Natural Bioactives Research Articles

Prediction, Discovery, and Characterization of Plant- and Food-Derived Health-Beneficial Bioactive Peptides.

Nature may have the answer to many of our questions about human, animal, and environmental health. Natural bioactives, especially when harvested from sustainable plant and food sources, provide a plethora of molecular solutions to nutritionally actionable, chronic conditions. The spectrum of these conditions, such as metabolic, immune, and gastrointestinal disorders, has changed with prolonged human life span, which should be matched with an appropriately extended health span, which would in turn favour more sustainable health care: "adding years to life and adding life to years". To date, bioactive peptides have been undervalued and underexploited as food ingredients and drugs. The future of translational science on bioactive peptides-and natural bioactives in general-is being built on (a) systems-level rather than reductionist strategies for understanding their interdependent, and at times synergistic, functions; and (b) the leverage of artificial intelligence for prediction and discovery, thereby significantly reducing the time from idea and concept to finished solutions for consumers and patients. This new strategy follows the path from benefit definition via design to prediction and, eventually, validation and production.

Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense.

Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (±)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.

Nature has the answers: Discovering and validating natural bioactives for human health

Nature has the answer to many of our questions about human health. Natural bioactives, especially when derived from sustainable plant and food sources, provide a plethora of molecular solutions to nutritionally actionable, chronic conditions. The spectrum of these conditions, such as metabolic, immune, and gastrointestinal disorders, has changed with prolonged human life span, which should be matched with an appropriately extended health span: “adding years to life and adding life to years”. Natural bioactives can be classified into micronutrients (i.e., vitamins, and minerals), phytonutrients, bioactive peptides,and pre-, pro-, post- and synbiotics. Bioactives act in concert and interact with the human host and its (gut) microbiome. Therefore, the future of translational science on natural bioactives is being built on a: (a) systems-level rather than reductionist approaches to understanding their interdependent, and at times additive functions, as well as their interactions with the human host and (gut) microbiome; and (b) the leverage of artificial intelligence for discovery and validation, thereby substantially reducing the time from idea and concept to finished solutions for consumers and patients. Rather than focusing on a particular class of bioactive food molecules, as often done in molecular food and nutrition articles, this review embraces a broad range of these bioactives and puts them into perspective regarding a more efficient and sustainable leverage of the biochemical richness of plants and foods for its diverse positive effects on human health.Keywords: bioactive, micronutrient, phytonutrient, prebiotic, probiotic, synbiotic, peptide, artificial intelligence, discovery, validation

Multiple Cancer Combating by Natural Bioactives: A Review

Background: Significant progress in the field of anticancer research has led to a rise in the study of bioactive chemicals with potential anticancer effects. Still, many bioactive natural chemicals must be investigated in order to generate more effective anti-cancer therapeutics. Outline: There have been many attempts to treat cancer, and this review summarizes many bioactive substances obtained from nature that have the ability to fight against different types of malignancies with minimal harm, based on diverse research. Polyphenolic flavonoids, carotenoid (fucoxanthin), tannin, and other notable natural bioactive with anticancer potential were examined and reviewed systematically with an eye toward their significance in many types of cancer treatment. Conclusion: Throughout the text, it was concluded that the natural bioactive play a very prominent role in combating different types of cancer, and the information related to the bioactive role in cancer treatment over the last 10 years was gathered from several research and review articles. The material kept in this paper can act as a template for future research in expressing the more beneficial role of other bioactive in acting as an adjuvant in chemotherapy practice for prevention and treatment of various cancer additionally with no or minimal adverse effects which are prominent with the conventional drugs used for the treatment of cancer.

Effects of the seasonal variation in the phytochemical composition and bioactivities of the wild halophyte Suaeda fruticosa

Suaeda fruticosa is an edible medicinal species belonging to the Amaranthaceae (Chenopodiaceae) family widely distributed in the Mediterranean regions, especially in Tunisia. This species shoots change their colour from green to red-violet along the different seasons, being an interesting matrix to study for its chemical composition. Therefore, in a ground-breaking study, the hydromethanolic extracts of green and red-violet Tunisian S. fruticosa shoots were profiled for their individual phenolic compounds and betalains by High Performance Liquid Chromatography coupled with a Diode-Array Detector and Mass Spectrometry by Electrospray Ionization (HPLC-DAD/ESI-MS), and the in vitro antioxidant, antibacterial, and hepatotoxic properties were also assessed. The obtained results revealed that the hydromethanolic extracts contain interesting levels of phenolic compounds especially O-glycosylated and acylated flavonoids, while betacyanins were the main betalain compounds found. As expected, red-violet shoots were richer in phenolic compounds (45.5 ± 0.2 mg/g extract) and betalains (33.3 ± 0.2 mg/g extract) than greener shoots. Flavonoid/betalains rich extracts presented lower EC50 values for ABTS+, DPPH, and TBARS; as also lower MIC values against Gram-positive bacteria. This study showed that the wild halophyte growing in a hard environment, were drought and salinity are dominant, is an important source of flavonoids and betanin, important molecules that can find application in different industries, given the constant demands for natural bioactives and colouring compounds. Overall, these natural compounds may be valorised and further investigated to validate their potential as functional ingredients.

Lipid-Based Nanoparticulate Systems for the Ocular Delivery of Bioactives with Anti-Inflammatory Properties.

The complexity of the eye structure and its physiology turned ocular drug administration into one of the most challenging topics in the pharmaceutical field. Ocular inflammation is one of the most common ophthalmic disorders. Topical administration of anti-inflammatory drugs is also commonly used as a side treatment in tissue repair and regeneration. The difficulty in overcoming the eye barriers, which are both physical and chemical, reduces drug bioavailability, and the frequency of administration must be increased to reach the therapeutic effect. However, this can cause serious side effects. Lipid nanoparticles seem to be a great alternative to ocular drug delivery as they are composed from natural excipients and can encapsulate both hydrophilic and lipophilic drugs of different sources, and their unique properties, as their excellent biocompatibility, safety and adhesion allow to increase the bioavailability, compliance and achieve a sustained drug release. They are also very stable, easy to produce and scale up, and can be lyophilized or sterilized with no significant alterations to the release profile and stability. Because of this, lipid nanoparticles show a great potential to be an essential part of the new therapeutic technologies in ophthalmology to deliver synthetic and natural anti-inflammatory drugs. In fact, there is an increasing interest in natural bioactives with anti-inflammatory activities, and the use of nanoparticles for their site-specific delivery. It is therefore expected that, in the near future, many more studies will promote the development of new nanomedicines resulting in clinical studies of new drugs formulations.

Saccorhiza polyschides-A Source of Natural Active Ingredients for Greener Skincare Formulations.

The growing knowledge about the harmful effects caused by some synthetic ingredients present in skincare products has led to an extensive search for natural bioactives. Thus, this study aimed to investigate the dermatological potential of five fractions (F1–F5), obtained by a sequential extraction procedure, from the brown seaweed Saccorhiza polyschides. The antioxidant (DPPH, FRAP, ORAC and TPC), anti-enzymatic (collagenase, elastase, hyaluronidase and tyrosinase), antimicrobial (Staphylococcus epidermidis, Cutibacterium acnes and Malassezia furfur), anti-inflammatory (nitric oxide, tumor necrosis factor-α, interleukin-6 and interleukin-10) and photoprotective (reactive oxygen species) properties of all fractions were evaluated. The ethyl acetate fraction (F3) displayed the highest antioxidant and photoprotective capacity, reducing ROS levels in UVA/B-exposed 3T3 fibroblasts, and the highest anti-enzymatic capacity against tyrosinase (IC50 value: 89.1 µg/mL). The solid water-insoluble fraction (F5) revealed the greatest antimicrobial activity against C. acnes growth (IC50 value: 12.4 µg/mL). Furthermore, all fractions demonstrated anti-inflammatory potential, reducing TNF-α and IL-6 levels in RAW 264.7 macrophages induced with lipopolysaccharides. Chemical analysis of the S. polyschides fractions by NMR revealed the presence of different classes of compounds, including lipids, polyphenols and sugars. The results highlight the potential of S. polyschides to be incorporated into new nature-based skincare products.

An Updated Review on Biologically Promising Natural Oxepines.

Benzo-oxepines and dibenzo-oxepines, a unique class of naturally occurring secondary metabolites, are distributed mainly in plants and fungi and have received much attention from phytochemists and biologists based on their fascinating structural features and health-promoting functions. This review summarizes 100 oxepine derivatives comprising three categories: benzo-oxepine, dibenzo-oxepine, and pyrano-oxepine. Studies on various structural features and pharmacological activities of oxepine derivatives promote further in-depth research on these potent natural products. This review portrays the natural occurrence, bioactivity and biosynthesis of oxepines reported from 1984 to 2021.

Is the Role of Hepcidin and Erythroferrone in the Pathogenesis of Beta Thalassemia the Key to Developing Novel Treatment Strategies?

Thalassemia is a disease of erythrocytes that varies largely on its genetic composition and associated clinical presentation. Though some patients may remain asymptomatic, those with a complicated course may experience severe anemia early in childhood, carrying into adulthood and requiring recurrent blood transfusions as a pillar of symptom management. Due to the consequences of ineffective erythropoiesis and frequent transfusions, patients with severe beta thalassemia may be subsequently susceptible to hemochromatosis. In light of the established role of hepcidin and erythroferrone in the pathogenesis of beta thalassemia, this review aims to discuss current clinical trials and studies in the field while presenting clinical implications of the HAMP gene polymorphisms and novel treatments. Research suggested incorporating erythroferrone and serum hepcidin testing as a part of routine workups for beta thalassemia, as they could be a predictive tool for early iron accumulation. Furthermore, ameliorating low hepcidin and high erythroferrone appeared to be crucial in treating beta thalassemia and its complications due to iron overload. Currently, hepcidin-like compounds, such as minihepcidins, LJPC-401, PTG-300, VIT-2763, and agents that promote hepcidin production by inhibiting TMPRSS6 expression or erythroferrone, were shown to be effective in restoring iron homeostasis in preliminary studies. Moreover, the natural bioactives astragalus polysaccharide and icariin have been recently recognized as hepcidin expression inductors.

Natural bioactives in the management of hyperuricemia

Hyperuricemia, also known as gout, has been identified as a well-known metabolic disorder associated with an elevated uric acid level in serum. Gout is commonly associated with various chronic disorders like hypertension, obesity, hyperlipidemia, cardiovascular disorders, and diabetes. Drugs, like nonsteroidal anti-inflammatory medications [NSAIDs] and glucocorticoids, are shown to exhibit serious side effects, when used in this therapy, although they are the first-line of treatment options available to date. Bioactive compounds have been explored for the management of hyperuricemia for their effectiveness and ability to minimize complications. Related research have reported the use of plant-based bioactives on hyperuricemia. The objective of the present review is to highlight the therapeutic effect of the naturally occurring phytochemicals and the pharmacology of the compounds involved in the same. These phytochemicals are categorized into five classes, namely alkaloids, flavonoids, saponins, and phenolic acids, that describe their anti-gout activity. Additionally, the mechanism of action by which these bioactive compounds display the hypouricemic consequences has been divided into three parts, namely, the inhibition of the production of uric acid, lowering of intestinal uric acid secretion, and enhancement of elimination of renal uric acid.

Dynamically crosslinked protien hydrogel composite as multifunctional wound dressing for cutaneous infection

In this work, we reported a dynamic hydrogel with sodium houttuyfonate (SH) for management of infected skin injuries. The hydrogel was designed by reversible crosslinking of phenylboronic acid-modified gelatin with diol-rich polyvinyl alcohol. Due to the reversible interactions between phenylboronic acid and diols, the resultant hydrogel exhibited typical dynamic nature including self-recovery and injectability. When the hydrogel was loaded SH, a highly shape-adapted, bactericidal and pro-healing hydrogel wound dressing was obtained. In vitro and in vivo experiments demonstrated that the SH-loaded hydrogel could significantly suppress infection and accelerate infected skin wound healing. It was further revealed that the improved wound healing depended on not only SH-assisted antibacterial ability but also the pro-healing effect caused by HIF-1α-associated antioxidative activity. Due to the dynamic of our hydrogel and the natural bioactivity of SH, this multifunctional wound dressing shows great potential as anti-infective and pro-healing tissue protective materials for management of skin infection.

A Cosmeceutical Topical Water-in-Oil Nanoemulsion of Natural Bioactives: Design of Experiment, in vitro Characterization, and in vivo Skin Performance Against UVB Irradiation-Induced Skin Damages.

IntroductionDamage to human skin occurs either chronologically or through repetitive exposure to ultraviolet (UV) radiation, where collagen photodegradation leads to the formation of wrinkles and skin imperfections. Consequently, cosmeceutical products containing natural bioactives to restore or regenerate collagen have gained a remarkable attention as an ameliorative remedy.MethodsThis study aimed to develop and optimize collagen-loaded water-in-oil nanoemulsion (W/O NE) through a D-optimal mixture design to achieve an ideal multifunctional nanosystem containing active constituents. Vit E was included as a constituent of the formulation for its antioxidant properties to minimize the destructive impact of UV radiation. The formulated systems were characterized in terms of their globule size, optical clarity, and viscosity. An optimized system was selected and evaluated for its physical stability, in vitro wound healing properties, and in vivo permeation and protection against UV radiation. In addition, the effect of collagen-loaded NE was compared to Vit C-loaded NE and collagen-/Vit C-loaded NEs mixture as Vit C is known to enhance collagen production within the skin.ResultsThe optimized NE was formulated with 25% oils (Vit E: safflower oil, 1:3), 54.635% surfactant/cosurfactant (Span 80: Kolliphor EL: Arlasolve, 1:1:1), and 20.365% water. The optimized NE loaded with either collagen or Vit C exhibited a skin-friendly appearance with boosted permeability, and improved cell viability and wound healing properties on fibroblast cell lines. Moreover, the in vivo study and histopathological investigations confirmed the efficacy of the developed system to protect the skin against UV damage. The results revealed that the effect of collagen-/Vit C-loaded NEs mixture was more pronounced, as both drugs reduced the skin damage to an extent that it was free from any detectable alterations.ConclusionNE formulated using Vit E and containing collagen and/or Vit C could be a promising ameliorative remedy for skin protection against UVB irradiation.

Selenium-Enriched Mushroom Powder Enhances Intestinal Health and Growth Performance in the Absence of Zinc Oxide in Post-Weaned Pig Diets.

Simple SummaryThe imminent ban on zinc oxide in pig diets within the European Union is a major challenge facing the swine industry. Commercial weaning is associated with abrupt dietary, environmental and social changes resulting in stress, reduced feed intake and gut developmental issues in the post-weaned pig. Mushrooms are rich in natural bioactives and have long been regarded as a health-promoting food due to their immunomodulatory and antioxidant effects and their ability to modulate the gut microbiota. Mushrooms can become abundant in organic selenium when grown under certain conditions. The present study aimed to determine the optimum Se level, using Se-enriched mushrooms and selenite, in weaned pig diets to enhance intestinal health, performance and antioxidant capacity. Our study demonstrated that 0.3 ppm selenium inclusion, using selenium-enriched mushroom powder, led to positive effects on faecal scores and had similar pig performance compared to zinc oxide during the first 21 days post-weaning. The selenium inclusion level of 0.6 ppm, using selenium-enriched mushroom powder and selenite, enhanced pig performance and aspects of gastrointestinal health during days 21 and 39 post-weaning.This study was conducted to examine the effects of varying selenium (Se) inclusion levels, in the form of Se-enriched mushroom powder (SeMP) and selenite, on post-weaning growth performance (Period 1; day 1–21), intestinal health and antioxidant capacity (Period 2; day 21–39). Weaned pigs were blocked according to live weight, sex and litter of origin and randomly assigned to the following experimental groups: basal (basal + selenite (0.3 ppm Se)); ZnO (basal + ZnO + selenite (0.3 ppm Se)); 0.15 SeMP (basal + SeMP (0.15 ppm Se)); 0.3 SeMP (basal + SeMP (0.3 ppm Se)) and 0.6 SeMP/Sel (basal + SeMP (0.3 ppm Se) + selenite (Sel) (0.3 ppm Se)) with eight replicates/experimental group. After 21 days, the ZnO experimental group was removed from the experiment and the remaining pigs continued on their respective diet until day 39 post-weaning (Period 2). In Period 1, 0.15 SeMP supplementation reduced (p < 0.05) average daily gain (ADG), average daily feed intake (ADFI) and day 21 body weight, and increased (p < 0.05) faecal scores compared to the ZnO group. Supplementation with 0.3 SeMP and 0.6 SeMP/Sel during Period 1 resulted in similar (p > 0.05) ADG, ADFI, gain-to-feed ratio (G:F) and body weight compared to the ZnO group. However, 0.6 SeMP/Sel supplementation increased (p < 0.05) faecal scores compared to the ZnO group. In Period 2, 0.6 SeMP/Sel increased (p < 0.05) ADG, feed efficiency and day 39 body weight compared to the basal group. Supplementation with Se-enriched mushroom powder, at all inclusion levels, increased (p < 0.05) the abundance of Prevotellaceae and Prevotella, decreased (p < 0.05) the abundance of Sporobacter and increased (p < 0.05) the expression of SELENOP in the jejunum compared to the basal group. Lactobacillaceae and Lactobacillus was increased (p < 0.05) in 0.15 SeMP and 0.3 SeMP pigs compared to the basal group. Selenium deposition in muscle and liver tissue increased (p < 0.001) as a function of inclusion level while pigs supplemented with 0.3 ppm organic Se (0.3 SeMP) had an increase (p < 0.05) in total Se in the muscle compared to pigs supplemented with 0.3 ppm inorganic Se (basal). In conclusion, 0.3 SeMP supplementation led to positive effects on faecal scores and had similar pig performance compared to ZnO in Period 1, while the addition of 0.3 ppm selenite to 0.3 SeMP (0.6 SeMP/Sel) in Period 2 led to enhanced pig performance and aspects of gastrointestinal health.

Bioactives From Coffee By-Products Stimulate Liver Metabolism and Mitochondrial Bioenergetics via AMPK/PGC-1α/Nrf2 and IRS/AKT/GLUT2 Pathways In Vitro

ObjectivesThis study aimed to investigate the effect of the main bioactive compounds from the coffee silverskin and coffee husk on hepatic lipid and glucose metabolism and mitochondrial bioenergetics using an in vitro model mimicking non-alcoholic fatty liver disease. MethodsHepG2 cells were treated with 50 μmol L–1 caffeine, chlorogenic, caffeic, protocatechuic, or gallic acids, or kaempferol, or the aqueous extracts from the coffee silverskin (CSE, 100 μg mL–1) or the coffee husk (CHE, 100 μg mL–1) in the presence of palmitic acid (500 μmol L–1). Cell metabolism biomarkers were assessed 24 h after the co-treatment in cell lysates and supernatants using chemical and immunochemical techniques. Differences among treatments were considered significant at p < 0.05. ResultsBioactive compounds in coffee by-products, CSE, and CHE decreased lipid accumulation (53–115%) by reducing fatty acid synthase expression (44–76%) and stimulated β-oxidation by triggering carnitine palmitoyltransferase I activity (1.6 to 2.6-fold) and up-phosphorylating AMP-activated protein kinase (AMPK, 1.5–2.4-fold). Glucose uptake was promoted via the increase in the insulin receptor substrate (IRS)-1 (1.5 to 2.1-fold) and protein kinase B (Akt1, 1.7–2.4-fold) phosphorylation, and glucose transporter (GLUT)-2 expression (2.1 to 3.7-fold). Mitochondrial function was enhanced (ATP production and O2 consumption rate, 1.7–2.5-fold and 1.8 to 2.5-fold, respectively), and oxidative phosphorylation complexes and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α expression restored (30–105%). Oxidative stress was diminished (56 – 85%) through augmented superoxide dismutase (1.3 to 1.7-fold) and catalase (1.5 to 2.0-fold) activities, and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression (2.3 to 3.8-fold). ConclusionsThe major bioactive compounds in coffee by-products, primarily chlorogenic and protocatechuic acids, could regulate hepatic lipid and glucose metabolism and prevent oxidative stress and mitochondrial dysfunction by activating AMPK/PGC-1α/Nrf2 and IRS/AKT/GLUT2 signaling pathways. Altogether, our results suggest the use of coffee by-products as a sustainable source of natural bioactives to counteract non-alcoholic fatty liver disease. Funding SourcesUSDA-NIFA-HATCH and the Spanish Ministry of Science and Innovation.

Characterization of lipid extracts from the Hermetia illucens larvae and their bioactivities for potential use as pharmaceutical and cosmetic ingredients

There is an increasingly growing demand for the use of natural and sustainable bioactives in the field of the pharmaceutical and cosmetic industries. The biomass from black soldier fly larvae (Hermetia illucens) can be viewed as an innovative source of compounds with high aggregate value and marketing potential due to the sustainable organic matter bioconversion process used as substrate for its development. This insect can be a source of lipid compounds with high added value, mainly due to its high content in fatty acids (FA) with potential applicability in the pharmaceutical and cosmetic industry. In this context, in this work different extraction methods were tested (decoction, microwaves, maceration and ultrasound), using water, acetone, n-hexane as extraction solvents, to evaluate yields of the BSF larvae lipid extracts, as well as their lipid profile, and a preliminary safety screening was conducted. Results show that despite using different extraction techniques and solvents, similar FA composition profiles were obtained. The lauric acid content (C12: 0) is elevated in all the extracts in relation to the other FA, ranging 37%–62%. The contents in palmitic (C16: 0) and oleic (C18: 1n-9) acids, were also high in all applied extraction methods. The omega-6 FA (ω-6 PUFAs), mainly linoleic acid (C18: 2n6c), were also identified in the lipid fraction of BSF larvae biomass, with a content variation between 4.5% and 17.7%, while the omega-3 group, namely α-Linolenic acid (C18: 3n3), presented values between 0.66% and 1.95%. None of the extracts presented toxicity in preliminary tests with the Artemia salina model. Through this study, it was possible to confirm that BSF larvae oil can be obtained by sustainable methods, containing a broad mixture of FA and being highly rich in lauric acid, with a promising skin care applicability.

Natural bioactives versus synthetic antibiotics for the attenuation of quorum sensing-regulated virulence factors of Pseudomonas aeruginosa.

Aim: To study the influence of plant volatiles, bioactives and synthetic antibiotics on the attenuation of the quorum sensing (QS)-regulated virulence factors of Pseudomonas aeruginosa. Materials & methods: QS inhibition; the QS-regulated virulence factors pyocyanin, hemolysin, elastase, protease, alginate and pyochelin; and motility phenotypes were performed at sub-MIC to check the attenuation effect of 24 agents on the virulence of P. aeruginosa. Results: Eighteen out of 24 assayed compounds exhibited anti-QS activity and reduced the production of all virulence factors. Cinnamaldehyde, zingerone and lavender oil exhibited a significant reduction in motility phenotypes. Conclusion: Natural phytomolecules as a whole or their bioactives could be used to develop antivirulence drugs after in vivo evaluation.

Lipid Extracts Obtained by Supercritical Fluid Extraction and Their Application in Meat Products

Supercritical fluid extraction (SFE) has been recognized as the green and clean technique without any negative impact on the environment. Although this technique has shown high selectivity towards lipophilic bioactive compounds, very few case studies on the application of these extracts in final products and different food matrices were observed. Considering the recent developments in food science and the increasing application of supercritical extracts in meat products in the last decade (2012–2022), the aim of this manuscript was to provide a systematic review of the lipid extracts and bioactives successfully obtained by supercritical fluid extraction and their application in meat products as antioxidant and/or antimicrobial agents. Lipophilic bioactives from natural resources were explained in the first step, which was followed by the fundamentals of supercritical fluid extraction and application on recovery of these bioactives. Finally, the application of natural extracts and bioactives obtained by this technique as functional additives in meat and meat products were thoroughly discussed in order to review the state-of-the-art techniques and set the challenges for further studies.

Mutagenesis of bracelet cyclotide hyen D reveals functionally and structurally critical residues for membrane binding and cytotoxicity

Cyclotides have a wide range of bioactivities relevant for agricultural and pharmaceutical applications. This large family of naturally occurring macrocyclic peptides is divided into three subfamilies, with the bracelet subfamily being the largest and comprising the most potent cyclotides reported to date. However, attempts to harness the natural bioactivities of bracelet cyclotides and engineer-optimized analogs have been hindered by a lack of understanding of the structural and functional role of their constituent residues, which has been challenging because bracelet cyclotides are difficult to produce synthetically. We recently established a facile strategy to make the I11L mutant of cyclotide hyen D that is as active as the parent peptide, enabling the subsequent production of a series of variants. In the current study, we report an alanine mutagenesis structure-activity study of [I11L] hyen D to probe the role of individual residues on peptide folding using analytical chromatography, on molecular function using surface plasmon resonance, and on therapeutic potential using cytotoxicity assays. We found that Glu-6 and Thr-15 are critical for maintaining the structure of bracelet cyclotides and that hydrophobic residues in loops 2 and 3 are essential for membrane binding and cytotoxic activity, findings that are distinct from the structural and functional characteristics determined for other cyclotide subfamilies. In conclusion, this is the first report of a mutagenesis scan conducted on a bracelet cyclotide, offering insights into their function and supporting future efforts to engineer bracelet cyclotides for biotechnological applications.

Advances in Research on Natural Distribution, Biosynthesis, Detection, Bioactivity, and Application of Lutein

Advances in Research on Natural Distribution, Biosynthesis, Detection, Bioactivity, and Application of Lutein

Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review.

Human papillomavirus (HPV) still represents an important threat to health worldwide. Better therapy in terms of further improvement of outcomes and attenuation of related side-effects is desirable. The pharmaceutical industry has always targeted natural substances—phytochemicals in particular—to identify lead compounds to be clinically validated and industrially produced as antiviral and anticancer drugs. In the field of HPV, numerous naturally occurring bioactives and dietary phytochemicals have been investigated as potentially valuable in vitro and in vivo. Interference with several pathways and improvement of the efficacy of chemotherapeutic agents have been demonstrated. Notably, some clinical trials have been conducted. Despite being endowed with general safety, these natural substances are in urgent need of further assessment to foresee their clinical exploitation. This review summarizes the basic research efforts conducted so far in the study of anti-HPV properties of bio-actives with insights into their mechanisms of action and highlights the variety of their natural origin in order to provide comprehensive mapping throughout the different sources. The clinical studies available are reported, as well, to highlight the need of uniformity and consistency of studies in the future to select those natural compounds that may be suited to clinical application.