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Habiba SU, Choi HJ, Munni YA, Yang IJ, Haque MN, Moon IS. Neurotrophic Effects of Foeniculum vulgare Ethanol Extracts on Hippocampal Neurons: Role of Anethole in Neurite Outgrowth and Synaptic Development. Int J Mol Sci 2024; 25:12701. [PMID: 39684414 DOI: 10.3390/ijms252312701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/22/2024] [Accepted: 11/23/2024] [Indexed: 12/18/2024] Open
Abstract
Foeniculum vulgare Mill, commonly known as fennel, is an aromatic herb traditionally used for culinary and medicinal purposes, with potential therapeutic effects on neurological disorders. However, limited research has focused on its neurotrophic impact, particularly on neuronal maturation and synaptic development. This study investigates the neurotrophic effects of F. vulgare ethanol extracts (FVSE) on the maturation of rat primary hippocampal neurons. Results show that FVSE and its prominent component, anethole, significantly promote neurite outgrowth in a dose-dependent manner. Optimal axonal and dendritic growth occurred at concentrations of 40 µg/mL FVSE and 20 µM anethole, respectively, without causing cytotoxicity, underscoring the safety of FVSE for neuronal health. Additionally, FVSE enhances the formation of synapses, essential for neuronal communication. Network pharmacology analysis revealed that FVSE components influence critical neurotrophic pathways, including PI3K-AKT and Alzheimer's disease pathways. Specifically, FVSE modulates key proteins, including tropomyosin receptor kinase (Trk), glycogen synthase kinase 3 (GSK3βser9), phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated protein kinase (Erk1/2). Anethole was found to play a key role in regulating these pathways, which was confirmed by immunocytochemistry experiments demonstrating its effect on promoting neuronal growth and synaptic development. In conclusion, this study highlights the neurotrophic properties of FVSE, with anethole emerging as a critical bioactive compound. These findings provide valuable insights into the therapeutic potential of fennel in treating neurological disorders, offering a basis for future research into interventions promoting neuronal growth and survival.
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Affiliation(s)
- Sarmin Ummey Habiba
- Department of Anatomy, College of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea
| | - Ho Jin Choi
- Department of Anatomy, College of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea
- Medical Institute of Dongguk University, Gyeongju 38066, Republic of Korea
| | - Yeasmin Akter Munni
- Department of Anatomy, College of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea
- Department of Physiology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea
| | - In-Jun Yang
- Department of Physiology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea
| | - Md Nazmul Haque
- Department of Fisheries Biology and Genetics, Patuakhali Science and Technology University, Dumki 8602, Bangladesh
| | - Il Soo Moon
- Department of Anatomy, College of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea
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Moise G, Jîjie AR, Moacă EA, Predescu IA, Dehelean CA, Hegheș A, Vlad DC, Popescu R, Vlad CS. Plants' Impact on the Human Brain-Exploring the Neuroprotective and Neurotoxic Potential of Plants. Pharmaceuticals (Basel) 2024; 17:1339. [PMID: 39458980 PMCID: PMC11510325 DOI: 10.3390/ph17101339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 09/19/2024] [Accepted: 10/02/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Plants have long been recognized for their potential to influence neurological health, with both neuroprotective and neurotoxic properties. This review explores the dual nature of plant-derived compounds and their impact on the human brain. DISCUSSION Numerous studies have highlighted the neuroprotective effects of various phytoconstituents, such as those found in Ginkgo biloba, Centella asiatica, Panax ginseng, Withania somnifera, and Curcuma longa. The neuroprotective compounds have demonstrated antioxidant, anti-inflammatory, and cognitive-enhancing properties, making them promising candidates for combating neurodegenerative diseases and improving brain function. Polyphenolic compounds, triterpenic acids, and specific phytocompounds like the ones from EGb 761 extract have shown interactions with key enzymes and receptors in the brain, leading to neuroprotective outcomes. However, this review also acknowledges the neurotoxic potential of certain plants, such as the Veratrum species, which contains steroidal alkaloids that can cause DNA damage and disrupt neurological function, or Atropa belladonna, which interfere with the normal functioning of the cholinergic system in the body, leading to a range of symptoms associated with anticholinergic toxicity. CONSLUSIONS This review also emphasizes the need for further research to elucidate the complex mechanisms underlying the neuroprotective and neurotoxic effects of plant-derived compounds, as well as to identify novel phytoconstituents with therapeutic potential. Understanding the complex relationship between plants and the human brain is crucial for harnessing the benefits of neuroprotective compounds while mitigating the risks associated with neurotoxic substances. This review provides a comprehensive overview of the knowledge on the neurological properties of plants and highlights the importance of continued research in this field for the development of novel therapeutic strategies targeting brain health and neurological disorders.
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Affiliation(s)
- Georgiana Moise
- Department of Clinical Pharmacology, The Doctoral School of Medicine, “Pius Brînzeu” County Emergency Clinical Hospital Timisoara, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania;
| | - Alex-Robert Jîjie
- Department of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (A.-R.J.); (E.-A.M.); (I.-A.P.); (C.A.D.)
- Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Elena-Alina Moacă
- Department of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (A.-R.J.); (E.-A.M.); (I.-A.P.); (C.A.D.)
- Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Iasmina-Alexandra Predescu
- Department of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (A.-R.J.); (E.-A.M.); (I.-A.P.); (C.A.D.)
- Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Cristina Adriana Dehelean
- Department of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (A.-R.J.); (E.-A.M.); (I.-A.P.); (C.A.D.)
- Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Alina Hegheș
- Department II—Pharmaceutical Technology, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
- Formulation and Technology of Drugs Research Center, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Daliborca Cristina Vlad
- Department IV—Department of Biochemistry and Pharmacology, Division of Pharmacology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (D.C.V.); (C.S.V.)
- Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania;
| | - Roxana Popescu
- Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania;
- Department II—Department of Microscopic Morphology, Division of Cell and Molecular Biology II, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania
| | - Cristian Sebastian Vlad
- Department IV—Department of Biochemistry and Pharmacology, Division of Pharmacology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, 300041 Timisoara, Romania; (D.C.V.); (C.S.V.)
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Sharma H, Yang H, Sharma N, An SSA. Neuroprotection by Anethum graveolens (Dill) Seeds and Its Phytocompounds in SH-SY5Y Neuroblastoma Cell Lines and Acellular Assays. Int J Mol Sci 2024; 25:7104. [PMID: 39000210 PMCID: PMC11241255 DOI: 10.3390/ijms25137104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 06/25/2024] [Accepted: 06/25/2024] [Indexed: 07/16/2024] Open
Abstract
Neurodegeneration diseases (NDs) are a group of complex diseases primarily characterized by progressive loss of neurons affecting mental function and movement. Oxidative stress is one of the factors contributing to the pathogenesis of NDs, including Alzheimer's disease (AD). These reactive species disturb mitochondrial function and accelerate other undesirable conditions including tau phosphorylation, inflammation, and cell death. Therefore, preventing oxidative stress is one of the imperative methods in the treatment of NDs. To accomplish this, we prepared hexane and ethyl acetate extracts of Anethum graveolens (dill) and identified the major phyto-components (apiol, carvone, and dihydrocarvone) by GC-MS. The extracts and major bioactives were assessed for neuroprotective potential and mechanism in hydrogen peroxide-induced oxidative stress in the SH-SY5Y neuroblastoma cell model and other biochemical assays. The dill (extracts and bioactives) provided statistically significant neuroprotection from 0.1 to 30 µg/mL by mitigating ROS levels, restoring mitochondrial membrane potential, reducing lipid peroxidation, and reviving the glutathione ratio. They moderately inhibited acetylcholine esterase (IC50 dill extracts 400-500 µg/mL; carvone 275.7 µg/mL; apiole 388.3 µg/mL), displayed mild anti-Aβ1-42 fibrilization (DHC 26.6%) and good anti-oligomerization activity (>40% by dill-EA, carvone, and apiole). Such multifactorial neuroprotective displayed by dill and bioactives would help develop a safe, low-cost, and small-molecule drug for NDs.
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Affiliation(s)
| | | | - Niti Sharma
- Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujung-gu, Seongnam-si 461-701, Gyeonggi-do, Republic of Korea
| | - Seong Soo A. An
- Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujung-gu, Seongnam-si 461-701, Gyeonggi-do, Republic of Korea
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Yuca H, Aydin B, Karakaya S, Goger G, Bingöl Z, Civas A, Koca M, Demirci B, Sytar O, Gulcin I, Guvenalp Z. Exploring Astrodaucus orientalis (L.) Drude: Phytochemical Analysis and its Biological Potential Against Alzheimer's and Diabetes. Chem Biodivers 2024; 21:e202301753. [PMID: 38156418 DOI: 10.1002/cbdv.202301753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/26/2023] [Accepted: 12/28/2023] [Indexed: 12/30/2023]
Abstract
In current study antioxidant, antidiabetic, antimicrobial, anticholinesterase, and human carbonic anhydrase I, and II (hCA I and II) isoenzymes inhibition activities of Astrodaucus orientalis different parts were investigated. Achetylcholinesterse (AChE) and butyrylcholinesterse (BChE) inhibitory activities of octyl acetate were determined via molecular docking. Quantitative assessment of specific secondary metabolites was conducted using LC-MS/MS. An examination of chemical composition of essential oils was carried out by GC-MS/MS. A thorough exploration of plant's anatomical characteristics was undertaken. The highest phenolics level and DPPH antioxidant capacity were seen in root and fruit. Fruit essential oil demonstrated the highest AChE inhibition (44.13±3.61 %), while root dichloromethane sub-extract had the best inhibition towards BChE (86.13±2.58 %). Cytosolic hCA I, and II isoenzymes were influentially inhibited by root oil with 1.974 and 2.207 μM IC50 values, respectively. The most effective extracts were found to be root all extract/sub-extracts (except water) against C. tropicalis and C. krusei strains with MIC value 160>μg/mL. Sabinene (29.4 %), α-pinene (20.2 %); octyl acetate (54.3 %); myrcene (28.0 %); octyl octanoate (71.3 %) were found principal components of aerial parts, roots, flowers, and fruits, respectively. Flower essential oil, fruit dicloromethane and ethyl acetate exhibited potent α-glucosidase inhibitory activity with 900, 40, and 937 μg/mL IC50 values, respectively.
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Affiliation(s)
- Hafize Yuca
- Department of Pharmacognosy, Ataturk University, Faculty of Pharmacy, Erzurum, 25240, Türkiye
| | - Bilge Aydin
- Department of Pharmacognosy, Erzincan Binali Yıldırım University, Faculty of Pharmacy, Erzincan, 24002, Türkiye
| | - Songul Karakaya
- Department of Pharmaceutical Botany, Ataturk University, Faculty of Pharmacy, Erzurum, 25240, Türkiye
| | - Gamze Goger
- Department of Pharmacognosy, Afyonkarahisar Health University, Faculty of Pharmacy, Afyonkarahisar, 03030, Türkiye
| | - Zeynebe Bingöl
- Department of Medical Services and Techniques, Gaziosmanpasa University, Vocational School of Health Services, Tokat, 60000, Türkiye
| | - Ayşe Civas
- Department of Pharmacy and Pharmaceutical Services, Igdir University, Igdir, 76400, Türkiye
| | - Mehmet Koca
- Department of Pharmaceutical Chemistry, Ataturk University, Faculty of Pharmacy, Erzurum, 25240, Türkiye
| | - Betül Demirci
- Department of Pharmacognosy, Anadolu University, Faculty of Pharmacy, Eskisehir, 26470, Türkiye
| | - Oksana Sytar
- Department of Plant Physiology, Slovak University of Agriculture, Nitra, 94976, Slovak Republic
| | - Ilhami Gulcin
- Department of Chemistry, Ataturk University, Faculty of Science, Erzurum, 25240, Türkiye
| | - Zuhal Guvenalp
- Department of Pharmacognosy, Ataturk University, Faculty of Pharmacy, Erzurum, 25240, Türkiye
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Sharma H, Kim DY, Shim KH, Sharma N, An SSA. Multi-Targeting Neuroprotective Effects of Syzygium aromaticum Bud Extracts and Their Key Phytocompounds against Neurodegenerative Diseases. Int J Mol Sci 2023; 24:8148. [PMID: 37175851 PMCID: PMC10178913 DOI: 10.3390/ijms24098148] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 04/20/2023] [Accepted: 04/26/2023] [Indexed: 05/15/2023] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that causes a gradual loss of normal motor and cognitive function. The complex AD pathophysiology involves various factors such as oxidative stress, neuroinflammation, amyloid-beta (Aβ) aggregation, disturbed neurotransmission, and apoptosis. The available drugs suffer from a range of side effects and are not able to cover different aspects of the disease. Therefore, finding a safer therapeutic approach that can affect multiple targets at a time is highly desirable. In the present study, the underlying neuroprotective mechanism of an important culinary spice, Syzygium aromaticum (Clove) extract, and major bioactive compounds were studied in hydrogen peroxide-induced oxidative stress in human neuroblastoma SH-SY5Y cell lines as a model. The extracts were subjected to GC-MS to identify important bioactive components. The extracts and key bio-actives reduced reactive oxygen species (ROS), restored mitochondrial membrane potential (MMP), and provided neuroprotection from H2O2-induced oxidative stress in cell-based assays due to the antioxidant action. They also reduced lipid peroxidation significantly and restored GSH content. Clove extracts have also displayed anti-acetylcholinesterase (AChE) activity, anti-glycation potential, and Aβ aggregation/fibrilization inhibition. The multitarget neuroprotective approach displayed by Clove makes it a potential candidate for AD drug development.
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Affiliation(s)
| | | | | | - Niti Sharma
- Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 461-701, Gyeonggi-do, Republic of Korea
| | - Seong Soo A. An
- Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 461-701, Gyeonggi-do, Republic of Korea
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Antioxidant Activity of Urtica dioica: An Important Property Contributing to Multiple Biological Activities. Antioxidants (Basel) 2022; 11:antiox11122494. [PMID: 36552702 PMCID: PMC9774934 DOI: 10.3390/antiox11122494] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
Urtica dioica (UD) is a multi-functional plant known to be used as both food and medicine from ancient times. The plant has the potential to be used as a fertilizer and for biological pest control. It is also used in textile and related industries for its quality fibers. In the recent past, the plant has received great attention for its numerous important biological activities and food applications. The antioxidant activity of UD is the crucial factor supporting its important biological activities, such as anticancer, antidiabetic and anti-inflammatory properties. The antioxidant activity of UD is also found to be protective in different organs, including the brain, liver, lungs, kidney, ovary, and uterus, and may also be protective against diseases associated with these organs. Few clinical studies have endorsed the antioxidant potential of UD in patients. The current work is an attempt to comprehensively compile and discuss the antioxidant activity of UD from in vitro, in vivo and human studies. The insights of the current study would be helpful in getting a panoramic view of the antioxidant potential of UD, and provide direction for optimizing and developing it for therapeutic applications against important diseases and conditions in the near future.
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Dibacto REK, Ngoumen DJN, Ella FA, Nanhah JVK, Ambamba BDA, Hagbe PV, Fonkoua M, Mandob DE, Minka RS, Ngondi JL. In vitro anticholinesterase potential of some spices consumed in Cameroon and their protective effects on hydrogen peroxide-mediated oxidative stress damage in SK-N-SH cells. IBRO Neurosci Rep 2022; 13:107-113. [PMID: 35874495 PMCID: PMC9305342 DOI: 10.1016/j.ibneur.2022.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/10/2022] [Accepted: 07/10/2022] [Indexed: 11/23/2022] Open
Abstract
Background Many neurodegenerative such as Alzheimer's disease (AD) are characterized by cholinergic dysfunction and oxidative stress which is a key event in neuronal death process. Thus, anticholinesterase and anti-oxidation compounds are two promising strategies in the development of AD drugs. Beyond their culinary use, spices are today studies for health purpose. In this study, some spices consumed in Cameroon were evaluated for their anticholinesterase and neuroprotective effects. Methods Colorimetric methods were used to determine total flavonoid and alkaloid content of a combinated extract (hydroethanolic + ethanolic extracts) of different selected spices. Aftermaths, anti-cholinesterase activity of spice extract was carried out using Ellman’s method. Finally, neuroprotective effects performed on human SK-N-SH cells stressed with H2O2 by assessing neuronal survival ( resazurin assay) and neuronal death (LDH assay). Results Flavonoid content of spices extract were ranged from 22.94 to 32.01 mg EQ/g DM and alkaloid content were ranged from 320 to 896 mg EQu/g DM. Among the spices studied, Xylopia parviflora presented the greatest acetylcholinesterase inhibition with an IC50 = 14 µg/mL. In Cell culture experiments, pre-incubation of SK-N-SH cell with the selected spices at different concentrations were improved neuronal survival and reduced the percentage of neuronal cells dead. Conclusion The present results reveal that selected spices consumed in Cameroon have good anticholinesterase activity as well as neuroprotective effect on SK-N-SH which may provide new natural compounds that could help in the management of Alzheimer's disease.
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Phyto-Carbazole Alkaloids from the Rutaceae Family as Potential Protective Agents against Neurodegenerative Diseases. Antioxidants (Basel) 2022; 11:antiox11030493. [PMID: 35326143 PMCID: PMC8944741 DOI: 10.3390/antiox11030493] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/11/2022] [Accepted: 02/22/2022] [Indexed: 12/12/2022] Open
Abstract
Plant-derived (phyto) carbazole alkaloids are an important class of compounds, presented in the family of Rutaceae (Genera Murraya, Clausena, Glycosmis, Micromelum and Zanthoxylum). Due to several significant biological activities, such as antitumor, antibacterial, antiviral, antidiabetic, anti-HIV and neuroprotective activities of the parent skeleton (3-methylcarbazole), carbazole alkaloids are recognized as an important class of potential therapeutic agents. Neurodegenerative diseases (NDs) may exhibit a vast range of conditions, affecting neurons primarily and leading ultimately to the progressive losses of normal motor and cognitive functions. The main pathophysiological indicators of NDs comprise increasing atypical protein folding, oxidative stresses, mitochondrial dysfunctions, deranged neurotransmissions and neuronal losses. Phyto-carbazole alkaloids can be investigated for exerting multitarget approaches to ameliorating NDs. This review presents a comprehensive evaluation of the available scientific literature on the neuroprotective mechanisms of phyto-carbazole alkaloids from the Rutaceae family in ameliorating NDs.
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