PP60). PP60 is a mixture of polyphenolic compounds, known for its active role in decreasing oxidative stress and metabolic risk factors involved in diabetes and in other chronic diseases. Chitosan-PP60 microspheres prepared by an emulsion cross-linking method were coated with Eudragit S100 to ensure the release of PP60 in the terminal ileum. Different core&ndash, coat ratios of Eudragit and chitosan were tested. Optimized chitosan microspheres were obtained with a chitosan:PP60 ratio of 8:1 (Ch-PP608:1), rotation speed of 1500 rpm, and surfactant concentration of 1.0% (m/v) achieving a mean size of 7.16 &micro, m. Their coating with the enteric polymer (S100Ch-PP60) increased the mean size significantly (51.4 &micro, m). The in vitro modified-release of PP60 from S100Ch-PP60 was confirmed in simulated gastrointestinal conditions. Mathematical fitting models were used to characterize the release mechanism showing that both Ch-PP608:1 and S100Ch-PP60 fitted the Korsmeyers&ndash, Peppas model. The antioxidant activity of PP60 was kept in glutaraldehyde-crosslinked chitosan microspheres before and after their coating, showing an IC50 of 212.3 &micro, g/mL and 154.4 &micro, g/mL, respectively. The potential of chitosan microspheres for the delivery of catechins was illustrated, with limited risk of cytotoxicity as shown in Caco-2 cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The beneficial effects of green tea and its derivatives in the management of metabolic disorders can be exploited using mucoadhesive chitosan microspheres coated with enteric polymers for colonic delivery.

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), &alpha, lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson&rsquo, s disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group, striatal 6-OHDA-lesioned control group, and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg, intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation, rotarod, and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.

Fenugreek seeds are widely used in Asia and other places of the world for their nutritive and medicinal properties. In Asia, fenugreek seeds are also recommended for geriatric populations. Here, we evaluated for the first time the effect of fenugreek seed feed supplementation on the liver antioxidant defense systems in aging mice. The study was conducted on 12-months aged mice which were given fenugreek seed dietary supplement. We evaluated the activities of various antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and also estimated the phenolics and free radical scavenging properties in mice liver upon fenugreek supplementation. The estimation of SOD, GPx, and GR activities in aged mice liver revealed a significant (p &lt, 0.01) difference among all the liver enzymes. Overall, this study reveals that fenugreek seed dietary supplementation has a positive effect on the activities of the hepatic antioxidant defense enzymes in the aged mice.

The essential oil from Croton argyrophyllus Kunth is known for its antiproliferative, anti-inflammatory, antinociceptive, and anticancer activities, and is recognized as a source of phytochemicals for potential use in pharmaceutic and food sectors. Solid lipid nanoparticles (SLN) have been produced to load Croton argyrophyllus (CA) Kunth essential oil (CAEO) and its antioxidant properties evaluated in vitro as a new approach for the treatment of neurodegenerative diseases. Cetyl palmitate SLN loading CAEO (CAEO-SLN) with a mean particle size of 201.4 &plusmn, 2.3 nm (polydispersity index 0.211) have been produced by hot high-pressure homogenisation. The release of the oil followed the Korsmeyers-Peppas model. The risk of lipid peroxidation has been determined by applying the production of thiobarbituric acid-reactive substances (TBARS) standard assay. The antioxidant activity was determined by the capacity of the antioxidants existing in CAEO to scavenge the stable radical DPPH&bull, The cytotoxicity of CA Kunth essential oil-loaded SLN (CAEO-SLN) was evaluated in a human cell line SH-SY5Y (derived from human neuroblastoma) by determining the reduction of the yellow dye 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). Both free essential oil (fEO) and loaded essential oil (CAEO-SLN) were demonstrated to inhibit the Fenton reaction. CAEO-SLN showed DPPH&bull, radical scavenging capacity. The loading of the oil into cetyl palmitate SLN reduced the risk of cytotoxicity.

We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde 1,2-epoxide-loaded cationic SLN (cPa-SLN), with a mean particle size (z-Ave) of 275.31 &plusmn, 4.78 nm and polydispersity index (PI) of 0.303 &plusmn, 0.081, were produced by high shear homogenization. An encapsulation efficiency of cPa-SLN above 80% was achieved. The release of perillaldehyde 1,2-epoxide from cationic SLN followed the Korsemeyer&ndash, Peppas kinetic model, which is typically seen in nanoparticle formulations. The lipid peroxidation of cPa-SLN was assessed by the capacity to produce thiobarbituric acid-reactive substances, while the antioxidant activity was determined by the capacity to scavenge the stable radical DPPH. The surface functionalization of cPa-SLN with the antibody was done via streptavidin-biotin interaction, monitoring z-Ave, PI and ZP of the obtained assembly (cPa-SLN-SAb), as well as its stability in phosphate buffer. The effect of plain cationic SLN (c-SLN, monoterpene free), cPa-SLN and cPa-SLN-SAb onto the MCF-7 cell lines was evaluated in a concentration range from 0.01 to 0.1 mg/mL, confirming that streptavidin adsorption onto cPa-SLN-SAb improved the cell viability in comparison to the cationic cPa-SLN.

In recent years, there has been a great deal of attention toward the molecular machinery relevant to age-related progression controlled through the external intervention of polyphenols- an epigenetic-modulating diet. Natural products modulate cellular longevity through histone post-translational modification and can also induce the upregulation of autophagy, thus reducing the level of acetyl coenzyme A (AcCoA). In addition, the effect of caloric restriction (CR) on cancer-related chronic inflammation is of great significance in aging. In line with this, SIRT1 protein levels are expanded in response to calorie restriction mimetics (CRM), in this way acting as autophagy inducers relevant to cancer prevention.

Phytol (PYT) is a diterpene member of the long-chain unsaturated acyclic alcohols. PYT and some of its derivatives, including phytanic acid (PA), exert a wide range of biological effects. PYT is a valuable essential oil (EO) used as a fragrance and a potential candidate for a broad range of applications in the pharmaceutical and biotechnological industry. There is ample evidence that PA may play a crucial role in the development of pathophysiological states. Focusing on PYT and some of its most relevant derivatives, here we present a systematic review of reported biological activities, along with their underlying mechanism of action. Recent investigations with PYT demonstrated anxiolytic, metabolism-modulating, cytotoxic, antioxidant, autophagy- and apoptosis-inducing, antinociceptive, anti-inflammatory, immune-modulating, and antimicrobial effects. PPARs- and NF-κB-mediated activities are also discussed as mechanisms responsible for some of the bioactivities of PYT. The overall goal of this review is to discuss recent findings pertaining to PYT biological activities and its possible applications.

Natural products are gaining much momentum worldwide because they have a broad spectrum of biological effects and present excellent opportunities for bioproducts development. With this fact, this study has been designed to investigate for the first time the effects of the ethyl acetate (EA), methanolic (MeOH), and water (W) extracts of Lotus aegaeus (La) and Iberis sempervirens (Is) on key enzymes as well as to quantify antioxidant capacities. The total phenolic and flavonoid content were determined using colorimetric methods and the individual phenolic compounds were assessed by LC–MS/MS analysis. Quercetin hexoside was the dominant compound in L. aegaeus, particularly in methanol extract, while the ethyl acetate and methanol extracts of I. sempervirens were characterized by the presence scopoletin and hinic acid. The antioxidant abilities of the investigated extracts were tested using different assays including free radical scavenging, reducing power, phosphomolybdenum, and metal chelating. All the extracts showed strong antioxidant abilities. For both species, the ethyl acetate extracts were more potent against cholinesterases and α-amylase, while the methanol extracts were most active against α-glucosidase. Only the water extract, followed by methanol of I. sempervirens exhibited notable inhibitory activity against tyrosinase. In addition, the dominant compounds were docked against tyrosinase and α-glucosidase to investigate their predicted binding affinity and interactions with the active site. In conclusion, L. aegaeus and I. sempervirens showed potent biological attributes, which advocates for further studies to explore their potential use as phytopharmaceuticals.

Alkaloids are well-studied secondary metabolites, with recent preclinical studies evidencing that many of them exhibit anti-cancer, anti-depressant, anti-nociceptive, anti-inflammatory, anti-pyretic, anti-platelet, anti-oxidant, and anti-bacterial properties. Aconitum is a genus rich of diverse alkaloids. More than 450 alkaloids have been identified in a variety of species. Songorine is a C20 diterpenoid alkaloid and 12-keto analog of napelline, isolated from Aconitum soongaricum and was associated with a heterogeneous panel of biological functions. However, the bioactivity profile of this natural product has not been reviewed up to now. The present manuscript aims to summarize the most important biological activities associated with songorine administration in preclinical models. The most significant data found in the scientific literature were evaluated in order to summarize the potential clinical utility of songorine in a diverse spectrum of pathologies and conditions. Songorine and its derivatives have many pharmacological effects including anti-arrhythmic, anti-cardiac-fibrillation, excitation of synaptic transmission, anxiolytic effects, anti-nociceptive, anti-inflammatory, anti-arthritis effects, and a regenerative effect in a skin excision wound animal model. Despite its outstanding pharmacotherapeutic potential, songorine has never been tested in clinical trials. Therefore, further evaluation is required to better evaluate its clinical utility.

Mechanisms how colorectal cancer (CRC) cells penetrate blood micro-vessel endothelia and metastasise is poorly understood. To study blood endothelial cell (BEC) barrier breaching by CRC emboli, an in vitro assay measuring BEC-free areas underneath SW620 cell spheroids, so called “circular chemorepellent induced defects” (CCIDs, appearing in consequence of endothelial retraction), was adapted and supported by Western blotting, EIA-, EROD- and luciferase reporter assays. Inhibition of ALOX12 or NF-κB in SW620 cells or BECs, respectively, caused attenuation of CCIDs. The FDA approved drugs vinpocetine [inhibiting ALOX12-dependent 12(S)-HETE synthesis], ketotifen [inhibiting NF-κB], carbamazepine and fenofibrate [inhibiting 12(S)-HETE and NF-κB] significantly attenuated CCID formation at low μM concentrations. In the 5-FU-resistant SW620-R/BEC model guanfacine, nifedipine and proadifen inhibited CCIDs stronger than in the naive SW620/BEC model. This indicated that in SW620-R cells formerly silent (yet unidentified) genes became expressed and targetable by these drugs in course of resistance acquisition. Fenofibrate, and the flavonoids hispidulin and apigenin, which are present in medicinal plants, spices, herbs and fruits, attenuated CCID formation in both, naive- and resistant models. As FDA-approved drugs and food-flavonoids inhibited established and acquired intravasative pathways and attenuated BEC barrier-breaching in vitro, this warrants testing of these compounds in CRC models in vivo.

Concanavalin A (ConA)-induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease is characterized by increase in serum levels of transaminases and massive immune infiltration of the livers. Type 1, type 2, and type 17 cytokines play a pathogenic role in the development of ConA-induced hepatitis. To understand further the immunoregulatory mechanisms operating in the development and regulation of ConA-induced hepatitis, we have evaluated the role of the anti-inflammatory pathway Nrf2/HO-1/CO (Nuclear Factor E2-related Factor 2/Heme Oxygenase-1/Carbon Monoxide) in this condition and determined whether the in vivo administration of CO via the CO-releasing molecule (CORM) CORM-A1, influences serological and histological development of Con-A-induced hepatitis. We have firstly evaluated in silico the genes belonging to the Nrf2/HO-1/CO pathway that are involved in the pathogenesis of autoimmune hepatitis (AIH). The data obtained from the in silico study demonstrate that a significant number of genes modulated in the liver of ConA-challenged mice belong to the Nrf2 pathway; on the other hand, the administration of CORM-A1 determines an improvement in several sero-immunological and histological parameters, and it is able to modulate genes identified by the in silico analysis. Collectively, our data indicate that the Nrf2/HO-1/CO pathway is fundamental for the regulation of the immune responses, and that therapeutic intervention aimed at its modulation by CORM-A1 may represent a valuable strategy to be considered for the treatment of autoimmune hepatitis in humans.

Citrinin (CIT) is a mycotoxin which causes contamination in the food and is associated with different toxic effects. A web search on CIT has been conducted covering the timespan since 1946. The accumulated data indicate that CIT is produced by several fungal strains belonging to Penicillium, Aspergillus and Monascus genera, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is evident that CIT exposure can exert toxic effects on the heart, liver, kidney, as well as reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. It is still controversial what are the genotoxic and mutagenic effects of CIT. Until now, its toxic effect has been linked to the CIT-mediated oxidative stress and mitochondrial dysfunction in biological systems. However, the toxicity strongly depends on its concentration, route, frequency and time of exposure, as well as from the used test systems. Besides the toxic effects, CIT is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro. This systematic review presents the current state of CIT research with emphasis on its bioactivity profile.

Background Neanotis wightiana (Wall. ex Wight & Arn) W.H. Lewis has been used in traditional medicine in India for the treatment of liver disorders. In fact, this plant is frequently used by the local people of Tripura for the treatment of liver disorder problems. In previous study on this plant we have isolated a hepatoprotective saponin, neanoside A. Purpose Evaluation of in vivo hepatoprotective effects of isolated compounds from N. wightiana aerial parts on serum hepatic-biomarkers in CCl4- induced hepatotoxicity in rats to validate the traditional use of the plant. Study design This study was designed to isolate more hepatoprotective compounds from N. wightiana aerial parts and evaluate their in vivo hepatoprotective activity in animal model. Methods The phytochemicals from the polar n-butanol fraction of methanolic extract of N. wightiana aerial parts were isolated by repeated column chromatography over Diaion HP-20 and silica gel. Among the isolated three compounds, two were known triterpenoids, ursolic acid and oleanolic acid. The new compound was named neanoside B and its structure was established as naphthalene diglucoside 1 on the basis of extensive spectroscopic (including 2D NMR) analysis. Furthermore, the hepatoprotective activity of 1 was evaluated on CCl4 -induced hepatic injured rats by oral administration at three doses (5, 10 mg and 20 mg/kg) for 7 d and the assay of serum hepatic injury marker enzymes, SGPT, SGOT, ALP and bilirubin contents and histopathological changes of injured liver tissue after 7 d The herbal hepatoprotective drug, silymarin (100 mg/kg) was as positive control. Results The structure of the new compound, neanoside B (1) was elucidated as 1,4-dihydroxy-2-(methoxymethyl)naphthalen-3-yl-methyl-3-β- d -glucopyranosyl-(1→6)-β- d -glucopyranoside on the basis of extensive spectroscopic (including 2D-NMR) and chemical studies. The compound 1 exhibited significant in vivo hepatoprotective effect at the tested doses of 5, 10 and 20 mg/kg bw in CCl4-induced hepatotoxicity in rats. In a dose-dependent manner, 1 normalized the elevated levels of hepatic injury marker enzymes, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin and ameliorated the damage of liver tissue by reducing the necrosis and vacuoles. Possibly compound 1 ameliorated the hepatic damage in hepatotoxic rats by improving the antioxidant status. The higher dose (20 mg/kg) showed more hepatoprotective effect by reducing the elevated levels of SGPT, SGOT, ALP and bilirubin content to 388.5 ± 2.156, 160.7 ± 3.00, 198.6 ± 4.562 and 0.652 ± 0.036 IU/ml, respectively, compared to the levels in the control group (583.2 ± 6.922, 324.6 ± 4.711, 263.9 ± 4.939 and 1.533 ± 0.042 IU/ml, respectively) and the effect was comparable to that of the positive control silymarin (100 mg/kg bw) (389.4 ± 6.348, 167.9 ± 4.289, 203.3 ± 4.448 and 0.816 ± 0.030 IU/ml, respectively). Conclusions This study indicated that isolated neanoside B (1) from Neanotis wightiana could be a potential drug in liver disorders. Further study in pharmacokinetics and long-term toxicity of compound 1 is requested for its clinical setting as effective drug in liver disorders.

A new method based on reverse-phase HPLC combined with photodiode array (PDA) was developed to quantify the release of trans-resveratrol (tRES) from solid lipid nanoparticles (SLN). The mobile phase was composed of 75:0:25 (V/V) water/methanol/acetonitrile at 03.5 min, 32.5:30.0:37.5 (V/V) water/methanol/acetonitrile at 3.65.8 min, and 75:0:25 (V/V) water/methanol/acetonitrile at 5.910 min. The flow rate was set at 1.0mL/min, and tRES was detected at the wavelength of 306.6 nm. A concentration range of 1100 µg/mL was used to obtain the linear calibration curve. SLN were produced by ultrasound technique to load 0.1% (wt/wt) of tRES, and the in vitro release of the drug was run in modified Franz diffusion cells. The mean recovery of tRES was found to be 96.84 ± 0.32%. The intra-assay and inter-assay coefficients of variation were less than 5%. The proposed method was applied to in vitro permeability studies, and the Weibull model was found to be the one that best fits the tRES release, which is characterized by a simultaneous lipid chain relaxation and erosion during drug release., The authors wish to acknowledge the financial support from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo). The financial support was also received from The Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project M-ERA-NET-0004/2015-PAIRED, co-financed by FEDER, under the Partnership Agreement PT2020. Authors also thank the support of the project: Nutraceutica come supporto nutrizionale nel paziente oncologico; CUP: B83D18000140007., info:eu-repo/semantics/publishedVersion