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1.
Arch Toxicol ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837048

RESUMO

As a critical cause of human dysfunctionality, hepatic failure leads to approximately two million deaths per year and is on the rise. Considering multiple inflammatory, oxidative, and apoptotic mechanisms behind hepatotoxicity, it urges the need for finding novel multi-targeting agents. Curcumin is a phenolic compound with anti-inflammatory, antioxidant, and anti-apoptotic roles. Curcumin possesses auspicious health benefits and protects against several diseases with exceptional safety and tolerability. This review focused on the hepatoprotective mechanisms of curcumin. The need to develop novel delivery systems of curcumin (e.g., nanoparticles, self-micro emulsifying, lipid-based colloids, solid lipid nanoparticles, cyclodextrin inclusion, phospholipid complexes, and nanoemulsions) is also considered.

2.
Phytother Res ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776136

RESUMO

Recently, malignant neoplasms have growingly caused human morbidity and mortality. Head and neck cancer (HNC) constitutes a substantial group of malignancies occurring in various anatomical regions of the head and neck, including lips, mouth, throat, larynx, nose, sinuses, oropharynx, hypopharynx, nasopharynx, and salivary glands. The present study addresses the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway as a possible therapeutic target in cancer therapy. Finding new multitargeting agents capable of modulating PI3K/Akt/mTOR and cross-linked mediators could be viewed as an effective strategy in combating HNC. Recent studies have introduced phytochemicals as multitargeting agents and rich sources for finding and developing new therapeutic agents. Phytochemicals have exhibited immense anticancer effects, including targeting different stages of HNC through the modulation of several signaling pathways. Moreover, phenolic/polyphenolic compounds, alkaloids, terpenes/terpenoids, and other secondary metabolites have demonstrated promising anticancer activities because of their diverse pharmacological and biological properties like antiproliferative, antineoplastic, antioxidant, and anti-inflammatory activities. The current review is mainly focused on new therapeutic strategies for HNC passing through the PI3K/Akt/mTOR pathway as new strategies in combating HNC.

3.
Cancer Metastasis Rev ; 43(1): 261-292, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38169011

RESUMO

Plasticity of phenotypic traits refers to an organism's ability to change in response to environmental stimuli. As a result, the response may alter an organism's physiological state, morphology, behavior, and phenotype. Phenotypic plasticity in cancer cells describes the considerable ability of cancer cells to transform phenotypes through non-genetic molecular signaling activities that promote therapy evasion and tumor metastasis via amplifying cancer heterogeneity. As a result of metastable phenotypic state transitions, cancer cells can tolerate chemotherapy or develop transient adaptive resistance. Therefore, new findings have paved the road in identifying factors and agents that inhibit or suppress phenotypic plasticity. It has also investigated novel multitargeted agents that may promise new effective strategies in cancer treatment. Despite the efficiency of conventional chemotherapeutic agents, drug toxicity, development of resistance, and high-cost limit their use in cancer therapy. Recent research has shown that small molecules derived from natural sources are capable of suppressing cancer by focusing on the plasticity of phenotypic responses. This systematic, comprehensive, and critical review analyzes the current state of knowledge regarding the ability of phytocompounds to target phenotypic plasticity at both preclinical and clinical levels. Current challenges/pitfalls, limitations, and future perspectives are also discussed.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias , Humanos , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transdução de Sinais , Adaptação Fisiológica , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
4.
J Ethnopharmacol ; 323: 117708, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38181932

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. AIM OF THE STUDY: The objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. MATERIALS AND METHODS: The maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. RESULTS: LC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. CONCLUSION: FE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.


Assuntos
Doença de Alzheimer , Fraxinus , Fármacos Neuroprotetores , Ratos , Animais , Cloreto de Alumínio/farmacologia , Cloreto de Alumínio/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Fraxinus/metabolismo , Doenças Neuroinflamatórias , Casca de Planta/metabolismo , Cromatografia Líquida , Ratos Wistar , Modelos Animais de Doenças , Espectrometria de Massas em Tandem , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cumarínicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
5.
Cancer Metastasis Rev ; 43(1): 501-574, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37792223

RESUMO

Tumor cells employ multiple signaling mediators to escape the hypoxic condition and trigger angiogenesis and metastasis. As a critical orchestrate of tumorigenic conditions, hypoxia-inducible factor-1 (HIF-1) is responsible for stimulating several target genes and dysregulated pathways in tumor invasion and migration. Therefore, targeting HIF-1 pathway and cross-talked mediators seems to be a novel strategy in cancer prevention and treatment. In recent decades, tremendous efforts have been made to develop multi-targeted therapies to modulate several dysregulated pathways in cancer angiogenesis, invasion, and metastasis. In this line, natural compounds have shown a bright future in combating angiogenic and metastatic conditions. Among the natural secondary metabolites, we have evaluated the critical potential of phenolic compounds, terpenes/terpenoids, alkaloids, sulfur compounds, marine- and microbe-derived agents in the attenuation of HIF-1, and interconnected pathways in fighting tumor-associated angiogenesis and invasion. This is the first comprehensive review on natural constituents as potential regulators of HIF-1 and interconnected pathways against cancer angiogenesis and metastasis. This review aims to reshape the previous strategies in cancer prevention and treatment.


Assuntos
Fator 1 Induzível por Hipóxia , Neoplasias , Humanos , Linhagem Celular Tumoral , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica , Transdução de Sinais
6.
Naunyn Schmiedebergs Arch Pharmacol ; 397(7): 4771-4790, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38150015

RESUMO

Rheumatoid arthritis (RA) is the most common chronic inflammatory disease, primarily affecting the joints and with stromal tissue dysregulation causing chronic inflammation and joint destruction. Rutin is a natural flavonoid with potential therapeutic properties in chronic destructive conditions including rheumatoid diseases. In this study, the protective effects of rutin nanoformulation in an animal model of rheumatoid arthritis caused by Freund's complete adjuvant (FCA) were investigated. Sixty male rats were randomly divided into ten groups including normal, negative control, prednisolone 10 mg/kg (positive control), 3 doses of rutin (15, 30, 45mg/kg), rutin nanoparticles (15, 30, 45 mg/kg), and nanoparticle without rutin, for 28 days. Different behavioral parameters including the open field test, acetone drop test, hot plate test, Von Frey test, and inclined plane test were evaluated. Serum levels of glutathione (GSH), catalase, and nitric oxide as well as histopathological analyses were measured in different groups. Also, matrix metalloproteinase (MMP)-2 and MMP-9 activity were appraised by gelatin zymography. The injection of FCA prolonged the rats' immobility duration in comparison to the control group. Rheumatoid arthritis induction also increased nitric oxide and decreased GSH and catalase levels, while these effects were reversed in the groups that received nanoparticles containing rutin and prednisolone. Rutin nanoparticles suppressed MMP-9 and activated MMP-2. Also, this rutin drug delivery system plays a significant role in the improvement of histopathological symptoms. Considering the improvement of behavioral and tissue symptoms and the modulation of the level of inflammatory cytokines, nanoparticles containing rutin can be proposed as a suitable approach in the management of patients with rheumatoid arthritis.


Assuntos
Anti-Inflamatórios , Artrite Experimental , Artrite Reumatoide , Quitosana , Adjuvante de Freund , Nanopartículas , Estresse Oxidativo , Ratos Wistar , Rutina , Animais , Rutina/farmacologia , Rutina/administração & dosagem , Rutina/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Quitosana/administração & dosagem , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Experimental/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Artrite Reumatoide/induzido quimicamente , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Ratos , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Portadores de Fármacos/química , Comportamento Animal/efeitos dos fármacos , Glutationa/metabolismo , Óxido Nítrico/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia
7.
Cancer Metastasis Rev ; 42(3): 959-1020, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37505336

RESUMO

The tumor microenvironment (TME) plays a pivotal role in cancer development and progression. In this line, revealing the precise mechanisms of the TME and associated signaling pathways of tumor resistance could pave the road for cancer prevention and efficient treatment. The use of nanomedicine could be a step forward in overcoming the barriers in tumor-targeted therapy. Novel delivery systems benefit from enhanced permeability and retention effect, decreasing tumor resistance, reducing tumor hypoxia, and targeting tumor-associated factors, including immune cells, endothelial cells, and fibroblasts. Emerging evidence also indicates the engagement of multiple dysregulated mediators in the TME, such as matrix metalloproteinase, vascular endothelial growth factor, cytokines/chemokines, Wnt/ß-catenin, Notch, Hedgehog, and related inflammatory and apoptotic pathways. Hence, investigating novel multitargeted agents using a novel delivery system could be a promising strategy for regulating TME and drug resistance. In recent years, small molecules from natural sources have shown favorable anticancer responses by targeting TME components. Nanoformulations of natural compounds are promising therapeutic agents in simultaneously targeting multiple dysregulated factors and mediators of TME, reducing tumor resistance mechanisms, overcoming interstitial fluid pressure and pericyte coverage, and involvement of basement membrane. The novel nanoformulations employ a vascular normalization strategy, stromal/matrix normalization, and stress alleviation mechanisms to exert higher efficacy and lower side effects. Accordingly, the nanoformulations of anticancer monoclonal antibodies and conventional chemotherapeutic agents also improved their efficacy and lessened the pharmacokinetic limitations. Additionally, the coadministration of nanoformulations of natural compounds along with conventional chemotherapeutic agents, monoclonal antibodies, and nanomedicine-based radiotherapy exhibits encouraging results. This critical review evaluates the current body of knowledge in targeting TME components by nanoformulation-based delivery systems of natural small molecules, monoclonal antibodies, conventional chemotherapeutic agents, and combination therapies in both preclinical and clinical settings. Current challenges, pitfalls, limitations, and future perspectives are also discussed.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Microambiente Tumoral , Células Endoteliais/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Neoplasias/patologia , Resistência a Medicamentos , Anticorpos Monoclonais/uso terapêutico , Sistemas de Liberação de Medicamentos
8.
Phytomedicine ; 115: 154821, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37119761

RESUMO

BACKGROUND: Multiple dysregulated pathways are behind the pathogenesis of neurodegenerative diseases (NDDs); however, the crucial targets are still unknown. Oxidative stress, apoptosis, autophagy, and inflammation are the most dominant pathways that strongly influence neurodegeneration. In this way, targeting the Ras/Raf/mitogen-activated protein kinases (MAPKs) pathway appears to be a developing strategy for combating NDDs like Parkinson's disease, Alzheimer's disease, stroke, aging, and other NDDs. Accordingly, plant secondary metabolites have shown promising potentials for the simultaneous modulation of the Ras/Raf/MAPKs pathway and play an essential role in NDDs. MAPKs include p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK 1/2), and c-Jun N-terminal kinase (JNK), which are important molecular players in neurodegeneration. Ras/Raf, which is located the upstream of MAPK pathway influences the initiation and progression of neurodegeneration and is regulated by natural products. PURPOSE: Thus, the present study aimed to investigate the neuroprotective roles of plant- and marine-derived secondary metabolites against several NDDs through the modulation of the Ras/Raf/MAPK signaling pathway. STUDY DESIGN AND METHODS: A systematic and comprehensive review was performed to highlight the modulatory roles of natural products on the Ras/Raf/MAPK signaling pathway in NDDs, according to the PRISMA guideline, using scholarly electronic databases, including PubMed, Scopus, and Web of Sciences. Associated reference lists were also searched for the literature review. RESULTS: From a total of 1495 results, finally 107 articles were included in the present study. The results show that several natural compounds such as alkaloid, phenolic, terpenoids, and nanoformulation were shown to have modulatory effects on the Ras/Raf/MAPKs pathway. CONCLUSION: Natural products are promising multi-targeted agents with on NDDs through Ras/Raf/MAPKs pathway. Nevertheless, additional and complementary studies are necessary to check its efficacy and potential side effects.


Assuntos
Antineoplásicos , Proteínas Quinases Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Sistema de Sinalização das MAP Quinases , Fosforilação , Antineoplásicos/farmacologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-37061329

RESUMO

Senescence-like cell cycle arrest is a critical state of cancer initiation and progression. Senescence is an irreversible cell cycle arrest in response to stress induced by extrinsic and intrinsic stimuli, including oxidative/genotoxic stress, oncogenic activation, irradiation, mitochondrial malfunction, or chemotherapeutic drugs. Several signaling pathways are involved in senescence-like cell cycle arrest, which is primarily induced by the activation of p53/p21-dependent apoptotic pathways and suppressing p16INK4A/retinoblastoma protein (pRB)-dependent oncogenic pathways. p21 is necessary for proper cell cycle advancement, is involved in cell death, and mediates p53-dependent cell cycle arrest caused by DNA damage. pRB's role in tumor suppression is through modulation of the G1 checkpoint in the cell cycle, as it has the ability to block S-phase entry and cell growth. The aforementioned pathways are also highly interconnected with significant crosstalk, such as cyclin-dependent kinases (CDK)/cyclin complexes, and the dimerization partner, RB-like, E2F and multi-vulval class B (DREAM) complex. The primary regulators of transcription are p53 and pRB, which maintain the senescent state through negative control of the cell cycle and process of tumorigenesis. Because CDK inhibitors comprise negative regulators of cell cycle progress, they are fundamental parts of each route. Prolonged overexpression of any of these four fundamental elements (p16, p53, p21, and pRB) suffices to induce senescence, demonstrating how the regulatory DREAM complex causes senescence and how its malfunction results in cell cycle progression. The present chapter aims at revealing the pivotal mechanisms behind the senescence-like cell cycle arrest in cancer.


Assuntos
Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Pontos de Checagem do Ciclo Celular , Ciclo Celular , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteína do Retinoblastoma/metabolismo , Neoplasias/genética
10.
Metabolites ; 13(3)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36984763

RESUMO

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

11.
Pharmaceutics ; 15(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36986865

RESUMO

As major public health concerns associated with a rapidly growing aging population, neurodegenerative diseases (NDDs) and neurological diseases are important causes of disability and mortality. Neurological diseases affect millions of people worldwide. Recent studies have indicated that apoptosis, inflammation, and oxidative stress are the main players of NDDs and have critical roles in neurodegenerative processes. During the aforementioned inflammatory/apoptotic/oxidative stress procedures, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role. Considering the functional and structural aspects of the blood-brain barrier, drug delivery to the central nervous system is relatively challenging. Exosomes are nanoscale membrane-bound carriers that can be secreted by cells and carry several cargoes, including proteins, nucleic acids, lipids, and metabolites. Exosomes significantly take part in the intercellular communications due to their specific features including low immunogenicity, flexibility, and great tissue/cell penetration capabilities. Due to their ability to cross the blood-brain barrier, these nano-sized structures have been introduced as proper vehicles for central nervous system drug delivery by multiple studies. In the present systematic review, we highlight the potential therapeutic effects of exosomes in the context of NDDs and neurological diseases by targeting the PI3K/Akt/mTOR signaling pathway.

12.
IET Nanobiotechnol ; 17(3): 154-170, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36949020

RESUMO

Alzheimer's disease (AD) is one of the chief neurological difficulties in the aged population, identified through dementia, memory disturbance, and reduced cognitive abilities. ß-amyloid (Aß) plaques aggregations, generation of reactive oxygen species, and mitochondrial dysfunction are among the major signs of AD. Regarding the urgent need for the development of novel treatments for neurodegenerative diseases, researchers have recently perused the function of natural phytobioactive combinations, such as resveratrol (RES), in vivo and in vitro (animal models of AD). Investigations have shown the neuroprotective action of RES. This compound can be encapsulated by several methods (e.g. polymeric nanoparticles (NPs), solid lipid nanoparticles, Micelles, and liposomes). This antioxidant compound, however, barely crosses the blood-brain barrier (BBB), thereby limiting its bioavailability and stability at the target sites in the brain. Thanks to nanotechnology, the efficiency of AD therapy can be improved by encapsulating the drugs in a NP with a controlled size (1-100 nm). This article addressed the use of RES, as a Phytobioactive compound, to decrease the oxidative stress. Encapsulation of this compound in the form of nanocarriers to treat neurological diseases to improve BBB crossing is also discussed.


Assuntos
Doença de Alzheimer , Nanopartículas , Animais , Doença de Alzheimer/tratamento farmacológico , Resveratrol/uso terapêutico , Encéfalo/metabolismo , Peptídeos beta-Amiloides , Barreira Hematoencefálica/metabolismo
13.
Brief Funct Genomics ; 22(2): 143-160, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-36722043

RESUMO

Neurodegenerative diseases (NDDs) are on the rise in the world. Therefore, it is a critical issue to reveal the precise pathophysiological mechanisms and novel therapeutic strategies to deal with such conditions. Passing through different mechanisms, non-coding RNAs (ncRNAs) play a pivotal role in NDDs through various mechanisms, by changing the expression of some genes, interference with protein translation and alterations in some signaling pathways. It urges the need to introduce novel strategies and therapeutic agents with multi-targeting potentials. Phytochemicals are hopeful antioxidants and anti-inflammatory agents with promising modulatory roles on dysregulated signaling pathways and protein translation during NDDs. In this study, the role of ncRNAs (e.g. lncRNAs, miRNA, siRNAs and piRNAs) was highlighted in NDDs. This study also aimed to investigate the role of phytochemicals (phenolic compounds, alkaloids, terpenoids and sulfur compounds) in the modulation of ncRNAs during NDDs such as Alzheimer's disease, Parkinson's disease, epilepsy, depression and amyotrophic lateral sclerosis.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , RNA não Traduzido/genética , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
14.
Phytomedicine ; 112: 154686, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36804755

RESUMO

BACKGROUND: Neurodegenerative diseases (NDDs) are characterized by progressive neuronal dysfunctionality which results in disability and human life-threatening events. In recent decades, NDDs are on the rise. Besides, conventional drugs have not shown potential effectiveness to attenuate the complications of NDDs. So, exploring novel therapeutic agents is an urgent need to combat such disorders. Accordingly, growing evidence indicates that polyphenols and alkaloids are promising natural candidates, possessing several beneficial pharmacological effects against diseases. Considering the complex pathophysiological mechanisms behind NDDs, Janus kinase (JAK), insulin receptor substrate (IRS), phosphoinositide 3-kinase (PI3K), and signal transducer and activator of transcription (STAT) seem to play critical roles during neurodegeneration/neuroregeneration. In this line, modulation of the JAK/STAT and IRS/PI3K signaling pathways and their interconnected mediators by polyphenols/alkaloids could play pivotal roles in combating NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), stroke, aging, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), depression and other neurological disorders. PURPOSE: Thus, the present study aimed to investigate the neuroprotective roles of polyphenols/alkaloids as multi-target natural products against NDDs which are critically passing through the modulation of the JAK/STAT and IRS/PI3K signaling pathways. STUDY DESIGN AND METHODS: A systematic and comprehensive review was performed to highlight the modulatory roles of polyphenols and alkaloids on the JAK/STAT and IRS/PI3K signaling pathways in NDDs, according to the PRISMA guideline, using scholarly electronic databases, including Scopus, PubMed, ScienceDirect, and associated reference lists. RESULTS: In the present study 141 articles were included from a total of 1267 results. The results showed that phenolic compounds such as curcumin, epigallocatechin-3-gallate, and quercetin, and alkaloids such as berberine could be introduced as new strategies in combating NDDs through JAK/STAT and IRS/PI3K signaling pathways. This is the first systematic review that reveals the correlation between the JAK/STAT and IRS/PI3K axis which is targeted by phytochemicals in NDDs. Hence, this review highlighted promising insights into the neuroprotective potential of polyphenols and alkaloids through the JAK/STAT and IRS/PI3K signaling pathway and interconnected mediators toward neuroprotection. CONCLUSION: Amongst natural products, phenolic compounds and alkaloids are multi-targeting agents with the most antioxidants and anti-inflammatory effects possessing the potential of combating NDDs with high efficacy and lower toxicity. However, additional reports are needed to prove the efficacy and possible side effects of natural products.


Assuntos
Alcaloides , Produtos Biológicos , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Janus Quinases/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Polifenóis/farmacologia , Transdução de Sinais , Alcaloides/farmacologia
15.
Life (Basel) ; 12(12)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36556325

RESUMO

Spinal cord injury (SCI) possesses a complicated etiology. There is no FDA-approved treatment for SCI, and the majority of current interventions focus on reducing symptoms. During SCI, inflammation, oxidative stress, apoptosis, and autophagy are behind the secondary phase of SCI and cause serious consequences. It urges the need for providing multi-targeting agents, that possess lower side effects and higher efficacy. The plant secondary metabolites are multi-targeting agents and seem to provide new roads in combating diseases. Flavonoids are phytochemicals of continual interest to scientists in combating neurodegenerative diseases (NDDs). Flavonoids are being studied for their biological and pharmacological effects, particularly as antioxidants, anti-inflammatory agents, anti-apoptotic, and autophagy regulators. Quercetin is one of the most well-known flavonols known for its preventative and therapeutic properties. It is a naturally occurring bioactive flavonoid that has recently received a lot of attention for its beneficial effects on NDDs. Several preclinical evidence demonstrated its neuroprotective effects. In this systematic review, we aimed at providing the biological activities of quercetin and related derivatives against SCI. Detailed neuroprotective mechanisms of quercetin derivatives are also highlighted in combating SCI.

16.
Iran J Basic Med Sci ; 25(9): 1150-1158, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36246060

RESUMO

Objectives: Therapeutic strategies that facilitate extinction are promising in the treatment of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has a crucial role in neural plasticity, a process needed for the retention of fear extinction. In this study, we investigated the effects of local administration of a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu), on BDNF transcription and behavioral markers of extinction in the single prolonged stress (SPS) model of PTSD. Materials and Methods: NaBu was infused into the infralimbic (IL) subregion of the medial prefrontal cortex (mPFC) of male rats. The freezing response was recorded as the criterion to assess fear strength on the day of extinction as well as 24 hr later in the retention test. Other behavioral tests were also measured to evaluate the anxiety level, locomotor activity, and working memory on the retention day. HDAC activity and BDNF mRNA expression were evaluated after the behavioral experiments. Results: NaBu facilitated the recall of fear extinction in SPS rats (P<0.0001). SPS rats had higher HDAC activity (P<0.0001) and lower BDNF expression (P<0.05) than non-SPS animals. Also, anxiety was higher in the SPS group (P<0.0001), but locomotor activity (P=0.61) and working memory (P=0.36) were not different between SPS and Non-SPS groups. Conclusion: Our findings provide evidence that the mechanism of action of NaBu in the improvement of extinction recall is mediated, in part, by enhancing histone acetylation and reviving BDNF expression in IL.

17.
Molecules ; 27(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36235012

RESUMO

Polydatin is a natural potent stilbenoid polyphenol and a resveratrol derivative with improved bioavailability. Polydatin possesses potential biological activities predominantly through the modulation of pivotal signaling pathways involved in inflammation, oxidative stress, and apoptosis. Various imperative biological activities have been suggested for polydatin towards promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, anti-microbial, as well as health-promoting roles on the renal system, the respiratory system, rheumatoid diseases, the skeletal system, and women's health. In the present study, the therapeutic targets, biological activities, pharmacological mechanisms, and health benefits of polydatin are reviewed to provide new insights to researchers. The need to develop further clinical trials and novel delivery systems of polydatin is also considered to reveal new insights to researchers.


Assuntos
Polifenóis , Estilbenos , Feminino , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Humanos , Resveratrol , Estilbenos/farmacologia , Estilbenos/uso terapêutico
18.
Mar Drugs ; 20(10)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36286449

RESUMO

The marine environment is important yet generally underexplored. It contains new sources of functional constituents that can affect various pathways in food processing, storage, and fortification. Bioactive secondary metabolites produced by marine microorganisms may have significant potential applications for humans. Various components isolated from disparate marine microorganisms, including fungi, microalgae, bacteria, and myxomycetes, showed considerable biological effects, such as anticancer, antioxidant, antiviral, antibacterial, and neuroprotective activities. Growing studies are revealing that potential anticancer effects of marine agents could be achieved through the modulation of several organelles. Mitochondria are known organelles that influence growth, differentiation, and death of cells via influencing the biosynthetic, bioenergetic, and various signaling pathways related to oxidative stress and cellular metabolism. Consequently, mitochondria play an essential role in tumorigenesis and cancer treatments by adapting to alterations in environmental and cellular conditions. The growing interest in marine-derived anticancer agents, combined with the development and progression of novel technology in the extraction and cultures of marine life, led to revelations of new compounds with meaningful pharmacological applications. This is the first critical review on marine-derived anticancer agents that have the potential for targeting mitochondrial function during tumorigenesis. This study aims to provide promising strategies in cancer prevention and treatment.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Mitocôndrias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antibacterianos , Antivirais/farmacologia , Neoplasias/tratamento farmacológico , Carcinogênese , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Organismos Aquáticos
19.
Behav Pharmacol ; 33(7): 505-512, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36148838

RESUMO

Astaxanthin (AST) is a lipid-soluble carotenoid with antioxidant and anti-inflammatory properties. Previous reports demonstrated the promising effects of AST on spinal cord injury (SCI)-induced inflammation and sensory-motor dysfunction. Macrophage migration inhibitory factor (MIF), as a cytokine, plays a critical role in the inflammatory phase of SCI. The aim of this study was to evaluate the effects of AST on post-SCI levels of MIF in serum and spinal cord. The possible correlation between MIF and mechanical pain threshold was also assessed. Adult male rats were subjected to a severe compression spinal injury and 30 min later were treated with AST (Intrathecal, 2 nmol) or vehicle. Neuropathic pain was assessed by von Frey filaments before the surgery, and then on days 7, 14, 21, and 28 post-SCI. Western blot and ELISA were used to measure the serum level and spinal expression of MIF following SCI in the same time points. AST treatment significantly attenuated the SCI-induced dysregulations in the serum levels and tissue expression of MIF. A negative correlation was observed between mechanical pain threshold and serum MIF level (r = -0.5463, P < 0.001), as well as mechanical pain threshold and spinal level of MIF (r = -0.9562; P < 0.001). AST ameliorates SCI-induced sensory dysfunction, probably through inhibiting MIF-regulated inflammatory pathways.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Traumatismos da Medula Espinal , Animais , Antioxidantes/farmacologia , Lipídeos , Fatores Inibidores da Migração de Macrófagos/metabolismo , Fatores Inibidores da Migração de Macrófagos/farmacologia , Masculino , Ratos , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Xantofilas/metabolismo , Xantofilas/farmacologia
20.
Crit Rev Food Sci Nutr ; : 1-25, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36073725

RESUMO

As a group of heterodimeric and transmembrane glycoproteins, integrin receptors are widely expressed in various cell types overall the body. During cardiovascular dysfunction, integrin receptors apply inhibitory effects on the antioxidative pathways, including nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch like ECH Associated Protein 1 (Keap1)/antioxidant response element (ARE) and interconnected mediators. As such, dysregulation in integrin signaling pathways influences several aspects of cardiovascular diseases (CVDs) such as heart failure, arrhythmia, angina, hypertension, hyperlipidemia, platelet aggregation and coagulation. So, modulation of integrin pathway could trigger the downstream antioxidant pathways toward cardioprotection. Regarding the involvement of multiple aforementioned mediators in the pathogenesis of CVDs, as well as the side effects of conventional drugs, seeking for novel alternative drugs is of great importance. Accordingly, the plant kingdom could pave the road in the treatment of CVDs. Of natural entities, polyphenols are multi-target and accessible phytochemicals with promising potency and low levels of toxicity. The present study aims at providing the cardioprotective roles of integrin receptors and downstream antioxidant pathways in heart failure, arrhythmia, angina, hypertension, hyperlipidemia, platelet aggregation and coagulation. The potential role of polyphenols has been also revealed in targeting the aforementioned dysregulated signaling mediators in those CVDs.

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