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1.
Metab Brain Dis ; 39(5): 783-801, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38739183

RESUMO

Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund's adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1ß and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1ß and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.


Assuntos
Anti-Inflamatórios , Antioxidantes , Carotenoides , Encefalomielite Autoimune Experimental , Camundongos Endogâmicos BALB C , Vitamina A , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Camundongos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Feminino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Vitamina A/análogos & derivados , Vitamina A/uso terapêutico , Camundongos Endogâmicos C57BL , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Interleucina-1beta/metabolismo
2.
Phytother Res ; 38(5): 2165-2181, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38396341

RESUMO

Ethanol toxicity is a major public health problem that can cause damage to various organs in the body by several mechanisms inducing oxidative stress, inflammation, and apoptosis. Recently, there has been a growing interest in the potential of herbal medicines as therapeutic agents for the prevention and treatment of various disorders. Turmeric (Curcuma longa) extracts and its main components including curcumin have antioxidant, anti-inflammatory, and anti-apoptotic properties. This review aims to evaluate the literature on the ameliorative effects of turmeric extracts and their main components on ethanol toxicity. The relevant studies were identified through searches of Google Scholar, PubMed, and Scopus without any time limitation. The underlying mechanisms of turmeric and curcumin were also discussed. The findings suggest that turmeric and curcumin ameliorate ethanol-induced organ damage by suppressing oxidative stress, inflammation, apoptosis, MAPK activation, TGF-ß/Smad signaling pathway, hyperlipidemia, regulating hepatic enzymes, expression of SREBP-1c and PPAR-α. However, the limited clinical evidence suggests that further research is needed to determine the efficacy and safety of turmeric and curcumin in human subjects. In conclusion, the available evidence supports the potential use of turmeric and curcumin as alternative treatments for ethanol toxicity, but further high-quality studies are needed to firmly establish the clinical efficacy of the plant.


Assuntos
Antioxidantes , Curcuma , Curcumina , Etanol , Extratos Vegetais , Curcuma/química , Curcumina/farmacologia , Humanos , Extratos Vegetais/farmacologia , Etanol/química , Animais , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico
3.
Phytother Res ; 38(6): 3037-3059, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38595123

RESUMO

Insomnia affects millions of people worldwide, prompting considerable interest in herbal remedies for its treatment. This review aims to assess the therapeutic potential of such remedies for insomnia by analyzing current scientific evidence. The analysis identified several herbs, including Rosmarinus officinalis, Crocus sativus, Rosa damascena, Curcuma longa, Valeriana officinalis, Lactuca sativa, Portulaca oleracea, Citrus aurantium, Lippia citriodora, and Melissa officinalis, which show promise in improving overall sleep time, reducing sleep latency, and enhancing sleep quality. These plants act on the central nervous system, particularly the serotonergic and gamma-aminobutyric acid (GABA)ergic systems, promoting sedation and relaxation. However, further research is necessary to fully understand their mechanisms of action, optimal dosages, and treatment protocols. Combining herbal medicines with conventional treatments may offer an effective natural alternative for those seeking medication. Nevertheless, individuals should consult their healthcare provider before using herbal remedies for insomnia. While this review provides evidence supporting their use, additional high-quality studies are needed to firmly establish their clinical efficacy.


Assuntos
Hipnóticos e Sedativos , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Hipnóticos e Sedativos/uso terapêutico , Plantas Medicinais/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Melissa/química , Sono/efeitos dos fármacos
4.
Phytother Res ; 38(1): 98-116, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37813398

RESUMO

Cigarette smoking (CS) is a crucial modifiable risk of developing several human diseases and cancers. It causes lung, bladder, breast, and esophageal cancers, respiratory disorders, as well as cardiovascular and metabolic diseases. Because of these adverse health effects, continual efforts to decrease the prevalence and toxicity of CS are imperative. Until the past decades, the impacts of natural compounds have been under investigation on the harmful effects of CS. Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant that belongs to the Zingiberaceae family, is the main source of curcumin. This review is an attempt to find out the current knowledge on CS's harmful effects and protective potential of curcumin in the pulmonary, liver, brain, gastrointestinal, and testis organs. According to the present review, simultaneous consumption of curcumin and CS can attenuate CS toxicities including chronic obstructive pulmonary disease, gastrointestinal toxicity, metabolic diseases, testis injury, and neurotoxicity. Moreover, curcumin suppresses carcinogenesis in the skin, liver, lungs, breast, colon, and stomach. Curcumin mediates these protective effects through antioxidant, anti-inflammatory, anti-apoptotic, and anti-carcinogenicity properties.


Assuntos
Fumar Cigarros , Curcumina , Doenças Metabólicas , Masculino , Humanos , Curcumina/farmacologia , Pulmão , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Curcuma
5.
Mol Biol Rep ; 50(6): 5439-5454, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37155017

RESUMO

BACKGROUND: Nigella sativa and its main bioactive ingredient, thymoquinone, exhibit various pharmacological activities, including neuroprotective, nephroprotective, cardioprotective, gastroprotective, hepatoprotective, and anti-cancer effects. Many studies have been conducted trying to elucidate the molecular signaling pathways that mediate these diverse pharmacological properties of N. sativa and thymoquinone. Accordingly, the goal of this review is to show the effects of N. sativa and thymoquinone on different cell signaling pathways. METHODS: The online databases Scopus, PubMed and Web of Science were searched to identify relevant articles using a list of related keywords such as Nigella sativa, black cumin, thymoquinone, black seed, signal transduction, cell signaling, antioxidant, Nrf2, NF-κB, PI3K/AKT, apoptosis, JAK/STAT, AMPK, MAPK, etc. Only articles published in the English language until May 2022 were included in the present review article. RESULTS: Studies indicate that N. sativa and thymoquinone improve antioxidant enzyme activities, effectively scavenges free radicals, and thus protect cells from oxidative stress. They can also regulate responses to oxidative stress and inflammation via Nrf2 and NF-κB pathways. N. sativa and thymoquinone can inhibit cancer cell proliferation through disruption of the PI3K/AKT pathway by upregulating phosphatase and tensin homolog. Thymoquinone can modulate reactive oxygen species levels in tumor cells, arrest the cell cycle in the G2/M phase as well as affect molecular targets including p53, STAT3 and trigger the mitochondrial apoptosis pathway. Thymoquinone, by adjusting AMPK, can regulate cellular metabolism and energy hemostasis. Finally, N. sativa and thymoquinone can elevate brain GABA content, and thus it may ameliorate epilepsy. CONCLUSIONS: Taken together, the improvement of antioxidant status and prevention of inflammatory process by modulating the Nrf2 and NF-κB signaling and inhibition of cancer cell proliferation through disruption of the PI3K/AKT pathway appear to be the main mechanisms involved in different pharmacological properties of N. sativa and thymoquinone.


Assuntos
Neoplasias , Nigella sativa , Humanos , Extratos Vegetais/farmacologia , NF-kappa B , Antioxidantes/farmacologia , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Proteínas Quinases Ativadas por AMP , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Neoplasias/tratamento farmacológico
6.
Mol Biol Rep ; 50(11): 8925-8935, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37707771

RESUMO

BACKGROUND: Olanzapine (OLZ) is an atypical antipsychotic agent for psychotic disorders. Evidence has shown that OLZ is related to metabolic side effects, including obesity, hypertension, and insulin resistance. Thymoquinone (TQ) is the principal bioactive component of Nigella sativa. Several studies have been conducted to investigate the effectiveness of TQ in alleviating metabolic abnormalities. In the current research work, the protective effects of TQ on metabolic disorders induced by OLZ and possible underlying mechanisms were investigated. METHODS AND RESULTS: Wistar rats were exposed to TQ alone (10 mg/kg), OLZ (5 mg/kg), or OLZ plus TQ (2.5, 5, or 10 mg/kg) given daily by intraperitoneal injection. After the treatment, variations in body weight, food intake, systolic blood pressure, serum leptin, biochemical factors, liver malondialdehyde (MDA), and glutathione (GSH) content were evaluated. Protein expression of AMPK in the liver was also measured by a western blotting test. OLZ increased body weight, food intake, MDA levels, and blood pressure. OLZ also elevated glucose, triglyceride, low-density lipoprotein cholesterol, and leptin serum levels. It decreased GSH. In the western blot, decreased AMPK protein level was obtained. These changes were attenuated by TQ co-administration. CONCLUSIONS: The present study demonstrates the effectiveness of TQ on OLZ-induced metabolic abnormalities related to its antioxidant activity and regulation of glucose homeostasis and lipid metabolism.


Assuntos
Resistência à Insulina , Leptina , Ratos , Animais , Olanzapina/efeitos adversos , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Wistar , Benzoquinonas/farmacologia , Glucose , Obesidade/induzido quimicamente
7.
Nutr Cancer ; 74(2): 747-760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34085575

RESUMO

Doxorubicin (DOX) is an anticancer medicine that may trigger cardiomyopathy. Rosmarinic acid (RA) has shown antioxidant, anti-inflammatory, and anticancer effects. This investigation assessed the cardioprotective effect of RA on DOX-induced-toxicity in both in vivo and in vitro experiments. Male rats were randomized on 7 groups: (1) control, (2) DOX (2 mg/kg, per 48 h, 12d, i.p), (3) RA (40 mg/kg, 12d, i.p.), (4-6) RA (10, 20, 40 mg/kg, 16d, i.p.)+ DOX, (7) Vitamin E (200 mg/kg, per 48 h, 16d, i.p.) + DOX and then indices of cardiac function were estimated. Also, DOX and rosmarinic acid effects were examined on MCF7 cells (breast cancer cells line) to clarify that both cardiotoxicity and anticancer effects were analyzed. DOX increased heart to body weight ratio, RRI, QA, STI, QRS duration and voltage, attenuated HR, blood pressure, Max dP/dt, Min dP/dt, LVDP, enhanced MDA, declined GSH amount, and caused fibrosis and necrosis in cardiac tissue. Administration of RA ameliorated the toxic effects of DOX. In vitro studies showed that RA did not affect the cytotoxic effect of DOX. RA as an antioxidant, anti-inflammatory, and cardioprotective compound could be a promising compound to help minimize DOX-induced cardiotoxicity.


Assuntos
Cardiotoxicidade , Doxorrubicina , Animais , Antibióticos Antineoplásicos/toxicidade , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Depsídeos/farmacologia , Depsídeos/uso terapêutico , Doxorrubicina/toxicidade , Masculino , Estresse Oxidativo , Ratos , Ácido Rosmarínico
8.
Phytother Res ; 36(10): 3859-3884, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35989419

RESUMO

Crocin is a hydrophilic carotenoid that is synthesized in the flowers of the Crocus genus. Numerous in vitro and in vivo research projects have been published about the biological and pharmacological properties and toxicity of crocin. Crocin acts as a memory enhancer, anxiolytic, aphrodisiac, antidepressant, neuroprotective, and so on. Here, we introduce an updated and comprehensive review of crocin molecular mechanisms based on previously examined and mentioned in the literature. Different studies confirmed the significant effect of crocin to control pathological conditions, including oxidative stress, inflammation, metabolic disorders, neurodegenerative disorders, and cancer. The neuroprotective effect of crocin could be related to the activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR), Notch, and cyclic-AMP response element-binding protein signaling pathways. The crocin also protects the cardiovascular system through the inhibitory effect on toll-like receptors. The regulatory effect of crocin on PI3K/AKT/mTOR, AMP-activated protein kinase, mitogen-activated protein kinases (MAPK), and peroxisome proliferator-activated receptor pathways can play an effective role in the treatment of metabolic disorders. The crocin has anticancer activity through the PI3K/AKT/mTOR, MAPK, vascular endothelial growth factor, Wnt/ß-catenin, and Janus kinases-signal transducer and activator of transcription suppression. Also, the nuclear factor-erythroid factor 2-related factor 2 and p53 signaling pathway activation may be effective in the anticancer effect of crocin. Finally, among signaling pathways regulated by crocin, the most important ones seem to be those related to the regulatory effect on the PI3K/AKT/mTOR pathway.


Assuntos
Ansiolíticos , Afrodisíacos , Fármacos Neuroprotetores , Monofosfato de Adenosina/farmacologia , Ansiolíticos/farmacologia , Afrodisíacos/farmacologia , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Janus Quinases/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , beta Catenina/metabolismo
9.
Phytother Res ; 36(11): 4063-4079, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36221815

RESUMO

Barberry (Berberis vulgaris L.) is a medicinal plant and its main constituent is an isoquinoline alkaloid named berberine that has multiple pharmacological effects such as antioxidant, anti-microbial, antiinflammatory, anticancer, anti-diabetes, anti-dyslipidemia, and anti-obesity. However, it has restricted clinical uses due to its very poor solubility and bioavailability (less than 1%). It undergoes demethylenation, reduction, and cleavage of the dioxymethylene group in the first phase of metabolism. Its phase two reactions include glucuronidation, sulfation, and methylation. The liver is the main site for berberine distribution. Berberine could excrete in feces, urine, and bile. Fecal excretion of berberine (11-23%) is higher than urinary and biliary excretion routes. However, a major berberine metabolite is excreted in urine greater than in feces. Concomitant administration of berberine with other drugs such as metformin, cyclosporine A, digoxin, etc. may result in important interactions. Thus, in this review, we gathered and dissected any related animal and human research articles regarding the pharmacokinetic parameters of berberine including bioavailability, metabolism, distribution, excretion, and drug-drug interactions. Also, we discussed and gathered various animal and human studies regarding the developed products of berberine with better bioavailability and consequently, better therapeutic effects.


Assuntos
Berberina , Berberis , Plantas Medicinais , Animais , Humanos , Berberina/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia
10.
Phytother Res ; 36(10): 3691-3708, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35841194

RESUMO

Cancer development entangles with mutation and selection for cells that progressively increase capacity for proliferation and metastasis at the cellular level. Surgery, chemotherapy, and radiotherapy are the standard treatments to manage several types of cancer. Chemotherapy is toxic for both normal and cancer cells and can induce unfavorable conditions, such as chemotherapy-induced nausea and vomiting (CINV), that reduce patients' quality of life. Emesis after chemotherapy is categorized into two classes acute and delayed. Since ancient times, herbal medicines have been used in various cultures to manage stomachache, vomiting, and nausea. In this manuscript, the antiemetic mechanisms of several herbal medicines and their preparations such as Zingiber officinale (5-HT, NK-1 receptor and muscarinic antagonist activity), Mentha spicata (5-HT antagonist activity), Scutellaria baicalensis (antioxidant activity), Persumac (useful in delayed phase through antioxidant, anti-inflammatory, and anti-contractile properties) and Rikkunshito (supportive in acute and delayed phase through 5-HT receptor antagonist activity) have been reviewed to show their potential effects on decreasing CINV and attract scientists attention to formulate more herbal medicine to alleviate CINV in cancer patients. However, it is crucial to say that additional high-quality investigations are required to firmly verify the clinical effectiveness and safety of each plant/compound.


Assuntos
Antieméticos , Antineoplásicos , Neoplasias , Plantas Medicinais , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Antioxidantes/uso terapêutico , Humanos , Antagonistas Muscarínicos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Qualidade de Vida , Receptores da Neurocinina-1/uso terapêutico , Receptores de Serotonina , Serotonina , Antagonistas da Serotonina/uso terapêutico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
11.
Phytother Res ; 36(6): 2300-2323, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35234312

RESUMO

Metabolic syndrome (MetS) is a multifactorial disease with medical conditions such as hypertension, diabetes, obesity, dyslipidemia, and insulin resistance. Alpha-lipoic acid (α-LA) possesses various pharmacological effects, including antidiabetic, antiobesity, hypotensive, and hypolipidemia actions. It exhibits reactive oxygen species scavenger properties against oxidation and age-related inflammation and refines MetS components. Also, α-LA activates the 5' adenosine monophosphate-activated protein kinase and inhibits the NFκb. It can decrease cholesterol biosynthesis, fatty acid ß-oxidation, and vascular stiffness. α-LA decreases lipogenesis, cholesterol biosynthesis, low-density lipoprotein and very low-density lipoprotein levels, and atherosclerosis. Moreover, α-LA increases insulin secretion, glucose transport, and insulin sensitivity. These changes occur via PI3K/Akt activation. On the other hand, α-LA treats central obesity by increasing adiponectin levels and mitochondrial biogenesis and can reduce food intake mainly by SIRT1 stimulation. In this review, the most relevant articles have been discussed to determine the effects of α-LA on different components of MetS with a special focus on different molecular mechanisms behind these effects. This review exhibits the potential properties of α-LA in managing MetS; however, high-quality studies are needed to confirm the clinical efficacy of α-LA.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Ácido Tióctico , Proteínas Quinases Ativadas por AMP/metabolismo , Colesterol , Humanos , Lipoproteínas LDL , Síndrome Metabólica/tratamento farmacológico , Obesidade , Fosfatidilinositol 3-Quinases , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico
12.
Phytother Res ; 36(1): 506-524, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34962009

RESUMO

The main adverse effect of doxorubicin is cardiotoxicity. Oxidative stress and apoptosis induction have been suggested as mechanisms involved in its cardiotoxicity. In this study, cardioprotective effects of alpha-mangostin against doxorubicin-induced cardiotoxicity have been investigated in rats. Forty-two rats were divided as follows: Control, doxorubicin (2 mg/kg every 48 hr), alpha-mangostin (200 mg/kg), alpha-mangostin (50, 100, 200 mg/kg) + doxorubicin (2 mg/kg every 48 hr), and vitamin E (200 IU/kg) + doxorubicin (2 mg/kg every 48 hr). Alpha-mangostin was administered by gavage for 19 days, while doxorubicin (12 days) and vitamin E (19 days) were injected intraperitoneally. Doxorubicin decreased heart rate, increased electrocardiogram signal components duration and reduced systolic and diastolic arterial blood pressure, and caused histological damage in the heart of rats. Doxorubicin decreased heart weight and heart/body weight ratio, as well as elevated creatine phosphokinase isoenzyme and lactate dehydrogenase. Doxorubicin increased malondialdehyde, inflammatory biomarkers, and caspases 3 and 9 and decreased reduced glutathione content in heart tissue but co-administration of alpha-mangostin (100 mg/kg) restored all doxorubicin toxic effects. Results show that alpha-mangostin has protective effects against doxorubicin-induced cardiotoxicity by antioxidant, antiinflammatory, and antiapoptotic effects that may ameliorate doxorubicin cardiotoxicity in human chemotherapy without reduction in its anticancer effect.


Assuntos
Cardiotoxicidade , Xantonas , Animais , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Miocárdio , Ratos , Xantonas/farmacologia
13.
Am J Drug Alcohol Abuse ; 48(4): 422-432, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35658689

RESUMO

Background: Quetiapine is an atypical antipsychotic that antagonizes dopamine and serotonin receptors. It has been suggested that quetiapine can be used to treat substance use disorders, including opioid use disorder. Opioids modulate dopaminergic functions associated with conditioned reinforcement and these effects can be measured via the conditioned place preference (CPP) paradigm. Opioids' unconditioned effects are regulated by several proteins, including extracellular signal-regulated kinase (ERK) and cAMP-responsive element-binding (CREB).Objective: To assess the effect of quetiapine on morphine-induced CPP and motor activity levels, and on the levels of ERK and CREB proteins in the hippocampus and cerebral cortex.Methods: 42 male rats were exposed to a CPP protocol, in which they underwent a conditioning paradigm with saline, quetiapine (40 mg/kg), morphine (10 mg/kg), morphine plus quetiapine (10, 20, or 40 mg/kg), or morphine plus memantine (7.5 mg/kg, a positive control drug) (n = 6 per group). The rats were tested for CPP and exploratory activity. Levels of ERK and CREB proteins in the hippocampus and cerebral cortex were also measured.Results: Quetiapine co-administered with morphine inhibited morphine-induced CPP [F (6, 70) = 11.67, p < .001] and morphine's effects on motor activity (p < .001). Morphine enhanced ERK phosphorylation in the hippocampus (p < .001) and cerebral cortex (p < .001), an effect inhibited by quetiapine.Conclusion: Quetiapine attenuates morphine-induced CPP and locomotion and these effects are associated with a reduction of ERK phosphorylation in the hippocampus and cerebral cortex. These results suggest that quetiapine should be further explored as a potential treatment for opioid use disorder.


Assuntos
Morfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/farmacologia , Animais , Córtex Cerebral/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/farmacologia , Hipocampo/metabolismo , Masculino , Morfina/metabolismo , Morfina/farmacologia , Fosforilação , Fumarato de Quetiapina/metabolismo , Fumarato de Quetiapina/farmacologia , Ratos
14.
Drug Chem Toxicol ; 45(4): 1528-1535, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33213219

RESUMO

Acrylamide (ACR), one of the most toxic chemical agents in humans and animals has several uses in different industries. Carnosic acid is an important biological antioxidant extracted from rosemary. In this study, the protective effect of carnosic acid on ACR-induced neurotoxicity in rat and PC12 cells has been investigated. Male Wistar rats were randomly divided into eight groups including (1) control group, (2) ACR (50 mg/kg, i.p.), (3-6) ACR plus carnosic acid (5, 10, 20, and 40 mg/kg, i.p.), (7) ACR plus vitamin E (200 mg/kg i.p., every other day), and (8) carnosic acid (40 mg/kg i.p.). After 11 days, behavioral tests were evaluated. Malondialdehyde (MDA), glutathione (GSH) and Bax, Bcl-2, and caspase 3 protein levels in brain tissue were measured. In in vitro study, the protective effects of carnosic acid on ACR toxicity were assessed by MTT assay. ACR caused severe motor impairment compared to control, increased MDA, and decreased GSH level. ACR increased Bax/Bcl-2 ratio and cleaved caspase-3. Carnosic acid (40 mg/kg) significantly recovered locomotor disorders. Additionally, carnosic acid increased GSH content, reduced MDA, and decreased Bax/Bcl-2 ratio, and caspase 3 protein levels. Carnosic acid increased cell viability compared to ACR at concentrations of 2.5-10 µM. Carnosic acid is the most abundant antioxidant compound found in the rosemary leaves. Recently, natural compounds have been suggested as potential treatment interventions for various diseases through their antioxidant properties. In this study, carnosic acid reduced ACR-induced toxicity through inhibition of oxidative stress and apoptosis.


Assuntos
Abietanos , Acrilamida , Neurotoxinas , Abietanos/farmacologia , Acrilamida/toxicidade , Animais , Antioxidantes/metabolismo , Caspase 3/metabolismo , Glutationa/metabolismo , Masculino , Neurotoxinas/toxicidade , Estresse Oxidativo , Ratos , Ratos Wistar , Proteína X Associada a bcl-2/metabolismo
15.
Phytother Res ; 35(3): 1130-1146, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33015894

RESUMO

OBJECTIVES: Currently, the use of iodinated contrast media in diagnostic imaging has been increased in clinical medicine. Contrast-induced nephropathy (CIN) is an important adverse effect of contrast media injection. According to the significant role of oxidative stress in the pathophysiology of CIN, different herbal antioxidants have been used for the prevention of nephropathy in different studies. In this review, we discussed the preventive effects of herbal medicine and natural products against CIN. METHODS: We searched the electronic databases or search engines including PubMed, Scopus, ISI, Google Scholar with search terms such as "Contrast-induced nephropathy" and "Herbal medicine," "Contrast acute kidney injury" AND "natural products" and similar headings such as plant and extract. RESULTS: Known medicinal plants and active ingredients such as green tea, ginger, garlic, silymarin, curcumin, resveratrol, and thymoquinone have been examined for prophylactic effects or treatment of contrast media nephropathy. CONCLUSION: Herbal medicines have promising effects in the laboratory-based studies for the prevention and/or treatment of CIN. However, more practical and completed clinical trials are needed to investigate the clinical benefits of natural products against CIN.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Fitoterapia/métodos , Plantas Medicinais , Humanos
16.
Phytother Res ; 35(2): 864-876, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32985017

RESUMO

Recently, the novel life-threatening coronavirus infection (COVID-19) was reported at the end of 2019 in Wuhan, China, and spread throughout the world in little time. The effective antiviral activities of natural products have been proved in different studies. In this review, regarding the effective herbal treatments on other coronavirus infections, promising natural products for COVID-19 treatment are suggested. An extensive search in Google Scholar, Science Direct, PubMed, ISI, and Scopus was done with search words include coronavirus, COVID-19, SARS, MERS, natural product, herb, plant, and extract. The consumption of herbal medicine such as Allium sativum, Camellia sinensis, Zingiber officinale, Nigella sativa, Echinacea spp. Hypericum perforatum, and Glycyrrhiza glabra, Scutellaria baicalensis can improve the immune response. It seems that different types of terpenoids have promising effects in viral replication inhibition and could be introduced for future studies. Additionally, some alkaloid structures such as homoharringtonine, lycorine, and emetine have strong anti-coronavirus effects. Natural products can inhibit different coronavirus targets such as S protein (emodin, baicalin) and viral enzymes replication such as 3CLpro (Iguesterin), PLpro (Cryptotanshinone), helicase (Silvestrol), and RdRp (Sotetsuflavone). Based on previous studies, natural products can be introduced as preventive and therapeutic agents in the fight against coronavirus.


Assuntos
Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , Tratamento Farmacológico da COVID-19 , Quimioprevenção/métodos , Infecções por Coronavirus/tratamento farmacológico , Fitoterapia/métodos , Alcaloides de Amaryllidaceae/uso terapêutico , Antivirais/classificação , Antivirais/farmacologia , Produtos Biológicos/farmacologia , COVID-19/epidemiologia , Coronavirus/classificação , Coronavirus/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Humanos , Fenantridinas/uso terapêutico , Extratos Vegetais/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Scutellaria baicalensis , Terapias em Estudo/métodos , Replicação Viral/efeitos dos fármacos
17.
Phytother Res ; 35(4): 2252-2266, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33325602

RESUMO

D-galactose (d-gal) induces aging and memory impairment via oxidative stress and neuroinflammation pathways. This study evaluated the neuroprotective activity of thymoquinone (TQ) against d-gal. d-gal (400 mg/kg, SC), d-gal plus TQ (2.5, 5, 10 mg/kg, i.p.), and TQ alone (2.5 and 10 mg/kg) for 8 weeks were administered to rats. The effect of TQ on learning and memory were studied using the Morris water maze test. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the hippocampus. The levels of MAPKs (p-ERK/ERK, p-P38/P38), cAMP response elements binding (p-CREB/CREB), advanced glycation end products (AGEs), inflammatory markers (TNFα, IL-1ß), glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF) were analyzed by western blotting. Telomere length was evaluated using real-time PCR. Memory and learning impairment, MDA enhancement, GSH reduction, and neuroinflammation via increasing the TNFα, IL-1ß, and GFAP contents were observed in d-gal group. TQ with d-gal, improved memory impairment, reduced oxidative stress, and alleviated neuroinflammation. The elevated level of AGEs decreased by TQ compared to d-gal. No changes were observed in the levels of p-ERK/ERK, p-CREB/CREB, p-P38/P38, BDNF, and telomere length following administration of d-gal or TQ plus d-gal. TQ improved memory deficits of d-gal through anti-oxidative and anti-inflammatory mechanisms.


Assuntos
Benzoquinonas/química , Galactose/efeitos adversos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Wistar , Homeostase do Telômero
18.
Phytother Res ; 35(12): 6552-6571, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34414608

RESUMO

Licorice is the dried roots and rhizomes of various species of the genus Glycyrrhiza (Fabaceae) that have been used in folk medicine from ancient times. Many important research projects have established several beneficial effects for this medicinal herb, including antiinflammatory, antimicrobial, antiviral, antiprotozoal, antioxidant, antihyperglycemic, antihyperlipidemic, hepatoprotective, and neuroprotective. Licorice contains important bioactive components, such as glycyrrhizin (glycyrrhizic, glycyrrhizinic acid), liquiritigenin, liquiritin, and glycyrrhetinic acid. The protective effects of licorice and its main chemical components against toxins and toxicants in several organs including the brain, heart, liver, kidney, and lung have been shown. In this comprehensive review article, the protective effects of these constituents against natural, industrial, environmental, and chemical toxicities with attention on the cellular and molecular mechanism are introduced. Also, it has been revealed that this plant and its main compounds can inhibit the toxicity of different toxins by the antioxidant, antiinflammatory, and anti-apoptotic properties as well as the modulation of Inhibitor of kappaB kinase (IKK), Extracellular signal-regulated protein kinase1/2 (ERK1/2), p38, inducible nitric oxide synthase, and nuclear factor-κB (NF-κB) signaling pathways. More high-quality investigations in both experimental and clinical studies need to firmly establish the efficacy of licorice and its main constituents against toxic agents.


Assuntos
Fabaceae , Glycyrrhiza , Antioxidantes/farmacologia , Ácido Glicirrízico/farmacologia , Extratos Vegetais
19.
Phytother Res ; 35(12): 6489-6513, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34312922

RESUMO

Turmeric (Curcuma longa) and its constituent, curcumin, have been used for their therapeutic properties for a long time. Most of the medicinal impacts of turmeric and curcumin might be attributed to their anti-inflammatory, antinociceptive, and antioxidant effects. In the present review, the preventive and therapeutic potentials of turmeric and its active constituent, curcumin, on inflammatory disorders and pain as well as patents related to their analgesic and anti-inflammatory effects, have been summarized to highlight their value on human health. A literature review was accomplished in Google Scholar, PubMed, Scopus, Google Patent, Patentscope, and US Patent. Several documents and patents disclosed the significance of turmeric and curcumin to apply in several therapeutic, medicinal, and pharmaceutical fields. These phytocompounds could be applied as a supplementary therapy in phytotherapy, inflammatory disorders such as arthritis, inflammatory bowel diseases, osteoarthritis, psoriasis, dermatitis, and different types of pain including neuropathic pain. However, because of inadequate clinical trials, further high-quality studies are needed to firmly establish the clinical efficacy of the plant. Consistent with the human tendency to the usage of phytocompounds rather than synthetic drugs, particular consideration must be dedicated to bond the worth of turmeric and curcumin from basic sciences to clinical applications.


Assuntos
Curcuma , Curcumina , Anti-Inflamatórios/uso terapêutico , Curcumina/uso terapêutico , Humanos , Dor/tratamento farmacológico , Fitoterapia
20.
Phytother Res ; 35(7): 3558-3574, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33590943

RESUMO

Metabolic syndrome is known as a group of metabolic abnormalities with features including central obesity, insulin resistance, hypercholesterolemia, hypertriglyceridemia, and hypertension as well as low level of high-density lipoprotein (HDL)-cholesterol. Previous studies showed the ameliorating effects of Scutellaria baicalensis on metabolic syndrome parameters, including antidiabetic, anti-hyperlipidemic, anti-obesity, and antihypertensive. In this review, we deeply and mechanistically evaluated different studies on the effect of S. baicalensis and its two major bioactive constituents, baicalin, and baicalein, on the critical components of metabolic syndrome, including diabetes, hyperlipidemia, obesity, hypertension, and atherosclerosis. Scientific databases, including PubMed, Scopus, and Google Scholar were searched in the English language until the end of June 2020. Accordingly, S. baicalensis, and its two major bioactive constituents, baicalin and baicalein, represent promising effects on the control of metabolic syndrome and its related disorders such as obesity, hyperlipidemia, atherosclerosis, diabetes, and their following complications. In summary, our findings show that S. baicalensis and its active constituents, baicalin and baicalein, by activation and upregulation of AMPK and PPAR-γ as the main signaling in the hemostasis of glucose and lipid metabolisms may be favorable candidates for the prevention and treatment of the metabolic syndrome.


Assuntos
Flavanonas , Flavonoides , Síndrome Metabólica , Scutellaria baicalensis/química , Flavanonas/farmacologia , Flavonoides/farmacologia , Humanos , Síndrome Metabólica/tratamento farmacológico , Compostos Fitoquímicos/farmacologia
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