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Faculty of Biology, Alexandru Ioan Cuza University of Iasi, Bd. Carol I, No. 11, 700506 Iasi, Romania

1. Pharmacognosy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
2. Center for Drug Discovery Research and Development, Ain Shams University, Abbassia, Cairo 11566, Egypt

Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain

Abstract submission deadline

closed (31 October 2022)

Manuscript submission deadline

closed (31 December 2022)

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Topic Information

Dear Colleagues,

Plants have been used to flavor and preserve food for thousands of years, as well as to treat health problems and prevent diseases such as epidemics. The medicinal powers of these plants have been passed down the generations within and among human communities. The biological qualities of some plant species used around the world for various purposes are usually due to active chemicals created during secondary vegetal metabolism. Many experimental, pharmacological, and clinical studies have shown that plant extracts exhibit various biological activities, such as antimicrobial, antioxidant, antimutagenic, anticytotoxic, anti-inflammatory, and neuroprotective properties.

The present Topic invites manuscript submissions, research, and review papers, targeting the identification and mechanistic characterization of novel pharmacological targets, signaling pathways, and mechanisms of action of natural compounds and their derivatives in multiple ways.

Potential topics include but are not limited to the following:

• Molecular docking studies;

• Neurobehavioral pharmacological studies;

• Antioxidants;

• Signaling pathways;

• Anti-inflammatory;

• Anti-neurodegenerative.

Prof. Dr. Lucian Hriţcu
Prof. Dr. Omayma A. Eldahshan
Topic Editors

Keywords

• bioactive products

• neurodegenerative diseases

• molecular docking

• neuroinflammation

• neurodegeneration

• signal pathways

• behavioral neuroscience

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antioxidants antioxidants	7.0	8.8	2012	13.9 Days	CHF 2900
Brain Sciences brainsci	3.3	3.9	2011	15.6 Days	CHF 2200
Molecules molecules	4.6	6.7	1996	14.6 Days	CHF 2700
Nutrients nutrients	5.9	9.0	2009	14.5 Days	CHF 2900
Plants plants	4.5	5.4	2012	15.3 Days	CHF 2700

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Published Papers (11 papers)

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2 pages, 2590 KiB

Open AccessCorrection

Correction: Tang et al. Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop. Nutrients 2022, 14, 1504

by Hengfang Tang, Zhiming Zheng, Han Wang, Li Wang, Genhai Zhao and Peng Wang

Nutrients 2023, 15(16), 3540; https://doi.org/10.3390/nu15163540 - 11 Aug 2023

Viewed by 536

Abstract

In the original publication [...] Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

16 pages, 4154 KiB

Open AccessCommunication

Improvement of Spatial Memory and Cognitive Function in Mice via the Intervention of Milk Fat Globule Membrane

by Yongjie Zhou, Xiaoxiao Zou, Ruifang Feng, Xin Zhan, Hui Hong, Yongkang Luo and Yuqing Tan

Nutrients 2023, 15(3), 534; https://doi.org/10.3390/nu15030534 - 19 Jan 2023

Cited by 4 | Viewed by 2129

Abstract

With the improvement of living standards, dietary interventions have become an appropriate approach to enhance memory and cognitive performance. The present study investigated the potential mechanisms of spatial memory and cognitive function improvement with the milk fat globule membrane (MFGM) intervention in mice. The Morris water maze experiment revealed that the trajectories of mice in group M were more disordered. Also, the immunohistochemical results demonstrated a significantly higher number of neurons in group M compared with group C, especially in the hippocampal dentate gyrus (DG) area. It is suggested that MFGM enhanced mice’s spatial memory and cognition from macroscopic behavior and microscopic cytology, respectively. Meanwhile, 47 differentially expressed proteins (DEPs) were identified, including 20 upregulated and 27 downregulated proteins. Upregulated (Sorbs 2, Rab 39, and Cacna 1e) and downregulated (Hp and Lrg 1) DEPs may improve spatial memory and cognition in mice by promoting synapse formation and increasing neurotransmitter receptors. KEGG enrichment analysis of the DEPs identified seven signaling pathways that were significantly enriched (p < 0.05). One of these pathways was neuroactive ligand-receptor interactions, which are strongly associated with improved spatial memory and cognitive performance. These findings give some new insights and references to the potential mechanisms of spatial memory and cognitive enhancement by MFGM. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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27 pages, 1502 KiB

Open AccessEditor’s ChoiceReview

The Neuroprotective Effects and Therapeutic Potential of the Chalcone Cardamonin for Alzheimer’s Disease

by Kimberly Barber, Patricia Mendonca and Karam F. A. Soliman

Brain Sci. 2023, 13(1), 145; https://doi.org/10.3390/brainsci13010145 - 14 Jan 2023

Cited by 13 | Viewed by 2880

Abstract

Neurodegenerative diseases (ND) include a wide range of conditions that result from progressive damage to the neurons. Alzheimer’s disease (AD) is one of the most common NDs, and neuroinflammation and oxidative stress (OS) are the major factors in the development and progression of the disease. Many naturally occurring phytochemical compounds exhibit antioxidant and anti-inflammatory activities with potential neuroprotective effects. Several plant species, including Alpinia katsumadai and Alpinia conchigera, contain cardamonin (CD). CD (2′,4′-dihydroxy-6′methoxychalcone) has many therapeutic properties, including anticancer, anti-inflammatory, antioxidant, antiviral, and antibiotic activities. CD is a potent compound that can reduce OS and modulate the inflammatory processes that play a significant part in developing neurodegenerative diseases. CD has been shown to modulate a variety of signaling molecules involved in the development and progression of ND, including transcription factors (NF-kB and STAT3), cytokines (TNF-α, IL-1, and IL-6), enzymes (COX-2, MMP-9, and ALDH1), and other proteins and genes (Bcl-2, XIAP, and cyclin D1). Additionally, CD effectively modulates miRNA levels and autophagy-related CD-protective mechanisms against neurodegeneration. In summary, this review provides mechanistic insights into CD’s ability to modify multiple oxidative stress–antioxidant system pathways, Nrf2, and neuroinflammation. Additionally, it points to the possible therapeutic potential and preventive utilization of CD in neurodegenerative diseases, most specifically AD. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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18 pages, 12883 KiB

Open AccessArticle

Protective Effects of Resveratrol on Adolescent Social Isolation-Induced Anxiety-Like Behaviors via Modulating Nucleus Accumbens Spine Plasticity and Mitochondrial Function in Female Rats

by Jinlan Zhao, Lihong Ye, Zuyi Liu, Yongfei Cui, Di Deng, Shasha Bai, Lei Yang, Yafei Shi, Zhongqiu Liu and Rong Zhang

Nutrients 2022, 14(21), 4542; https://doi.org/10.3390/nu14214542 - 28 Oct 2022

Cited by 5 | Viewed by 1982

Abstract

Social isolation (SI) is a major risk factor for mood disorders in adolescents. The nucleus accumbens (NAc) is an important reward center implicated in psychiatric disorders. Resveratrol (RSV) is one of the most effective natural polyphenols with anti-anxiety and depression effects. However, little is known about the therapeutic effects and mechanisms of RSV on behavioral abnormality of adolescent social stress. Therefore, this study aimed to investigate the underlying mechanism of RSV on the amelioration of SI-induced behavioral abnormality. We found that SI induced anxiety-like behavior and social dysfunction in isolated female rats. Moreover, SI reduced mitochondrial number and ATP levels and increased thin spine density in the NAc. RNA sequencing results showed that SI changed the transcription pattern in the NAc, including 519 upregulated genes and 610 downregulated genes, especially those related to mitochondrial function. Importantly, RSV ameliorated behavioral and spine abnormalities induced by SI and increased NAc ATP levels and mitochondria number. Furthermore, RSV increased the activity of cytochrome C oxidase (COX) and upregulated mRNA levels of Cox5a, Cox6a1 and Cox7c. These results demonstrate that the modulation of spine plasticity and mitochondrial function in the NAc by RSV has a therapeutic effect on mood disorders induced by social isolation. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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13 pages, 3670 KiB

Open AccessArticle

Caffeic Acid Alleviates Memory and Hippocampal Neurogenesis Deficits in Aging Rats Induced by D-Galactose

by Rasa Saenno, Oabnithi Dornlakorn, Tanaporn Anosri, Soraya Kaewngam, Apiwat Sirichoat, Anusara Aranarochana, Wanassanun Pannangrong, Peter Wigmore and Jariya Umka Welbat

Nutrients 2022, 14(10), 2169; https://doi.org/10.3390/nu14102169 - 23 May 2022

Cited by 6 | Viewed by 2460

Abstract

Hippocampal neurogenesis occurs throughout life, but it declines with age. D-galactose (D-gal) enhances cellular senescence through oxidative stress leading to neurodegeneration and memory impairment. Caffeic acid (CA) acts as an antioxidant via decreasing brain oxidative stress. This study aims to investigate the advantages of CA in alleviating the loss of memory and neurogenesis production in the hippocampus in aged rats activated by D-gal. Fifty-four male Sprague-Dawley rats were unpredictably arranged into six groups. In the D-gal group, rats were administered D-gal (50 mg/kg) by intraperitoneal (i.p.) injection. For the CA groups, rats received 20 or 40 mg/kg CA by oral gavage. In the co-treated groups, rats received D-gal (50 mg/kg) and CA (20 or 40 mg/kg) for eight weeks. The results of novel object location (NOL) and novel object recognition (NOR) tests showed memory deficits. Moreover, a decline of neurogenesis in the hippocampus was detected in rats that received D-gal by detecting rat endothelial cell antigen-1 (RECA-1)/Ki-67, 5-bromo-2′-deoxyuridine (BrdU)/neuronal nuclear protein (NeuN), doublecortin (DCX) by means of staining to evaluate blood vessel associated proliferating cells, neuronal cell survival and premature neurons, respectively. By contrast, CA attenuated these effects. Our results postulate that CA attenuated the impairment of memory in D-gal-stimulated aging by up-regulating levels of hippocampal neurogenesis. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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14 pages, 16183 KiB

Open AccessArticle

Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop

by Hengfang Tang, Zhiming Zheng, Han Wang, Li Wang, Genhai Zhao and Peng Wang

Nutrients 2022, 14(7), 1504; https://doi.org/10.3390/nu14071504 - 04 Apr 2022

Cited by 12 | Viewed by 5222 | Correction

Abstract

Vitamin K2, a natural fat-soluble vitamin, is a potent neuroprotective molecule, owing to its antioxidant effect, but its mechanism has not been fully elucidated. Therefore, we stimulated SH-SY5Y cells with 6-hydroxydopamine (6-OHDA) in a proper dose-dependent manner, followed by a treatment of vitamin K2. In the presence of 6-OHDA, cell viability was reduced, the mitochondrial membrane potential was decreased, and the accumulation of reactive oxygen species (ROS) was increased. Moreover, the treatment of 6-OHDA promoted mitochondria-mediated apoptosis and abnormal mitochondrial fission and fusion. However, vitamin K2 significantly suppressed 6-OHDA-induced changes. Vitamin K2 played a significant part in apoptosis by upregulating and downregulating Bcl-2 and Bax protein expressions, respectively, which inhibited mitochondrial depolarization, and ROS accumulation to maintain mitochondrial structure and functional stabilities. Additionally, vitamin K2 significantly inhibited the 6-OHDA-induced downregulation of the MFN1/2 level and upregulation of the DRP1 level, respectively, and this enabled cells to maintain the dynamic balance of mitochondrial fusion and fission. Furthermore, vitamin K2 treatments downregulated the expression level of p62 and upregulated the expression level of LC3A in 6-OHDA-treated cells via the PINK1/Parkin signaling pathway, thereby promoting mitophagy. Moreover, it induced mitochondrial biogenesis in 6-OHDA damaged cells by promoting the expression of PGC-1α, NRF1, and TFAM. These indicated that vitamin K2 can release mitochondrial damage, and that this effect is related to the participation of vitamin K2 in the regulation of the mitochondrial quality-control loop, through the maintenance of the mitochondrial quality-control system, and repair mitochondrial dysfunction, thereby alleviating neuronal cell death mediated by mitochondrial damage. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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16 pages, 26120 KiB

Open AccessArticle

The Neuroprotection of Verbascoside in Alzheimer’s Disease Mediated through Mitigation of Neuroinflammation via Blocking NF-κB-p65 Signaling

by Shanshan Chen, Honghan Liu, Shimiao Wang, Hongbo Jiang, Le Gao, Lu Wang, Lesheng Teng, Chunyue Wang and Di Wang

Nutrients 2022, 14(7), 1417; https://doi.org/10.3390/nu14071417 - 29 Mar 2022

Cited by 19 | Viewed by 3539

Abstract

Verbascoside (VB) is a phenylethanoid glycoside extracted from the herbaceous plant Verbascum sinuatum and plays a neuroprotective role in Alzheimer’s disease (AD). The goal of this study was to explore the neuroprotective mechanism of VB. Based on the proteomics analysis, immunohistochemistry, immunofluorescence, Western blot, and ELISA were utilized to explore the neuroprotective mechanism of VB in context of neuroinflammation in APP/PS1 mice, LPS-induced BV2 cells, and/or Aβ_1-42-stimulated N2a cells. Proteomic analysis demonstrated that the neuroprotection of VB correlated closely to its anti-inflammatory effect. VB significantly blocked microglia and astrocyte against activation in brains of APP/PS1 mice, suppressed the generation of IL-1β as well as IL-6, and boosted that of IL-4, IL-10 and TGF-β in vivo, which were analogous to results acquired in vitro. Furthermore, VB effectively restrained the phosphorylation of IKKα+β, IκBα, and NF-κB-p65 in APP/PS1 mice; LPS-induced BV2 cells, and Aβ_1-42-stimulated N2a cells and lowered the tendency of NF-κB-p65 translocation towards nucleus in vitro. These results demonstrate that the neuroprotective effect of VB correlates to the modulation of neuroinflammation via NF-κB-p65 pathway, making VB as a hopeful candidate drug for the prevention and treatment of AD. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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13 pages, 11940 KiB

Open AccessArticle

Effects of Peppermint Essential Oil on Learning and Memory Ability in APP/PS1 Transgenic Mice

by Xiaofan Lv, Yueyang Feng, Rui Ma, Yin Tang, Ye Li, Donghong Cui and Yani Wu

Molecules 2022, 27(7), 2051; https://doi.org/10.3390/molecules27072051 - 22 Mar 2022

Cited by 6 | Viewed by 5175

Abstract

Objective: To explore the effect and mechanism of peppermint essential oil on learning and memory ability of APP/PS1 transgenic mice. Methods: Morris water maze test and shuttle box test were used to explore the changes in learning and memory ability of APP/PS1 transgenic mice after sniffing essential oil. The cellular status of neurons in the hippocampal CA1 region of the right hemisphere, Aβ deposition, oxidative stress level, and serum metabonomics were detected to explore its mechanism. Results: Sniffing peppermint essential oil can improve the learning and memory ability of APP/PS1 transgenic mice. Compared with the model group, the state of neurons in the hippocampal CA1 region of the peppermint essential oil group returned to normal, and the deposition of Aβ decreased. The MDA of brain tissue decreased significantly, and the activity of SOD and GSH-PX increased significantly to the normal level. According to the results of metabonomics, it is speculated that peppermint essential oil may improve cognitive function in AD by regulating arginine and proline metabolism, inositol phosphate metabolism, and cysteine and methionine metabolism. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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18 pages, 3923 KiB

Open AccessArticle

Natural Dietary Compound Xanthohumol Regulates the Gut Microbiota and Its Metabolic Profile in a Mouse Model of Alzheimer’s Disease

by Wei Liu, Kaiwu He, Desheng Wu, Li Zhou, Guowei Li, Zequn Lin, Xifei Yang, Jianjun Liu and Maggie Pui Man Hoi

Molecules 2022, 27(4), 1281; https://doi.org/10.3390/molecules27041281 - 14 Feb 2022

Cited by 10 | Viewed by 2645

Abstract

Discovering new and effective drugs for the treatment of Alzheimer’s disease (AD) is a major clinical challenge. This study focuses on chemical modulation of the gut microbiome in an established murine AD model. We used the 16S rDNA sequencing technique to investigate the effect of xanthohumol (Xn) on the diversity of intestinal microflora in 2-month- and 6-month-old APP/PS1 mice, respectively. APP/PS1 and wild-type mice were treated by gavage with corn oil with or without Xn every other day for 90 days. Prior to and following treatment, animals were tested for spatial learning, cognitive and memory function. We found Xn reduced cognitive dysfunction in APP/PS1 mice and significantly regulated the composition and abundance of gut microbiota both in prevention experiments (with younger mice) and therapeutic experiments (with older mice). Differential microflora Gammaproteobacteria were significantly enriched in APP/PS1 mice treated with Xn. Nodosilineaceae and Rikenellaceae may be the specific microflora modulated by Xn. The penicillin and cephalosporin biosynthesis pathway and the atrazine degradation pathway may be the principal modulation pathways. Taken together, oral treatment with Xn may have a neuroprotective role by regulating the composition of intestinal microflora, a result that contributes to the scientific basis for a novel prophylactic and therapeutic approach to AD. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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10 pages, 653 KiB

Open AccessArticle

Synthesis and Insecticidal Activity of Fire Ant Venom Alkaloid-Based 2-Methyl-6-alkyl-Δ^1,6-piperideines

by Xiaoqing Wu, Guangyu Wang, Guangxin Xu and Li Chen

Molecules 2022, 27(3), 1107; https://doi.org/10.3390/molecules27031107 - 07 Feb 2022

Cited by 3 | Viewed by 2417

Abstract

2,6-dialkylpiperideines found in the venom of Solenopsis (Hymenoptera, Formicidae) fire ants are a range of compounds possessing various biological activities. A series of racemic 2-methyl-6-alkyl-Δ^1,6-piperideines were synthesized for chemical confirmation of the natural products found in fire ant venom, and the evaluation of their biological activity. Synthetic Δ^1,6-piperideines and the natural compounds in the cis-alkaloid fraction of Solenopsis invicta had identical mass spectra and retention times. Their insecticidal activities against the third-instar larvae of cotton bollworm (Helicoverpa armigera) were evaluated by using injection and topical application methods. All three compounds exhibited no lethal effect at concentrations of 0.05–0.4 mol/L by topical treatment, but moderate lethal effect at 0.4 mol/L through injection treatment. Compound 6a showed significantly higher activity than the natural insecticide nicotine. The differences in activity among compounds 6b, 6c and nicotine were not significant. The elongation of the carbon chain at the 6-position of the piperideine ring appears to decrease insecticidal activity. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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32 pages, 3122 KiB

Open AccessArticle

Guggulsterone Mediated JAK/STAT and PPAR-Gamma Modulation Prevents Neurobehavioral and Neurochemical Abnormalities in Propionic Acid-Induced Experimental Model of Autism

by Rishabh Khera, Sidharth Mehan, Sonalika Bhalla, Sumit Kumar, Abdulrahman Alshammari, Metab Alharbi and Satya Sai Sadhu

Molecules 2022, 27(3), 889; https://doi.org/10.3390/molecules27030889 - 28 Jan 2022

Cited by 24 | Viewed by 3888

Abstract

Autism spectrum disorder is a neurodevelopmental disorder marked by repetitive behaviour, challenges in verbal and non-verbal communication, poor socio-emotional health, and cognitive impairment. An increased level of signal transducer and activator of transcription 3 (STAT3) and a decreased level of peroxisome proliferator-activated receptor (PPAR) gamma have been linked to autism pathogenesis. Guggulsterone (GST) has a neuroprotective effect on autistic conditions by modulating these signalling pathways. Consequently, the primary objective of this study was to examine potential neuroprotective properties of GST by modulating JAK/STAT and PPAR-gamma levels in intracerebroventricular propionic acid (ICV PPA) induced experimental model of autism in adult rats. In this study, the first 11 days of ICV-PPA injections in rats resulted in autism-like behavioural, neurochemical, morphological, and histopathological changes. The above modifications were also observed in various biological samples, including brain homogenate, CSF, and blood plasma. GST was also observed to improve autism-like behavioural impairments in autistic rats treated with PPA, including locomotion, neuromuscular coordination, depression-like behaviour, spatial memory, cognition, and body weight. Prolonged GST treatment also restored neurochemical deficits in a dose-dependent manner. Chronic PPA administration increased STAT3 and decreased PPAR gamma in autistic rat brain, CSF, and blood plasma samples, which were reversed by GST. GST also restored the gross and histopathological alterations in PPA-treated rat brains. Our results indicate the neuroprotective effects of GST in preventing autism-related behavioural and neurochemical alterations. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antioxidants antioxidants	7.0	8.8	2012	13.9 Days	CHF 2900
Brain Sciences brainsci	3.3	3.9	2011	15.6 Days	CHF 2200
Molecules molecules	4.6	6.7	1996	14.6 Days	CHF 2700
Nutrients nutrients	5.9	9.0	2009	14.5 Days	CHF 2900
Plants plants	4.5	5.4	2012	15.3 Days	CHF 2700

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Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain

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