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Natural Products for Neuroprotection and Neurodegeneration
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Natural Products for Neuroprotection and Neurodegeneration

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

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1875

Special Issue Editor

Dr. Patrycja Kupnicka

E-Mail Website
Guest Editor
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
Interests: neurodegeneration; tissue regeneration; neuroprotection; toxicity; natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,  

Natural products exhibit promising neuroprotective properties and may play a significant role in treating and preventing neurodegenerative diseases such as Alzheimer's and Parkinson's. Their bioactive compounds, including antioxidants and anti-inflammatory agents, can modulate key biological pathways that are crucial to neuron survival. Numerous studies have demonstrated the role of bioactive compounds derived from plants, fruits, vegetables, and nuts, as well as aquatic biota, in stimulating nerve growth factor release, regulating inflammatory processes, reducing oxidative stress, and safeguarding nerve cells from apoptosis. Their efficacy in preclinical models is well documented. However, challenges remain in their application, concerning their physicochemical stability, solubility, metabolism, blood–brain barrier penetration, and therapeutic effectiveness. Despite these challenges, natural products offer potential benefits in the treatment and prevention of neurodegenerative diseases, and further research is required, to fully harness their capabilities. 

This Special Issue of IJMS will address the following topics:  

  • Natural products in the treatment and prevention of neurodegenerative diseases;
  • Molecular and cellular mechanisms of bioactive compounds in the central nervous system;
  • Bioactive compounds in neuroprotection;
  • Bioactive compounds in neuroregeneration;
  • Optimizing natural compounds for enhanced therapeutic effectiveness.  

Dr. Patrycja Kupnicka
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • natural products
  • bioactive compounds
  • neuroprotection
  • neurodegeneration

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Published Papers (3 papers)

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Research

18 pages, 9930 KiB  
Article
The Neuroprotective Potential of Seed Extract from the Indian Trumpet Tree Against Amyloid Beta-Induced Toxicity in SH-SY5Y Cells
by Nut Palachai, Benjaporn Buranrat, Parinya Noisa and Nootchanat Mairuae
Int. J. Mol. Sci. 2025, 26(13), 6288; https://doi.org/10.3390/ijms26136288 - 29 Jun 2025
Viewed by 447
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with an unclear etiology. Multiple factors, including oxidative stress and the accumulation of amyloid beta (Aβ) protein in the brain, contribute to neuronal damage. This study investigated Aβ-induced oxidative stress and cellular damage in SH-SY5Y [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with an unclear etiology. Multiple factors, including oxidative stress and the accumulation of amyloid beta (Aβ) protein in the brain, contribute to neuronal damage. This study investigated Aβ-induced oxidative stress and cellular damage in SH-SY5Y cells, as well as the neuroprotective potential of Indian trumpet tree seed extract (ITS). SH-SY5Y cells were co-treated with Aβ(25–35) (20 µM) and ITS extract at concentrations of 25 and 50 µg/mL. Cell viability, reactive oxygen species (ROS), malondialdehyde (MDA) levels, and the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were assessed. The expression levels of B-cell lymphoma 2 (Bcl-2) and caspase-3, along with the phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and cAMP response element-binding protein (CREB), were also evaluated. ITS extract at concentrations of 25 and 50 µg/mL significantly improved SH-SY5Y cell viability following Aβ-induced damage; reduced ROS and MDA levels; and enhanced CAT, SOD, and GSH-Px activities. In addition to upregulating Bcl-2 expression, ITS downregulated caspase-3 expression and increased the phosphorylation of Akt, ERK1/2, and CREB. High-performance liquid chromatography (HPLC) analysis identified baicalin, baicalein, and chrysin as major phenolic compounds in ITS extract. In conclusion, ITS extract attenuated Aβ-induced oxidative stress, enhanced antioxidant defenses and cell viability, suppressed apoptotic signaling, and activated key neuroprotective pathways. These findings provide new insights into the neuroprotective potential of ITS extract; however, further in vivo studies are needed to validate its clinical applicability. Full article
(This article belongs to the Special Issue Natural Products for Neuroprotection and Neurodegeneration)
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20 pages, 1856 KiB  
Article
Pharmacological Evaluation of a Traditional Thai Polyherbal Formula for Alzheimer’s Disease: Evidence from In Vitro and In Silico Studies
by Pornthip Waiwut, Pitchayakarn Takomthong, Rutchayaporn Anorach, Nattareeyada Lomaboot, Supawadee Daodee, Yaowared Chulikhit, Orawan Monthakantirat, Charinya Khamphukdee and Chantana Boonyarat
Int. J. Mol. Sci. 2025, 26(13), 6287; https://doi.org/10.3390/ijms26136287 - 29 Jun 2025
Viewed by 369
Abstract
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by multifactorial pathogenesis, including oxidative stress, cholinergic dysfunction, β-amyloid (Aβ) aggregation, and neuroinflammation. In this study, we investigated the neuroprotective potential of the Pheka capsule (PC) formula, a traditional Thai polyherbal medicine comprising Oroxylum [...] Read more.
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by multifactorial pathogenesis, including oxidative stress, cholinergic dysfunction, β-amyloid (Aβ) aggregation, and neuroinflammation. In this study, we investigated the neuroprotective potential of the Pheka capsule (PC) formula, a traditional Thai polyherbal medicine comprising Oroxylum indicum (OI), Zingiber officinale (ZO), and Boesenbergia rotunda (BR). Phytochemical analysis by HPLC confirmed the presence of key bioactive compounds including baicalein, baicalin, oroxylin A, 6-gingerol, 6-shogaol, pinocembrin, and pinostrobin. The PC formula exhibited strong antioxidant activity, highly selective butyrylcholinesterase (BChE) inhibition with a selectivity index (SI) of BChE > 20, suppression of Aβ aggregation, and protection against H2O2-induced neuronal damage in vitro. Network pharmacology analysis identified multiple AD-relevant targets and pathways, including APP, GSK3B, CASP3, GAPDH, PTGS2, and PPARG, implicating the PC formula in modulating oxidative stress, apoptosis, and inflammation. Notably, OI emerged as the primary contributor to the formula’s multitargeted actions. These findings support the therapeutic potential of the PC formula as a multitarget agent for AD, aligning with the growing interest in polypharmacological strategies for complex neurodegenerative diseases. Further in vivo and clinical studies are warranted to confirm its efficacy and safety. Full article
(This article belongs to the Special Issue Natural Products for Neuroprotection and Neurodegeneration)
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20 pages, 3284 KiB  
Article
Suk-SaiYasna Remedy, a Traditional Thai Medicine, Mitigates Stress-Induced Cognitive Impairment via Keap1-Nrf2 Pathway
by Wuttipong Masraksa, Supawadee Daodee, Orawan Monthakantirat, Chantana Boonyarat, Charinya Khamphukdee, Pakakrong Kwankhao, Abdulwaris Mading, Poowanarth Muenhong, Juthamart Maneenet, Suresh Awale, Kinzo Matsumoto and Yaowared Chulikhit
Int. J. Mol. Sci. 2025, 26(11), 5388; https://doi.org/10.3390/ijms26115388 - 4 Jun 2025
Viewed by 816
Abstract
Suk-SaiYasna (SSY) is a well-documented traditional Thai herbal formula in the Royal Scripture of King Narai’s Traditional Medicine. SSY contains Cannabis sativa leaves as a key ingredient and has traditionally been used to promote sleep, alleviate stress-related symptoms, and stimulate appetite. This study [...] Read more.
Suk-SaiYasna (SSY) is a well-documented traditional Thai herbal formula in the Royal Scripture of King Narai’s Traditional Medicine. SSY contains Cannabis sativa leaves as a key ingredient and has traditionally been used to promote sleep, alleviate stress-related symptoms, and stimulate appetite. This study aimed to investigate the neuroprotective effects of SSY in a mouse model of unpredictable chronic mild stress (UCMS)-induced cognitive impairment and explore the underlying mechanisms, particularly antioxidant enzyme pathways. Behavioral tests, including the Y-maze test, novel object recognition test, and Morris water maze test, demonstrated that UCMS-exposed mice exhibited cognitive impairment compared to non-stress mice. However, SSY treatment significantly improved learning and memory performance in UCMS-exposed mice. Mechanistic studies revealed that SSY reduced lipid peroxidation in the hippocampus and frontal cortex, key brain regions affected by chronic stress. Furthermore, UCMS significantly reduced the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), whereas SSY treatment restored their activity, indicating antioxidative and neuroprotective effects in vivo. Gene expression analysis further revealed that SSY regulates oxidative stress via the Nrf2/Keap1 signaling pathway. In vitro studies using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay confirmed the radical scavenging activities of SSY and its herbal components, demonstrating significant antioxidant potential. Phytochemical analysis identified delta-9-tetrahydrocannabinol, delta-9-tetrahydrocannabinolic acid A, and cannabinoids as bioactive compounds in SSY, along with potent antioxidants such as gallic acid, myricetin, myristicin, piperine, costunolide, and gingerol. These findings suggest that the SSY formula mitigates UCMS-induced cognitive function through its antioxidant properties via multiple pathways, including radical scavenging activities, modulating the Nrf2-Keap1 pathway, inducing the expression of HO-1, NQO1 mRNAs, and other antioxidant enzymes. This work bridges traditional Thai medicine with modern neuropharmacology. Full article
(This article belongs to the Special Issue Natural Products for Neuroprotection and Neurodegeneration)
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