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Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms
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Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 16594

Special Issue Editors

Dr. Wei Peng

E-Mail Website
Guest Editor
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Interests: natural product; herbal medicine; apoptosis; tumor; neurodegenerative diseases; rheumatoid arthritis
Dr. Yunhui Chen

E-Mail Website
Guest Editor
College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Interests: natural product; alternative and complementary medicine; neurodegenerative diseases; depression; clinical trial; drug discovery
Dr. Yongmei Xie

E-Mail Website
Guest Editor
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Interests: PROTAC technology-based innovative drug development; radiological diagnosis reagents; synthesis and activity of small molecule drugs; targets of active small molecules
Prof. Dr. Xiuping Chen

E-Mail Website
Guest Editor
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
Interests: pharmacology; reactive oxygen species; cell death; epithelial–mesenchymal transition; cancer; fibrosis; drug discovery

Special Issue Information

Dear Colleagues,

There is no doubt that neuron injury is closely related to various diseases, such as neurodegenerative diseases (NDDs), stroke, epilepsy, and depression. However, drugs for neuroprotection in these diseases are currently unavailable. Interestingly, research has increasingly suggested that natural herbal medicines and their products are beneficial for controlling or preventing neuron injury. This Special Issue, "Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms", aims to publish original research and review articles that explore potential topics, including but not limited to the following: 

  1. Novel natural products with neuroprotective activities;
  2. New strategies for finding potential drugs with neuroprotective activities from plants, animals, microorganisms, and minerals, in particular network pharmacology, artificial intelligence, computer-aided design, etc.;
  3. Novel drug targets for natural neuroprotective agents against neuron injury in NDDs, stroke, epilepsy, depression, etc.;
  4. Recent advances of natural neuroprotective agents from plants, animals, microorganisms, and minerals and their potential molecular mechanisms;
  5. Potential natural agents alleviating toxicities of currently available drugs for neuroprotection in NDDs, stroke, epilepsy, and depression.

Dr. Wei Peng
Dr. Yunhui Chen
Dr. Yongmei Xie
Prof. Dr. Xiuping Chen
Guest Editors

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Keywords

  • natural product
  • neuroprotective agents
  • neuron injury
  • recent advances
  • potential molecular mechanisms

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Published Papers (6 papers)

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Research

15 pages, 5018 KiB  
Article
Protective Effect of Ferulic Acid on Lipopolysaccharide-Induced BV2 Microglia Inflammation via AMPK/mTOR Signaling Pathway
by Xingru Chen, Xiaolan Zhou, Xiaoqing Cheng, Liting Lin, Qi Wang, Ruoting Zhan, Qingguang Wu and Sijun Liu
Molecules 2023, 28(8), 3482; https://doi.org/10.3390/molecules28083482 - 14 Apr 2023
Cited by 15 | Viewed by 2373
Abstract
In neurodegenerative diseases, microglial activation and neuroinflammation are essential for the control and progression of neurodegenerative diseases. Mitigating microglium-induced inflammation is one strategy for hindering the progression of neurodegenerative diseases. Ferulic acid (FA) is an effective anti-inflammatory agent, but its potential role and [...] Read more.
In neurodegenerative diseases, microglial activation and neuroinflammation are essential for the control and progression of neurodegenerative diseases. Mitigating microglium-induced inflammation is one strategy for hindering the progression of neurodegenerative diseases. Ferulic acid (FA) is an effective anti-inflammatory agent, but its potential role and regulation mechanism in neuroinflammatory reactions have not been fully studied. In this study, the neuroinflammation model was established by lipopolysaccharide (LPS), and the inhibitory effect of FA on neuroinflammation of BV2 microglia was studied. The results showed that FA significantly reduced the production and expression of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), leukocyte-6 (IL-6) and interleukin-1β (IL-1β). We further studied the mechanism of FA’s regulation of LPS-induced BV2 neuroinflammation and found that FA can significantly reduce the expression of mTOR in BV2 microglia induced by LPS, and significantly increase the expression of AMPK, indicating that FA may have an anti-inflammatory effect by activating the AMPK/mTOR signaling pathway to regulate the release of inflammatory mediators (such as NLRP3, caspase-1 p20 and IL-1β). We further added an autophagy inhibitor (3-MA) and an AMPK inhibitor (compound C, CC) for reverse verification. The results showed that FA’s inhibitory effects on TNF-α, IL-6 and IL-1β and its regulatory effect on AMPK/mTOR were destroyed by 3-MA and CC, which further indicated that FA’s inhibitory effect on neuroinflammation is related to its activation of the AMPK/mTOR autophagy signaling pathway. In a word, our experimental results show that FA can inhibit LPS-induced neuroinflammation of BV2 microglia by activating the AMPK/mTOR signaling pathway, and FA may be a potential drug for treating neuroinflammatory diseases. Full article
(This article belongs to the Special Issue Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms)
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16 pages, 5748 KiB  
Article
Gastrodin and Gastrodigenin Improve Energy Metabolism Disorders and Mitochondrial Dysfunction to Antagonize Vascular Dementia
by Sha Wu, Rong Huang, Ruiqin Zhang, Chuang Xiao, Lueli Wang, Min Luo, Na Song, Jie Zhang, Fang Yang, Xuan Liu and Weimin Yang
Molecules 2023, 28(6), 2598; https://doi.org/10.3390/molecules28062598 - 13 Mar 2023
Cited by 15 | Viewed by 2780
Abstract
Vascular dementia (VD) is the second most common dementia syndrome worldwide, and effective treatments are lacking. Gastrodia elata Blume (GEB) has been used in traditional Chinese herbal medicine for centuries to treat cognitive impairment, ischemic stroke, epilepsy, and dizziness. Gastrodin (p-hydroxymethylphenyl-b- [...] Read more.
Vascular dementia (VD) is the second most common dementia syndrome worldwide, and effective treatments are lacking. Gastrodia elata Blume (GEB) has been used in traditional Chinese herbal medicine for centuries to treat cognitive impairment, ischemic stroke, epilepsy, and dizziness. Gastrodin (p-hydroxymethylphenyl-b-D-glucopyranoside, Gas) and Gastrodigenin (p-hydroxybenzyl alcohol, HBA) are the main bioactive components of GEB. This study explored the effects of Gas and HBA on cognitive dysfunction in VD and their possible molecular mechanisms. The VD model was established by bilateral common carotid artery ligation (2-vessel occlusion, 2-VO) combined with an intraperitoneal injection of sodium nitroprusside solution. One week after modeling, Gas (25 and 50 mg/kg, i.g.) and HBA (25 and 50 mg/kg, i.g.) were administered orally for four weeks, and the efficacy was evaluated. A Morris water maze test and passive avoidance test were used to observe their cognitive function, and H&E staining and Nissl staining were used to observe the neuronal morphological changes; the expressions of Aβ1-42 and p-tau396 were detected by immunohistochemistry, and the changes in energy metabolism in the brain tissue of VD rats were analyzed by targeted quantitative metabolomics. Finally, a Hippocampus XF analyzer measured mitochondrial respiration in H2O2-treated HT-22 cells. Our study showed that Gas and HBA attenuated learning memory dysfunction and neuronal damage and reduced the accumulation of Aβ1-42, P-Tau396, and P-Tau217 proteins in the brain tissue. Furthermore, Gas and HBA improved energy metabolism disorders in rats, involving metabolic pathways such as glycolysis, tricarboxylic acid cycle, and the pentose phosphate pathway, and reducing oxidative damage-induced cellular mitochondrial dysfunction. The above results indicated that Gas and HBA may exert neuroprotective effects on VD by regulating energy metabolism and mitochondrial function. Full article
(This article belongs to the Special Issue Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms)
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13 pages, 3887 KiB  
Article
Characterization of Polysaccharides from the Pericarp of Zanthoxylum bungeanum Maxim by Saccharide Mapping and Their Neuroprotective Effects
by Mei-Bian Hu, Kui-Xu Gao, Yao Wang and Yu-Jie Liu
Molecules 2023, 28(4), 1813; https://doi.org/10.3390/molecules28041813 - 15 Feb 2023
Cited by 6 | Viewed by 1797
Abstract
The pericarp of Zanthoxylum bungeanum maxim (PZM) is a commonly used spice and herbal medicine in China. In the present study, the structural characteristics of PPZM were investigated by saccharide mapping after enzymatic digestion by using high-performance thin layer chromatography (HPTLC) and polysaccharide [...] Read more.
The pericarp of Zanthoxylum bungeanum maxim (PZM) is a commonly used spice and herbal medicine in China. In the present study, the structural characteristics of PPZM were investigated by saccharide mapping after enzymatic digestion by using high-performance thin layer chromatography (HPTLC) and polysaccharide analysis by using carbohydrate gel electrophoresis (PACE). The mechanisms of protective effects of PPZM on Aβ25–35-induced oxidative damage were explored in PC12 cells. The results showed that PPZM contained 1,4-α-D-galactosidic, 1,4-α-D-galactosiduronic, and (1→4)-β-D-glucosidic linkages. Pretreatment with PPZM significantly increased the cell viability of Aβ25–35-injured PC12 cells. Flow cytometry and Hoechst/PI staining indicated that PPZM gradually relieved the apoptosis of the Aβ25–25-treated cells. PPZM markedly decreased the ROS level of PC12 cells and suppressed Aβ25–35-induced oxidative stress by increasing the SOD level, and decreasing the level of MDA and LDH. The mRNA expressions of caspase-3 and Bax were significantly downregulated, and Bcl-2 expression was upregulated by treatment with PPZM. PPZM significantly increased the mRNA expression of Nrf2 and HO-1 in Aβ25–35 treated cells. The results indicated that PPZM alleviated apoptosis and oxidative stress induced by Aβ25–25 through the inhibition of mitochondrial dependent apoptosis and activation of Nrf2/HO-1 pathway. PPZM can be used as a potential protective agent against Aβ25–25-induced neurotoxicity. Full article
(This article belongs to the Special Issue Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms)
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12 pages, 3138 KiB  
Article
Neuroprotective Effect of α-Lipoic Acid against Aβ25–35-Induced Damage in BV2 Cells
by Xinrong Pei, Fangyan Hu, Zehui Hu, Feiya Luo, Xiaoling Li, Shuxia Xing, Lei Sun and Dingxin Long
Molecules 2023, 28(3), 1168; https://doi.org/10.3390/molecules28031168 - 24 Jan 2023
Cited by 6 | Viewed by 2401
Abstract
The prevalence of Alzheimer’s disease (AD) is significantly increasing due to the aging world population, and the currently available drug treatments cannot cure or even slow its progression. α-lipoic acid (LA) is a biological factor widely found in spinach and meat and can [...] Read more.
The prevalence of Alzheimer’s disease (AD) is significantly increasing due to the aging world population, and the currently available drug treatments cannot cure or even slow its progression. α-lipoic acid (LA) is a biological factor widely found in spinach and meat and can dissolve in both lipid and aqueous phases. In medicine, LA has been shown to reduce the symptoms of diabetic polyneuropathy, acute kidney injury, cancers, and some metabolism-related diseases. This study to proves that α-lipoic acid (LA) can stabilize the cognitive function of patients with Alzheimer’s disease (AD). BV2 cells were divided into control, LA, Aβ25–35, and LA + Aβ25–35 groups. Cell growth; IL-6, IL-1β, TNF-α, IFN-γ, SOD, GPx, CAT, ROS, NO, and iNOS secretion; Wnt-related proteins; cell apoptosis; and cell activation were examined. Here, we found that LA could effectively repress apoptosis and changes in the morphology of microglia BV2 cells activated by Aβ25–35, accompanied by the inhibition of the inflammatory response induced by Aβ25–35. The Wnt/β-catenin pathway is also involved in preventing Aβ25–35-induced cytotoxicity in microglia by LA. We found an inhibitory effect of LA on microglia toxicity induced by Aβ25–35, suggesting that a combination of anti-inflammatory and antioxidant substances may offer a promising approach to the treatment of AD. Full article
(This article belongs to the Special Issue Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms)
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21 pages, 3056 KiB  
Article
Cleistocalyx nervosum var. paniala Berry Promotes Antioxidant Response and Suppresses Glutamate-Induced Cell Death via SIRT1/Nrf2 Survival Pathway in Hippocampal HT22 Neuronal Cells
by Wanchanok Nantacharoen, Seung Joon Baek, Waluga Plaingam, Somsri Charoenkiatkul, Tewin Tencomnao and Monruedee Sukprasansap
Molecules 2022, 27(18), 5813; https://doi.org/10.3390/molecules27185813 - 8 Sep 2022
Cited by 7 | Viewed by 3424
Abstract
Excessive glutamate neurotransmitters result in oxidative neurotoxicity, similar to neurodegeneration. An indigenous berry of Thailand, Cleistocalyx nervosum var. paniala (CNP), has been recognized for its robust antioxidants. We investigated the effects and mechanisms of CNP fruit extracts on antioxidant-related survival pathways against glutamate-induced [...] Read more.
Excessive glutamate neurotransmitters result in oxidative neurotoxicity, similar to neurodegeneration. An indigenous berry of Thailand, Cleistocalyx nervosum var. paniala (CNP), has been recognized for its robust antioxidants. We investigated the effects and mechanisms of CNP fruit extracts on antioxidant-related survival pathways against glutamate-induced neurotoxicity. The extract showed strong antioxidant capability and had high total phenolic and flavonoid contents, particularly resveratrol. Next, the protective effects of the CNP extract or resveratrol on the glutamate-induced neurotoxicity were examined in HT22 hippocampal cells. Our investigation showed that the pretreatment of cells with the CNP extract or resveratrol attenuated glutamate-induced neuronal death via suppression of apoptosis cascade by inhibiting the levels of cleaved- and pro-caspase-3 proteins. The CNP extract and resveratrol suppressed the intracellular ROS by increasing the mRNA expression level of antioxidant enzymes (SODs, GPx1, and CAT). We found that this extract and resveratrol significantly increased SIRT1 expression as a survival-related protein. Moreover, they also promoted the activity of the Nrf2 protein translocation into the nucleus and could bind to the promoter containing the antioxidant response element, inducing the expression of the downstream GPx1-antioxidant protein. Our data illustrate that the CNP extract and resveratrol inhibit apoptotic neuronal death via glutamate-induced oxidative neurotoxicity in HT22 cells through the activation of the SIRT1/Nrf2 survival mechanism. Full article
(This article belongs to the Special Issue Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms)
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24 pages, 9441 KiB  
Article
A Novel Based-Network Strategy to Identify Phytochemicals from Radix Salviae Miltiorrhizae (Danshen) for Treating Alzheimer’s Disease
by Bo Li, Yu-Rui Wu, Lan Li, Yu Liu and Zhu-Yun Yan
Molecules 2022, 27(14), 4463; https://doi.org/10.3390/molecules27144463 - 12 Jul 2022
Cited by 3 | Viewed by 2700
Abstract
Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that strikes millions worldwide. Herein, we demonstrate a new approach based on network target to identify anti-AD compounds from Danshen. Network pharmacology and molecular docking were employed to establish the DS-AD network, which mainly [...] Read more.
Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that strikes millions worldwide. Herein, we demonstrate a new approach based on network target to identify anti-AD compounds from Danshen. Network pharmacology and molecular docking were employed to establish the DS-AD network, which mainly involved apoptosis of neuron cells. Then network scoring was confirmed via Connectivity Map analysis. M308 (Danshenxinkun D) was an anti-AD candidate with a high score (p < 0.01). Furthermore, we conducted ex vivo experiments with H2O2-treated PC12 cells to verify the neuroprotective effect of Salvia miltiorrhiza-containing plasma (SMP), and UPLC-Q-TOF/MS and RT-qPCR were performed to demonstrate the anti-AD activity of M308 from SMP. Results revealed that SMP could enhance cell viability and level of acetylcholine. AO/EB staining and Mitochondrial membrane potential (MMP) analysis showed that SMP significantly suppressed apoptosis, which may be due to anti-oxidative stress activity. Moreover, the effects of M308 and SMP on expressions of PSEN1, DRD2, and APP mRNA were consistent, and M308 can significantly reverse the expression of PSEN1 and DRD2 mRNA in H2O2-treated PC12 cells. The strategy based on the network could be employed to identify anti-AD compounds from Chinese herbs. Notably, M308 stands out as a promising anti-AD candidate for development. Full article
(This article belongs to the Special Issue Neuroprotective Agents from Natural Products and Their Related Molecular Mechanisms)
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