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1.
Mol Cell Biochem ; 479(3): 693-705, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37166541

RESUMO

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.


Assuntos
Curcumina , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , DNA/metabolismo , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
2.
Can J Physiol Pharmacol ; 102(3): 150-160, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37955633

RESUMO

The Toll-like receptor (TLR)/mammalian target of rapamycin (mTOR) signaling pathway is involved in the intracellular regulation of protein synthesis, specifically the ones that mediate neuronal morphology and facilitate synaptic plasticity. The activity of TLR/mTOR signaling has been disrupted, leading to neurodevelopment and deficient synaptic plasticity, which are the main symptoms of schizophrenia. The TLR receptor activates the mTOR signaling pathway and increases the elevation of inflammatory cytokines. Interleukin (IL)-6 is the most commonly altered cytokine, while IL-1, tumor necrosis factor, and interferon (IFN) also lead to SCZ. Anti-inflammatory and anti-oxidative agents such as celecoxib, aspirin, minocycline, and omega-3 fatty acids have shown efficiency against SCZ. As a result, inhibition of the inflammatory process could be suggested for the treatment of SCZ. So mTOR/TLR blockers represent the treatment of SCZ due to their inflammatory consequences. The objective of the present work was to find a novel anti-inflammatory agent that may block the mTOR/TLR inflammatory signaling pathways and might pave the way for the treatment of neuroinflammatory SCZ. Data were collected from experimental and clinical studies published in English between 1998 and October 2022 from Google Scholar, PubMed, Scopus, and the Cochrane library.


Assuntos
Esquizofrenia , Humanos , Aspirina , Citocinas , Interleucina-6 , Esquizofrenia/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR
3.
Phytother Res ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899632

RESUMO

A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated-disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.

4.
Cytokine ; 166: 156206, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37120946

RESUMO

Inflammation and oxidative stress play pivotal roles in pathogenesis of many diseases including cancer, type 2 diabetes, cardiovascular disease, atherosclerosis, neurological diseases, and inflammatory diseases such as inflammatory bowel disease (IBD). Inflammatory mediators such as interleukins (ILs), interferons (INF-s), and tumor necrosis factor (TNF)-α are related to an extended chance of inflammatory diseases initiation or progression due to the over expression of the nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLR), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. These pathways are completely interconnected. Theindoleamine 2,3 dioxygenase (IDO) subset of the kynurenine (KYN) (IDO/KYN), is a metabolic inflammatory pathway involved in production of nicotinamide adenine dinucleotide (NAD + ). It has been shown that IDO/KYN actively participates in inflammatory processes and can increase the secretion of cytokines that provoke inflammatory diseases. Data were extracted from clinical and animal studies published in English between 1990-April 2022, which were collected from PubMed, Google Scholar, Scopus, and Cochrane library. IDO/KYN is completely associated with inflammatory-related pathways, thus leading to the production of cytokines such as TNF-α, IL-1ß, and IL-6, and ultimately development and progression of various inflammatory disorders. Inhibition of the IDO/KYN pathway might be a novel therapeutic option for inflammatory diseases. Herein, we gathered data on probable interactions of the IDO/KYN pathway with induction of some inflammatory diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Cinurenina , Animais , Cinurenina/metabolismo , Triptofano/metabolismo , Inflamação , Citocinas , Fator de Necrose Tumoral alfa , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Mamíferos/metabolismo
5.
Adv Exp Med Biol ; 1412: 457-476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37378783

RESUMO

The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important options. Various inflammatory pathways such as nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways and mediators, such as interleukin (IL)-6, IL-1ß, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), cause cell apoptosis, reduce respiratory capacity and oxygen supply, eventually inducing respiratory system failure and death. Statins are well known for controlling hypercholesterolemia and may serve to treat COVID-19 due to their pleiotropic effects among which are anti-inflammatory in nature. In this chapter, the anti-inflammatory effects of statins and their possible beneficial effects in COVID-19 treatment are discussed. Data were collected from experimental and clinical studies in English (1998-October 2022) from Google Scholar, PubMed, Scopus, and the Cochrane Library.


Assuntos
COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Tratamento Farmacológico da COVID-19 , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Interleucina-6
6.
Inflammopharmacology ; 31(5): 2201-2212, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37498375

RESUMO

Curcumin (diferuloylmethane) is a herbal remedy which possesses numerous biological attributes including anti-inflammatory, anti-oxidant and anti-cancer properties. Curcumin has been shown to impact a number of signaling pathways including nuclear factor kappa B (NF-KB), reactive oxygen species (ROS), Wingless/Integrated (Wnt), Janus kinase-signal transducer and activator of mitogen-activated protein kinase (MAPK) and transcription (JAK/STAT). P38 belongs to the MAPKs, is known as a stress-activated MAPK and is involved in diverse biological responses. P38 is activated in various signaling cascades. P38 plays a role in inflammation, cell differentiation, proliferation, motility and survival. This cascade can serve as a therapeutic target in many disorders. Extensive evidence confirms that curcumin impacts the P38 MAPK signaling pathway, through which it exerts anti-inflammatory, neuroprotective, and apoptotic effects. Hence, curcumin can positively affect inflammatory disorders and cancers, as well as to increase glucose uptake in cells. This review discusses the pharmacological and therapeutic effects of curcumin as effected through p38 MAPK.


Assuntos
Curcumina , Curcumina/farmacologia , Curcumina/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais , NF-kappa B/metabolismo , Janus Quinases/metabolismo , Sistema de Sinalização das MAP Quinases
7.
Inflammopharmacology ; 31(1): 57-75, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36574095

RESUMO

Inflammation plays a critical role in several diseases such as cancer, gastric, heart and nervous system diseases. Data suggest that the activation of mammalian target of rapamycin (mTOR) pathway in epithelial cells leads to inflammation. Statins, the inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), seem to be able to inhibit the mTOR. Statins are considered to have favorable effects on inflammatory diseases by reducing the complications caused by inflammation and by regulating the inflammatory process and cytokines secretion. This critical review collected data on this topic from clinical, in vivo and in vitro studies published between 1998 and June 2022 in English from databases including PubMed, Google Scholar, Scopus, and Cochrane libraries.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Neurodegenerativas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Serina-Treonina Quinases TOR , Inflamação/tratamento farmacológico , Sirolimo/uso terapêutico
8.
Pharmacol Res ; 177: 106116, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35122954

RESUMO

Pediatric acute lymphoblastic leukemia (pALL), a malignancy of the lymphoid line of blood cells, accounts for a large percentage of all childhood leukemia cases. Although the 5-year survival rate for children with ALL has greatly improved over years, using chemotherapeutics as its first-line treatment still causes short- and long-term side effects. Furthermore, induction of toxicity and resistance, as well as the high cost, limit their application. Phytochemicals, with remarkable cancer preventive and chemotherapeutic characteristics, may serve as old solutions to new challenges. Bioactive plant secondary metabolites have exhibited promising antileukemic and adjunctive effects by targeting various molecular processes, including autophagy, cell cycle, angiogenesis, and extrinsic/intrinsic apoptotic pathways. Although numerous reports have shown that various plant secondary metabolites can interfere with the progression of malignancies, including leukemia, there was no comprehensive review article on the effect of phytochemicals on pALL. This systematic review aims to provide critical and cohesive analysis of the potential of various naturally-occurring plant secondary metabolites in the management of pALL with the understanding of underlying molecular and cellular mechanisms of action.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Apoptose , Autofagia , Criança , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Transdução de Sinais
9.
Phytother Res ; 36(3): 1258-1267, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35072307

RESUMO

Almost half of the treatments with common antidepressants are failed or result in a relapse of symptoms after cessation. Moreover, the antidepressants side effects rationalize the use of complementary medicine as an adjunctive therapy. This study aimed to evaluate the efficacy and safety of propolis in complementary therapy of depressive disorder. Chromatography technics were used to detect propolis components. A double-blind, randomized, placebo-controlled trial was designed, and 54 participants were randomly assigned to receive either propolis or Placebo for 6 weeks. Treatment was defined as a decrease in 17-item Hamilton Depression Scale (HAMD-17) and Beck depression inventory (BDI). On D42, there was a significant reduction in HAMD score in the propolis group compared with the placebo group (p < .0001). HAMD score significantly decreased in the propolis group from 20.92 ± 3.77 on D0 to 10.03 ± 5.55 on D42, and BDI score was improved from 29.25 ± 3.06 on D0 to 14.17 ± 4.86 on D42. Our findings confirmed that complementary treatment of propolis with SSRIs could safely attenuate symptoms of moderate-severe MDD. These antidepressant effects might result from the rich phenolic acids and flavonoids content of Azerbaijan propolis.


Assuntos
Depressão , Própole , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Método Duplo-Cego , Humanos , Própole/uso terapêutico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
10.
Toxicol Mech Methods ; 32(4): 288-301, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34711111

RESUMO

Aluminum phosphide (AlP) poisoning is common in many countries responsible for high mortality. The heart is the main target organ in AlP poisoning. Several studies have reported the beneficial effects of cannabidiol (CBD) in reducing heart injuries. This study aimed to investigate the possible protective effect of CBD on cardiac toxicity caused by AlP poisoning. Study groups included almond oil, normal saline, sole CBD (100 µg/kg), AlP (11.5 mg/kg), and four groups of AlP + CBD (following AlP gavage, CBD administrated at doses of 5, 25, 50, and 100 µg/kg via intravenous (iv) injection). Thirty minutes after AlP treatment, an electronic cardiovascular device (PowerLab) was used to record electrocardiographic (ECG) changes, heart rate (HR), and blood pressure (BP) for three hours. Cardiac tissue was examined for the activities of mitochondrial complexes, ADP/ATP ratio, the release of cytochrome C, mitochondrial membrane potential (MMP), apoptosis, oxidative stress parameter, and cardiac biomarkers at 12 and 24 hours time points. AlP administration caused abnormal ECG, decreased HR, and BP. AlP also significantly reduced mitochondrial complex I and IV activity and ADP/ATP ratio. The level of cytochrome C release, apoptosis, oxidative stress, and cardiac biomarkers was considerably increased by AlP, which was compensated following CBD administration. CBD was able to improve hemodynamic function to some extent in AlP poisoned rats. CBD restored ATP levels and mitochondrial function and decreased oxidative damage and thus, prevented the heart cells from entering the apoptotic stage. Further clinical trials are needed to explore any possible benefits of CBD in AlP-poisoned patients.


Assuntos
Canabidiol , Fosfinas , Animais , Canabidiol/toxicidade , Eletrocardiografia , Frequência Cardíaca , Humanos , Mitocôndrias , Fosfinas/toxicidade , Ratos , Ratos Wistar
11.
Prostaglandins Other Lipid Mediat ; 157: 106587, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34517113

RESUMO

Neurological disorders result in disability and morbidity. Neuroinflammation is a key factor involved in progression or resolution of a series of neurological disorders like Huntington disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Spinal Cord Injury (SCI), and Seizure. Thereby, anti-inflammatory drugs have been developed to improve the neurodegenerative impairments. Licofelone is an approved osteoarthritis drug that inhibits both the COX (cyclooxygenase) and 5-LOX (lipoxygenase) pathways. Licofelone has pain-relieving and anti-inflammatory effects and it was shown to have neuroprotective properties in the central nervous system, which is implicated in its regulatory effect on the COX/5-LOX pathway, inflammatory cytokines, and immune responses. In this study, we briefly review the various features of neurological disorders and the function of COX/LOX in their flare up and current pharmacological products for their management. Moreover, this review attempts to summarize potential therapeutics that target the immune responses within the central nervous system. A better understanding of the interactions between Licofelone and the nervous systems will be crucial to demonstrate the possible efficacy of Licofelone in neurological disorders.


Assuntos
Inibidores de Lipoxigenase , Doenças do Sistema Nervoso , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Humanos , Inibidores de Lipoxigenase/farmacologia , Inibidores de Lipoxigenase/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Pirróis
12.
Mol Biol Rep ; 48(1): 855-874, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33394234

RESUMO

Inflammatory bowel diseases (IBD) belong to a subgroup of persistent, long-term, progressive, and relapsing inflammatory conditions. IBD may spontaneously develop in the colon, resulting in tumor lesions in inflamed regions of the intestine, such as invasive carcinoma. The benefit of opioids for IBD treatment is still questionable, thereby we investigated databases to provide an overview in this context. This review demonstrates the controversial role of opioids in IBD therapy, their physiological and pharmacological functions in attenuating the IBD symptoms, and in improving inflammatory, oxidative stress, and the quality of life factors in IBD subjects. Data were extracted from clinical, in vitro, and in vivo studies in English, between 1995 and 2019, from PubMed, Google Scholar, Scopus, and Cochrane library. Based on recent reports, there are promising opportunities to target the opioid system and control the IBD symptoms. This study suggests a novel approach for future treatment of functional and inflammatory disorders such as IBD.


Assuntos
Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Receptores Opioides/genética , Animais , Ensaios Clínicos como Assunto , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/patologia , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Qualidade de Vida/psicologia , Receptores Opioides/imunologia , Transdução de Sinais
13.
Molecules ; 26(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673088

RESUMO

The dysregulation of Notch signaling is associated with a wide variety of different human cancers. Notch signaling activation mostly relies on the activity of the γ-secretase enzyme that cleaves the Notch receptors and releases the active intracellular domain. It is well-documented that γ-secretase inhibitors (GSIs) block the Notch activity, mainly by inhibiting the oncogenic activity of this pathway. To date, several GSIs have been introduced clinically for the treatment of various diseases, such as Alzheimer's disease and various cancers, and their impacts on Notch inhibition have been found to be promising. Therefore, GSIs are of great interest for cancer therapy. The objective of this review is to provide a systematic review of in vitro and in vivo studies for investigating the effect of GSIs on various cancer stem cells (CSCs), mainly by modulation of the Notch signaling pathway. Various scholarly electronic databases were searched and relevant studies published in the English language were collected up to February 2020. Herein, we conclude that GSIs can be potential candidates for CSC-targeting therapy. The outcome of our study also indicates that GSIs in combination with anticancer drugs have a greater inhibitory effect on CSCs.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Inibidores Enzimáticos/química , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Secretases da Proteína Precursora do Amiloide/genética , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Humanos , Células-Tronco Neoplásicas/patologia , Receptores Notch/antagonistas & inibidores , Receptores Notch/genética
14.
Crit Rev Clin Lab Sci ; 56(7): 472-492, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31418340

RESUMO

Regarding the widespread progression of diabetes, its related complications and detrimental effects on human health, investigations on this subject seems compulsory. AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a key player in energy metabolism regulation. AMPK is also considered as a prime target for pharmaceutical and therapeutic studies on disorders such as diabetes, metabolic syndrome and obesity, where the body energy homeostasis is imbalanced. Following the activation of AMPK (physiological or pharmacological), a cascade of metabolic events that improve metabolic health is triggered. While there are several publications on this subject, this is the first report that has focused solely on polyphenols targeting diabetes via AMPK pathway. The multiple characteristics of polyphenolic compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the AMPK signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. PPs could potentially occupy a significant position in the future anti-diabetic drug market.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/enzimologia , Descoberta de Drogas , Polifenóis/uso terapêutico , Transdução de Sinais , Animais , Ativação Enzimática/efeitos dos fármacos , Humanos , Polifenóis/farmacologia
15.
J Cell Biochem ; 120(4): 4766-4782, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30362597

RESUMO

We aimed to review and meta-analyze the inflammatory and oxidative factors following alpha lipoic acid (ALA) and its derivative "andrographolid-lipoic acid-1" (AL-1) in ulcerative colitis (UC). ALA plays an important role in scavenging intracellular radicals and inflammatory elements. AL-1 is found in herbal medicines with potent anti-inflammatory properties. Data were collected from the Google Scholar, PubMed, Scopus, Evidence-based medicine/clinical trials, and Cochrane library database until 2017, which finally resulted in 22 animal studies (70 rats and 162 mice). The beneficial effects of ALA or AL-1 on the most important parameters of UC were reviewed; also, studies were considered separately in mice and rats. Administration of ALA and AL-1 significantly reduced the tumor necrosis factor-α level compared with the controls, while data were not noteworthy in the meta-analysis (mean differences = -18.57 [95% CI = -42.65 to 5.51], P = 0.13). In spite of insignificant decrease in meta-analysis outcomes (differences = 6.92 [95% CI = -39.33 to 53.16], P = 0.77), a significant reduction in myeloperoxidase activity was shown following ALA or AL-1 treatment compared with the controls. Despite significant differences in each study, we had to exclude some studies to homogenize data for meta-analyzing as they showed insignificant results. Interleukin 6, cyclooxygenase-2, glutathione, malondialdehyde, superoxide dismutase, histopathological score, macroscopic and microscopic scores, disease activity index, body weight change, and colon length were also reviewed. Most studies have emphasized on significant positive effects of ALA and AL-1. Comprehensive clinical trials are obligatory to determine the precious position of ALA or AL-1 in the management of UC.


Assuntos
Antioxidantes/farmacologia , Colite Ulcerativa/tratamento farmacológico , Ácido Tióctico/farmacologia , Animais , Antioxidantes/química , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Camundongos , Ratos , Ácido Tióctico/química
16.
J Cell Biochem ; 120(4): 6209-6222, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30474871

RESUMO

Aging contributes to an increased risk of developing a number of neurodegenerative and chronic disorders, predominantly related to oxidative stress (OS) and defects in the antioxidant balance. This study focused on the antisenescence effect of four plant species (Falcaria vulgaris, Ixiolirion tataricum, Ajuga chamaecistus, and Scabiosa flavida) on H2 O2 -induced premature senescence in rat NIH3T3 fibroblasts, which were found to be rich in effective phytochemicals with traditional ethnobotanical backgrounds. Plant materials were collected, identified, and extracted. To determine the viability of NIH3T3 cells, an MTT assay was conducted. The levels of OS markers and the senescence-associated ß-galactosidase (SA-ß-GAL) activity were analyzed by the Elisa reader. The cell cycle pattern was evaluated by flow cytometry. The expression of senescence-related inflammatory cytokines and the molecules involved in aging signaling pathways were investigated using the real-time reverse transcription polymerase chain reaction (RT-PCR). H2 O2 treatment decreased cell viability and increased lipid peroxidation (LPO) and the reactive oxygen species (ROS) in NIH3T3s. However, S. flavida exhibited low cytotoxicity, reduced OS and SA-ß-GAL activities in NIH3T3 cells compared with the H2 O2 -treated group. I. tataricum was the second best plant, although it was more toxic to NIHT3T cells. S. flavida decreased G0/G1 arrest and facilitated the G2/M transition of NIH3T3s, also downregulated the expression of p38, p53, p16, and the related inflammatory mediators. S. flavida potentially modulated senescence-associated hallmarks in fibroblasts exposed to H2 O2 , thus it may inhibit the aging process via controlling the OS. Therefore it is a promising candidate for future antiaging explorations.


Assuntos
Fibroblastos/citologia , Peróxido de Hidrogênio/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Animais , Apiaceae/química , Asparagales/química , Ciclo Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Dipsacaceae/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Lamiaceae/química , Camundongos , Células NIH 3T3 , Espécies Reativas de Oxigênio/metabolismo
17.
Rev Endocr Metab Disord ; 20(2): 173-186, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31065943

RESUMO

We summarized 16 controlled studies and evaluated the correlation of resveratrol supplementation with metabolic parameters such as the body weight, waist circumference (WC), systolic blood pressure (sbp), HDL, total cholesterol, triglyceride and glucose levels. This meta-analysis was carried out to determine the association between the resveratrol intake with metabolic parameters in metabolic syndrome patients. PubMed, Scopus, Cochrane and Google Scholar were searched from inception to December 2018 using relevant keywords. All articles were independently reviewed by two authors using predetermined selection criteria. We have selected the studies that investigated the effects of resveratrol on metabolic parameters. Of 16 studies, 10 were performed on human subjects, and in 6 studies animal models were used. Standard mean difference (SMD) with 95% confidence interval were determined using Der Simonian and Laird random-effects modeling, when there was a significant heterogeneity between studies. Funnel plot and Egger's test were conducted to examine the risk of publication bias. Pooled effect sizes in human studies indicated a significant impact of resveratrol supplementation on glucose level [-1.73 (-2.99, -0.47); p = 0.007)] and WC [-1.73 (-2.79, -0.67); p = 0.001] compared with the control group. Also combining the results of studies on rat samples (n = 6), indicated significant effect of resveratrol on decreasing weight [-22.95 (-44.74, -1.17); p = 0.04], TGs [-6.76 (-11.10, -2.42); p = 0.001], sbp [-7.30 (-12.48, -2.13); p = 0.006], and it can influence significantly on increasing HDL level (4.75 (1.87, 7.63); p = 0.001). However, resveratrol was not significantly effective on total cholesterol in both samples. The results of subgroup analysis of human studies showed that resveratrol has significant effect on metabolic parameters (glucose level and WC) at the dosage of > 500 mg and with long-term interventions ≥ 10 weeks. Administration of resveratrol can meaningfully reduce the BW, WC, TGs, and glucose level, also it can increase HDL, but not total cholesterol.


Assuntos
Resveratrol/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , Humanos , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Circunferência da Cintura/efeitos dos fármacos
18.
Int J Mol Sci ; 20(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597283

RESUMO

A balanced metabolic profile is essential for normal human physiological activities. Disproportions in nutrition give rise to imbalances in metabolism that are associated with aberrant immune function and an elevated risk for inflammatory-associated disorders. Inflammation is a complex process, and numerous mediators affect inflammation-mediated disorders. The available clinical modalities do not effectively address the underlying diseases but rather relieve the symptoms. Therefore, novel targeted agents have the potential to normalize the metabolic system and, thus, provide meaningful therapy to the underlying disorder. In this connection, polyphenols, the well-known and extensively studied phytochemical moieties, were evaluated for their effective role in the restoration of metabolism via various mechanistic signaling pathways. The various flavonoids that we observed in this comprehensive review interfere with the metabolic events that induce inflammation. The mechanisms via which the polyphenols, in particular flavonoids, act provide a promising treatment option for inflammatory disorders. However, detailed clinical studies of such molecules are required to decide their clinical fate.


Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Inflamação/metabolismo , Doenças Metabólicas/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Biomarcadores , Ensaios Clínicos como Assunto , Suscetibilidade a Doenças , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Flavonoides/uso terapêutico , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Mediadores da Inflamação/metabolismo , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
19.
Pharmacol Res ; 130: 241-258, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29258915

RESUMO

Over the last decades, an exponential increase of efforts concerning the treatment of Alzheimer's disease (AD) has been practiced. Phytochemicals preparations have a millenary background to combat various pathological conditions. Various cinnamon species and their biologically active ingredients have renewed the interest towards the treatment of patients with mild-to-moderate AD through the inhibition of tau protein aggregation and prevention of the formation and accumulation of amyloid-ß peptides into the neurotoxic oligomeric inclusions, both of which are considered to be the AD trademarks. In this review, we presented comprehensive data on the interactions of a number of cinnamon polyphenols (PPs) with oxidative stress and pro-inflammatory signaling pathways in the brain. In addition, we discussed the potential association between AD and diabetes mellitus (DM), vis-à-vis the effluence of cinnamon PPs. Further, an upcoming prospect of AD epigenetic pathophysiological conditions and cinnamon has been sighted. Data was retrieved from the scientific databases such as PubMed database of the National Library of Medicine, Scopus and Google Scholar without any time limitation. The extract of cinnamon efficiently inhibits tau accumulations, Aß aggregation and toxicity in vivo and in vitro models. Indeed, cinnamon possesses neuroprotective effects interfering multiple oxidative stress and pro-inflammatory pathways. Besides, cinnamon modulates endothelial functions and attenuates the vascular cell adhesion molecules. Cinnamon PPs may induce AD epigenetic modifications. Cinnamon and in particular, cinnamaldehyde seem to be effective and safe approaches for treatment and prevention of AD onset and/or progression. However, further molecular and translational research studies as well as prolonged clinical trials are required to establish the therapeutic safety and efficacy in different cinnamon spp.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cinnamomum zeylanicum , Fármacos Neuroprotetores/uso terapêutico , Preparações de Plantas/uso terapêutico , Doença de Alzheimer/genética , Animais , Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Epigenômica , Humanos , Fármacos Neuroprotetores/farmacologia , Preparações de Plantas/farmacologia
20.
Arch Toxicol ; 91(1): 109-130, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27761595

RESUMO

This review discusses the past and recent advancements of biosensors focusing on detection of organophosphorus pesticides (OPs) due to their exceptional use during the last decades. Apart from agricultural benefits, OPs also impose adverse toxicological effects on animal and human population. Conventional approaches such as chromatographic techniques used for pesticide detection are associated with several limitations. A biosensor technology is unique due to the detection sensitivity, selectivity, remarkable performance capabilities, simplicity and on-site operation, fabrication and incorporation with nanomaterials. This study also provided specifications of the most OPs biosensors reported until today based on their transducer system. In addition, we highlighted the application of advanced complementary materials and analysis techniques in OPs detection systems. The availability of these new materials associated with new sensing techniques has led to introduction of easy-to-use analytical tools of high sensitivity and specificity in the design and construction of OPs biosensors. In this review, we elaborated the achievements in sensing systems concerning innovative nanomaterials and analytical techniques with emphasis on OPs.


Assuntos
Técnicas Biossensoriais , Monitoramento Ambiental/instrumentação , Modelos Biológicos , Compostos Organofosforados/análise , Resíduos de Praguicidas/análise , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/tendências , Biologia Computacional/tendências , Nanotecnologia/tendências , Redes Neurais de Computação , Compostos Organofosforados/toxicidade , Resíduos de Praguicidas/toxicidade
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