Shrimp Waste Upcycling: Unveiling the Potential of Polysaccharides, Proteins, Carotenoids, and Fatty Acids with Emphasis on Extraction Techniques and Bioactive Properties.

Shrimp processing generates substantial waste, which is rich in valuable components such as polysaccharides, proteins, carotenoids, and fatty acids. This review provides a comprehensive overview of the valorization of shrimp waste, mainly shrimp shells, focusing on extraction methods, bioactivities, and potential applications of these bioactive compounds. Various extraction techniques, including chemical extraction, microbial fermentation, enzyme-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, and pressurized techniques are discussed, highlighting their efficacy in isolating polysaccharides, proteins, carotenoids, and fatty acids from shrimp waste. Additionally, the bioactivities associated with these compounds, such as antioxidant, antimicrobial, anti-inflammatory, and antitumor properties, among others, are elucidated, underscoring their potential in pharmaceutical, nutraceutical, and cosmeceutical applications. Furthermore, the review explores current and potential utilization avenues for these bioactive compounds, emphasizing the importance of sustainable resource management and circular economy principles in maximizing the value of shrimp waste. Overall, this review paper aims to provide insights into the multifaceted aspects of shrimp waste valorization, offering valuable information for researchers, industries, and policymakers interested in sustainable resource utilization and waste-management strategies.

Potential Therapeutic Properties of Olea europaea Leaves from Selected Cultivars Based on Their Mineral and Organic Profiles.

Olive leaves are consumed as an extract or as a whole herbal powder with several potential therapeutic benefits attributed to polyphenols, tocopherol's isomers, and flavonoids, among others. This study assessed the potential variance in the functional features presented by olive leaves from three different Portuguese cultivars-Cobrançosa, Madural, and Verdeal-randomly mix-cultivated in the geographical area of Vale de Salgueiros. Inorganic analysis determined their mineral profiles while an organic analysis measured their total phenolic and flavonoid content, and scanned their phenolic and tocopherol and fatty acid composition. The extracts' biological activity was tested by determining their antimicrobial and antioxidant power as well as their ability to inhibit acetylcholinesterase, butyrylcholinesterase, MAO-A/B, and angiotensin-I-converting enzyme. The inorganic profiles showed them to be an inexpensive source able to address different mineral deficiencies. All cultivars appear to have potential for use as possible antioxidants and future alternative antibiotics against some multidrug-resistant microorganisms, with caution regarding the arsenic content in the Verdeal cultivar. Madural's extract displayed properties to be considered a natural multitarget treatment for Alzheimer's and Parkinson's diseases, depression, and cardiometabolic and dual activity for blood pressure modulation. This work indicates that randomly cultivating different cultivars significantly modifies the leaves' composition while keeping their multifaceted therapeutic value.

Phytochemical compounds with promising biological activities from Ascophyllum nodosum extracts using microwave-assisted extraction.

Phytochemical-rich antioxidant extracts were obtained from Ascophyllum nodosum (AN) using microwave-assisted extraction (MAE). Critical extraction factors such as time, pressure, and ethanol concentration were optimized by response surface methodology with a circumscribed central composite design. Under the optimal MAE conditions (3 min, 10.4 bar, 46.8 % ethanol), the maximum recovery of phytochemical compounds (polyphenols and fucoxanthin) with improved antioxidant activity from AN was obtained. In addition, the optimized AN extract showed significant biological activities as it was able to scavenge reactive oxygen and nitrogen species, inhibit central nervous system-related enzymes, and exhibit cytotoxic activity against different cancer cell lines. In addition, the optimized AN extract showed antimicrobial, and anti-quorum sensing activities, indicating that this extract could offer direct and indirect protection against infection by pathogenic microorganisms. This work demonstrated that the sustainably obtained AN extract could be an emerging, non-toxic, and natural ingredient with potential to be included in different applications.

Single and Multitarget Systems for Drug Delivery and Detection: Up-to-Date Strategies for Brain Disorders.

This review summarizes the recent findings on the development of different types of single and multitarget nanoparticles for disease detection and drug delivery to the brain, focusing on promising active principles encapsulated and nanoparticle surface modification and functionalization. Functionalized nanoparticles have emerged as promising tools for the diagnosis and treatment of brain disorders, offering a novel approach to addressing complex neurological challenges. They can act as drug delivery vehicles, transporting one or multiple therapeutic agents across the blood-brain barrier and precisely releasing them at the site of action. In diagnostics, functionalized nanoparticles can serve as highly sensitive contrast agents for imaging techniques such as magnetic resonance imaging and computed tomography scans. By attaching targeting ligands to the nanoparticles, they can selectively accumulate in the affected areas of the brain, enhancing the accuracy of disease detection. This enables early diagnosis and monitoring of conditions like Alzheimer's or Parkinson's diseases. While the field is still evolving, functionalized nanoparticles represent a promising path for advancing our ability to diagnose and treat brain disorders with greater precision, reduced invasiveness, and improved therapeutic outcomes.

The neuroprotective effect of traditional Chinese medicinal plants-A critical review.

Neurodegenerative and neuropsychiatric diseases are increasingly affecting individuals' quality of life, thus increasing their cost to social and health systems. These diseases have overlapping mechanisms, such as oxidative stress, protein aggregation, neuroinflammation, neurotransmission impairment, mitochondrial dysfunction, and excitotoxicity. Currently, there is no cure for neurodegenerative diseases, and the available therapies have adverse effects and low efficacy. For neuropsychiatric disorders, such as depression, the current therapies are not adequate to one-third of the patients, the so-called treatment-resistant patients. So, searching for new treatments is fundamental. Medicinal plants appear as a strong alternative and complement towards new treatment protocols, as they have been used for health purposes for thousands of years. Thus, the main goal of this review is to revisit the neuroprotective potential of some of the most predominant medicinal plants (and one fungus) used in traditional Chinese medicine (TCM), focusing on their proven mechanisms of action and their chemical compositions, to give clues on how they can be useful against neurodegeneration progression.

From Plants to Psycho-Neurology: Unravelling the Therapeutic Benefits of Bioactive Compounds in Brain Disorders.

The brain's sensitivity to oxidative stress and neuronal cell death requires effective pharmacotherapy approaches. Current pharmacological therapies are frequently ineffective and display negative side effects. Bioactive chemicals found in plants may provide a potential alternative due to their antioxidant and neuroprotective properties and can be used in therapy and the management of a variety of neuropsychiatric, neurodevelopmental, and neurodegenerative illnesses. Several natural products, including vitamin C, Cammelia sinensis polyphenols, Hypericum perforatum, and Crocus sativus have shown promise in lowering oxidative stress and treating symptoms of major depressive disorder (MDD). Similarly, bioactive compounds such as curcumin, luteolin, resveratrol, quercetin, and plants like Acorus gramineus, Rhodiola rosea, and Ginkgo biloba are associated with neuroprotective effects and symptom improvement in neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Furthermore, in neurodegenerative diseases, natural compounds from Rhodiola rosea, Morinda lucida, and Glutinous rehmannia provide neurological improvement. Further study in clinical samples is required to thoroughly investigate the therapeutic advantages of these bioactive substances for persons suffering from these illnesses.

Tracing the Path between Mushrooms and Alzheimer's Disease-A Literature Review.

Alzheimer's disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and ß-secretase (BACE 1); the prevention of amyloid beta (Aß) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms.

Kinetic Extraction of Fucoxanthin from Undaria pinnatifida Using Ethanol as a Solvent.

Fucoxanthin (Fx) has been proven to exert numerous biological properties, which makes it an interesting molecule with diverse industrial applications. In this study, the kinetic behavior of Fx was studied to optimize three variables: time (t-3 min to 7 days), temperature (T-5 to 85 °C), and concentration of ethanol in water (S-50 to 100%, v/v), in order to obtain the best Fx yield from Undaria pinnatifida using conventional heat extraction. The Fx content (Y1) was found through HPLC-DAD and expressed in µg Fx/g of algae sample dry weight (AS dw). Furthermore, extraction yield (Y2) was also found through dry weight analysis and was expressed in mg extract (E)/g AS dw. The purity of the extracts (Y3) was found and expressed in mg Fx/g E dw. The optimal conditions selected for Y1 were T = 45 °C, S = 70%, and t = 66 min, obtaining ~5.24 mg Fx/g AS; for Y2 were T = 65 °C, S = 60%, and t = ~10 min, obtaining ~450 mg E/g AS; and for Y3 were T = 45 °C, S = 70%, and t = 45 min, obtaining ~12.3 mg Fx/g E. In addition, for the selected optimums, a full screening of pigments was performed by HPLC-DAD, while phenolics and flavonoids were quantified by spectrophotometric techniques and several biological properties were evaluated (namely, antioxidant, antimicrobial, and cholinesterase inhibitory activity). These results could be of interest for future applications in the food, cosmetic, or pharmaceutical industries, as they show the Fx kinetic behavior and could help reduce costs associated with energy and solvent consumption while maximizing the extraction yields.

Moringa oleifera Lam. Commercial Beverages: A Multifaceted Investigation of Consumer Perceptions, Sensory Analysis, and Bioactive Properties.

This study employs a multidisciplinary approach to evaluate consumers' perceptions and acceptance of Moringa oleifera Lam. beverages, examining sensory attributes, chemical composition, and bioactivities. High-performance liquid chromatography with diode array detection (HPLC-DAD) analyses revealed significant chemovariation in phenolic compositions among commercial moringa beverages. A soluble moringa powder drink exhibited the greatest concentrations of phenolic and flavonoid compounds, along with powerful antioxidant capacity powers assessed with ABTS•+, DPPH•, FRAP assays, •NO, and H2O2 scavenging activities. However, this sample was the least preferred and presented high Cd levels, exceeding WHO-acceptable values of 0.3 mg/kg. Sensory testing indicated that sweet and floral flavors contributed to beverages being liked, while green, grass, herbal flavors, sour, bitter, and precipitate presence were considered unfavorable sensory attributes. Health claims positively influenced acceptance, particularly among women. Consumers associated feelings of health, wellness, relaxation, and leisure with moringa beverages. During purchase, the most observed information included the ingredient list, health benefits, and type/flavor. These findings emphasize the importance of consumer awareness in reading labels, verifying product origins, and ensuring the absence of contaminants. By understanding consumer preferences and the impact of health claims, producers can better tailor M. oleifera beverages to meet consumer expectations while maintaining safety and quality standards.

Multiple Organic Contaminants Determination Including Multiclass of Pesticides, Polychlorinated Biphenyls, and Brominated Flame Retardants in Portuguese Kiwano Fruits by Gas Chromatography.

Global production of exotic fruits has been growing steadily over the past decade and expanded beyond the originating countries. The consumption of exotic and new fruits, such as kiwano, has increased due to their beneficial properties for human health. However, these fruits are scarcely studied in terms of chemical safety. As there are no studies on the presence of multiple contaminants in kiwano, an optimized analytical method based on the QuEChERS for the evaluation of 30 multiple contaminants (18 pesticides, 5 polychlorinated biphenyls (PCB), 7 brominated flame retardants) was developed and validated. Under the optimal conditions, satisfactory extraction efficiency was obtained with recoveries ranging from 90% to 122%, excellent sensitivity, with a quantification limit in the range of 0.6 to 7.4 µg kg-1, and good linearity ranging from 0.991 to 0.999. The relative standard deviation for precision studies was less than 15%. The assessment of the matrix effects showed enhancement for all the target compounds. The developed method was validated by analyzing samples collected from Douro Region. PCB 101 was found in trace concentration (5.1 µg kg-1). The study highlights the relevance of including other organic contaminants in monitoring studies in food samples in addition to pesticides.

Bioactive Compounds of Shrimp Shell Waste from Palaemon serratus and Palaemon varians from Portuguese Coast.

The production and consumption of shrimp species create massive amounts of shrimp bio-waste. In this study, shrimp shell waste from Palaemon serratus and Palaemon varians from the Portuguese coast was characterized. Regarding the antioxidant capacity, the obtained values were between 4.7 and 10.4 mg gallic acid equivalents (GAE)/g dry weight (dw) for Total phenolic content (TPC); 3 and 7 mg ascorbic acid equivalents (AAE)/g dw for Ferric reducing antioxidant power assay (FRAP); 0.4 and 1.2 mg Trolox equivalent (TE)/g dw for 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical scavenging (DPPH•); 4 and 11 mg TE/g dw for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity (ABTS•+); and 72 and 130 mg TE/g dw for Oxygen radical absorbance capacity (ORAC). For the antimicrobial activity, shrimp shell waste from P. varians formed inhibition zones between 14 and 23 mm. Total carotenoid content values were in the range of 28 and 134 µg/g dw, and according to their HPLC-PAD profile, ß-carotene and astaxanthin contents were between 0.3 and 7.6 µg/g dw and 1.1 and 26.1 µg/g dw, respectively. These studies are critical to recognizing the potential added value of shrimp shell waste as possible colorants and preservatives with antioxidant protection capacity to be used in the food industry.

A Critical Comparison of the Advanced Extraction Techniques Applied to Obtain Health-Promoting Compounds from Seaweeds.

Marine macroalgae are rich in bioactive compounds that can be applied in several fields, mainly food, cosmetics, and medicine. The health-promoting effects of bioactive compounds, such as polyphenols, polysaccharides, carotenoids, proteins, and fatty acids, have been increasingly explored, especially regarding their antioxidant activity and improvement in human health. To extract these valuable compounds, advanced technologies that include Supercritical-Fluid Extraction (SFE), Pressurised-Liquid Extraction (PLE), Ultrasound-Assisted Extraction (UAE), Microwave-Assisted Extraction (MAE), Enzyme-Assisted Extraction (EAE), Ultrasound-Microwave-Assisted Extraction (UMAE) and Liquefied Gas Extraction (LGE) have been assessed due to their notable advantages over the conventional methods (Solid-Liquid and Soxhlet extraction). These advanced techniques are considerably influenced by different extraction parameters such as temperature, pressure, type of solvent, extraction time, solvent:solid material ratio, power (MAE, UAE, and UMAE), enzymes used (EAE), and factors related to the macroalgae matrix itself. Optimizing these process parameters for each method is critical to obtain better efficiency results for the targeted bioactive compounds. Macroalgae are natural sources with undeniable beneficial effects on human health. In this context, optimising the extraction techniques discussed in this review should prioritise exploiting these valuable resources' wide range of bioactive properties.

Recent advances in biological properties of brown algae-derived compounds for nutraceutical applications.

The increasing demand for nutraceuticals in the circular economy era has driven the research toward studying bioactive compounds from renewable underexploited resources. In this regard, the exploration of brown algae has shown significant growth and maintains a great promise for the future. One possible explanation could be that brown algae are rich sources of nutritional compounds (polyunsaturated fatty acids, fiber, proteins, minerals, and vitamins) and unique metabolic compounds (phlorotannins, fucoxanthin, fucoidan) with promising biological activities that make them good candidates for nutraceutical applications with increased value-added. In this review, a deep description of bioactive compounds from brown algae is presented. In addition, recent advances in biological activities ascribed to these compounds through in vitro and in vivo assays are pointed out. Delivery strategies to overcome some drawbacks related to the direct application of algae-derived compounds (low solubility, thermal instability, bioavailability, unpleasant organoleptic properties) are also reviewed. Finally, current commercial and legal statuses of ingredients from brown algae are presented, considering future therapeutical and market perspectives as nutraceuticals.

Biological Potential, Gastrointestinal Digestion, Absorption, and Bioavailability of Algae-Derived Compounds with Neuroprotective Activity: A Comprehensive Review.

Currently, there is no known cure for neurodegenerative disease. However, the available therapies aim to manage some of the symptoms of the disease. Human neurodegenerative diseases are a heterogeneous group of illnesses characterized by progressive loss of neuronal cells and nervous system dysfunction related to several mechanisms such as protein aggregation, neuroinflammation, oxidative stress, and neurotransmission dysfunction. Neuroprotective compounds are essential in the prevention and management of neurodegenerative diseases. This review will focus on the neurodegeneration mechanisms and the compounds (proteins, polyunsaturated fatty acids (PUFAs), polysaccharides, carotenoids, phycobiliproteins, phenolic compounds, among others) present in seaweeds that have shown in vivo and in vitro neuroprotective activity. Additionally, it will cover the recent findings on the neuroprotective effects of bioactive compounds from macroalgae, with a focus on their biological potential and possible mechanism of action, including microbiota modulation. Furthermore, gastrointestinal digestion, absorption, and bioavailability will be discussed. Moreover, the clinical trials using seaweed-based drugs or extracts to treat neurodegenerative disorders will be presented, showing the real potential and limitations that a specific metabolite or extract may have as a new therapeutic agent considering the recent approval of a seaweed-based drug to treat Alzheimer's disease.

Evaluation of the Biological Potential of Himanthalia elongata (L.) S.F.Gray and Eisenia bicyclis (Kjellman) Setchell Subcritical Water Extracts.

Neuroprotection is a need that remains unmet in treating chronic neurodegenerative disorders, despite decades of extensive research. To find new neuroprotective compounds, extracts of Himanthalia elongata (L.) S.F.Gray and of Eisenia bicyclis (Kjellman) Setchell were obtained through subcritical water extraction applying a four-step temperature gradient. The fractions obtained were screened against brain enzymes involved in neurodegenerative etiology, namely in Alzheimer's and Parkinson's diseases, and against reactive oxygen and nitrogen species, all contributing factors to the progression of neurodegeneration. Results showed no significant enzyme inhibition but strong radical scavenging activities, particularly in the fourth fraction, extracted at the highest temperature (250 °C), highlighting their ability to retard oxidative and nitrosative stresses. At higher temperatures, fractions were composed of phenolic compounds and Maillard reaction products, a combination that contributed to their antioxidant activity and, consequently, their neuroprotective properties. All fractions were evaluated for the presence of iodine, 14 organochlorine and 7 organophosphorus pesticides, and pharmaceuticals used in Alzheimer's and Parkinson's diseases (14), psychiatric drugs (8), and metabolites (8). The fractions studied did not present any of the screened contaminants, and only fraction 1 of E. bicyclis should be used with caution due to iodine content.

Multi-target neuroprotective effects of herbal medicines for Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. AIM OF THE STUDY: This study intended to explore the neuroprotective potential of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. MATERIALS AND METHODS: Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH•, ABTS•+, O2•‒ and •NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3ß). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 21 pesticides residues were screened. RESULTS: Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3ß inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. CONCLUSIONS: The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.

Marine Health-Promoting Compounds: Recent Trends for Their Characterization and Human Applications.

Seaweeds represent a rich source of biologically active compounds with several applications, especially in the food, cosmetics, and medical fields. The beneficial effects of marine compounds on health have been increasingly explored, making them an excellent choice for the design of functional foods. When studying marine compounds, several aspects must be considered: extraction, identification and quantification methods, purification steps, and processes to increase their stability. Advanced green techniques have been used to extract these valuable compounds, and chromatographic methods have been developed to identify and quantify them. However, apart from the beneficial effects of seaweeds for human health, these natural sources of bioactive compounds can also accumulate undesirable toxic elements with potential health risks. Applying purification techniques of extracts from seaweeds may mitigate the amount of excessive toxic components, ensuring healthy and safer products for commercialization. Furthermore, limitations such as stability and bioavailability problems, chemical degradation reactions during storage, and sensitivity to oxidation and photo-oxidation, need to be overcome using, for example, nanoencapsulation techniques. Here we summarize recent advances in all steps of marine products identification and purification and highlight selected human applications, including food and feed applications, cosmetic, human health, and fertilizers, among others.

Critical Review of Lipid-Based Nanoparticles as Carriers of Neuroprotective Drugs and Extracts.

The biggest obstacle to the treatment of diseases that affect the central nervous system (CNS) is the passage of drugs across the blood-brain barrier (BBB), a physical barrier that regulates the entry of substances into the brain and ensures the homeostasis of the CNS. This review summarizes current research on lipid-based nanoparticles for the nanoencapsulation of neuroprotective compounds. A survey of studies on nanoemulsions (NEs), nanoliposomes/nanophytosomes and solid lipid nanoparticles (SLNs)/nanostructured lipid carriers (NLCs) was carried out and is discussed herein, with particular emphasis upon their unique characteristics, the most important parameters influencing the formulation of each one, and examples of neuroprotective compounds/extracts nanoencapsulated using these nanoparticles. Gastrointestinal absorption is also discussed, as it may pose some obstacles for the absorption of free and nanoencapsulated neuroprotective compounds into the bloodstream, consequently hampering drug concentration in the brain. The transport mechanisms through which compounds or nanoparticles may cross BBB into the brain parenchyma, and the potential to increase drug bioavailability, are also discussed. Additionally, factors contributing to BBB disruption and neurodegeneration are described. Finally, the advantages of, and obstacles to, conventional and unconventional routes of administration to deliver nanoencapsulated neuroprotective drugs to the brain are also discussed, taking into account the avoidance of first-pass metabolism, onset of action, ability to bypass the BBB and concentration of the drug in the brain.

Interactions between Ginkgo biloba L. and Scutellaria baicalensis Georgi in multicomponent mixtures towards cholinesterase inhibition and ROS scavenging.

This study gives new insights to understand the type of interactions between Ginkgo biloba L. and Scutellaria baicalensis Georgi, two Chinese medicinal plants with well documented neuroprotective effects, on three targets in Alzheimer's disease (AD): acetylcholinesterase (AChE) and butyrylcholnesterase (BuChE) inhibition and hydrogen peroxide scavenging. Individual samples, binary mixtures with different proportions of both plant species, and also a commercial multicomponent combination containing both plants together with unroasted Coffea arabica L. and quercetin-3-O-rutinoside were used to perform this in vitro evaluation. Sample phenolic profiles were also determined by HPLC-DAD, showing the presence of several flavonoid glycosides, phenolic acids and a methylxanthine. In order to investigate the possible synergism/antagonism interaction, data obtained were analyzed by CompuSyn software. The results showed that G. biloba and S. baicalensis alone display better activities than in mixtures, most of the interactions exhibiting different degrees of antagonism. A slight synergism interaction was only observed for the commercial multicomponent mixture tested against H2O2. Further analysis was carried out to understand which compounds could be responsible for the antagonistic interaction. Seventeen single pure compounds present in all extracts were tested against AChE inhibition, most of them displaying weak or no activity. Only caffeine had a remarkable activity. Five different binary and quaternary mixture compositions were design to deepen the interaction between these compounds, revealing mainly phenolic acid-flavonoid, flavonoid-flavonoid and methylxanthine-flavonoid-phenolic acid antagonistic interactions. These results clearly show that, for the targets evaluated, there is no potentiation of the neuroprotective effect by combining S. baicalensis and G. biloba extracts.

Comprehensive review on the interaction between natural compounds and brain receptors: Benefits and toxicity.

Given their therapeutic activity, natural products have been used in traditional medicines throughout the centuries. The growing interest of the scientific community in phytopharmaceuticals, and more recently in marine products, has resulted in a significant number of research efforts towards understanding their effect in the treatment of neurodegenerative diseases, such as Alzheimer's (AD), Parkinson (PD) and Huntington (HD). Several studies have shown that many of the primary and secondary metabolites of plants, marine organisms and others, have high affinities for various brain receptors and may play a crucial role in the treatment of diseases affecting the central nervous system (CNS) in mammalians. Actually, such compounds may act on the brain receptors either by agonism, antagonism, allosteric modulation or other type of activity aimed at enhancing a certain effect. The current manuscript comprehensively reviews the state of the art on the interactions between natural compounds and brain receptors. This information is of foremost importance when it is intended to investigate and develop cutting-edge drugs, more effective and with alternative mechanisms of action to the conventional drugs presently used for the treatment of neurodegenerative diseases. Thus, we reviewed the effect of 173 natural products on neurotransmitter receptors, diabetes related receptors, neurotrophic factor related receptors, immune system related receptors, oxidative stress related receptors, transcription factors regulating gene expression related receptors and blood-brain barrier receptors.