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Investigation of Natural Products as Sources of Bioactive Molecules

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 20 September 2024 | Viewed by 9339

Special Issue Editor

Special Issue Information

Dear Colleagues,

Natural products can derive from plants and animals and considering their rich composition, they certainly represent an inexhaustible source of high potential substances that can be exploited in multiple sectors. Their various physiological and biological activities are based on their specific chemical structures. However, the process of identifying bioactive components from natural product mixtures can be quite difficult, since many of them are quite complex. For the purposes of chemical characterization, various extractive and analytical techniques are applied for the detection and identification of the constituent molecules.

Based on the bioactivity exerted by most of the molecules that characterize natural products, in recent years, there has been a growing interest in the study of biological activities such as antioxidant, antibacterial, cytotoxic, anti-inflammatory activities and so on.

This Special Issue therefore welcomes original research and reviews on topics such as the methods of extraction and characterization of bioactive molecules from natural products, also associated with the evaluation of biological properties.

Dr. Stefania Garzoli
Guest Editor

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Keywords

  • metabolomic
  • secondary metabolites
  • phytochemical analysis
  • bioactivity
  • chemical investigation

Published Papers (11 papers)

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Research

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23 pages, 5241 KiB  
Article
Chlorogenic Acid and Cinnamaldehyde in Combination Inhibit Metastatic Traits and Induce Apoptosis via Akt Downregulation in Breast Cancer Cells
by Yusuff Olayiwola and Lauren S. Gollahon
Int. J. Mol. Sci. 2024, 25(12), 6417; https://doi.org/10.3390/ijms25126417 - 11 Jun 2024
Viewed by 283
Abstract
Most reported breast cancer-associated deaths are directly correlated with metastatic disease. Additionally, the primary goal of treating metastatic breast cancer is to prolong life. Thus, there remains the need for more effective and safer strategies to treat metastatic breast cancer. Recently, more attention [...] Read more.
Most reported breast cancer-associated deaths are directly correlated with metastatic disease. Additionally, the primary goal of treating metastatic breast cancer is to prolong life. Thus, there remains the need for more effective and safer strategies to treat metastatic breast cancer. Recently, more attention has been given to natural products (or phytochemicals) as potential anticancer treatments. This study aimed to investigate the synergistic effects of the combination of the phytochemicals chlorogenic acid and cinnamaldehyde (CGA and CA) toward inhibiting metastasis. The hypothesis was that CGA and CA in combination decrease the metastatic potential of breast cancer cells by inhibiting their invasive and migratory abilities as well as the induction of apoptosis via the downregulation of the Akt, disrupting its signal transduction pathway. To test this, wound-healing and Transwell™ Matrigel™ assays were conducted to assess changes in the migration and invasion properties of the cells; apoptosis was analyzed by fluorescence microscopy for Annexin V/propidium iodide; and immunoblotting and FACSort were performed on markers for the epithelial-to-mesenchymal transition status. The results show that CGA and CA significantly downregulated Akt activation by inhibiting phosphorylation. Consequently, increased caspase 3 and decreased Bcl2-α levels were observed, and apoptosis was confirmed. The inhibition of metastatic behavior was demonstrated by the attenuation of N-cadherin, fibronectin, vimentin, and MMP-9 expressions with concomitant increased expressions of E-cadherin and EpCAM. In summary, the present study demonstrated that CGA and CA in combination downregulated Akt activation, inhibited the metastatic potential, and induced apoptosis in different breast cancer cell lines. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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26 pages, 5723 KiB  
Article
In Vitro Screening of Ecotoxic and Cytotoxic Activities of Ailanthus altissima Leaf Extract against Target and Non-Target Plant and Animal Cells
by Maria Denisa Cocîrlea, Natalia Simionescu, Anca Roxana Petrovici, Mihaela Silion, Barbara Biondi, Luana Lastella and Simona Oancea
Int. J. Mol. Sci. 2024, 25(11), 5653; https://doi.org/10.3390/ijms25115653 - 22 May 2024
Viewed by 467
Abstract
Ailanthus altissima, an invasive plant species, exhibits pharmacological properties, but also some allergic effects on humans. This study aimed to evaluate the potential toxicity of A. altissima leaves, using a complex approach towards different organisms. The ecotoxic impact of a crude extract [...] Read more.
Ailanthus altissima, an invasive plant species, exhibits pharmacological properties, but also some allergic effects on humans. This study aimed to evaluate the potential toxicity of A. altissima leaves, using a complex approach towards different organisms. The ecotoxic impact of a crude extract was investigated on seeds germination and brine shrimp lethality. Cytotoxicity was studied in vitro using non-target (haemolysis, liposomal model, fibroblast), and target (cancer cells) assays. Leaf extract at 1000 µg/mL significantly inhibited wheat and tomato germination, while no significant effects were found on parsley germination. A slight stimulatory effect on wheat and tomato germination was found at 125 µg/mL. In a brine shrimp-test, the extract showed a low toxicity at 24 h post-exposure (LC50 = 951.04 ± 28.26 μg/mL), the toxic effects increasing with the exposure time and extract concentration. Leaf extract caused low hematotoxicity. The extract was biocompatible with human gingival fibroblasts. No anti-proliferative effect was found within the concentration range of 10–500 µg/mL on malignant melanoma (MeWo) and hepatocellular carcinoma (HepG2). In a liposomal model-test, the extract proved to possess low capability to alter the eukaryotic cell-mimicking membranes within the tested concentration range. Given the low to moderate toxicity on tested organisms/cells, the A. altissima autumn leaves may find useful applications. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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17 pages, 739 KiB  
Article
Determination of Post-Fermentation Waste from Fermented Vegetables as Potential Substitutes for Preservatives in o/w Emulsion
by Anna Herman, Olga Matulewicz, Eliza Korzeniowska and Andrzej Przemysław Herman
Int. J. Mol. Sci. 2024, 25(10), 5510; https://doi.org/10.3390/ijms25105510 - 18 May 2024
Viewed by 480
Abstract
Post-fermentation wastes are rich sources of various biologically active compounds with antimicrobial activity, whose potential is not being fully exploited. One of the possible applications of post-fermentation waste may be its use as a natural preservative that effectively combats pathogens found in formulations. [...] Read more.
Post-fermentation wastes are rich sources of various biologically active compounds with antimicrobial activity, whose potential is not being fully exploited. One of the possible applications of post-fermentation waste may be its use as a natural preservative that effectively combats pathogens found in formulations. The study aims included the following: (1) compare the antimicrobial and antioxidant activity of fermented vegetable extracts (FVEs), (2) examine the inhibition of cosmetic-borne pathogens by FVEs, and (3) estimate the preservative effectiveness of FVEs in o/w emulsions. It was found that fermented white cabbage, cucumber, celery, and the mixture of fermented white cabbage, cucumber, and celery (1:1:1) showed antibacterial and antifungal activity against all the tested reference microbial strains. The addition of fermented cucumber, celery, and the mixture of fermented white cabbage, cucumber, and celery (1:1:1) to the o/w emulsion fulfilled criterion A of the preservative effectiveness test for S. aureus, E. coli, and A. brasiliensis, but did not fulfill the criterion for P. aeruginosa and C. albicans. The tested FVEs have comparable activity to inhibit pathogens in o/w emulsion as sodium benzoate. The results of our study prove that FVEs can be valuable raw materials supporting the preservative system, which, in turn, can significantly reduce the concentration of preservatives used in o/w emulsion. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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22 pages, 7994 KiB  
Article
Protopine and Allocryptopine Interactions with Plasma Proteins
by Aleksandra Marciniak, Aleksandra Kotynia, Edward Krzyżak, Żaneta Czyżnikowska, Sylwia Zielińska, Weronika Kozłowska, Marcel Białas, Adam Matkowski and Anna Jezierska-Domaradzka
Int. J. Mol. Sci. 2024, 25(10), 5398; https://doi.org/10.3390/ijms25105398 - 15 May 2024
Viewed by 403
Abstract
A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids, i.e., allocryptopine (ACP) and protopine (PP), was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for [...] Read more.
A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids, i.e., allocryptopine (ACP) and protopine (PP), was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA’s drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/quinaldine red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged, suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural product–protein interactions and the future design of isoquinoline alkaloid-based therapeutics. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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19 pages, 3995 KiB  
Article
Microbial Polysaccharides Extracted from Different Mature Muds of the Euganean Thermal District Show Similar Anti-Inflammatory Activity In Vivo
by Micol Caichiolo, Raffaella Margherita Zampieri, Alessandra Adessi, Matilde Ciani, Fabrizio Caldara, Luisa Dalla Valle and Nicoletta La Rocca
Int. J. Mol. Sci. 2024, 25(9), 4999; https://doi.org/10.3390/ijms25094999 - 3 May 2024
Viewed by 699
Abstract
The Euganean Thermal District, situated in North-East Italy, is one of Europe’s largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides [...] Read more.
The Euganean Thermal District, situated in North-East Italy, is one of Europe’s largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides produced by the mud microbiota have been recently identified as anti-inflammatory bioactive molecules. In this paper we analysed the efficacy of Microbial-Polysaccharides (M-PS) derived from mature muds obtained at different maturation temperatures, both within and outside the codified traditional mud maturation range. M-PSs were extracted from six mature muds produced by five spas of the Euganean Thermal District and investigated for their chemical properties, monosaccharide composition and in vivo anti-inflammatory potential, using the zebrafish model organism. Additionally, mature muds were characterized for their microbiota composition using Next-Generation Sequencing. The results showed that all M-PSs exhibit similar anti-inflammatory potential, referable to their comparable chemical composition. This consistency was observed despite changes in cyanobacteria populations, suggesting a possible role of the entire microbial community in shaping the properties of these biomolecules. These findings highlight the importance of scientific research in untangling the origins of the therapeutic efficacy of Euganean Thermal muds in the treatment of chronic inflammatory conditions. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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19 pages, 3863 KiB  
Article
Hypolipidemic Effect of Rice Bran Oil Extract Tocotrienol in High-Fat Diet-Induced Hyperlipidemia Zebrafish (Danio Rerio) Induced by High-Fat Diet
by Naicheng Liu, Peng Zhang, Mingyang Xue, Mengwei Zhang, Zhenyu Huang, Chen Xu, Yan Meng, Yuding Fan, Wei Liu, Feixiang Zhang, Peng Chen and Yong Zhou
Int. J. Mol. Sci. 2024, 25(5), 2954; https://doi.org/10.3390/ijms25052954 - 3 Mar 2024
Viewed by 1049
Abstract
In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol’s hypolipidemic impact and the corresponding mechanisms in aquatic species [...] Read more.
In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol’s hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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20 pages, 6700 KiB  
Article
Isolation, Characterization, Genome Annotation, and Evaluation of Tyrosinase Inhibitory Activity in Secondary Metabolites of Paenibacillus sp. JNUCC32: A Comprehensive Analysis through Molecular Docking and Molecular Dynamics Simulation
by Yang Xu, Xuhui Liang and Chang-Gu Hyun
Int. J. Mol. Sci. 2024, 25(4), 2213; https://doi.org/10.3390/ijms25042213 - 12 Feb 2024
Viewed by 797
Abstract
A potential strain, Paenibacillus sp. JNUCC32, was isolated and subjected to whole-genome sequencing. Genome functional annotation revealed its active metabolic capabilities. This study aimed to investigate the pivotal secondary metabolites in the biological system. Fermentation and extraction were performed, resulting in the isolation [...] Read more.
A potential strain, Paenibacillus sp. JNUCC32, was isolated and subjected to whole-genome sequencing. Genome functional annotation revealed its active metabolic capabilities. This study aimed to investigate the pivotal secondary metabolites in the biological system. Fermentation and extraction were performed, resulting in the isolation of seven known compounds: tryptophol (1), 3-(4-hydroxyphenyl)propionic acid (2), ferulic acid (3), maculosin (4), brevianamide F (5), indole-3-acetic acid (6), and butyric acid (7). Tryptophol exhibited favorable pharmacokinetic properties and demonstrated certain tyrosinase inhibitory activity (IC50 = 999 μM). For further analysis of its inhibition mechanism through molecular docking and molecular dynamics (MD) simulation, tryptophol formed three hydrogen bonds and a pro-Michaelis complex with tyrosinase (binding energy = −5.3 kcal/mol). The MD simulation indicated favorable stability for the tryptophol–mushroom tyrosinase complex, primarily governed by hydrogen bond interactions. The crucial residues VAL-283 and HIS-263 in the docking were also validated. This study suggests tryptophol as a potential candidate for antibrowning agents and dermatological research. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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14 pages, 4650 KiB  
Article
Zingiber officinale Root Capsule Extract Synergistically Enhance the Anti-Inflammatory Effects of Diclofenac Sodium in Experimental Acute Inflammation
by Ioana Boarescu, Paul-Mihai Boarescu, Raluca Maria Pop, Ioana Corina Bocșan, Dan Gheban, Adriana Elena Bulboacă, Anca Dana Buzoianu and Sorana D. Bolboacă
Int. J. Mol. Sci. 2024, 25(3), 1781; https://doi.org/10.3390/ijms25031781 - 1 Feb 2024
Viewed by 1592
Abstract
The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of [...] Read more.
The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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22 pages, 4347 KiB  
Article
Identification of Volatile Molecules and Bioactivity of Gruyt Craft Beer Enriched with Citrus aurantium var. dulcis L. Essential Oil
by Cosimo Taiti, Antonella Di Sotto, Giovanni Stefano, Ester Percaccio, Matteo Iannone, Andrea Marianelli and Stefania Garzoli
Int. J. Mol. Sci. 2024, 25(1), 350; https://doi.org/10.3390/ijms25010350 - 26 Dec 2023
Viewed by 1275
Abstract
In this work, for the first time, a gruyt beer and the same one after the addition of Citrus aurantium essential oil (AEO), were investigated to determine the composition of the volatile fraction. The applied analytical techniques, such as Head Space/Solid Phase Microextraction-Gas [...] Read more.
In this work, for the first time, a gruyt beer and the same one after the addition of Citrus aurantium essential oil (AEO), were investigated to determine the composition of the volatile fraction. The applied analytical techniques, such as Head Space/Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry (HS/SPME-GC-MS) and Proton Transfer Reaction-Time of Flight-Mass Spectrometer (PTR-ToF-MS), allowed us to identify the content of volatile organic compounds (VOCs). From the comparison between the two beer samples, it showed that the one after the addition of AEO was particularly richened in limonene and a series of minor terpene compounds. AEO was also characterized by GC/MS analysis and the results showed that limonene reached 95%. Confocal microscopy was used to look at riboflavin autofluorescence in yeast cells. It was found that beer with AEO had twice as much fluorescence intensity as the control. A spectrophotometric analysis of total polyphenols, tannins, and flavonoids, and a bioactivity screening, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-Azinobis-(3-Ethylbenzthiazolin-6-Sulfonic Acid) (ABTS) radical scavenger, chelating, reducing, antiglycative ones, were also carried out. Moreover, the tolerability of the tested samples in human H69 cholangiocytes and the cytoprotection towards the tert-butyl hydroperoxide (tBOOH)-induced oxidative damage were evaluated. Under our experimental conditions, the beers were found to be able to scavenge DPPH and ABTS radicals and chelate iron ions, despite weak antiglycative and reducing properties. The tested samples did not affect the viability of H69 cholangiocytes up to the highest concentrations; moreover, no signs of cytoprotection against the damage induced by tBOOH were highlighted. Adding AEO to beer resulted in a moderate enhancement of its DPPH scavenging and chelating abilities, without improvements in the other assays. Conversely, AEO and its major compound limonene were ineffective when assessed at the concentrations added to beer. This evidence suggests that the addition of AEO may enhance the organoleptic features of the beer and slightly potentiate some of its bioactivities. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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Review

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23 pages, 2547 KiB  
Review
Unveiling the Chemical Composition and Biofunctionality of Hericium spp. Fungi: A Comprehensive Overview
by Elizabeth Kostanda, Sanaa Musa and Idan Pereman
Int. J. Mol. Sci. 2024, 25(11), 5949; https://doi.org/10.3390/ijms25115949 - 29 May 2024
Viewed by 424
Abstract
In recent years, research on mushrooms belonging to the Hericium genus has attracted considerable attention due to their unique appearance and well-known medicinal properties. These mushrooms are abundant in bioactive chemicals like polysaccharides, hericenones, erinacines, hericerins, resorcinols, steroids, mono- and diterpenes, and corallocins, [...] Read more.
In recent years, research on mushrooms belonging to the Hericium genus has attracted considerable attention due to their unique appearance and well-known medicinal properties. These mushrooms are abundant in bioactive chemicals like polysaccharides, hericenones, erinacines, hericerins, resorcinols, steroids, mono- and diterpenes, and corallocins, alongside essential nutrients. These compounds demonstrate beneficial bioactivities which are related to various physiological systems of the body, including the digestive, immune, and nervous systems. Extensive research has been conducted on the isolation and identification of numerous bioactive chemicals, and both in vitro and in vivo studies have confirmed their antimicrobial, antioxidant, immunomodulatory, antidiabetic, anticholesterolemic, anticancer, and neuroprotective properties. Therefore, this review aims to provide a comprehensive summary of the latest scientific literature on the chemical composition and secondary metabolites profile of Hericium spp. through an introduction to their chemical characteristics, speculated biosynthesis pathways for key chemical families, potential toxicological aspects, and a detailed description of the recent updates regarding the bioactivity of these metabolites. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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39 pages, 1870 KiB  
Review
Nutraceuticals in Psychiatric Disorders: A Systematic Review
by Paola Bozzatello, Roberta Novelli, Cristiana Montemagni, Paola Rocca and Silvio Bellino
Int. J. Mol. Sci. 2024, 25(9), 4824; https://doi.org/10.3390/ijms25094824 - 28 Apr 2024
Cited by 1 | Viewed by 1156
Abstract
Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory [...] Read more.
Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research. Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
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